6,062 Matching Annotations
  1. May 2026
    1. On 2021-05-23 07:26:54, user disqusWVOR wrote:

      Fig.2 pg.25 graph indicates ~5% grade 3 (severe) systemic adverse effects with NVX 2nd dose vs. <1% with placebo. How was this addressed in the article other than pg.13 "similar frequencies of severe adverse events (1.0% vs. 0.8%)"?

    1. On 2021-05-25 00:37:20, user Dr J wrote:

      A glass of wine drinking with food slows the rate of absorption alcohol as has been shown by many studies. What is the effect of with food and without food in this study? Any difference or no difference?

    1. On 2021-05-26 07:10:41, user Robert Clark wrote:

      To the authors: with millions of lives at stake, you do not want to be on the wrong side of history on this.

      The most ethical response considering the extreme importance of the issue is to go beyond just retracting and actually rewrite to conclude IVM by best available evidence does appear to have effectiveness as a treatment for COVID.

      Robert Clark

    1. On 2021-05-26 16:03:04, user japhetk wrote:

      Also, what is the percentage of people who were vaccinated (by the COVID-19's vaccine) in both groups? Also, how many people in both groups received the COVID-19's vaccine before the antibody test and tested positive?<br /> If I understand correctly, Greece started vaccinating the general elderly population on January 16 and the data lock of this study was on April 28, and the antibody test should have been completed by January 28 or earlier.<br /> I would like to know if the antibody test results that showed more infections in the BCG group were affected by the vaccination of COVID-19's vaccine.

    1. On 2021-05-27 02:28:39, user Stel-1776 wrote:

      It did not look at the effectiveness of masks, but the effectiveness of mask MANDATES. It should read "Mask MANDATES did not slow the spread". Why? Too many people who think they know better than professionals who dedicate their lives to studying this field. Too many people not wearing them, wearing them incorrectly, wearing the wrong type, not cleaning them, etc.

      N95 masks are better, but there is solid evidence that regular surgical masks also reduce chance of spreading in the community.

      This is supported by a systematic review (a review and critique of published studies to date) published in one of the most highly respected medical journals in the world.

      "The authors identified 172 observational coronavirus studies across 16 countries; 38 of these studies specifically studied face masks and the risk of COVID-19 illness. The authors found that the use of either an N95 respirator or face mask (e.g., disposable surgical masks or similar reusable 12–16-layer cotton masks) by those exposed to infected individuals was associated with a large reduction in risk of infection (up to an 85% reduced risk). The use of face masks was protective for both health-care workers and people in the community exposed to infection."<br /> [Chu et al. COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020]

    1. On 2021-06-05 15:33:22, user Scandinavian Journal wrote:

      Imo the twelve (13·5%) patients that had comorbidities associated with risk for severe disease [17] made a courageous contribution by accepting the possibility of ending up receiving placebo in the trial.

    1. On 2021-06-09 18:09:15, user Paul Cwik wrote:

      Peer Review in this case does not mean that peers reconduct the experiments. It simply means that others (with suitable credentials) have read and accepted the paper as having correctly followed the scientific methods. In other words, they are simply looking for errors in the paper, not re-doing and confirming the results.

    1. On 2021-06-10 09:22:10, user cat's eyes wrote:

      What were the baseline characteristics of the 37 patients who survived on HCQ compared to the patients who died? From Table 1 patients who survived were generally healthier and younger than those who died. Table 4 should provide adjusted and unadjusted hazard ratios. Also, did you test for interactions between HCQ/AZM and predictors such as age and steroid use?

    1. On 2021-03-13 18:13:49, user Sean Patrick Murphy wrote:

      This study focuses on hospitalized COVID patients. Many longhaulers were never hospitalized and some were completely asymptomatic. The authors attempt to address this issue with the likely erroneous statement - "Secondly, this is an initially hospitalised cohort so we cannot directly extrapolate to individuals who initial infection did not result in hospitalisation although there is no reason to suggest the effect would be any different." Patient-led research has demonstrated that there are clear subcategories of longCOVID based on symptomatology and to lump these all together is simply wrong.

    1. On 2021-03-15 10:49:33, user Mav Rick wrote:

      If NHS staff were not being tested when community prevalence was high, or only being tested once a week for a virus that van be infectious in 3 days the floodgates were open for staff both in hospitals and care homes to transmit the virus through asymptomatic/presymptomatic transmission.

      The move to testing more staff 3 times a week was far too late, and not reliably implemented. A lesson not learned from first wave.The virus effectively went through an open door.

      This testing policy failure was far more responsible for thousands of infections and deaths in care home and hospital settings than the unsafe discharges from hospital, but almost never reported on, or researched.

    1. On 2021-03-27 15:05:23, user Rogerblack wrote:

      I note the severe concerns raised before the trial about inaccuracy of mental health scales used in this paper are not addressed at all in version 2. To find that comment, click on 'view comments on earlier vesions of this paper'.

      In short, mental health scales with physically ill patients risk being akin to asking patients 'do you wobble when you stand up' and concluding that one-leggedness puts you at great risk of low blood pressure.

      The measures used confuse 'I can't as I am physically unable to' with 'I cannot as I have anxiety/depression'

      Emailed coresponding author and other two leads on 25th, raising these concerns.

    1. On 2021-03-30 07:17:34, user Eunji Lee wrote:

      This is a good study to supplement the results of previous studies that showed the high false-positive rate of PET in early cervical cancer for pelvic lymph node detection. In particular, it is impressive that this cause was evaluated by correlating with inflammatory changes after conization. However, it would have been better if other imaging evaluations, such as CT and MRI, were added to the analysis to provide a way to supplement this limitation of PET.

    1. On 2021-04-06 09:02:36, user Hieraaetus wrote:

      1) An observational study on 90 patients from the end of 2020 compared with 90 patients treated during the first wave (Mar-Apr 2020): this is a bias! They should compare patients observed exactly during the same period. <br /> 2) In the paper there is no trace about the "Home-Therapy Algorithm": there is a list of allowed drugs but there is not an Algorithm that describes how use these drugs. Thus , the 90 patients did not underwent to a standardized treament.

    1. On 2021-04-06 13:27:57, user Roseland67 wrote:

      So,

      Under what conditions Is a fully vaccinated person at risk of infection again?

      And, can this fully vaccinated person, once reinfected, pass this infection on to others?

    1. On 2021-04-10 18:48:39, user Daniel Haake wrote:

      Regarding version 6 of your study, I have pointed out with my comment which statistical problems are present due to your study design, which leads to an overestimation of the calculated IFR (cf. https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.07.23.20160895v6?versioned=true#disqus_thread)"). Thank you very much for your reply to my statement. I think that an exchange is important, because this is the only way to get reasonable results. Therefore, please do not regard my comments as criticism, but as suggestions for improvement on how to achieve correct values. Since my statement is still valid with version 7, I answer to your answer, in which I comment here in version 7.


      Re: Re: The time of the determination of the death figures

      Here you seem to have misunderstood me. I meant that with your example wave of infections and starting the study shortly after the peak of the wave, there is the problem that antibodies have not yet been formed by many people by the time the study starts. By choosing the time of death then, you caught 95% of the deaths, but only a much smaller proportion of those infected. This leads to an underestimated numerator and thus an overestimated IFR.

      Just because it was also done that way in the Geneva seropaevelence study does not automatically mean it is correct. So there are also very much studies where the study date was chosen for the number of deaths. For example:

      https://www.who.int/bulleti...<br /> https://www.medrxiv.org/con... <br /> https://www.medrxiv.org/con...

      ?However, I agree with you that the Santa Clara County study should be taken with a grain of salt, as here the subjects were called via a Facebook ad and thus bias may have occurred.? As I said, I understand the idea of taking a later date for the number of deaths. However, the associated problems regarding the underestimation of the infected, which I wrote about in the previous answer, still remain.

      It is still incomprehensible that you calculate a difference of 22-24 days, but then take a value 28 days after the study midpoint. This puts them 4-6 days behind your own calculation and thus automatically increases the IFR. Why do you elaborately calculate the difference of 22-24 days to determine the correct time, but then don't use that value??? Let me open up another example. Let's say we are testing at the peak of an infection wave. But now we count all the dead who showed up after a certain time, but we don't take into account that a large number of people still got infected after that. Some of the counted dead will also have become infected after the study. Then we have recorded all the dead, but not all the infected. Or do you want to say that all the dead are from the first half of the infection wave and none from the second part of the infection wave (especially since that would lead to an IFR of 0% for the second part of the infection wave). As you can see, it is problematic if you assume the number of deaths in the much later course, because you then choose the denominator of the quotient too small and arrive at an IFR that is too high.

      In general, only deceased persons who are clear to have been infected before the latest time at which study participants may have become infected may then be included. This is not the time of the study, since the antibody tests can only be positive after some time following an infection.


      Re: Re: PCR tests from countries with tracing programs

      Is it really "PCR testing per confirmed case", not "PCR testing per capita" that is the important parameter? Let us assume two example scenarios for this purpose. Let's assume that we test every resident and at that time 1% of the population is in the status where the PCR test is positive. Then we currently know from everyone what their status is. But then we would only get 1 positive tested person out of 100 tests performed. This test would then not be taken because of the too low ratio of tests per positive case. And this, although we would have tested even everyone. Now let's assume the opposite case. We test in a country where we don't know exactly where how many people are infected. Now we test in one region and assume that this result is transferable for the whole country. But actually this region is not as affected as other regions, we just don't know. Now we do 10,000 tests and find 20 infected people there. Then we come up with a ratio of 1 positive test per 500 tests performed. That test would then be included in your selection, even though the ratio of infected is actually higher. Therefore, it is just not the "per confirmed case" that is the important parameter. Because if there is a high number of cases in the country, you could now double and triple test everyone and know very well and still this investigation would be excluded. At the same time, however, studies can be included with few tests and thus a high statistical uncertainty for the reasons mentioned earlier.??

      The comparison with South Korea is also problematic. 0 or 1 seropositive results are far too few to have any statistical significance. The statistical uncertainty here is simply too high. And, as already mentioned, the results of these investigations cannot be transferred across the board to the other investigations. ??

      Including reported case numbers from countries that have a tracking system that works well for you leads to an overestimation of IFR.


      Re: Re: Study selection

      That you screen out studies, based on recruitment I can understand. I think that is statistically correct. I also see the danger with recruitment that you can't get representative results. Therefore, it is also understandable that you want to see which studies are useful and which are not.<br /> Nevertheless, you just sort out the studies that have a low calculation of IFR and leave studies with high values in your study. This leads to a shift toward the high values. Furthermore, studies that are straight up deviant are more problematic because a larger shift is possible in that direction. Let's say there is a hypothetical virus with an IFR of actually 0.5%. Then we have a study with a value of 0.3% and a study with 1.5%. The high value in particular is further away from the actual value and thus shifts the calculated value upward. If you have an actual IFR of 0.5%, you can misestimate by a maximum of 0.5 percentage points on the downside and by 99.5 percentage points on the upside in theory. This is also not surprising because such distributions are right skewed. If I remove both, the study with the too low value and the study with the too high value, the actual value does not change. If I remove both, the calculated value shifts upwards, because a stronger shift is possible in this direction. This leads to an overestimation of the IFR.


      Re: Re: Adjustment of death rates for Europe due to excess mortality

      You write in your reply that this is not relevant because reported deaths were used and not excess mortality. In Appendix Q you write: <br /> "For example, the Belgian study used in our metaregression computed age-specific IFRs using seroprevalence findings in conjunction with data on excess mortality in Belgium“. You may not have applied this to other studies. However, you are using a study that did. Accordingly, this is crucial and has an impact on your result.


      Re: Re: Calculation of the IFR of influenza

      You nevertheless calculate an age-specific IFR for COVID-19 and calculate the IFR as it would look if there were an equal distribution across age groups, which in fact there is not. At the same time, you say what the IFR is for influenza, which, as shown, you understate. After all, the comparability of numbers due to changing life circumstances do not change in a short period of time. Therefore it is no problem to use the IFR for influenza of several years. Thus you suggest a comparability of the numbers. It is not possible to compare an IFR that assumes an equal distribution of age groups with an IFR that does not assume an equal distribution. However, this is exactly what is being suggested. By the way, it is not only the media, it was also taken up by Dr. Drosten. For another reason the comparability is difficult. Namely, an IFR is compared of influenza, where we could already protect the vulneable groups to some extent by vaccination and also an infection could have been gone through in the past, which helps to fight the disease and can therefore lead to fewer problems. However, to be honest, one can of course argue here that this is just the way the situation is. Therefore it is also understandable for me if one nevertheless makes such a comparison. Then, however, by assuming an equal distribution over the age structure for both viruses, or the actual distribution for both. By the way, there is another problem. There is a comparison of an estimated IFR with a measured one.

      ---------------------------------------------------


      Additional comment

      With the studies to date, it is very difficult to estimate how high the IFR actually is. This is because there are problems with all methods. If you take antibody studies, there is the problem that antibodies are not detectable in all infected people. If you take the reported numbers of cases, there is the problem of the dark field. How could one calculate a clean IFR? By actually testing a certain proportion of the population as a representative group on a regular basis. For example, you can test 1 per thousand of the population every week and see if they are positive for COVID-19. Then look at how many people have died over time from the group of positives. Those deceased could then be autopsied by default to determine whether they died from or with COVID-19. In doing so, one must then determine what period of time after infection is still valid to count as a COVID-19 dead person. After all, is a person who died 10 months after infection still a COVID-19 dead person? After all, it is the elderly who are dying. But it is not atypical that they would have died over time even without infection. Now imagine that a 94-year-old dies 10 months after an infection. Can one then still say whether it was due to COVID-19? In this case, one would probably have to look at the medical history before and after COVID-19 and also see what symptoms the deceased had after the infection. Only with such a procedure it is possible to calculate a clean IFR. For a correct comparability with influenza, this procedure would also have to be used for the calculation of the IFR of influenza. If you are really interested in a scientific comparability of the IFR, you should proceed in this way.

