On 2021-01-29 21:08:41, user Jonas Ludvigsson wrote:

Very interesting study. We reported very similar data in late 2020 in Acta Paediatrica. https://onlinelibrary.wiley...

On 2021-01-30 11:55:17, user Doctor Avios wrote:

Why didn't you include a control group in your study? You have a database of 2.6 million members. You haven't "demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose." By only analysing data from vaccine recipients you have demonstrated that the relative risk of an RT-PCR positive case is 51% lower 13-24 days after the first dose compared to 1-12 days after the first dose. That is not the same as demonstrating effectiveness. If you want to demonstrate this you need to analyse the incidence of RT-PCR positive cases in the vaccinated group compared to an unvaccinated group.

On 2021-01-30 22:31:36, user Raghu SN wrote:

It is surprising that the effect of the difference in prevalence of the infection in the general population during the two periods being compared is not accounted for. For example, if the total cases per 100,000 is 40 in the first period and 80 in the second; if 4000 of the inoculated cohort were infected in the first period. It will be statistically expected that without the vaccine 8000 of the cohort would have been infected in the second period. And if actually only 2000 were infected, then the vaccine protected 6000 out of 8000 potential infections, that is 75% efficient. For these numbers, the methodology adopted in the study would calculate only 2000 out of 4000, that is 50%.<br /> Hope my drift is clear, though rustic.

On 2021-02-06 06:40:50, user David Epperly wrote:

Here's something that addresses Pfizer and Moderna and I agree that the 2nd dose is important. "While durability is improved with a 2 or more dose regimen, dose timing is subject to optimization."<br /> Evidence For COVID-19 Vaccine Deferred Dose 2 Boost Timing<br /> 1. Good efficacy of dose 1<br /> 2. Greater than 3 month durability of dose 1<br /> 3. Double vaccinated population<br /> 4. Dramatically reduce hospitalizations<br /> 5. Save ~ 90K US lives in 2021<br /> https://doi.org/10.2139/ssr...

On 2021-02-07 02:46:04, user Mark wrote:

When will updated results be posted?

On 2021-02-09 15:09:34, user Gemma Quinn wrote:

i would say Colchicine should be considered and to avoid steroids for chronic situations

On 2021-02-09 23:10:30, user Robert van Loo wrote:

Why do the authors talk about overdispersion as some infections seem to occur in clusters, and for me that would mean underdispersion.

On 2021-02-10 17:17:13, user bert jindal wrote:

could you provide me with more clarity on the parameters being measured to service the algorithm. As a clinician important diagnostic indicators include the history and presentation .does the system use patients symptoms age sex an ethnicity to derive its predictive value?

On 2021-02-10 18:47:50, user moshkreit wrote:

This study does not show anything until the authors release the details of the age distribution for the two groups. W/o that, UC groups could have 10 people above 75, mitigated by 10 younger people to keep the mean in check. Naturally, a group with people over 75 would have more subjects at risk at day 26 than a group where the oldest subject is only 71.

On 2021-02-13 09:00:43, user Guy André Pelouze wrote:

Hello,<br /> May we have any explanation and evidence for the choice of this strategy: "Success will be declared if there is a 90% probability that the intervention arm is better than usual care in<br /> reducing CRP. "? Is it based on preliminary data or on a choice of efficacy which is lower than usual in order to catch small effects?<br /> Thank you,<br /> Guy-André Pelouze MD MSc

On 2021-02-15 23:10:19, user Meredith Weiner wrote:

I beg you to change the bird Robin to a different bird. My daughter’s name is Robin as well as many other men and women. I appreciate the effort not to stigmatize people based on geography by naming variants after birds, but if the “Robin” variant takes off, you will be impacting my daughter and every other person named Robin.

On 2021-02-17 15:37:25, user Jules wrote:

Please review the pros and cons of using the names of birds (or any living animal) to differentiate between COVID variants. If a loved one dies from the bluebird variant, say, how might survivors feel when they see bluebirds? Might it not be a repetitive trigger for grief? And might not some people seek revenge on the birds? Furthermore, it is almostt inevitable that some will mistakenly think the birds carry or are responsible for COVID, putting robins and pelicans at risk the world over. And as Meredith rightly pointed out, it is damaging and most unfair to Robins everwhere.<br /> Why not use the names of colours? Or minerals? I am sure there are many alternatives that will serve the purpose.<br /> Having said all that, congratulations on your incredible work and contributions to public health. Thank you.

On 2021-02-19 20:02:18, user Miguel Blacutt wrote:

Note from authors: The title of this manuscript was previously, "I want to move my body - right now! The CRAVE Scale to measure state motivation for physical activity and sedentary behavior".