    1. On 2021-04-12 05:38:07, user ICUC wrote:

      What were the results of these breakthrough infections? Were the symptoms severe? Did anyone need hospitalizations? Was there any death?

    2. On 2021-04-16 16:04:08, user Dirk Van Essendelft wrote:

      Just curious about the age distribution. The FE vaccinated cohort appears to be significantly older than any other cohort and also exhibits the highest B.1.351 infection rate. Is it fair to conclude that the vaccine is less effective against this strain or is it fair to conclude that the B.1.135 strain is more infectious for an elderly population.

    1. On 2021-04-14 12:02:43, user ingokeck wrote:

      Dear authors!<br /> Thanks a lot for publishing these interesting results as preprint! Reading it I arrived at a few questions and comments you might be able to answer to me:

      (1) You have the gold standard to detect an infection: Viral cultures with confirmation of the viral agent via test. Yet you decided to use the less reliable RT-PCR as basis. Why? RT-PCR does not measure the existence of infectious virions, it only measures the existence and concentration of specific genes as RNA and DNA in a sample. There is a big issue with old gene material still „hanging around“ after all virions have been destroyed.

      (2) Using your numbers from Figure 2 and the viral cultures as basis one can calculate that RT-PCR correctly detected 69% (77 of 112) of the cultured cases as positive and wrongly claimed 31% (35 of 112) to be positive. The BD test correctly identified 93% (66 of 71) of the cultured cases as positive and 73% (30 of 41) to be negative, but wrongly claimed 27% (11 of 41) of the cultured cases to be positive and 7% (5 of 71) to be negative. You clearly should not use RT-PCR as basis for the performance estimation!

      (3) You call copies/ml a „viral load“. Why? This is not the definition of viral load. What you have is a concentration of gene copies. Viral load is defined by virions per host cells in a given volume. There is no simple relationship between viral load and gene copy concentration as the number of copies produced per virion depend on the host cells and the gene.

      Thanks in advance for looking into this!

    1. On 2021-04-25 17:39:35, user Mikko Heikkilä wrote:

      There are multiple errors in this systematic review and meta-analysis that have been reported to the authors already once the second version was published December 2nd 2020 and they have not been corrected to the third version either.

      The intervention group total for the Aiello et al. 2010 paper is 663 and not 745 thus changing also the Relative Risk for that RCT.<br /> The third version has the mask and mask+hand hygiene groups separated but the numbers are still wrong. Aiello et al. subtracted the cases with previous symptoms so that the correct totals are 316 (367 in Ollila et al.) and 347 (378 Ollila et al.).<br /> The RRs for

    2. On 2021-04-25 17:46:32, user Mikko Heikkilä wrote:

      The RRs for the Macintyre et al. 2015 and Suess et al. 2012 are also not what they are in the original papers.

      For the Cowling et al. 2009 Ollila et al. have used 18 events in an intervention group of 258. The orginal paper has three definitions for an event in the groups: RT-PCR confirmed, Clinical definition 1 (2 symptoms) and Clinical definition 2 (3 symptoms). There were 18 RCT confirmed, 55 Clinical def 1 and 18 Clinical def 2 cases in the intervention group.

    1. On 2021-04-27 03:16:13, user vijayaddanki wrote:

      Very interesting paper. Once you identified the mutations and found that these are unique variants, how did you determine the parent lineage? Did you use any programming tools or did you manually identify the parent lineage. I have a set of new unique variants (with a detailed list of mutations in the Spike protein), their GISAID Accession IDs, origin dates/locations and current dates/locations where it is prevalent. But I am very confused on how to submit it to get a new Pangolin lineage designation.

    1. On 2021-04-27 22:06:58, user Tom Argoaic wrote:

      I've looked over the public data set released by the Minnesota group, plus their later publication about their studies, and I can't figure out how to correlate the shipping times you used in this paper with their data set. Did you alter or adjust the shipping times in your paper? And if so, how? I didn't see any description of this in your methods, which makes me wonder where you came up with your numbers as I try to replicate the data you presented here.

      Data sets I used, sent by their team:<br /> https://drive.google.com/dr...<br /> https://drive.google.com/dr...

      Their paper that goes over their protocol and shipping times:<br /> https://academic.oup.com/of...

    2. On 2022-02-09 01:07:23, user Avi Bitterman wrote:

      This paper dichotomizes a continuous variable to get a barely statistically significant result (P=0.044). But this is just dichotomania. Time to treatment is a continuous variable, not a binary variable. The appropriate test for this continuous variable is a regression along the continuous variable. Not a dichotomized sub-group analysis.

      Using the same numbers this author uses from Table 1, we ran a regression which failed to show a significant effect of treatment delay on outcome P=0.13

      Aside from being the appropriate test, another advantage of a regression here is it avoids the possibility selective dichotomization along the proposed moderator variable to get the desired result (a barely significant P value the authors just so happen to have found).

      I would also be happy to have a discussion with the authors to elaborate on the above as well as discuss numerous other critical errors with this analysis as well.

    1. On 2021-04-28 10:31:51, user Steve Winter wrote:

      In terms of Altmetric attention score, this potentially includes both positive and negative comments on social media. Did you account for this in your analysis? This is an important limitation when it comes to interpretation of Altmetric scores, and could be discussed in your manuscript.

    1. On 2021-05-01 23:02:46, user Nick Day wrote:

      The logistic fit for the B.1.1.7 lineage looks good. It is interesting to see that it works for such a range of (spatial, sampling, etc.) scales. It may also be of interest to see the logistic curve fits (for two individual mutations across all lineages) during 2020 for the initial spread phase of P681H and the saturation phase of D614G. The data for this is presented at https://www.biorxiv.org/con... - see also the comment there.

    1. On 2021-05-06 19:34:30, user disqus_p0Pq7NxFg7 wrote:

      Maybe I missed it, but you did not include a control group of individuals that had Covid and no vaccination. So, I curious how you can reach a conclusion that the vaccination improves immunity for individuals that had Covid.

    1. On 2021-05-12 01:30:10, user Heidi Connahs wrote:

      Interesting paper! I have one comment though. I am noticing an increasing number of papers using the term post-exertional malaise (PEM) without providing any definition of what this condition represents. This is important because PEM is not a term widely known in the medical community and it has a distinct presentation. PEM is the worsening of a variety of symptoms following even minor physical or mental exertion and moreover, the severity of the impact is often delayed by hours or days and can take days, weeks or months to recover from. The reason why PEM is not widely known is because it is the cardinal symptom of the disease ME/CFS which has been significantly ignored and underfunded. PEM is unique to ME/CFS and any mention of PEM should really provide appropriate references to ME/CFS literature.

    1. On 2021-09-18 19:05:19, user OBS wrote:

      These long-term results from Pfizer's clinical trial are quite informative- does anyone know of a corresponding preprint from Moderna containing their long-term (i.e. 6 months or so) clinical trial results, particularly regarding safety (total deaths, adverse events, etc.) Moderna has said it's efficacy at 6 months was 93% (a tiny bit better than Pfizer), and all 3 COVID deaths by 6 months were in the placebo group (also better than Pfizer's result of 1 COVID death with vaccine vs. 2 COVID deaths with placebo). This is not at all surprising considering that Moderna's vaccine dose is over 3x higher than Pfizer's. But what about Moderna's results for total deaths, how do they compare to Pfizer's? Surely, so many people here would like to know.

      The following is stated in an article from 3 days ago on Moderna's website:

      "Additionally, the Company shared a new analysis of follow-up through 1 year in the Phase 3 COVE study suggesting a lower risk of breakthrough infection in participants vaccinated more recently (median 8 months after first dose) compared to participants vaccinated last year (median 13 months after first dose). Manuscripts summarizing both findings have been posted to preprint servers and will be submitted for peer-reviewed publication."

      However, no such preprint from the COVE study seems to show up- does anyone know how to find it?

    2. On 2021-10-18 22:45:59, user Sir Henry wrote:

      Table S3 of the Supplementary Materials shows 262 "severe" adverse events for the vaccine, compared to 150 for the placebo. The difference of 112 is too large to be a statistical fluke (p < 0.001) and is a multiple of the number of "severe COVID-19" cases (30) for the placebo (Table S6). In terms of "severe" outcomes (COVID-19 or adverse events), the vaccine appears significantly more dangerous than the placebo over the four month observation period.

    1. On 2021-09-18 21:17:19, user Mike wrote:

      This study did an awesome job! One of the reason it didn't have the political bias rather letting the science flow instead of putting on a show to sway people in a particular direction to fit a particular narrative. I predict more studies will bare this out, that natural immunity is better than vaccines but it doesn't mean people shouldn't get vaccinated if they want to but shouldn't be forced! Israel is an example of weakness with the Pfizer vaccine, most likely the other have this weakness too. One of the weaknesses of this vaccine and others is the fact that it's the same, viruses change. This is why the delta variant spreads easier than previous versions.

      Back in August almost 60 percent of the hospitalizations in Israel were people at least 60 years old and fully vaccinated! Israel's government a great believer in vaccinations will be going on their 4th booster! I don't see a high rate of re-infections of those who already had Covid along with hospitalizations, but I do believe Covid is here to stay and re-infections will become common and some people will have major health issues with it. People 18 or younger which total so far 74 million Covid infections, 362 have died due to Covid complications.

    2. On 2021-09-20 23:38:51, user BaboliDaboli wrote:

      The study states: "Symptoms for all analyses were recorded in the central database within 5 days of the positive RT-PCR test for 90% of the patients, and included chiefly fever, cough, breathing difficulties, diarrhea, loss of taste or smell, myalgia, weakness, headache and sore throat." I understand this as follows: 90% of recorded symptomatic COVID-19 cases in the study were first recorded as positive on RT-PCR test. That would mean that any correlation between recorded number of positive RT-PCR tests, recorded symptomatic COVID-19 outcomes, and recorded COVID-19 related hospitalization outcomes may stem from the fact that positive RT-PCR test was a prerequisite for any other outcome to be recorded at all. As there were no fatal outcomes recorded, most hospitalizations recorded in the study might have been due to mild symptoms and a previous positive RT-PCR test (study fails to present the breakdown of hospitalizations by disease severity or duration of hospitalization). An earlier study of the link between hospital load and increased COVID-19 mortality in Israel (Rossman, H., Meir, T., Somer, J. et al. Hospital load and increased COVID-19 related mortality in Israel. Nat Commun 12, 1904 (2021). https://doi.org/10.1038/s41467-021-22214-z) found that between July 15th 2020, and January 1st 2021, on average, almost 60% of people were hospitalized while presenting mild initial clinical state. So, if most breakthrough infections or re-infections in the study never progressed past the mild clinical state, and if such patients wouldn't even be considered for hospitalization in Israel without a positive RT-PCR test, it is quite possible that all study outcomes depend directly on people taking a RT-PCR test and testing positive. While it may be difficult to assess and account for the difference between vaccinated and previously recovered people in terms of their inclination towards taking the test in case of mild or non-existent symptoms, any possible bias in terms of testing policies in Israel should be addressed and accounted for in the study. An example of such potential bias can be found on the Israel Ministry of Health "Testing for COVID-19" webpage (https://www.gov.il/en/departments/general/corona-tests) which states: "As a general rule, save for few exceptional cases, it is not necessary for confirmed patients or recovered patients to take a swab test for coronavirus, unless there is clinical suspicion for repeated infection with the virus." As clinical suspicion depends on severity and combination of symptoms typical for COVID-19, and as the set of symptoms related to delta variant seems to differ slightly from the set of symptoms related to previous variants, some or maybe even many reinfected people never got tested by RT-PCR as they had no symptoms or had only mild symptoms that never progressed beyond that. If that were the case the number of reinfections and related outcomes might be significantly underestimated in this study.

    3. On 2021-10-04 13:50:29, user Steve Vlad wrote:

      To the study authors:

      As an epidemiologist, if I was reviewing this paper for publication I would send it back to you for major revisions or reject it outright. I would not even bother looking at the results.

      The major issue is that you have conditioned study group entry by an event that happens at the end of the study. I.e. you have created a cohort of unvaccinated persons who must remain unvaccinated throughout the study. This is guaranteed to introduce selection bias, more specifically immortal-time bias. This further guarantees a biased estimate. This topic has been written about many times. Cf any of many articles by Sammie Souza at McGill.

      Imagine someone in your unvaccinated cohort. Soon after the initial study date they develop an infection. 5 weeks later they have recovered and decided they should have had the vaccine, so they get one. Because you have insisted this group remain vaccine free you throw them out of the group and you lose their data. You have just thrown out an infection. Do this just a few times and it is guaranteed that your ‘vaccinated’ group is not reporting as many infections as it actually experienced. This easily accounts for the effect you report.

      Note that this does NOT happen with the fully vaccinated/boosted group who must receive all vaccinations prior to study entry. You capture each and every infection with no drop out. Thus you’ve created a situation where you have non-random drop-out between the groups. That is selection bias.

      To get around this problem you MUST use methods such as Cox proportional hazards modeling with time-varying exposure variables so that persons can move between cohorts based on exposure to the vaccine during the study period.

      Hope this helps.

    4. On 2021-10-15 21:36:23, user Mary V wrote:

      Please add results for the unvaccinated individuals who recovered from Covid prior to Feb 28, 2021. How does their risk of symptomatic infection during the delta uptick compare with the individuals who were fully vaccinated by Feb 28, 2021 and didn't have a positive Covid test before 6/1/21? Did one shot of the Pfizer vaccine improve the immunity of that group during the delta uptick? Other studies have shown a very strong immunity for those who have recovered from Covid symptoms. The data in this paper only supports a vaccine recommendation for people who've had asymptomatic cases of Covid. Hence the data for those who've had symptomatic cases needs to be added or your conclusion about the vaccine recommendation should be qualified.

    1. On 2021-09-25 10:12:08, user Jan Podhajsky wrote:

      I forgot to add that researchers allowed persons below 15yo to enter the survey without parental/guardian consent. This is illegal in Czechia.