On 2021-02-22 02:12:28, user Sanjeev Mangrulkar wrote:

Was there a control group in this study where the neutralising antibodies developed after natural infection were tested for their efficacy against the newer mutants of the virus?

On 2021-02-25 14:32:20, user Haitham kussaibi wrote:

Dear valuable readers,

The current manuscript has been peer reviewed and published by<br /> the saudi medical journal<br /> DOI: <br /> https://doi.org/10.15537/sm...

Thank you for your interest.<br /> The Authors

On 2021-02-26 03:35:39, user Larisa Tereshchenko wrote:

Because this preprint was very large, we divided it and so we now have two separate (completely different) manuscripts published out of this preprint:<br /> (1) in European Heart Journal - Digital Health, ztab003, https://doi.org/10.1093/ehj... <br /> (2) in BMJ Open: BMJ Open. 2021 Jan 31;11(1):e042899. doi: 10.1136/bmjopen-2020-042899. PubMed PMID: 33518522

On 2021-03-02 18:20:29, user Martin Hepp wrote:

Ok, this is only a preprint. However, a wording like "provides a precise estimate of the true underlying SARS-CoV-2 transmission risk in schools and day-care centres." in the introduction sets all alarm bells of any scientist ringing. "precise" and "true" are bold words, rarely used in serious academic publications (where typically a prominent "threats to validity" section would highlight and discuss the limitations of the findings) - in particular, if the underlying method is relatively weak. Some limitations are discussed on pp.12 and 13, but in a rather superficial way.

Just a few major questions that challenge the overall contribution:

1. During the major part of the period of the analysis, the incidence was very low, in particular among young people. See https://corona-data.eu/medi... for a heatmap. Of the total duration of the study of ca. 17 weeks, only the last 5 - 6 weeks and thus less a mere 30 % had a significant incidence in the age-groups 0-4, 5-9, and 10-14, and it was lower than in the general population.

2. As children are less likely to be symptomatic and the testing regime has a strong bias towards symptomatic patients, it is a valid assumption that the share of undetected infections is higher among students and children than in the general population. As the authors' entire analysis and model for transmission is based on test-confirmed public health cases, the authors should have tested this hypothesis, e.g. by random PCR tests in areas and during periods with a sufficient community incidence. If you miss asymptomatic cases, you are not only invalidating your aggregate statistics, but of course also the entire graph of infections becomes incomplete and questionable.

3. On pp. 6 an 7, the authors cite the official definitions for cases and procedures; however, there is no information whether the theoretical guidelines for contact tracing, testing, non-pharmaceutical interventions like social distancing, masks, ventilation etc. were actually followed, and if the compliance remained stable over the course of the analysis and representative for the different groups. For instance, one could hypothesize that the effect of wearing mask in classrooms after November 20 is partially obscured by a reduction in ventilation due to cool weather and in general more time spent indoors. Taking the textbook definition of a characteristic of an observation and then assuming it to match the data is a significant threat to validity.

4. The same holds for the approach of instructing the DPHAs on how to use the questionnaire but not testing the quality of the results statistically or by cross-validation. How do you know that the DPHAs understood and applied your instructions properly? And even if they did, how do you know that the data they were using was correct? it is not a lot of effort to rule out or estimate the margin of error of a potential weakness.

5. The entire statistical analysis method is only a bit over half a page of largely spaced text (p. 8).

6. The claim that children are less likely to produce a sufficient viral load to infect others is highly disputed in the literature, see e.g. https://zoonosen.charite.de... these findings are not uniformly agreed (see e.g. https://www.sciencemediacen... "https://www.sciencemediacentre.org/expert-reaction-to-a-preprint-looking-at-the-amount-of-virus-from-those-with-covid-19-in-different-age-groups/)"), but it is not commonly accepted that children are unlikely to infect others. This challenges the assumption that asymptomatic individuals are unlikely to infect others even if they are themselves infected.

7. The authors state on p.12 that the rate of asymptomatic infections was relatively low with ca. 17%. Unfortunately, this population aggregate used by the authors obscures the influence of age on the likelihood of asymptomatic infections and hence on the number of undetected infections in school settings. A recent meta-study https://www.frontiersin.org... suggests that the rate is higher in children (p=0.5, CI 0.21 - 0.79) than in adults (p=0.3, CI 0.13 - 0.56). There is a lot of variance observed in the underlying studies, but the order of magnitude could explain a major share of the reported higher likelihood of infections originating from teachers than from students alone.

8. The focus on "hygiene practices" (p.13) as a recommendation conflicts with the widely accepted view that SARS-CoV-2 transmission is largely airborne and that sustained social contact in indoor environments is a high-risk setting, even with masks.

9. If the risk of students in school infecting teachers is so low, one should immediately stop the priority vaccination of teachers. I think the priority vaccination is justified.

For lay people: If children are less likely to show symptoms than adults, and testing and hence becoming an index case is more likely for symptomatic individuals, it will be no surprise that teachers, who are adults, are more often identified as index cases than children. If the data graph of humans interacting in the pandemic is incomplete, and there is a systematic bias that leads to more missing index patients being children, your findings can easily be a simple artifact resulting from the chosen approach.

Now, all science is tentative; we all know our papers could be improved, the evidence or data be more convincing, additional aspects be considered. The problem arises when this is combined with politics. The introduction (p. 5, 2nd paragraph) is heavily focussed on a positive view on re-opening school. The arguments raised are not wrong per se, but they are also not balanced - in a pandemic with a novel virus against which the majority of the human population seems to be immunologically naïve, other societal risks should be given the same space. If you motivate your research with the wish to reopen schools, readers have reason to assume that you are not neutral as to the outcome.

This is all common in the daily struggle of anybody in research and academia.

But when you combine such very preliminary work with substantial threats to validity with a bold claim in the intro and a conclusion in which you report with certainty that only 1 in 100 infected students will infect another person in school, knowing that there is a lot of heated debate in the society, then your "Ethical Statement" should be amended by "We knowingly accept that populist media like BILD, interest groups, and decision makers will use our fragile findings and our wording as solid evidence for a risk-prone opening strategy. Since we are so confident in our research, we take full responsibility for the societal consequences."

Doing preliminary research is unavoidable. Distributing it in a form that is the perfect bait for media and decision makers is unethical.

This

https://www.bild.de/ratgebe...

is the direct effect of your work.

More than ca. 3 million daily visitors on bild.de (likely largely from the German population) have seen their variant of your message.

On 2021-03-02 18:53:07, user Olivier Cazier wrote:

Contrary to MHS study of Pfizer in Israel , who took care of having vaccinated groups and unvaccinated groups with the same age, genre profile, comorbidities, etc, in this study, the two groups have very different profiles. They did a weighted correction, but give no details.<br /> As the results are quite different from MHS results, who gave a 57% efficiency for Pfizer first dose, one can be sceptical of the correftion method

On 2021-03-03 18:20:01, user LabMonkey wrote:

Eager to see the temporal distribution of some of these variants - any clue as to when they'll be visible in GISAID?

On 2021-03-04 14:34:51, user Paul McKeigue wrote:

Now published in BMC Medicine:

https://bmcmedicine.biomedc...

On 2021-03-10 11:48:29, user Erick wrote:

The percentage of participants who were female was Group 3 > Group 2 > Group 1, and women were shown to have more robust response than men to the infection and the vaccines. Based on this, what was the prior probability that the result obtained here would be due to the differing proportions of female/male in the three groups? Was the p-value adjusted for this or a test done to ascertain the Sex-effect?

What was the evidence presented to support conclusion (b) about the vaccine prioritization? Seems a lot of factors go into that decision than addressed here.

On 2021-03-10 13:52:58, user Jeffrey Brown wrote:

Seems as though an EHR system cannot answer the question posed no matter the inclusion\exclusion criteria. EHRs can only see care within their walls and we know that patients move across providers frequently even in short windows. This means that the look-back period for continuity of care is incomplete and introduces bias, that the look-back for prior conditions is also incomplete, and the outcome data are incompletely captured. Patients often moving across health systems in large cities (example in LA: https://www.ncbi.nlm.nih.go... "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3052345/)"). It is critical to match data to the question, I don't think EHR data can answer the important question posed.

On 2021-03-10 15:41:21, user Theodore Petrou wrote:

Thank you very much for this study. I have a concern regarding your calendar adjusted calculation.

You report the overall IR of the unvaccinated LTCF to be 0.46. Looking at the VEca, I calculated the IRca for the unvaccinated to be 0.39, 0.23, 0.19, 0.05. Not one is above 0.46, the overall rate. How is this possible? Can you provide your code used to calculate VEca?

Also, I would have liked to see the all-cause death rate in unvaccinated vs vaccinated group.

Thank you,<br /> Ted Petrou

On 2021-03-11 05:04:28, user dick mazess wrote:

This is problematic as MRA using GWAS accounts for under 5% of the variance in calcifediol. It certainly does not account for UV exposure, dietary supplementation, sequestration of calcifediol in fat (which underlies the increased risk of COVID in the obese), factors affecting RAAS, seasonal variation, factors affecting FGF23 and 24-hydroxylase.