    1. On 2021-11-04 18:32:24, user Libres Penseurs wrote:

      By looking roughly at the numbers, the authors seemed to be right. Ottawa area population is around 1 million. If Ottawa is aligned with the rest of Canada, 78% of the population received at least 1 dose since the beginning of the vaccination campaign. On the two months stated in the study, the increase was about 10% (overall Canada data). This means that around 100 000 people were vaccinated in the Ottawa area during those two months. Ottawa have a lot of hospitals so you cannot assume that everybody with adverse reaction to the vaccine will show up at the same hospital. The authors use 1/3 of that total number (32k). The 800000 number refers only to people having received at least one dose since the beginning of the vaccination campaign. <br /> Myopericarditis cases at one hospital for a period of two month cannot be used as a numerator on this number to calculate risk.

    1. On 2021-10-03 07:16:11, user kdrl nakle wrote:

      Sort of expected stuff, nothing surprising. Delta variant comes way ahead which is something we already know. So the real increase of airborne transmissions is a feature of Delta.

    1. On 2021-10-03 07:33:26, user kdrl nakle wrote:

      Ukraine's real disaster starts in 2021, in particular now with Delta variant since the country is in the bottom of European vaccination rates. 13% fully vaccinated versus 63% in EU. Absolutely catastrophic. Even worse than rather poorly vaccinated neighbors Slovakia, Romania, and Russia.

    1. On 2021-10-08 13:47:58, user Mazda Sabouri wrote:

      The IFR formula on page 9 appears to assume that the number of excess deaths and Covid deaths are equal. Certainly possible in certain regions, but also not a proper assumption to make universally.

      Also there does come a point where IFR exceeds PFR in a given region. Especially for a highly contagious virus that aggressive targets large numbers of vulnerable people each and every year. This study admits that certain regions in Iran have had 200%+ attack rates already.

    1. On 2021-10-08 20:58:14, user AbsurdIdea wrote:

      Referring to "However, if prior infection does not afford protection against some of the newer variants of concern, there is little reason to suppose that the currently available vaccines would either.": The mRNA vaccines are targeted specifically to the "spike". There appears to be no information as to what the infection used or uses to identify the virus, and thus while new variants have a "spike" and likelihood of maintained resistance there is zero evidence of what natural immunity would or would not recognise in a variant. Thus the argument provided has no substance.

    1. On 2021-10-09 20:30:31, user j` wrote:

      Are you under the impression antibodies are the immune system's only means of protection?

      Have you reviewed previous studies showing robust immunity of mild infections?

    1. On 2021-10-10 04:14:01, user kdrl nakle wrote:

      Nice. So you are 20 times more likely to have COVID induced myocarditis than vaccine induced one. And on the top of that the COVID induced one will last longer.

    1. On 2021-10-10 05:19:33, user kdrl nakle wrote:

      I don't know about UK but in case of US this is useless since the mitigation measures are so heavily politicized in the US to the point of absurd actions. For example Alabama, does not even report outbreaks in schools any more and does not quarantine nor test exposed students.

    1. On 2021-10-19 17:10:24, user Jeremy Gustafson wrote:

      It's too bad they didn't break out a 5th group of previously infected and not vaccinated to compare their immunity similar to the study that was done in Israel.

    1. On 2021-10-22 07:52:48, user Adrien MP wrote:

      Hi,<br /> Could you make Tables 1 and 2 available in order one can take the full extent of the work presented here?<br /> Thanks

    1. On 2021-10-24 07:24:16, user Otmar S wrote:

      Dysguesia is the leading indicator which can also be seen for children regarding other studies (for example CLOCK). I can´t find the question/incidence of Dysgeusia for children in this study. I wonder why. No data?

    1. On 2021-12-01 14:08:31, user watcher wrote:

      The authors mention that vaccination efficacy might be affected by underreporting of mild symptomps. This raises another issue, which was not accounted for in the model. Asymptomatic infected individuals may still transmit the virus, but due to the lack of symptoms will not alter their behavior. It should be assumed that the more prominent symptoms are, the more individuals will reduce their contacts, to protect themselves and others. As unvaccinated infections generally result in more symptoms, these individuals will likely reduce their contacts naturally. Symptoms alter the behavior of individuals and thus transmissions, which is not accounted for in the model, but could change the outcome quite a bit.

    2. On 2021-12-07 17:04:15, user LizzyJ wrote:

      ''Pandemic modeling'' is quickly becoming the astrology of mathematics & physics.

      Want to get a lot of media attention and citations? Simply code up a little model and write up a paper about your unscientific predictions. As in all models, the chosen values for the parameters in this simulation are naive assumptions. There is no sufficiently high-quality or complete data on vaccine status and mode of infection (e.g. infected by a vaccinated or unvaccinated person) currently being reported by hospitals or health departments.

      Pandemic modeling is an abstract and theoretical mathematical exercise with very high bias and uncertainty based on the underlying assumptions, factors included or excluded, incomplete input data, very poor data quality with big non-random gaps in the data, etc. It should not guide public policy. Only clinical studies and real-world medical data should guide policy.

    1. On 2023-03-08 12:30:58, user Carlos Oliveira wrote:

      This study has been published on Frontiers in Public Health: <br /> Routine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers<br /> Frontiers in Public Health, 11, 1003158 - February 2023<br /> https://doi.org/10.3389/fpu...

    1. On 2022-01-12 17:15:59, user Rick Sheridan wrote:

      This was a laudable effort and I congratulate all of the authors and the study’s primary driver for pushing this through. Am in agreement that insight from results is likely limited by the maximum dosage as stipulated by the NNHPD guidelines. I enclose here daily quantitative PCR results from a high-quality PCR vendor during my own Jan '22 experience with high-dose hesperidin in context of a documented SC2 infection during the omicron wave.

      https://emskephyto.medium.c...

      As can be seen in the data log made available, subject (100 kg male) was taking multiple grams at a dose, often successively within hours of each other. Critically for DDI, no other pharmaceutical drugs were taken concurrently. For independent auditing purposes, will be happy to disclose the PCR vendor, the collector, and the hesperidin nutritional supplement brand to any relevant reachout.

      With what little one has to go on from the posted results, I would offer a model that during an active infection, the minimum possible Ct value is correlated to the sustained serum hesperetin glucuronide level during the 0.5 - 2 days prior to the nasopharyngeal sampling from which Ct is determined.

      Addressing the standing issue that viral load has often peaked prior to trial enrollment, this challenge remains tolerable in context of a clinical trial because one can still show an accelerated viral load reduction in the experimental group as compared with control, sufficient to demonstrate the mechanism.

      Rick Sheridan<br /> EMSKE Phytochem<br /> 11-Jan 2022

    1. On 2022-01-12 20:21:08, user Mike B wrote:

      Do we know it's VOC? Dogs detect Parkinson's using same technique, perhaps from minor expression of misfolded protein. Discrimination and scent memory by dogs is much more complex than we know. <br /> Implies we could build a molecular filter to mimic dog's nose. That however, is elusive.<br /> Fantastic study. Much ??? to working dogs, especially Belgian Malinois!

    1. On 2022-01-13 12:47:09, user kdrl nakle wrote:

      On Christmass Eve Dec 24, 2021 there was 948 in ICUs in California. Yesterday CA DoH posted 1903 in ICUs. What happened? Most of that in Southern California, imagine. This flies in the face of this paper. This paper lacks multivariate analysis as most infected by Omicron were double vaccinated and most infected by Delta were unvaccinated. That way these people make sensational paper without serious research. <br /> We had 2730 deaths yesterday in the US (NYT), now the 7-day-avg is approaching the height of Delta wave, currently 1825. The peak of Delta wave was 2087 on Sep 20. I actually expect Omicron will crash this Delta record shorty as it will crash ICU overall record in no more than two days from today. Currently 24,711 in ICUs on January 11, 2022.<br /> This sad attempt to make Omicron look mild will actually cost many lives for all the people that took masks off and are believing this "mild Omicron" propaganda. Wait until you see.

    1. On 2022-01-14 20:11:27, user Boback wrote:

      Why are the event number exactly the same between vaccine arms in Table 1 in multiple places. Calculated point estimates and CI also the same for those. Did you have a coding error with events? I wouldn't expect so many exact event counts to overlap.

    1. On 2022-01-18 13:58:07, user William Henry Talbot Walker wrote:

      Were all of the vaccinated participants studied for pre-existing cellular response or globulin levels before the vaccines were administered?

    1. On 2022-01-21 05:16:30, user Victor Schoenbach wrote:

      I found this article both valuable and important, but I do not understand the last two sentences ("Despite the small numbers of individuals included in this study, the findings are uniquely valuable because of the early detection of Omicron infection in frequent workplace Covid-19 testing to prevent spread. In real-world antigen testing, the limit of detection was substantially lower than manufacturers have reported to the FDA based on laboratory validation.")

      The first of these sentences is confusingly worded; copy editing would help.<br /> The second sentence refers to a lower limit of detection. Perhaps I do not understand the technical meaning of that term, but I would have thought that meant that the real-world sensitivity of the antigen test was higher (virus detected at a lower level), whereas the article suggests the opposite.

    1. On 2022-01-21 14:18:29, user Rosanna wrote:

      It will be interesting to know which organs are mostly affected by these autoantibodies. No mention about it is done in the manuscript. Do the authors have this information? Are lungs more affected in patients that suffered a critical COVID-19? <br /> Also, do the authors have data in male patients?

      Rosanna Paciucci, Ph.D. Faculty Attending, Vall d'Hebron University Hospital, Barcelona, Spain

    1. On 2022-01-21 21:47:18, user Brian Roberts wrote:

      Thanks for this most up-to-date study. The only "sensitivity" number that matters to the clinician is how the BinaxNOW compared to the PCR for the entire group. That number was not provided. Or how they compare in symptomatic vs. asymptomatic groups, since that information is known to the clinician. How they compare in groups defined by the PCR Ct counts is all but useless, since it is unknown information at the bedside.

    1. On 2022-01-22 13:19:19, user Torsten Selle wrote:

      Is it possible to extend the measurement series to smaller aerosols (5-2µm). I am asking in regards to aerosols that cannot be stopped by ffp2 or n95 masks.

    1. On 2022-01-24 01:15:03, user Fergal Daly wrote:

      The paper uses linear regression on a non-linear variable (cases/100k). Does it apply directly to cases/100k or is it against log(cases) which should be somewhat linear?

    1. On 2022-01-28 20:32:03, user Ranya Srour wrote:

      The article is a good baseline for future studies involving suicidal ideation and bar graphs are very clear and easy to interpret. By extension, the study addresses the question: is it necessary to wait for sobriety before defining a patient as suicidal?

      Maybe discuss this question directly in the discussion more; since it is the main question it may be valuable to expand on the in discussion.

    2. On 2022-01-28 20:32:54, user Dhuha Al-Rasool wrote:

      Very interesting article! It would be interesting to see the impact of THC on the SI results considering that it does not wear off as quickly as alcohol.

      • D and T
    3. On 2022-01-28 20:26:41, user Hussein Turfe wrote:

      Was there any relation found between those who had THC in their urine and coming into the ED stating that they had a suicidal ideation?

    4. On 2022-01-28 20:33:22, user Mohamad Kabbani wrote:

      Fantastic article! Very informative and the ideas are easy to understand. This is a good baseline to get a better understanding on how different things have become during and after covid-19. We can learn what a pandemic can do to a population and compare it to this data as a reference point.

    1. On 2022-01-29 14:26:08, user Alberto wrote:

      Thank you for this study. It's important to have this kind of study in a country like Greece where mortality has been very high in 2021 (compared to other European and worldwide countries and compared to itself in 2020) because we can appreciate the difference between the reality observed and the projected modeling based on the data that is available about vaccination status. The resulting model, which is incompatible with the reality observed worldwide, is a good measurement of the quality of the data available. I hope this can be looked at in more <br /> detail by more people thanks to this study.

    1. On 2022-01-30 23:47:58, user HereHere wrote:

      I'm a registered massage therapist in Ontario. We received no clear advice from our regulatory college about ventilation. I was waiting and waiting and waiting. They were very slow with recommending N95s and KN95s, and to my knowledge, still have not acknowledged that surface transmission is exceedingly rare. I don't know how they coordinate with Public Health Ontario, but you would think that, given we work in close contact with patients in typically small, poorly ventilated rooms, ventilation would have been given greater consideration.

    1. On 2022-02-01 14:15:41, user Richard Reynolds wrote:

      There is another reason, the most likely one, why immune cell aggregates were not found in the meninges in this study, which is due to the nature of the tissue used. This study used formalin fixed paraffin embedded tissues which are suboptimal for studying the delicate meningeal compartment. Cells are lost from the meninges at every stage of the embedding, cutting and section mounting stages, when compared to using snap frozen blocks. When you float FFPE sections on to a water bath before mounting them on slides you can actually see with the naked eye parts of the meninges floating away from the sections. Presumably this would also results in losing various components of the meninges, including immune cells. We dont find nearly as many immune cell aggregates in the meninges when we use FFPE sections and in order to see them in the FFPE sections we needed to change out protocols substantially to much milder procedures in order to better preserve the cellular components of the meninges.

    1. On 2022-02-02 07:40:56, user Gerald Zavorsky, PhD, FACSM wrote:

      I have no idea why studies like these are coming out all of a sudden. Politics should not be a part of science and I think these diversity studies and social injustice studies actually do a disservice to the minority groups in the U.S. There are several studies that show racial differences in lung function. I, for one, have published one of these studies (10.1186/s12890-021-01591-7) that demonstrate differences lung function after correcting for several factors. In order for these authors to truly test the hypothesis that reference equations should not be adjusted for race (i.e., no adjustment if you are African American, Hispanic, or Asians), then you would need to perform a Kappa Statistic and ROC analysis in both whites and the other ethnic groups. In addition, in each race/ethnic group, you would need a substantial proportion of individuals with CONFIRMED DISEASE. That is, confirmed disease via CT imaging or via strict criteria (i.e., GOLD criteria). Using a subjective assessment of breathlessness is not right, in my opinion. The authors have not used the objective criteria of FEV1/FVC ratio for definitive obstruction; they only used FEV1 and FVC separately, and according to ATS/ERS guidelines, it is strictly the FEV1/FVC ratio that confirms obstruction. Then, using the LLN criteria for FEV1/FVC, then one should assess the sensitivity, specificity, positive predictive value, etc., comparing reference equations for different races in those with confirmed disease and those without the disease OR at least confirmed obstructive pattern (FEV1/FVC < LLN). That is, what is the sensitivity in detecting lung disease (or confirmed obstruction via the FEV1/FVC ratio) in blacks when using the GLI reference equation for blacks? What are the false negatives in blacks when using the black reference equation? THEN compare these results against the same group using the prediction equations for whites. This is really the only way. Subjective scores of breathlessness do not confirm the disease. All that their tables and figures show that if you use a white reference equation in blacks you can falsely over-diagnose lung disease in blacks. In this case, 870-890 blacks had falsely low FEV1 or FVC when using the white reference equation. The authors data actually go against their conclusions. First, 9% of whites were below the LLN for FEV1 when the white equation was used. Similarly, 9% of blacks were < LLN for FEV1 when the black equation was used. To me, this shows that the equations for blacks correctly identify low FEV1 values in blacks, and the reference equations in whites correctly identify low FEV1 in whites. The proportions are the same! As well, their Figure 1b, the mortality for Blacks that had an FEV1 that was normal when using black reference equation (orange line) was the SAME as when using the white reference equation for whites (blue line). This shows that the reference equations for whites used on whites are just as appropriate as the reference equation for blacks used on blacks. Indeed, if anything, Figure 1b demonstrates that using the white reference equation in blacks underscored mortality in blacks by 5% (i.e., 5% of the deaths are missed in blacks when using white reference equations). Thus, in conclusion, the authors have this all wrong and have misinterpreted the data. We should be correcting for race.

    1. On 2021-10-18 18:05:16, user Francis Bascelli wrote:

      How can I access this data on UK Biobank? The data/code section says the data can be accessed though UK Biobank, but I am having trouble finding it.

    1. On 2022-02-02 11:42:04, user Philip Ashton wrote:

      Hello,

      Thanks for posting this really fascinating paper, so much food for thought!

      We looked at this in our journal club today, and one practical issue that came up is that we would like to know over what period and what season sampling was done at each site and how this relates to typhoid season at each site. Because Typhi is often seasonal and this could influence the results.

      Thanks again!

      Phil

    1. On 2022-02-03 08:04:13, user dgatwood wrote:

      Any chance a future update to this article could include the VE data against hospitalization *prior* to the third dose of mRNA-1273 (for comparison purposes)? Even a citation would help.

    1. On 2022-02-03 21:59:47, user Suzy Huijghebaert wrote:

      Line 148: "susceptibility of potential secondary cases was highest among the unvaccinated"<br /> Yet, some % in Table 1 striked me, and Table 9 does not really confirm that in the OR values. So I checked a few numbers, as when it comes to transmission of the omicron it is not so much sex or age that will matter, but - in real life - rather the total number of people you are in contact with, in view of the speed of transmission and the fact kids are affected by this mutants as well. Neither does it matter - economic-wise- whether the secondary case is vaccinated or not (yet, I agree an interesting aspect to study).So, how did you define the "potential cases"? The potential cases (per group of index cases) were apparently much lower in the vaccinated group than in the unvaccinated, and just proportionally correcting for that parameter, suggests that the rough highest attack rate -t as would be in real life - would have occurred with both BA1 and BA2 among the fully vaccinated (62-63%), provided they would have been in contact with as many potential cases in their households as the unvaccinated. Please clarify what induces the divergence/where the divergence with the outcomes arise from. Another question: what was the proportion of omicron cases among the people having already received vaccine, yet not considered fully vaccinated and now counted among the unvaccinated in your unvaccinated sample? Already thank you for clarifying.

    1. On 2021-10-20 16:54:26, user helgarhein wrote:

      You reported a surprising result: in the group of 51health care workers who were replete (above 75 nmol/l) only 2 took supplements. I would not have expected so many people (49) to have replete 25(OH)D levels in indoor workers in Birmingham (52ºN) in May, without supplements. However we had in the UK an unusually sunny and pleasant spring in 2020. I guess many people used their free time to go outdoors, because it was so sunny and dry, cinemas, restaurants etc were closed and socialising happened mostly outdoors. I presume that the unusual finding of so many people with excellent 25(OH)D levels could be explained by having acquired those levels in the week or two before May 2020. But maybe a longer timespan with good vitamin D supply is needed to make really all immune actions work optimally?? Could this have skewed the curve to make it look U-shaped?<br /> But, as pointed out by Dr. Gareth Davies, the most important observation was missing: the out comes of those infected, the ICU admissions and the mortality rate.<br /> Helga Rhein, ?retired GP, Edinburgh

    1. On 2022-02-07 21:44:51, user Isaac Tian wrote:

      Hello, we're the authors of citation #20. We had a few suggestions after reading your work.

      1. A practical deployment of the network would ideally use some other silhouette imaging method such as a CT scan or an RGB photo like you suggested in the Study Limitations section. The sentences that referenced our work didn't mention our attempt to estimate total and regional body fat using a 2D RGB camera image.<br /> Our study data, composed of 2D coronal and sagittal images coupled with 2-fold DXA composition measurements, may be relevant to validating your method on non-MRI inputs. Additionally, I believe our parallel effort in estimating body composition from 2D silhouettes should be cited and compared against. We also did estimate compartmental body fat as arm, leg, and visceral fat. Our initial model was not very flexible in pose due to the smaller training set available at the time, but we have since corrected for this.

      2. I recomputed our errors as MAEs to directly compare against your results, and assuming an adipose tissue density of 900 g / L, this came out to 121 g and 151 g for males and females, respectively. This is about 3-4x less than the magnitude of error reported in your draft. An analysis on the RMSE may be appropriate as large scale data may inflate R2.

      A collaboration may be appropriate once this draft has passed peer review in which your network is used as the pre-trained initialization to fine-tune on silhouettes segmented from another imaging source, such as our Shape Up! dataset which was stratified by age and BMI. This also addresses the bias concern you mentioned as your MRI dataset has an average age of 65.

      Thanks for sharing your work!

    1. On 2022-02-25 06:26:07, user Abhishek Mallela wrote:

      As of February 24, 2022, Figure 5 in the published version of this manuscript is missing axis labels. Please refer to the preprint version of Figure 4 for the axis labels.

    1. On 2022-04-10 09:05:20, user dyctiostelium wrote:

      The manuscript describes an analysis made from a database of suspected and confirmed COVID cases, with information about whether they had received any COVID vaccine at least 14 days prior and in the case they were, which one of 7 different vaccines.

      It is stated that "vaccination status, date and specific vaccine<br /> product was collected from evaluated persons as part of epidemiological follow-up of suspected COVID-19 cases" and table S1 includes a row titled "Follow-up - person days", but the design does not seem to involve any clinical follow-up, given that the persons had either been vaccinated or not at the time their data was included in the database.

      Could the authors clarify what is the source of the numbers in the row "follow-up" of figure S1?<br /> Of note, when the person-day is divided by the n of each column it gives a number of 114 days for the unvaccinated and around 200 days for the 7 different vaccines.

    1. On 2022-04-15 17:26:22, user Young Juhn wrote:

      A version of this article has been accepted for publication in the Journal of the American Medical Informatics Association (JAMIA) published by Oxford University Press. A link will be forthcoming.

    1. On 2021-11-06 19:24:57, user Eleutherodactylus Sciagraphus wrote:

      : This preprint includes data from human subjects that are under ethical scrutiny. The<br /> majority of patients enrolled were not informed nor agreed on participating in the study. The Brazilian National Comission forResearch Ethics (CONEP) has been bypassed, documents have been tampered, and the situation is now under investigation.

      References supporting this statement (both in English and in Portuguese):<br /> https://brazilian.report/li...<br /> https://www.emergency-live....<br /> https://www.dire.it/14-10-2...<br /> https://www.matinaljornalis...<br /> https://g1.globo.com/rs/rio...

    1. On 2022-06-07 10:39:46, user M. M. Welling wrote:

      For the 2 patients, both were vaccinated before the PET scans. The control patents were from 2019 thus uninfected and not vaccinated for COVID-19. Neuroinflammation can be initiated by the vaccination after liposomal transfer of the mRNA through the BBB. This needs to be discussed as well.issue

    1. On 2022-07-11 07:19:17, user Thijs Blok wrote:

      Question: <br /> - A PCR can stay positive for weeks after infection, is that taking in account?<br /> - Is a throat swap executed with the selftests ?

    1. On 2023-06-29 09:40:33, user Nensi wrote:

      The idea behind this study is truly interesting and highlights the critical importance of addressing the issues surrounding poor reporting and the quality of systematic reviews.<br /> However, some things could be changed to improve the quality of this study. Below you can find some of my comments regarding your manuscript.<br /> 1) The manuscript could use extensive language editing, as there are many grammatical and spelling errors. Many language editing programmes can be very useful for these purposes (Grammarly, Instatext etc.).<br /> 2) You begin the Methods section with the aim of your study, but you state that the aim was to do a study. You can see why that does not make sense. The aim of your study was to do a study. You should report here the specific purpose or what you wanted to assess (for example, the aim was to assess the reporting quality of systematic reviews published by authors from India from 2015 to 2020).<br /> 3) In Results, you decided to report the data in text and with two figures. However, when you have so much descriptive data, it could be presented more clearly with just a table. The table allows the authors to store large amounts of data in a small place, making it easier for the readers to go through the data and understand the results. <br /> 4) Another detail about presenting the results is that they should be written in the past tense instead of the present tense you used.<br /> 5) Also, when presenting descriptive data, it is recommended to report both absolute and relative numbers (for example, „Only 20 (15%) of the reviews have been registered in PROSPERO registry“).<br /> 6) You could benefit from using STROBE reporting guidelines for observational studies (https://www.equator-network... "https://www.equator-network.org/reporting-guidelines/strobe/)"). Reporting guidelines are handy in ensuring you have reported everything that needs to be written in an article.<br /> 7) There is also much room for improvement regarding the referencing. A small detail would be the in-text referencing where you put [1] after the full stop. So the general rule would be that if you use brackets, it should be placed inside the sentence, and if you want to put the number in superscript, it should be after the sentence. That could use a bit of tidying up. <br /> 8) Additionally, regarding the referencing, you have used different styles of referencing in the reference list and some of the references are not referenced correctly or at all. There are many programmes that can help you organize and write the references (EndNote, Zotero, Mendeley etc.).<br /> 9) And one more thing for future referencing, even though a study is methodological, it should be preregistered. All studies should be preregistered to promote open science and transparency in conducting scientific research.<br /> I hope these suggestions will help. Good luck with your work!

    1. On 2021-12-01 22:19:03, user Kevin J. Black, M.D. wrote:

      You'll want to cite and discuss this article:<br /> Snowden JS, Craufurd D, Griffiths HL, Neary D. Awareness of involuntary movements in Huntington disease. Archives of Neurology. 1998;55(6):801-805.

    1. On 2020-12-03 21:43:53, user kdrl nakle wrote:

      It could also be that association is purely coincidental. Meaning people that die more often are older people and they are also more likely to be vitamin D deficient. So you really have nothing here.

    1. On 2020-04-05 22:12:33, user Soarintothesky wrote:

      What delay was used for the time adjustment. A 10 day delay for cases>deaths in the Aneirin Bevan University Health Board in Gwent in South Wales shows a 22% CFR.

    1. On 2020-06-04 00:48:58, user James Van Zandt wrote:

      Vitamin C is a common supplement. I suggest you track whether patients had taken vitamin C (and how much) before or in the early stages of their illness. If it is helpful, then we would like to know when it is most helpful.

    1. On 2020-04-10 00:26:48, user Brothers in arm wrote:

      Curious to know why the BCG vaccination last only about 20 years. I have had mine as an infant, without any further boosters. Still my skin tuberculin test remains reactive after almost 50 years. The reaction subsides before follow up check on day 3. This is read as negative for active TB. I assume the slight reaction as due to having had BCG, and I still have immunity. People who never had it do not get any reaction or erythema. Maybe any immunization can confer some cross immunity?

    2. On 2020-04-02 07:42:02, user japhetk wrote:

      I don't know why, but medrxiv keeps deleting my warning comments.

      So, I write brief comments again.

      This study doesn't control important variables as kept suggested in comments and probably the findings are due to spurious correlations.

      The one of uncontrolled important variable is "when the infection spread in the country". This study should have used the measure like "number of deaths or patients 10 days after 100th patients were detected in the country". Other analyses are doing that.<br /> The second uncontrolled important variable is "how long the country advanced BCG measure". UK, for example, advanced the BCG measure for more than 50 years. So, majority of nations are experienced with BCG.<br /> The third uncontrolled important variable is GDP. You can see the most of nations without BCG is Western rich countries which can do more tests, which are popular from tourists.<br /> I did analyses controlling these variables, and all the correlations between the length of BCG measure with coronavirus data (how fast the 100th patients were detected in the country, number of patients or deaths ten days after the 100th patients were detected in the country) are all insignificant. They did not even show the statistical tendencies.

      Many people have wrong ideas how effective BCG is though this preprint. Somebody has to give warnings. Please do not delete this warning.

    1. On 2020-06-30 08:50:43, user Simon Liebing wrote:

      I have 2 questions to the study:<br /> What explanation have the authors that only 2 of 5 indicators are positive?<br /> Why the virus vanishes after March 2019 again?

    1. On 2020-06-30 11:18:06, user Kevin McKernan wrote:

      Interesting work. Great to see the qPCR replicated at another lab and spike in controls.<br /> It would be very helpful to sequence the Amplicons to see if any variation exists that can augment the phylogenetkcs of the disease.

    1. On 2020-07-01 22:29:58, user John wrote:

      Loneliness is prevalent in COVID-19 crisis. Patients with Coronavirus are more lonely during the pandemic. Interesting findings for health psychology, psychological impact, public health, epidemiology and psychiatry.

    1. On 2020-07-07 14:29:11, user Anika Knuppel wrote:

      This article has been accepted for publication in the International Journal <br /> of Epidemiology, published by Oxford University Press.