The authors state that the results do not apply to vitamin D deficiency yet 80% of hospitalizations are in the deficient. The selection of UK Biobank (401,460 of 443,734 cases) where the average calcifediol is 18ng/ml, well below the sufficiency level of 30ng/ml, may be problematic. Some other factor operative-Horizontal effect or collider bias.

The Castillo study (Andalucia) did not use a high dose of calcifediol but rather ????g266/week which is the equivalent of 34,000IU (ie 5000IU/day). The effectiveness of that dosing was confirmed by Nogues et al (Barcelona) in a much larger sample. The Murai study was a farce if only because bolus dosing induces FGF23 and 24-hydroxylation; also the followup was only 7 days.

The authors claim on line 417 that 10 MRA studies were of value but only #23 Trajanoska seems valid, #21 on D2 is wrong (see Dawson Hughes), as are #22 and #24) . MRA analyses of vitamin D have never been valid because of poor association with the phenotype. The authors should recognize this and note "GWAS, to date, have generally not focused on phenotypes that directly relate to the progression of disease and thus speak to disease treatment" Paternoster 2017 https://doi.org/10.1371/jou...

RB Mazess, Emeritus Professor

On 2021-03-14 00:26:00, user Nathan Weiss wrote:

Great analysis, two comments: The prevalence of suspected re-infections appears to be grouped closer to initial infections (days 100 to 149) rather than increasing over time as should be the case if deteriorating seroprevalence were the culprit. Also, while the cluster in cases in January is interesting, the authors suggest this is due to new strains while the number of suspected re-infections appears to increase from roughly 27 cases in December to 97 in January, matching the background increase in community new cases.

But I commend your work as one of the best accountings of the likelhood of secondary infections in a large (non-prison) population!

On 2021-03-14 07:19:10, user debernardis wrote:

Congratulations for this paper! I am excited that you could confirm the outcome of our observational study on disulfiram-treated patients in Northern Italy. Now waiting for the results of those two RCTs...

On 2021-03-17 11:01:56, user Olaf Storbeck wrote:

I hope this excellent paper receives the same attention like the rather poor work recently published ( https://www.medrxiv.org/con... ) which used a similar approach and failed to see the significant correlation between Vitamin D deficiency and Covid-19 due to severe errors in the data set and the methodology. <br /> However the message "Vitamin D is not correlated to Covid-19 outcome" was very fast amplified by the media worldwide as:<br /> - The Guardian (https://www.theguardian.com... )<br /> - The Business Insider (https://www.businessinsider... )<br /> - The Independent (https://www.independent.co.... )<br /> - Russia Today (https://www.rt.com/news/517... )<br /> - Politifact (https://www.politifact.com/... )<br /> - Hospital Health Care (https://hospitalhealthcare.... )<br /> - News Medical (https://www.news-medical.ne... )<br /> It is incomprehensible to me how this very obvious safe and efficient measure (sufficient Vitamin D supplementation for all) is neglected by nearly all authorities.<br /> I hope publications like this help to spread the meassage...

On 2021-03-19 23:07:51, user David Epperly wrote:

I am unable to access the supplementary data file. Please explain.

Also, I am unable to find the clinical definitions of moderate and mild from a symptom and test result perspectives. Please elucidate.

On 2021-03-20 15:21:28, user drmoienkhan wrote:

Published <br /> Khan MA, Menon P, Govender R, Samra A, Nauman J, Ostlundh L, Mustafa H, Allaham KK, Smith JEM, Al Kaabi JM. Systematic review of the effects of pandemic confinements on body weight and their determinants. Br J Nutr. 2021 Mar 12:1-74. doi: 10.1017/S0007114521000921. Epub ahead of print. PMID: 33706844.

On 2021-03-24 14:05:15, user Marvin K wrote:

I am a bit surprised that more CoV 2 RNA was found on the supply dampers downstream of the final filters. How do you explain this? Why would damper surfaces attract and hold virus elements with greater effectiveness than the final filters?