    1. On 2021-01-26 03:42:24, user Terran Melconian wrote:

      Thanks for sharing this very interesting article.

      On page 6, for the definition of the x and z transforms, they are both given as sin(2*pi*t/tau). One of them is presumably meant to be a cosine, right?

    1. On 2020-06-21 11:55:23, user Dirk Monsieur wrote:

      Rough estimate: 1% infected at 12th of March; chances that 84 random people are not infected: 0,99^84 = 43%<br /> I'm not a statistical expert, but I think a power analysis would be good.

    1. On 2020-07-13 22:41:50, user Jim Coote wrote:

      I share the concerns expressed in the previous 2 comments. Surely the decrease in antibody levels would be entirely expected after the primary response. The acid test would surely be whether there was a good secondary response to any Covid19 based antigen. Any analysis of that should examine the cell based response as well as the humoral.

      Considering the concerns likely to be raised by their findings, I think it is a serious omission not to compare the data to antibody levels typically seen following primary responses to infections on which we have solid information on long term immunity, (both weak and strong). However this would be a completely academic consideration provided a good secondary response to Covid 19 antigen / virus was seen.

    1. On 2020-04-17 15:25:24, user Dr. James R. Baker wrote:

      Interesting approach and pretty convincing, but it does not take into account the number of asymptomatic infections associated with COVID. That is really substantial; some estimates of 30-50 percent. That would then double your number, wouldn't it?

    1. On 2019-11-12 00:51:39, user Guyguy wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT NOVEMBER 10, 2019

      Monday, November 11, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,287, of which 3,169 confirmed and 118 probable. In total, there were 2,193 deaths (2075 confirmed and 118 probable) and 1067 people cured.<br /> 411 suspected cases under investigation;<br /> No new cases confirmed;<br /> No new deaths of confirmed cases have been recorded;<br /> 3 people healed from the CTE in North Kivu in Mabalako;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths;

      NEWS

      Awareness and vaccination day for Beni mototaxi drivers with the support of Unicef S / Coordination MVE Beni, Wednesday 06-11 - 2019 HIVUM room

      • There were many, about three hundred, the drivers of Mototaxi Beni invited to a day of awareness and vaccination against Ebola Virus Disease this Wednesday, November 06, 2019 in the HIVUM room.

      • This day is welcome for the city of Beni during this period of EVD epidemic which, unfortunately, displays a lethality of 86.3% among motorcyclists, as pointed out by Dr. Pierre ADIKEY, Coordinator of the response of Sub Coordination of Beni.

      • Thus, in his presentation, he focused his message on the risk of transmission of EVD among motorotaxi drivers and the conduct to be held in the exercise of their craft to protect themselves and the community.

      • He asked bikers more often to respect the measures of prevention, namely: washing hands regularly, stopping at checkpoints, not being bribed to divert checkpoints, not carrying suspicious parcels and reporting and / or direct any suspicions of illness to colleagues or the community.

      • In order to circumscribe the day, Dr. P. ADIKEY traced the path of the last Motard who died of EVD before his death confirmed at the CTE. To close his presentation, he made a reminder of the various events that prevented the teams of the response from working: among other things the days of the dead city, the fire of the vehicles of the riposte, the destruction of the structures of the care, the cases of resistance and others whose bikers were part of it.

      • Dr. Bibiche MATADY, as Epidemiologist and Chair of the Monitoring Commission, introduced to the participants the importance of accepting to be listened to if you are in contact with a case, to let yourself be followed for the entire period indicated and to orient in a management structure as soon as the first sign appears. She also emphasized the collaboration between the bikers and the teams of the response.

      • To justify this day again, one of the 3 Hikers shared his testimony and urged his colleagues to collaborate and follow the recommendations of the response teams starting with vaccination.

      • Vaccination is one of the preventive measures against EVD, said Dr Adonis TERANYA, the Chair of the Immunization Subcommission. In his presentation, he explained the evolution of the vaccination protocol, the current targets, the side effects and the action to take in the event of an adverse event. Before calling for the voluntary vaccination of participants, he spoke about vaccines currently used in the DRC.

      • In his words, the President of Bikers reiterated to the Coordinator the commitment of his organization and all its members to support the interventions of the response, while affirming its availability to any solicitation for the fight against the disease to Ebola virus in the city of Beni and its surroundings.

      • The day ended with the vaccination of 100 Bikers and some of their dependents.

      VACCINATION

      • Since vaccination began on 8 August 2018, 250,234 people have been vaccinated;
      • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

      MONITORING AT ENTRY POINTS

      • Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 115,778,240 ;
      • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    2. On 2019-11-15 16:53:09, user GuyguyKabundi Tshima wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT NOVEMBER 13, 2019

      Thursday, November 14, 2019

      • Since the beginning of the epidemic, the cumulative number of cases is 3,292, of which 3,174 are confirmed and 118 are probable. In total, there were 2,193 deaths (2075 confirmed and 118 probable) and 1067 people cured.<br /> • 527 suspected cases under investigation;<br /> • 1 new case confirmed in North Kivu in Mabalako;<br /> • No new deaths of confirmed cases have been recorded;<br /> • No cured person has emerged from ETCs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths;

      NEWS

      Ebola Virus Disease Response Co-ordination Announces Three Road Traffic Accident in Bunia, Ituri

      • The overall coordination of the response to the Ebola Virus Disease epidemic in North, South Kivu and Ituri was informed on Thursday 13 November 2019 of the tragic traffic accident between two motorcycles, one of which carried three agents of the riposte;<br /> • These three officers, who work for the Epidemiological Surveillance Commission at the Point of Entry and Control, were returning from Bunia to Mambasa, where they are respectively delivering;<br /> • This accident occurred around Marabo in Bunia on the evening of Wednesday 13 November 2019;<br /> • The balance sheet reports an officer who died at the scene and two others who were seriously injured, including one in a coma. The two wounded were taken to the Nyakunde Reference General Hospital in Ituri for appropriate care;<br /> • The overall coordination of the response sends its deepest condolences to the grieving family and expresses all its compassion and solidarity to the injured officers, while wishing them a quick recovery.

      Effective start of Johnson & Johnson vaccination in two Goma health areas

      • Ebola vaccination with the Ad26.ZEBOV / MVA-BN-Filo vaccine, produced by Janssen Pharmaceuticals for Johnson & Johnson, began on Thursday, November 14, 2019 in two Karisimbi health areas in Goma City , North Kivu Province;<br /> • The Epidemic Response Coordinator for Ebola Virus Disease in North, South Kivu and Ituri. For this purpose, Prof. Steve Ahuka Mundeke visited the vaccination sites to inquire about the evolution of activities in the field. He was satisfied with the work of the teams;<br /> • He took the opportunity to invite the population of the targeted areas to be vaccinated in order to protect themselves from the resurgence of the Ebola virus;<br /> • Several people were present in Majengo and Kahembe health areas to get vaccinated. The first person to be vaccinated is a Kahembe community leader who has been protected against the Ebola virus today and also in case of a possible new Ebola outbreak. This community leader has appealed to all residents of his community and sites targeted to come take this second vaccine. "This is an opportunity not to be missed, because it is said that prevention is better than cure, " he said;<br /> • The logistics of this vaccination are provided by the international non-governmental organization Médecins Sans Frontières of France (MSF / France).<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, this second vaccine, called Ad26.ZEBOV / MVA-BN -Filo , is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine complements the first, the rVSV-ZEBOV, the vaccine used until then in this epidemic. Manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018, it was recently approved.

      Closing of the training workshop for media professionals in Beni on the role and responsibility of journalists during public health crises

      • The Deputy Mayor of the city of Beni, Muhindo Bakwanamaha Modeste, closed this Thursday, November 14, 2019 in Beni in the province of North Kivu the training of media professionals on the role and responsibility during public health crises;<br /> • The coordinator of the Beni Ebola Ebola response sub-coordination, Dr. Pierre Adikey, on behalf of the Coordinator-General of the Response, Prof. Steve Ahuka, wished to see these kinds of trainings be organized, not only in other sub-Coordination of the response, but also throughout the Democratic Republic of the Congo so that journalists from all over the country are ready to face any possible epidemic crisis;<br /> • This training, he said, is part of the zero-case Ebola strategy and strengthening the health system of tomorrow;<br /> • The focal point of Beni's journalists, Moustapha MULONDA, reaffirmed the commitment of journalists to combat Ebola Virus Disease through various programs and publications disseminated and published by their respective media thanks to the new tools acquired during this period. training;<br /> • This training was organized by the Ministry of Health in collaboration with the World Health Organization and benefited from the facilitation of the overall coordination of the response, UNICEF, CDC Africa and MSF.

      VACCINATION

      • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 251,637 people have been vaccinated;

      • Vaccination with the second Ad26.ZEBOV / MVA-BN-Filo vaccine, produced by Janssen Pharmaceuticals for Johnson & Johnson, began on Thursday November 14, 2019 in Goma. This vaccine was approved on 22 October 2019 by the decisions of the Ethics Committee of the School of Public Health of the University of Kinshasa and 23 October 2019 of the National Ethics Committee;

      • Until then, only one vaccine was used in this outbreak. This is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee in its decision of 20 May 2018 and which has recently been approved.

      MONITORING AT ENTRY POINTS

      • A 27-year-old woman from Butembo for Goma, an escaped suspect from Makasi Hospital in Butembo, North Kivu, was intercepted at the Kanyabayonga checkpoint in Kayna. When she was intercepted, she experienced signs such as fever at 38.4 ° C, severe asthenia, abdominal pain and vaginal bleeding. It was sent to the KAYNA Transit Center.

      • Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 116,622,388 ;

      • To date, a total of 112 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    3. On 2019-11-30 17:00:40, user Guyguy wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT NOVEMBER 27, 2019

      Thursday, November 28, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,309, of which 3,191 are confirmed and 118 are probable. In total, there were 2,201 deaths (2,083 confirmed and 118 probable) and 1077 people healed.<br /> • 443 suspected cases under investigation;<br /> • 5 new confirmed cases, including:<br /> o 4 in Ituri in Mandima;<br /> o 1 in North Kivu in Mabalako;<br /> • 2 new deaths of confirmed cases, including:<br /> o 2 new community deaths in Ituri in Mandima;<br /> o No deaths among confirmed cases in CTEs;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths.

      NEWS

      Three members of the Ebola Virus Epidemic response killed during an attack in Biakato, Ituri

      • Following the attack on the sub-coordination of the Biakato response in Ituri on the night of Wednesday 27th to Thursday 28 November 2019, three members of the Ebola response teams in this sector lost their lives ;<br /> • It is a provider and a driver of the vaccination committee and another driver;<br /> • In addition to these three deaths, there are 7 wounded and 6 others with psychological disorders and extensive material damage.<br /> • A good number of these teams from Biakato were evacuated in three waves to Goma. As soon as they arrived, they were greeted by a coordination team led by Prof. Steve Ahuka, general coordinator, who also visited the wounded before going to inquire about the security conditions and accommodation of evacuees. He did not fail to comfort them.

      VACCINATION

      • The vaccination commission is in mourning. A service provider and a driver of his team were killed on the night of Wednesday 27 November 2019 following attacks at the Biakato base in Ituri;<br /> • 2nd day without vaccination activity with the 2nd J & J vaccine following the disorders initiated by young people related to the security situation in Beni;<br /> • 724 people were vaccinated, until Tuesday, November 26, 2019, with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two health zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 255,373 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine is in addition to the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. has recently been pre-qualified for registration.

      MONITORING AT ENTRY POINTS

      • Sanitary control activities are disrupted in the towns of Beni and Butembo in North Kivu province following demonstrations by the population which decries killings of civilians;<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 121,159,810 ;<br /> • To date, a total of 109 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    1. On 2021-10-10 03:44:51, user kdrl nakle wrote:

      The results on T-cells is quite murky here, without much explanation. You really need a bigger sample to be able to see this better, your sample of 46 is too small.

    1. On 2020-01-25 23:16:22, user White_Runner wrote:

      There is another study that puts the R0 value in 1.4 to 2.6, still very high.<br /> However not apocaliptic levels like the one described here.<br /> Also, this R0 value can change in time as long as the adequate restrictions are taken in place.<br /> So, yeah guys, expect the best, have some precautions and happy lunar new year.

    1. On 2020-03-22 15:56:46, user Sinai Immunol Review Project wrote:

      Main findings<br /> The authors characterized the immune response in peripheral blood of a 47-year old COVID-19 patient. <br /> SARS-CoV2 was detected in nasopharyngeal swab, sputum and faeces samples, but not in urine, rectal swab, whole blood or throat swab. 7 days after symptom onset, the nasopharyngeal swab test turned negative, at day 10 the radiography infiltrates were cleared and at day 13 the patient became asymptomatic.

      Immunofluorescence staining shows from day 7 the presence of COVID-19-binding IgG and IgM antibodies in plasma, that increase until day 20. <br /> Flow cytometry on whole blood reveals a plasmablast peak at day 8, a gradual increase in T follicular helper cells, stable HLA-DR+ NK frequencies and decreased monocyte frequencies compared to healthy counterparts. The expression of CD38 and HLA-DR peaked on T cells at D9 and was associated with higher production of cytotoxic mediators by CD8+ T cells.<br /> IL-6 and IL-8 were undetectable in plasma.<br /> The authors further highlight the presence of the IFITM3 SNP-rs12252-C/C variant in this patient, which is associated with higher susceptibility to influenza virus.

      Limitations of the study<br /> These results need to be confirmed in additional patients.<br /> COVID-19 patients have increased infiltration of macrophages in their lungs{1}. Monitoring monocyte proportions in blood earlier in the disease might help to evaluate their eventual migration to the lungs.<br /> The stable concentration of HLA-DR+ NK cells in blood from day 7 is not sufficient to rule out NK cell activation upon SARS-CoV2 infection. In response to influenza A virus, NK cells express higher levels of activation markers CD69 and CD38, proliferate better and display higher cytotoxicity{2}. Assessing these parameters in COVID-19 patients is required to better understand NK cell role in clearing this infection. <br /> Neutralization potential of the COVID-19-binding IgG and IgM antibodies should be assessed in future studies.<br /> This patient was able to clear the virus, while presenting a SNP associated with severe outcome following influenza infection. The association between this SNP and outcome<br /> upon SARS-CoV2 infection should be further investigated.