On 2021-03-25 12:37:30, user Bernhard Brodowicz wrote:

Protocol from one of the labs involved in vienna, the Vienna Covid-19 Detection Initiative (https://www.maxperutzlabs.a... "https://www.maxperutzlabs.ac.at/fileadmin/user_upload/VCDI/News/COVID19_Testing_VCDI_v1.1.pdf)") states that 'Ct values <40 are considered positive' (this is acc. to US CDC EUA protocol, when CDC-N1 and CDC-N2 target are used; for other targets a Ct reference was not reported). <br /> Sensitivity/specificity of the targets are described there as follows:<br /> CDC-N1: Very sensitive; SARS-CoV2-specific; low false-positive rate;<br /> IMP-ORF1b: SARS-CoV2-specific version of HKU-ORF1b-nsp14; very sensitive; low false-positive rate;<br /> CDC-N2: Very sensitive; SARS-CoV2-specific; false positives in presence of genomic DNA;<br /> E_Sarbeco: Sensitive; not SARS-CoV2 specific; reduced sensitivity in 384-well format;<br /> Especially as IMP-ORF1b and CDC-N2, which are described as 'very sensitive' but also false positives are mentioned, the interpretation of high Ct values > 40 as positives could raise questions when validation data (sensitivity, specificity, LOD) is not given and was not verified by individual labs (and different analytical setups) involved.

On 2021-03-29 23:21:53, user Javier wrote:

To estimate the age- and sex-adjusted <br /> proportions of cataract, diabetic retinopathy, glaucoma, and macular <br /> degeneration among the Arab American community, a notably understudied <br /> minority that is aggregated under whites.

On 2021-04-04 02:48:44, user SurgeonGate wrote:

Great Arab eye study! Arab Americans need more studies understanding their burden of disease compared to whites. Hopefully more soon!

On 2021-10-03 16:42:16, user Luke Yaldo wrote:

The peer reviewed, published version of this article can be found here: https://link.springer.com/a...

On 2021-03-30 15:12:27, user Derrick Lonsdale wrote:

When Japanese investigators found that Allithiamine was produced in garlic bulbs from thiamine by the action of an enzyme, they found that its biologic effect was better than that of the thiamine from which it was derived. Many different derivatives were synthesized and the one with the best biologic action was thiamine tetrahydrofurfuryl disulfide (TTFD).For example, pretreatment of mice with TTFD gave a significantly greater protection from cyanide poisoning than controls. It has little or no toxicity and should be used in a trial for Covid-19 patients.

On 2021-04-07 10:34:02, user Ariane Fillmer wrote:

The results you present appear to be really interesting. Thank you for sharing this. In order to allow the experienced reader to assess the data you show in a bit more detail, it would be great if you could add some more information on what you actually did: What scanner did you use (field strength does have a massive influence on the appearance of spectra)? What sequence did you use, and what methods did you use to calibrate for optimal data quality? How did you generate the basis sets that you used in LCModel? (Btw. in the data set of the COVID-A patient there is some signal contribution (at both echo times) that is clearly higher than noise but was not accounted for in your model, that might indeed be an interesting finding as well)

To help improve overall reporting standards in MRS and MRSI studies, a few colleagues of mine recently published a consensus paper on minimal reporting standards. This is also meant as a guide to help authors who are somewhat new to the field of MR spectroscopy, and help make the work better comparable to other studies and hence lead to overall improvement of impact of MRS papers: https://doi.org/10.1002/nbm...

On 2021-04-14 14:48:37, user David de Jong wrote:

The article has been published. <br /> Silveira, M., De Jong, D., Berretta, A. A., Galvão, E., Ribeiro, J. C., Cerqueira-Silva, T., Amorim, T. C., Conceição, L., Gomes, M., Teixeira, M. B., Souza, S., Santos, M., Martin, R., Silva, M., Lírio, M., Moreno, L., Sampaio, J., Mendonça, R., Ultchak, S. S., Amorim, F. S., … for the BeeCovid Team (2021). Efficacy of Brazilian Green Propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: a randomized, controlled clinical trial. Biomedicine & Pharmacotherapy, 138:111526. https://doi.org/10.1016/j.b...

On 2021-04-15 10:01:38, user NA wrote:

What's going on with the publication status? It's been five months and we are in pandemic: why has not the review been completed more expeditiously? What journal was it submitted to?

On 2021-04-16 14:11:38, user Claudio Marabotti wrote:

I'd like to ask Authors why they did a retrospective study rather than a prospective one. The high number of cases in Italy in the so-called "second wave" would make easy to recruit two parallel matched groups, one "actively treated" and one serving as a control group, possibly in a couple of weeks. Moreover, even if some reason may explain the need of a restrospective analisys, I think that comparing patients in different epidemic phases seems to represent a source of bias. Actually, knowledge about the disease, and therefore clinical approach to it, was definitely different in the two phases.

On 2021-04-17 09:20:30, user Anna Kena wrote:

Politically biased?

It is surprising and appears bold to include a category "values" (Werte) in a study of drivers of the Corona-pandemic. And if so, to associate it with only two very restricted indicators: the election behaviour for just one political party (out of six) and the creed Catholic, neglecting the main other creeds Protestants, and Muslim.