      Relevance<br /> This study is among the first to describe the appearance of COVID-19-binding IgG and IgM antibodies upon infection. The emergence of new serological assays might contribute to monitor more precisely the seroconversion kinetics of COVID-19 patients{3}. Further association studies between IFITM3 SNP-rs12252-C/C variant and clinical data might help to refine the COVID-19 outcome prediction tools.

      References<br /> 1. Liao, M. et al. The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing. http://medrxiv.org/lookup/d... (2020) doi:10.1101/2020.02.23.20026690.<br /> 2. Scharenberg, M. et al. Influenza A Virus Infection Induces Hyperresponsiveness in Human Lung Tissue-Resident and Peripheral Blood NK Cells. Front. Immunol. 10, 1116 (2019).<br /> 3. Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. http://medrxiv.org/lookup/d... (2020) doi:10.1101/2020.03.17.20037713.

      Review by Bérengère Salomé as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai

    1. On 2021-10-29 15:37:00, user Rogerblack wrote:

      I find refreshing the repeated ''these associations did not survive correction for multiple comparisons'.<br /> An interesting paper.

    1. On 2020-05-20 16:50:49, user Peter Ellis wrote:

      Table 1 presents the data, showing 40 positive tests and 689 negative tests, i.e. an average prevalence of 5.49% across the course of the study. Elsewhere in the manuscript, the sensitivity is given as 100% (meaning none were missed) and the specificity as 98.3% (meaning there is a 1.7% false positive rate.

      This being the case, can the authors please explain:

      1) Why the caption for Table 1 reports 789 patients given that 40 + 689 = 729?

      2) How they adjusted for false positives. 40 / 729 = 5.49%, which minus the 1.7% false positive rate leaves around 3.79% positive across the course of the whole study.<br /> [A Bayesian adjustment would be more accurate, this will suffice for now]

      3) Given that the true positive rate in the samples they measured is around 3.79% across the whole study, how do they calculate a population prevalence of 4.6% at the start, rising to 7.1% at the end of the study. The methodology for this is entirely lacking.

    1. On 2020-04-22 02:20:27, user Mike wrote:

      This was certainly an interesting paper. It's done a lot of work and the findings are notable. IMHO it warrants as much attention as the pro-HCQ study via Dr. Raoult. While it is entertaining, I will add that it is not conclusive, nor without fault. A double-blind study is still required, but it is worth the read.

      Observations/Questions:

      1. "hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease”<br /> 2. "we cannot rule out the possibility of selection bias or residual confounding”<br /> 3. demographic: 100% male, 66% black, median age ~70 (59 youngest)<br /> 4. uses PSM, which despite a common practice, could be considered controversial (https://gking.harvard.edu/f... "https://gking.harvard.edu/files/gking/files/psnot.pdf)")<br /> 5. Unless I missed it, I didn't see any specifics about how the treatments were administered.<br /> - How long before death were patients treated? <br /> - What was the quantity/frequency of the treatments? <br /> - Were the treatments consistent between hospitals?<br /> 6. The rate of ventilation was less in HC+AZ (half of the HC and no-HC rates). Why was that and what does that suggest?<br /> 7. Although they were statistically insignificant, what was the result of the 17 women not included in the study?<br /> 8. Why does the paper seem to address political points? It seems like the Abstract is editorialized, which I'm not accustomed to. The Conclusions portion (and page after) seeming to address topical issues of the times. Perhaps this introduces my own subjective bias, but I infer potential for analysis/deciphering bias when the study shows awareness of other controversial studies being conducted, rather than being a standalone independent study of its own; essentially, it leaves me to question motivations of the author, rather than that motivation being scientific discovery. I don't mind such commentary in the Discussion section, I'm just not as accustomed to seeing it in the Abstract.

    1. On 2022-10-28 07:00:48, user Sujoy Ghosh wrote:

      This manuscript has now been published as follows: <br /> Ghosh, S., Roy, S.S. Global-scale modeling of early factors and <br /> country-specific trajectories of COVID-19 incidence: a cross-sectional <br /> study of the first 6 months of the pandemic.<br /> BMC Public Health 22, 1919 (2022). https://doi.org/10.1186/s12...

      Kindly update the link in medrxiv. Regards, Sujoy Ghosh

    1. On 2022-11-07 06:03:04, user Daniel Corcos wrote:

      I don't see any adjustment for the date of infection. There is a high probability that nirmatrelvir treatment was used on average at a different time, against infections with a different ratio of viral variants.

    1. On 2022-12-12 06:18:02, user Stephanie Byrne wrote:

      This article has been accepted for publication in the International Journal of Epidemiology, published by Oxford University Press. A DOI and link to the published article will be available soon.

    1. On 2022-12-29 19:11:31, user tshann wrote:

      Given the stated benefits of these vaccines, why are we doing modeling studies rather than real RCT's. It's been over 2 years with these products, when will we see the science instead of more modeling studies?

    1. On 2023-11-21 02:18:06, user Marco Confalonieri wrote:

      The finding that high glucose levels can predict glucorticoids (GCs) benefit surprised most of us. All we who performed the included RCTs thincked to hyperglycemia as an adverse effect of GCs, not paying attention to glucose blood level at admission. Nevertheless, there are several reports pointing out hyperglycemia but not diabetes alone associated with increased in-hospital mortality in community-acquired pneumonia (BMJ Open Diab Res Care 2022;10:e002880). It should be noted that AI doesn't have the same prejudices than human researchers.

    1. On 2020-04-16 00:27:24, user Adam Danischewski wrote:

      China has a BCG Vaccination policy and there may be other aspects that may cause Chinese results to differ from the United States.

    1. On 2024-10-16 16:27:20, user CDSL JHSPH wrote:

      I quite enjoyed this article. I found it very interesting as it proposed significant thoughts to how we can improve antibiotic treatment. I wanted to comment about some of the thoughts I had while reading this article. I first wanted to see if the results that were found in TB could be translated into other bacteria infections, such as staph. or strep. species. I also wanted to see if the results found for antibiotics in this article could be translated to other pathogenic treatments including antivirals or antifungals. Finally, in terms of future approaches could we see a systemic or ordered approach when it came to treatment duration whether bacterial, viral, or fungal in nature, or is it mostly going to be drug/ species specific?

    2. On 2024-10-23 00:04:57, user Mohammad Shah wrote:

      Hello!

      Thank you for sharing this preprint. I really enjoyed reading it. Your application of techniques like MCP-Mod and FP for duration-ranging trials provides valuable insights into detecting duration-response relationships much more effectively than traditional approaches. I also appreciate how you highlight the risks of underestimating the MED in smaller sample sizes and suggest using conservative thresholds to mitigate those risks—this is such a critical point.

      One thing that really stood out to me was how you clearly lay out the limitations of traditional duration-response methods, while proposing model-based techniques, like MCP-Mod, as a better alternative. Your comparison of different models and how they behave with varying sample sizes and regimen responses is especially insightful for optimizing TB treatment duration.

      Like others have mentioned, it’d be fascinating to see how this approach could be applied to other chronic diseases, such as HIV or hepatitis. Is that something you’re considering or perhaps already working on? Additionally, applying these model-based techniques to real-world patient data, where comorbidities and adherence issues add more complexity, seems like a natural next step. It would be interesting to see how that plays out in practice.

      I also found your discussion on model selection particularly thought-provoking. Your suggestion of using MCP-Mod alongside Fractional Polynomials under different assumptions opens up an exciting possibility for integrating multi-model approaches in early-phase trials. I wonder if combining these models, maybe in a hybrid MCP-Mod/FP approach, could improve adaptability, especially in trials with more heterogeneous patient populations—those with comorbidities or fluctuating adherence, for example.

      Lastly, your use of simulations to predict treatment efficacy in the face of sample size imbalances touches on a key challenge in trial design. Have you thought about how this framework might be extended to adaptive trial designs? It seems like interim analyses could help adjust treatment durations dynamically based on early patient responses, which could make trials even more efficient.

      Overall, this was a great article, very informative and forward-thinking!

    1. On 2020-05-01 10:56:16, user Ivan Berlin wrote:

      Rentsch CT et al. Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54-75 Years. <br /> medRxiv preprint doi: https://doi.org/10.1101/202... version posted April 14, 2020<br /> Comment of the results concerning smoking related issues. Corrected Version. Please ignore the previous one.<br /> Ivan Berlin, Paris, France<br /> The title is somewhat misleading. Only 3789 persons were tested for SARS-CoV-2, no data on the 2,022,438 are reported.<br /> Data are extracted from the Veteran Administration (USA) Birth Cohort born between 1945 and 1965 electronic database. Between February 8 and March 30, 2020, 3789 persons were tested for SARS-CoV-2. Among them 585 were tested SARS-CoV-2 positive (15.4%) and 3204 SARS-CoV-2 negative. (Remark: the authors frequently confound testing for SARS-CoV-2 and having the disease: COVID-19 +.)<br /> Testing used nasopharyngeal swabs, 1% of the testing samples was from other unspecified sources. Testing was performed “in VA state public health and commercial reference laboratoires”, page 7. No further specification about the testing method is provided. Data are analyzed as if no between test-sources variability existed. However, it is unlikely that between test-source variability would influence the findings.<br /> It seems that only individuals with symptoms were tested, however this is not clearly stated.<br /> Data extraction included diagnostics by diagnostic codes of comorbidities, non-steroid inflammatory drug (NSAID), angiotensin converting enzyme inhibitor (ACE) and angiotensin II receptor blocker (ARB) use, vital signs, laboratory results, hepatic fibrosis score, presence or absence of alcohol use disorder and smoking status.<br /> Smoking status data, never, former, current smokers were extracted using the algorithm described in McGinnis et al. Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source. Nicotine & Tobacco Research, Volume 13, Issue 12, December 2011, Pages 1233–1239, https://doi.org/10.1093/ntr... used for HIV patients. According to this paper, the algorithm correctly classified 84% of never-smokers 95% of current smokers but only 43% of former smokers. The reported overall kappa statistic was 0.66. When categories were collapsed into ever/never, the kappa statistic was somewhat better: 0.72 (sensitivity = 91%; specificity = 84%), and for current/not current, 0.75 (sensitivity = 95%; specificity = 79%). Thus, classification error cannot be excluded in particular in classifying former smokers. <br /> In unadjusted analyses (Table 1) factors associated significantly with SARS-CoV-2 positivity were: male sex, black race, urban residence, chronic kidney disease, diabetes, hypertension, higher body mass index, vital signs but not NSAID or ACE/ARB exposure. It is to note, that among the laboratory findings, severity of hepatic fibrosis was associated with positive SARS-CoV-2 tests. <br /> Among those with positive SARS-CoV2 alcohol use disorder was reported by 48/585 (8.2%), versus 480/3204 (15%) among those with negative SARS-CoV-2 test. Among those with alcohol use disorder, 9.1 tested positive. <br /> Among SARS-CoV-2 positives there were 216/585 (36.9%) never smokers vs 826/3204 (25.8%) among SARS-CoV-2 negatives. 20.7% tested positive among never smokers. Among SARS-CoV-2 positive persons 179 (30.6%) were former smokers vs 704 (22%) among SARS-CoV-2 negatives. 20.3 % tested positive among former smokers. Among SARS-CoV-2 positive individuals 159 (27.7%) were current smokers vs 1444 (45.1%) among SARS-CoV-2 negative individuals. 9.9% tested positive among current smokers. Expressed otherwise, among SARS-CoV-2 negative individuals, there were less never smokers, less former smokers and more current smokers. Among individuals with SARS-CoV-2 positivity there were 338/585 (61%) persons with smoking history (former + current smokers=ever smokers) and among those with SARS-CoV-2 negativity 2149/3204 (72%) were ever smokers. <br /> COPD, known to be strongly related to former or current smoking, was more frequent among SARS-CoV-2 negative (28.2%) than among SARS-CoV-2 positive (15.4%) individuals.<br /> In multivariable analyses (Table 2), male sex, black ethnicity, urban residence, lower systolic blood pressure, prior use of NSAID but not ACE/ARB use and obesity were associated with SARS-CoV-2 positive test; current smoking (OR: 0.45, 91% CI: 0.35-057), alcohol use disorder (OR 0.58, 95% CI: 0.41-0.83) and COPD (OR: 0.67, 95%CI: 0.50-0.88) were associated with decreased likelihood of SARS-CoV-2 positive test. No association with age and SARS-CoV-2 positive test was observed. The association with hepatic fibrosis with SARS-CoV-2 positive tests remained significant in the multivariable analysis and the authors point out (page 15) that the “pronounced independent association with FIB-4 (fibrosis) and albumin suggest that virally induced haptic inflammation may be a harbinger of the cytokine storm.”, page 15. <br /> The main risk factors for hospitalization or ICU among SARS-CoV-2 positive persons are those that associated with worse clinical signs (status). This is expected: clinical decision about severity is based on current clinical signs and not on previous history. <br /> Neither co-morbidities, nor smoking status or alcohol use disorder were associated with hospitalization/ICU. Surprisingly, age was inversely associated with hospitalization (Table 4) among SARS-CoV-2 positive individuals.<br /> Conclusion

      To the best of our knowledge, this is the first report showing that there are less current smokers among SARS-CoV-2 positive persons. However, looking at smoking history (former + current smoking=ever smokers), less subject of classification bias, the difference seems to be less. It is not known what is the percent of former smokers who were recent quitters; duration of previous abstinence from smoking is a crucial variable in assessing associations with smoking status. There is no report of biochemical verification of smoking status. <br /> It is not known when smoking status is reported with respect of the SARS-CoV-2 testing. It is likely that individuals with clinical symptoms stopped smoking some days before testing and considered themselves as former smokers.