You state:

"During the period of intense exponential increase in infections, the proportion of the population that voted for the Alternative for Germany (AfD) party in the last federal election was among the top characteristics correlated with high incidence and death rates."

The obvious question is, what was your motivation to select just one political party for your study?

There are these six parties in the German Parliarment (Bundestag), listed here with their results in the 2017 election: CDU/CSU (32.9%), SPD (20.5%), AfD (12.6%), FDP (10.7%), Linke (9.2%), Grüne (8.9%).

Hence the study seems politically biased which makes its scientific value questionable and spoiles your otherwise interesting work.

It is desirable that you mend this flaw during the peer-review process by considering now all parties and the relevant creeds. As a spin-off you might even explain the currently highest values of infection in Thuringia from the "values" of the gouverning party Die Linke.

On 2021-04-17 15:33:53, user Geng Wang wrote:

There are 11 cases (8+1+1+1) of B.1.351 in less than 800 samples, but the authors state "the B.1.351 strain was at an overall frequency of less than 1% in our sample". Did I miss something?

On 2021-04-26 04:10:49, user ????' ???? ??? wrote:

Tables S4-S7 show coefficients for both male and female. How come? One should be the reference.

On 2021-04-26 18:39:17, user William Alexander wrote:

Question: in Figure 4B, a vaccination rate of 5000 per day is purported to reduce daily deaths and total cumulative infections over rates of 8000 and 12000. Why is your model predicting this non-intuitive result?

On 2021-08-10 16:09:56, user Vilkus wrote:

https://newatlas.com/health...

On 2021-08-10 21:39:41, user Paul Gordon wrote:

Hi,

Thanks for posting. I am trying to reconcile the text and Figure 1, but am having trouble. The B.1 graphs appear to be identical to the B graphs, even though the stated fold-changes at the top of each NT graph are different between B and B.1. Secondly, the text highlights a very large changes in Kappa neutralization efficacy, but it is marked in the Figure 1a B.1 graph as not statistically significant. Could you please clarify?

Cheers,

Paul

On 2021-08-11 20:20:37, user amalio telenti wrote:

Please check the text: purifying selection = negative selection

On 2021-08-21 16:43:18, user Mark J Kropf wrote:

A good many issues are of question in regards to this work, after mulling it over a good time. Firstly, evolution is always going on. If one is defining mutations in the most general sense, no treatment alters that rate. However, if one means by mutation the generation of some particularly problematic change causing a variant, then perhaps the logic dealt with here is relevant. Evolution is not a process which can be terminated or quelled, though it may be channeled and controlled! Secondly, a period of about 5.5 months can give some possible resonance to the supposed finding, but the ability to alter progression needs to really have significant follow up. Is the process of some unfavorable change (i.e my latter use of 'mutation' above) really limited or is it only impeded and delayed? A true ability to confirm requires a longer period of analysis and the current argument conclusion may be somewhat presumptuous in its statement. Thirdly, I am concerned that the numbers may yet be a bit too small for the conclusion reached, though running a study with the proper enrolled numbers for such comparisons is probably too problematic to be practical.

I believe there is some evidence here, but perhaps not so complete as to be given the full impact that the conclusion provides. It is likely, but it is not confirmed to nearly the extent that I might desire for such a paper.

On 2021-08-12 01:05:28, user SkylarkV wrote:

CDC and FDA won't act on increasing calls for mRNA boosters for the J&J vaccinated unless the data support it, yet researchers appear to be simply ignoring J&J in their research, so those data can't be obtained. So much for for #HealthEquity!

On 2021-08-15 00:21:45, user Covid Hospitalist wrote:

This abstract of this pre-publication is highly irresponsible. There is no clear delineation between 'infection' and 'illness'. This is going to be taken out of context as 'vaccine failure' by multiple groups and news media sources. The drop in prevention of 'infection' ei detectable virus on PCR is important. AND without the data showing that it is still exceptionally effective at preventing hospitalization, is reckless. The authors need to fill in the rest of the blank... they quote the ability of the vaccine to decrease illness/hospitalization from the wild-type "wuhan" strain EUAs in the intro, but then completely leave it out of the results portion of the abstract??? How many antivaxxers/news media are actually scrolling down to table 7 to see that the rate of covid death for pfizer was 0/38,000(n rounded) and moderna 1/36000(n rounded). Seriously irresponsible headline grabbing abstract.

On 2021-08-20 12:18:37, user Jodi Schneider wrote:

Were there any differences in the underlying populations vaccinated with Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System?

On 2021-08-13 16:42:49, user Dr. Jon wrote:

Isn't it pretty normal to assume those who have recovered from a disease are unlikely to get the same disease again?<br /> Why is this a controversy?