      The fact that alcohol use disorder, which is frequently associated with tobacco use disorder, is also less frequent among SARS-CoV-2 positive individuals raises the question of the specificity of the smoking finding and raises the contribution of substance use disorders overall i.e. the finding about current smoking is part of a cluster of various previous or current substance use disorders e.g. cannabis use, potentially associated with SARS-CoV-2 negative test directly or through associated health disorders e.g. hepatic disorders as a consequence of alcohol use. <br /> COPD as well as current smoking are being reported to be more frequent among SARS-CoV-2 negative individuals raising the possibility that reduced respiratory function (entry of SARS-CoV-2 is by the respiratory tract) is associated with lower likelihood of SARS-CoV-2 positive tests. <br /> It seems that all individuals included were tested because they had symptoms suggestive of COVID-19. It is surprising that only 585/3789 (15.4%) tested positive. This should be discussed.<br /> The paper does not report on analyses of smoking by clinical signs/co-morbidities interactions. It is likely that former smokers or those with alcohol use disorders are more frequent among individuals with comorbidities. Based on previous knowledge about smoking associated health disorders, one can assume that more severe clinical signs were associated with current smoking or among recent quitters; the smoking x clinical signs interaction is not tested. <br /> The authors conclude on page 14 “To wit, we found that current smoking, COPD, and alcohol use disorder, factors that generally increase risk of pneumonia, were associated with decreased probability of testing positive. While they were not associated with hospitalization or intensive care, it is too early to tell if these factors are associated with subsequent outcomes such as respiratory failure or mortality.”<br /> The reduced current smoking rate among SARS-CoV-2 positive individuals is an interesting but preliminary finding. It is likely that it is part of a more complex symptomatology and not specific to current smoking. Smoking status should have been assessed on a more detailed manner. The current findings, from a retrospective, cross sectional analysis, are insufficient to support the hypothesis that current smoking protects against SARS-CoV-2 positivity.

    1. On 2020-04-16 21:17:49, user Sinai Immunol Review Project wrote:

      Key findings:

      The authors wanted to better understand the dynamics of production SARS-CoV-2-specific IgM and IgG in COVID-19 pneumonia and the correlation of virus-specific antibody levels to disease outcome in a case-control study paired by age. The retrospective study included 116 hospitalized patients with COVID-19 pneumonia and with SAR-CoV-2 specific serum IgM and IgG detected. From the study cohort, 15 cases died. SARS-CoV-2 specific IgG levels increased over 8 weeks after onset of COVID-19 pneumonia, while SARS-CoV-2 specific IgM levels peaked at 4 weeks. SARS-CoV-2 specific IgM levels were higher in the deceased group, and correlated positively with the IgG levels and increased leucocyte count in this group, a indication of severe inflammation. IgM levels correlated negatively with clinical outcome and with albumin levels. The authors suggest that IgM levels could be assessed to predict clinical outcome.

      Potential limitations:

      There are limitations that should be taken into account. First, the sample: small size, patients from a single-center and already critically ill when they were admitted. Second, the authors compared serum IgM levels in deceased patients and mild-moderate patients and found that the levels were higher in deceased group, however even if the difference is statistically significant the number of patients in the two groups was very different. Moreover, receiving operating characteritics (ROC) curves were used to evaluate IgM and IgG as potential predictors for clinical outcome. Given the low number of cases, specially in the deceased group, it remains to be confirmed if IgM levels could be predictive of worst outcome in patients with COVID-19 pneumonia. The study did not explore the role of SARS-CoV-2-specific IgM and IgG in COVID-19 pneumonia.

      Overall relevance for the field:

      Some results of this study have been supported by subsequent studies that show that older age and patients who have comorbidities are more likely to develop a more severe clinical course with COVID-19, and severe SARS-CoV-2 may trigger an exaggerated immune response. The study seems to demonstrate that the increase of SARS-CoV-2-specific IgM could indicate poor outcome in patients with COVID-19 pneumonia, however given the very small sample size, the results are not yet conclusive.

      Review by Meriem Belabed as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

    1. On 2020-04-16 22:12:24, user Amy E. Herr wrote:

      During the COVID-19 pandemic, we are grateful for the authors’ urgency in assessing N95 respirator decontamination methods. It is in this spirit of collegiality that we draw attention to an aspect that could (unintentionally) cause confusion: the PS19Q thermopile sensor mentioned in the Methods section does not appear to be suited to detect the virus-killing UV-C light emitted from the source. The authors are aware of the possible confusion and are working diligently to check into and, if needed, address the concern.

      As background: from the manufacturer’s specifications, the PS19Q thermopile sensor mentioned in the preprint appears to only detect wavelengths as low as 300 nm, which is above the UV-C germicidal wavelength range (<280 nm). Low-pressure mercury UVGI bulbs emit a 253.7 nm peak [EPA]. 260 nm is the peak UV-C germicidal wavelength for inactivating virus via DNA and RNA damage [Kowalski et al., 2009, Ito and Ito, 1986]. The germicidal efficacy arises primarily from the UV-C dose, with the UV-B dose (280-320 nm) providing significantly lower germicidal efficacy. At 300 nm, UV light is ~10x less effective at killing pathogens than at 254 nm [Lytle and Sagripanti 2005]. UV-A dose (320-400 nm) is considered minimally germicidal [Kowalski et al., 2009; Lytle and Sagripanti 2005; EPA]. We are concerned about the potential adverse health outcomes that might stem from use of the PS19Q thermopile sensor not matched to the UVGI wavelengths for N95 FFR decontamination.

      As best practices, all researchers working on UV-C methods are encouraged to use a calibrated, NIST-traceable, UV-C-specific radiometer to report not just UV-C irradiance, but also UV-C specific dose, as a minimally acceptable UV-C dose of 1.0 J/cm^2 is sought on all N95 FFR surfaces. For additional detail from the peer-reviewed literature, please see the 2020 scientific consensus summaries on N95 FFR decontamination at: n95decon.org

      Again, we thank the authors for their timely research and quick action to confirm suitability of their experimental design, all of which aim to better inform decision makers working to protect the health of heroic front-line healthcare professionals during the COVID-19 pandemic.

      References cited: <br /> • Manufacturer’s specifications, the PS19Q thermopile sensor: https://www.coherent.com/me...<br /> • EPA: ULTRAVIOLET DISINFECTION GUIDANCE MANUAL FOR THE FINAL LONG TERM 2 ENHANCED SURFACE WATER TREATMENT RULE: https://nepis.epa.gov/Exe/Z...<br /> • Kowalski et al., 2009: https://link.springer.com/c...<br /> • Ito and Ito, 1986: https://onlinelibrary.wiley...<br /> • Lytle and Sagripanti 2005: https://www.ncbi.nlm.nih.go...

    1. On 2025-06-15 21:35:28, user CP wrote:

      Great paper! The text makes reference to a "Supplementary Notes" section that doesn't seem to be in the PDF - is this part of the material that will be made available after peer reviewed publication? Sorry if this is a naive question; I'm new to preprints.

    1. On 2022-01-26 22:15:44, user Siguna Mueller, PhD, PhD wrote:

      Does the "fully vaccinated" group ALWAYS include those with (partial) natural immunity (i.e., those previously infected? This is at least what Table 1 says: these belong into the same group. Yet, throughout, this group is referred to as the "fully vaccinated." This does not seem to affect the conclusion that vaccination is in large part responsible for driving O's increased transmissibility (because the incr. OR is seen for the booster group as well). Apart from this, I am struggling to see how the other results are obtained. I seem to be missing how the factor of previously infection gets incorporated in the study. It would be helpful if this could be made explicit, please. Thanks!

    1. On 2022-02-03 17:13:18, user Brian R Wood wrote:

      Has the study accounted for the fact that if Omicron has less severe symptoms than Delta or COVID-19 Classic, the number of reported infections is likely to be significantly lower? Additionally, I would speculate that those who got vaccinated and boosted are also more likely to be tested than those who did not, but just speculation, no data to back it up.

    1. On 2022-02-08 21:10:34, user Sara wrote:

      Thank you for your comment, unfortunately, I did not receive your comment once you replied. 1- we are in the era in the big data, more projects are aimed at generation of large cohort that we can depend upon to derive our clinical decision. <br /> The analysis used the data from US, the model will be deployed and can be used after that to predict the survival time of small cohorts. <br /> 2- We investigated the hazards assumption, we agree with you, we should add the results in the manuscript<br /> 3- SEER database identify the surgery as the surgical removal of the tumour.<br /> 4- I agree with you on the grade, it was on the old grading system for glioblastoma which is mentioned on SEER guidelines. Updated version will be posted and will update the analysis removing this one<br /> 5- we agree with you, we will change it in the updated comments<br /> 6- It is not insane! Developing models that consider these cases is a challenge. These models will be deployed for survival prediction of different cases of glioblastoma with different survival times.

      7- we are developing a model that can be used for the routine data "we use", in this case US cancer data. We have a model that performed well so it can be deployed in the future for the clinical use for our routine data. the model is trained on large sample size that we believe it will achieve accurate prediction results for any routine data. The deployment of the model and its use in clinical practice is the goal. I hope you see the full picture.

      Thank you for your comments.

    1. On 2022-02-09 11:30:32, user Felix Schlichter wrote:

      The authors explain that the data was gathered from community testing. They further note that mass testing has been available to "Dutch citizens experiencing COVID-19 like symptoms or who have been in contact with someone testing positive for SARS-CoV-2".

      If one assumes that the inmune status affects the intensity and probability of exhibiting symptoms, wouldn't the sample be biased? Even if the real odds of being positive for individuals with primary vaccionation and booster were equal, the ones with booster would be underrepresented as they would not test as often if they tend to exhibit less symptoms. Is this not a limitation of the study?

      Could the authors not show the results separated by the reason for testing (contact vs symptomatic) to account for this limitation? if the reason for testing was having been a contact, this limitation would not be there.

    1. On 2025-11-11 03:32:18, user Evolutionary Health Group wrote:

      We at the Evolutionary Health Group ( https://evoheal.github.io/) "https://evoheal.github.io/)") really enjoyed this paper.

      Here are our highlights:

      In the week after the Jan 7 ignitions, virtual (clinic) respiratory visits jumped 41% in highly exposed areas and 34% in moderately exposed areas, totaling 3,221 excess visits, a clear, short-term signal health systems can act on.

      Virtual cardiovascular visits rose by ~35% across exposure groups in that first week (~2,424 excess visits), pointing directly to surge planning for virtual care during wildfire weeks.

      On the day of ignition (Jan 7) in highly exposed areas, outpatient neuropsychiatric and injury visits were about 18% higher than expected, evidence that mental-health demand starts immediately, not just respiratory care.<br /> The exposure framing is reproducible: simple proximity bands (<20 km vs >=20 km within LA County) applied to a 3.7-million-member health system and a five-category visit dashboard (all-cause, cardiovascular, injury, neuropsychiatric, respiratory) that others can copy.

      Scaled to all LA County residents, the estimates imply ~16,171 excess cardiovascular and ~21,541 excess respiratory virtual visits in the week after ignition, strong justification to expand virtual capacity during major fires.

    1. On 2022-02-17 20:55:31, user RT1C wrote:

      Table 3 (bottom) contains HR for boosted vs. non-boosted at various times (<6, 6-9, >=9 months). Aside from the minor labeling issue (hopefully not actual analysis issue!) that 6-9 months and >=9 months are not distinct subsets, overlapping at 9 months, I don't see how you could have made this analysis in the first place unless you have incorrectly defined POIC. You wrote, "we defined the proximate overt immunologic challenge (POIC) as the most recent exposure to SARS-CoV-2 by infection or vaccination." That means POIC for boosted subjects would be time since the booster dose as that is the most recent vaccination. Yet, considering how recently boosting began, how could you have boosted subjects with 6-9 or >=9 months POIC? (In your text you wrote, "For those boosted, the median time to being boosted was 16 days prior to the study start date (IQR -38 to 6 days).")

    2. On 2022-02-17 21:29:51, user RT1C wrote:

      You state, "For those boosted, the median time to being boosted was 16 days prior to the study start date (IQR -38 to 6 days)." Is that a typo or did you truly mean a positive 6? i.e., did you mean -38 to -6 days, or -38 to 6 days? If the latter, you actually included subjects who were vaccinated with boosters after the study period began? If that's the IQR, then I assume the full range extends much further into the study range. Those are VERY recently boosted. In your discussion, you should not say, "boosting with a vaccine designed for an<br /> earlier variant of COVID-19 still provides significant protection against infection with the Omicron variant." without also providing a time associated with that. For example, you might add to that sentence "for a period of at least 1 month" or whatever. It seems important to stress the limitation of the study in this manner, to avoid giving the impression that the booster provides long-lasting protection against infection when that is not shown by your study.

      Finally, on a related matter, how did you treat individuals who tested positive before 7 days after their booster? If, as some research suggests, vaccination temporarily increases susceptibility to infection (for about 2 weeks), by including subjects who were vaccinated within the study period, you may have biased findings against those without boosters.

    1. On 2022-03-04 16:06:11, user Tracy Beth Høeg, MD, PhD wrote:

      The peer reviewed version including numerous international datasets estimating rates of post vaccination myocarditis is now available. We have included risk-benefit calculations for children with a history of infection and used overall infection hospitalization risks (rather than just 120 days risks) both pre and during omicron. http://doi.org/10.1111/eci....

    1. On 2022-03-28 18:14:47, user August Blond wrote:

      Dear colleagues,<br /> I am having difficulty understanding figure 3, the two graphs that are plotted with GFP/EGFR.<br /> Zooming in on the four ovals - red, blue, black, green - I see that the scattered-plots are themselves contained in a smaller perfect ovoid.<br /> Can you explain how you manage the computer processing of your samples?<br /> In reference 13, the method for doing multiplex FACS, these close to perfect ovals do not appear. There are still points that are not perfectly integrated into the "virtual" geometrical structure.<br /> As is the case with all FACS using gating.<br /> Would it be possible to generate point clouds that have not been "artificially" modified after gating?<br /> Best regards,<br /> August Blond

    1. On 2022-06-08 17:08:32, user Ted Gunderson wrote:

      Should this be considered a scientific study or an advertisement?