On 2021-10-17 22:54:41, user Rob Reck wrote:

If appears that there is no differentiation given to to the amount of time that passed since a subject contracted CoVid19. Waning immunity is an issue that has been studied. Certainly more study would be a good thing. But there is enough current data to know that it does happen. People who have had CoVid19 do get re-infected.

Given the existence of even a small number of reinfections, the claim that a person who previously was infected with CoVid19 need not be vaccinated is not supported by this study.

On 2021-08-13 17:27:45, user Chuck Crane wrote:

If you look at the questionnaire (the "supplementary materials" link) you find that the MD's and DVM's are "professional degree," and there is no "PhD" classification at all. It says "Doctorate," which includes Jill Biden's Ed.D. and so on. So the chart is deceptive.

D8 What is the highest degree or level of school you have completed?<br /> 1. Less than high school<br /> 2. High school graduate or equivalent (GED)<br /> 3. Some college<br /> 4. 2 year degree<br /> 5. 4 year degree<br /> 6. Master’s degree<br /> 7. Professional degree (e.g. MD, JD, DVM)<br /> 8. Doctorate

The paper is not in sync with the questionnaire, saying, e.g., "Those with professional degrees (e.g., JD, MBA) and PhDs were the only education groups without a decrease in hesitancy, and by May, those with PhDs had the highest hesitancy." I can't see how an MBA could look at the question and check "Professional degree" instead of "Master's Degree."

Think the paper needs a good proofreading.

Participation bias is a big issue. They asked a lot of people to participate, but only a small percentage did. The rather inane attempt to correct for this is to assume that if a particular class of respondents is under-represented, just assign responses from that class more weight, according to their proportion of the population ("post stratification adjustment").

On 2021-08-14 00:52:29, user Meredith Olson wrote:

Those with a doctorate who choose to spend time on facebook and are also willing to take the time to fill out the survey there are a particular subset of people with doctorates.

On 2021-08-15 02:02:46, user bcwbcwbcw wrote:

An online survey, where anyone can claim to have a PhD and no tests or controls for whether that's true? If you're anti-vax what better way to claim credibility than to lie and claim to have a PhD? In other past surveys , 6% of PhD's said they are Republican, yet the hesitancy results for PhD's are nearly the same as the strongest Trump supporters. (statistically possible but very unlikely.) (https://www.pewresearch.org... ) If I was a reviewer, I would ask see the breakdown of Trump support versus education level. If not consistent with other studies, the educational attainment data should be discounted.

I took this survey and it likely has some use as far as changes in totals over time but PhD's not really.

Let me give you a data point from a lab with about 1500 PhD's and tech staff. Everyone I've asked is vaccinated and I've asked everyone I'm in contact with.

On 2021-08-15 10:02:06, user Anna Z. wrote:

This paper is circulating among no-vax groups and used as a prof that educated people don't get the vaccine because they are not fooled by the government.<br /> How did you make sure that the survey was not circulated among no-wax groups that on purpose answered to obtain this result?

On 2021-10-05 10:08:23, user Samantha Hester wrote:

Members of the trans community are raising questions about your new exclusion criteria that eliminated people who self-identified as unicorns. Unicorns belong to the otherkin community and their responses could be in good faith.

Please review this post from a trans advocacy organization for more details:

https://www.facebook.com/pe...

On 2021-08-16 15:59:43, user A. Jamie Saris wrote:

There are some excellent comments below that I will not rehash, but I agree that this pre-print "as is" would not survive peer review without some serious revisions. Unfortunately, as this site is Open Source, this "study" is appearing in a lot of anti-vaxx rants on social media (it's been cited twice to me on Twitter so far today). It would be a great help if there were some printed caveats on sites like this (especially around topics where pseudoscience to outright quackery is rife) to dissuade people from taking VERY provisional results (from a flawed study with a modest number of participants) as "settled" science "proving the effectiveness" of Ivermectin.

On 2021-08-17 14:22:29, user Jon Hillman wrote:

'Taken together our results indicate that state implemented NPIs can lead to less COVID-19 cases and mortality.' How much less? CDC concluded it was no more than 1.8% reduction in cases: https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e3.htm Quantifying the reduction matters to anyone concerned with objectively measuring NPI cost vs outcomes.

On 2021-08-17 14:26:39, user Andrew Sefton wrote:

In the research, how were those previously infected by COVID-19 categorized? As unvaccinated? Excluded?

Specifically, I am interested in the viral loads of those previously infected by COVID-19 as it relates to:<br /> "Delta viral loads were similar for both groups for the first week of infection, but dropped quickly after day 7 in vaccinated people."