      What evidence is there that what the authors refer to as "(non-variola orthopoxvirus and monkeypoxvirus specific)" actually causes the disease that is currently being diagnosed all over the world as "monkeypox".

      This is a paper funded by Roche that says "Our tests work!"

      "ML and DN received speaker honoraria and related travel expenses from Roche Diagnostics."

      Roche has gotten lots of press recently about their monkeypox tests.

      https://medicalxpress.com/n...

    1. On 2022-06-09 20:11:19, user John Doe wrote:

      Interesting paper that confirms and complements prior molecular findings on this devastating malignancy. A strength of this study is the inclusion of a relatively large series of patients (n = 47) considering the rareness of the disease. The results suggesting a diverse origin of BPDCN are of special interest, and the figure on potential therapies against the disease is visually appealing. However, data analysis and data interpretation have certainly problems and inconsistencies. In particular, the results on CNV pathogenicity produced by X-CNV are highly questionable and dubious, and I would strongly advise against using those results to guide data interpretation. Among deleted regions (suppl. data) classified as non-pathogenic by X-CNV are: 1p36.11 (ARID1A), 5q33.1 (NR3C1), 7p12.2 (IKZF1) and 9p21.3 (CDKN2A–B). All these are well-known tumor suppressors with demonstrated pathogenicity in numerous human cancers. Besides, prior studies back up the recurrent deletion and pathogenicity of these cancer genes in BPDCN [refer to papers by Lucioni M et al. Blood. 2011;118(17), Emadali et al. Blood. 2016;127(24), Bastidas AN et al. Genes Chromosomes Cancer. 2020;59(5), Renosi F et al. Blood Adv. 2021 9;5(5)].

      Puzzling enough, despite claiming the use of the X-CNV results to determine pathogenicity of CNVs, it appears that the authors chose to highlight anyway some deleted and gained regions classified as non-pathogenic by X-CNV (ARID1A, CDKN2A) as well as other regions not even formally called by GISTIC (e.g. TET2). This is even harder to comprehend considering that 7p12.2 (IKZF1) is clearly one of the most conspicuous peaks in the analysed cohort (Figure 3A); yet, completely ignored in the text and figure!? Quite baffling. In short, the paper would greatly benefit and improve from re-interpreting and discussing the data considering the existing literature on BPDCN genetics.

    1. On 2020-04-21 21:10:27, user Bruno Vuan wrote:

      Article says, page 7,

      "This study had several limitations. First, our sampling strategy selected for members of Santa Clara County with access to Facebook and a car to attend drive-through testing sites. This resulted in an overrepresentation of white women between the ages of 19 and 64, and an under-representation of Hispanic and Asian populations, relative to our community. Those imbalances were partly addressed by weighting our sample population by zip code, race, and sex to match the county. We did not account for age imbalance in our sample, and could not ascertain representativeness of SARS-CoV-2 antibodies in homeless populations. Other biases, such as bias favoring individuals in good health capable of attending our testing sites, or bias favoring those with prior COVID-like illnesses seeking antibody confirmation are also possible. The overall effect of such biases is hard to ascertain."

      In summary sample has

      Overrepresentation white woman 19-64<br /> Age imbalance not accounted <br /> Partial weighting by zip code, race and sex<br /> Biased favoring good health individuals and those seeking antibody confirmation

      Conclusion: "overall effect of such biases is hard to ascertain"

      1. Not balanced by age is a signal of impossibility of weighting by age without significative umbalance in the other dimmensions, as mentioned "result in small-N bins". Ignoring age balancing in a phenomena which is strongly age related is something that may bring a strong source of additional errors.
      2. If authors recognize that these biases are hard to ascertain, and no further discussion appears, is that this uncertainty is not included in error range. So, error range of this experiment appears to be totally unknown for the authors.

      Additionally

      There is no discusion on sampling effect by facebook ads, as answering rates, impact of facebook ads algorithm which is optimized to get maximum amount of answers. It is well known that this convenience samples are non probabiistical, so this has to be included in error range evaluation, (1)

      1. Baker R. et al, Non-Probability Sampling, AAPOR, June 2013 https://www.aapor.org/Educa...
    1. On 2022-06-24 22:03:50, user Charles Warden wrote:

      Hi,

      Thank you very much for posting this preprint. This certainly represents a large amount of work and careful consideration!

      I have some questions / comments:

      1) Is there a way for me to calculate enhanced scores for myself?

      For example, I would like to learn more, but I was not very satisfied with the PRS that I listed for my own genomic sequence in this blog post:

      https://cdwscience.blogspot...

      2) In the blog post link above, there seemed to be a noticeable disadvantage to the PRS without taking the BMI into consideration for Type 2 Diabetes.

      In this paper, age is an important factor in Figure 1 for the PRS.

      If other non-genetic factors are known, do you have a comparison for non-PRS models? <br /> For example, I wonder how performance of age + BMI (+ other established factors) compares to the plot for Type 2 diabetes in Figure 1.

      3a) I see that the percent variance explained is sometimes provided (such as Supplemental Figure 5), but sometimes it is not.

      For example, in Figure 3, the effect per 1 SD of PRS is higher for LDL cholesterol than height. However, how does the ability to predict an individual's height from genetics alone compare to the ability to predict an individual's LDL from genetics alone?

      After a certain age (as an adult), the exact value for my own LDL has varied more than my height. However, I was not sure how that variation by year compared to others and/or the variation over decades.

      In general, I would like to have a better sense of how absolute predictability compares for height versus disease scores. I also understand that there are complications with binary versus continuous assignments, but it is something that I thought might be helpful.

      3b) I see AUC statistics in Supplemental Figure 2, described as for AUROC. However, am I correct that some of the cases are not well balanced with controls?

      If so, should something like AUPRC be provided (possibly as a complementary supplemental figure)? I believe the idea is described in Saito and Rehmsmeier 2015; the application is very different, but you can see the inflated AUROC values in Figure 1A of Xi and Yi 2021. I expect that there are other good ways to illustrate the differences with PRS in cases and controls of varying proportions, but that was one thought.

      In the context of genomic risk, I might expect that high predictability in a small number of individuals may be preferable over a small difference in low predictability in a large number of individuals. There is emphasis on thresholds like top/bottom 3% (in many but not all figures), which I thought might be consistent with that opinion.

      So, I think something like Figure 1 was helpful. In order to try and capture how false positives change when sensitivity increases, I am not sure if something similar for positive predictive value might help? I would consider that very important if the PRS might be used for screening purposes.

      4) In the Supplemental Methods, I believe that you have a minor typo:

      Current: 100,000 Genomes Project (100KGP). The 100,00 Genomes Project, run by Genomics England,<br /> Corrected: 100,000 Genomes Project (100KGP). The 100,000 Genomes Project, run by Genomics England,

      Thank you very much!

      Sincerely,<br /> Charles

    1. On 2022-08-06 11:55:02, user Dieter Mergel wrote:

      I have a question concerning the following passage:

      "Previous work demonstrated that vaccination reduces severe COVID-19 and hospitalisation 46 and also the risk of Long COVID 7, 47. However, we did not observe evidence of qualitatively different symptom clustering in vaccinated vs. unvaccinated individuals, with either alpha or delta variants."

      Does it mean: <br /> (a) Vaccination does not reduce the risk of Long Covid.<br /> or<br /> (b) Vaccination reduces the risk of Long Covid, but if (!) vaccinated people get Long Covid, then (!) the symptoms are similar to those of unvaccinated people.

    1. On 2022-08-14 15:08:34, user Peter J. Yim wrote:

      The trial registration at ClinicalTrials.gov listed three primary endpoints:<br /> 1. Number of hospitalizations as measured by patient reports. [ Time Frame: Up to 14 days ]<br /> 2. Number of deaths as measured by patient reports [ Time Frame: Up to 14 days ]<br /> 3. Number of symptoms as measured by patient reports [ Time Frame: Up to 14 days ]

      The publication reports the outcomes for none of those endpoints. (the endpoints were changed after publication on ClinicalTrials.gov)

      1. The rate of hospitalization was reported at 28 days. That was registered as a secondary outcome.
      2. Mortality was reported at 28 days. That was registered as a secondary outcome.
      3. The number of symptoms was only reported at baseline.

      This article is close to irrelevance on the question of the efficacy of ivermectin in COVID-19.

    1. On 2021-08-11 10:34:14, user Apriyano Oscar wrote:

      I am sorry, I am just a layman. I want to ask about the 1.8% tested positive (608 people). Does it mean that the effectiveness of the Pfizer vaccine in this study is 98.2% ? And is this also the same as what is called as 'efficacy' ?

    1. On 2021-05-24 16:53:32, user Gustavo Bellini wrote:

      Congratulations on the work! It would be interesting to analyze the action of vitamin D in the MHC complex, MICA / MICB.

      • A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I-related chain A<br /> https://doi.org/10.1111/cei...

      "Indeed, immune cells significantly up-regulate vitamin D receptor (VDR) transcription upon activation and proliferation (reviewed in [28]). In turn, through the binding of VDR, vitamin D induces the expression of anti-proliferative/pro-apoptotic molecules, thereby evoking immune tolerance 29, 30. Interestingly, recent data showed that MICA stands as a VDR-sensitive molecule, through which vitamin D renders tumour cells susceptible to NK cytotoxicity 31. According to this view, in our patients the gene expression of MICA in T cells was not associated with the up-regulation of TLR or ISG, as could have been expected, but paralleled levels of vitamin D instead. All these observations suggest that vitamin D could help to restore homeostasis of the immune system during flares, and that its deprivation may jeopardize MICA-dependent cell growth control."

      In addition, the inverse relationship between circulating sMICA and vitamin D found in our cohort suggests that the vitamin could prevent MICA shedding. Alternatively, sMICA impairment of NK functions could promote the uncontrolled proliferation of immune cells which, in turn, would facilitate the depletion of vitamin D.

      In summary, we propose a particular disease pheno-type characterized by the disruption of MICA-dependent cytotoxicity in patients with innate activation of T cells and possibly facilitated by low vitamin D levels."

      "Basically all cellular components of PBMCs belong to the innate and adaptive immune system. Therefore, it is not surprising that the immunologically most important region of the human genome, the HLA cluster, also highlights as a “hotspot” in the epigenome of PBMCs.<br /> However, it is remarkable that the HLA cluster is also a focused region of the vitamin D responsiveness of the epigenome. This observation provides a strong link to the impact of vitamin D on the control of theimmune system.<br /> In conclusion, in this proof-of-principle study we demonstrated that under in vivo conditions a rather minor rise in 25(OH)D3 serum levels results in significant changes at hundreds of sites within the epigenome of human leukocytes."

      The study below has shown evidence that the vitamin D endocrine system is dysregulated in sars-cov-2 infection.

    1. On 2020-11-24 09:59:43, user Lee Rague wrote:

      This paper has been recently published:<br /> Labrague LJ, De Los Santos JAA. Prevalence and predictors of coronaphobia among frontline hospital and public health nurses. Public Health Nurs. 2020 Nov 23. doi: 10.1111/phn.12841. Epub ahead of print. PMID: 33226158.

    1. On 2021-12-13 11:53:14, user Undertow of Discourse wrote:

      The summary of findings in the abstract is defective in relation to PIMS-TS. It says “ The overall PIMS-TS rate was 1 per 4,000 SARS-CoV-2 infections”. Rate of what? Occurrence of PIMS-TS? Hospitalization with PIMS-TS? Death from PIMS-TS?

    1. On 2023-05-09 17:56:41, user Dr. Gerald Zincke wrote:

      I am missing indication at which point in time after the vaccination an infected patient was counted to the vaccinated group.

      (For the importance of this, please refer to Prof. Norman Fenton's description of the statistical illusion that can occur when vaccinated people are counted as unvaccinated for a period of time after the shot. https://youtu.be/Gkh6N-ZL3_k )

    1. On 2021-08-14 17:37:30, user Uwe Schmidt wrote:

      The study states a hospitalisation rate of 6% for children.

      This rate needs to be strongly questioned as it is internationally significantly higher than any other rate observed. In fact, it is higher by roughly factor 10-12. E.g. in Germany, at the peak of the pandemic in week 51/2020, less than 100 children were hospitalised nationwide, 1/3 of them newborn, who just stayed in hospital a little longer. The number of positive tested children in that week was ~20,000. For July 2021, the number of hospitalised children is less than 10, no ICU.<br /> In England, one out of 200 (0.5%) children are hospitalised.<br /> In Israel, no patient below the age of 30 is in critical condition.

      Questions for the authors:<br /> 1. Does the total number of children tested positive really consist of ALL PCR-positive or only a subgroup reported by certain institutions?<br /> 2. Of those 5,213 hospitalised, how many were hospitalised because of COVID-19 and how many because of other conditions?

    1. On 2020-07-25 23:24:04, user BannedbyN4stickingup4Marjolein wrote:

      I'm not a bio-mathematician but I've had a similar idea in my head for some time. I'm not comfortable with all of the maths so to an extent I have to take some of this on trust.

      But the basics of it, as I understand it, is that transmission takes place when some yet to be defined criteria are satisfied (through air, via a surface, without a mask, indoors, whilst singing, who knows?) through a temporal network. It would certainly help to understand this mechanism better, but that's not the focus of the paper.

      Early infection removes the easiest nodes from this network - those people most easily susceptible overlapping with those peole with the most contacts. The mechanism of node removal is death in a few cases and post infection immunity in the majority.

      Just a couple of notes of caution then:

      One obvious one is how long does immunity last? Suppose some kind of herd immunity is achieved at 20% infection of the population, but that a typical population (not a densely populated city like New York) is not infected to this level until infection acquired immunity starts to wane?

      The second - and I am disappointed not to see more mention of this in the paper - what if a significant element of node removal is down not to post infection immunity but to changes in social behaviour in response to the epidemic?

      R is a function not just of the pathogen but of the population it infects - its density is relevant, but so is its behaviour. This applies whether one models the population as a simple homogenous mass (SIR type models) or as a set of discrete interconnected agents.

      Then no sooner does everyone revert gung ho to their previous pattern of behaviour (we're at herd immunity, we're safe!) then infection takes off again.