On 2021-10-05 22:04:39, user Brooke wrote:

It would be useful to know what sorts of samples were used for PCR testing — were they nasal swabs or saliva?

On 2021-08-18 18:37:59, user Sumit Rawat wrote:

https://timesofindia.indiat...

On 2021-08-18 18:40:47, user Sumit Rawat wrote:

News article by ET health <br /> https://indianewsrepublic.c...

On 2021-08-20 23:58:21, user Chris Raberts wrote:

This model ignores the wave form observed repeatedly over the past year and a half. Covid infection is not a never-ending exponential function. Terrible.

On 2021-08-21 00:31:20, user Sonia Villapol wrote:

This article has been published in "Scientific Reports" on 09 August 2021, a Nature Publishing Group's open access research journal: <br /> https://www.nature.com/arti... <br /> Thanks! <br /> - Sonia Villapol

On 2021-08-21 19:03:01, user Jonathan C wrote:

Hello,

Thanks for an interesting analysis. CDC estimates a far higher infection rate (36.77/100k, <br /> https://www.cdc.gov/coronav... "https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html)"), <br /> at a similar rate for the 0-17 y group, although they do not seem to show data for the 12-17 y group).

Am I correct in interpreting your assumption that the infection rate for the <br /> investigated COVID-19-related period was at a far lower <10%? (and that 2.5% of all COVID-19 cases should represent males aged 12-17)

Or is there some information missing regarding your analysis?

On 2021-08-24 07:21:17, user Red wrote:

This paper is missing one very crucial piece of information: 6-month adverse event followup. Table S3 still reports only adverse event counts up to 1 month after the second dose, but nothing about longer followup periods. This is a violation of a commitment from the study's protocol where it was stated that 6-month safety data will be reported (section 9.5.1). And the only reason I can think of why such a data was not reported is because it suggests the treatment is not as safe as it is claimed.

On 2021-08-04 07:40:42, user Mike wrote:

I'm curious about the HIV infected patients. There were exactly 100 in both vaccine and placebo group. If you look at the co-morbidity tables, no other co-morbidity is balanced in that way. I suppose it's possible that this occurred by chance but it's a very small one if so. Also, why did they include HIV+ patients in the study at all, if they exclude them from all reporting of deaths and adverse events? The HIV+ can lead long lives these days, it's not quite clear to me why they are being treated separately here, especially as it should hopefully be clear if they died of AIDS.

On 2021-08-05 17:53:36, user pedro paulo castro wrote:

It doesn't seem right that a much lower number of subjects from the vaccinated group came down with COVID 19, but the same number died as in the placebo group, which seems to indicate therefore a higher proportion of deaths among those who contracted COVID 19 AND were vaccinated. There is a conspicuous lack of what would have been a very useful breakdown of the instances of death, in such a way that we could see, for both groups, what number of deaths was among those who had COVID or those who didn't have COVID. This prevents us from seeing whether a subject had COVID, but had his or her death reported as, say, cardiac arrest, for example, which might change the context a bit.

On 2021-10-03 02:28:34, user OBS wrote:

How come this preprint (and the very recent publication of this in NEJM) both say 15 deaths vaccine vs. 14 deaths placebo, but the FDA briefing document for the booster shot (which summarizes the safety of the primary 2-dose series, see page 7), says 21 deaths vaccine vs. 17 deaths placebo?

https://www.fda.gov/media/1...

21 vs. 17 doesn't seem to be an update of the 15 vs. 14 result, since the booster FDA briefing document specifies March 13, 2021 as the data cutoff date corresponding to the 21 vs. 17 result, and that is the exact same cutoff date mentioned in this preprint / NEJM article. So why the discrepancy- what is going on here?

On 2021-08-26 07:10:10, user William Brooks wrote:

To help readers clearly see the difference in infectiousness before, during, and after the various interventions (i.e., the states of emergency, school closures, and GoTo travel campaign),the authors should add the start and end points of the interventions in Figure 2.

On 2021-08-27 02:57:37, user Jason Eshleman wrote:

The author's model assumes that the generation time for the variants is the same. This seems to run counter to observations of a markedly shorter incubation period with delta. This analysis absolutely needs to be rerun without that assumption. Are we seeing greater transmission between generations or are we seeing a fitness advantage due to a shorter generation time?

On 2021-08-27 12:30:01, user Nikos Salingaros wrote:

Hello everyone. Alarming results indeed. Are there any data on the visual complexity of the indoor environment in which these babies were raised? Our group is trying to relate low intelligence to the lack of mathematical stimulation coming from visual patterns. This is especially relevant since exposure to natural complexity such as outdoor plants is severely limited during the lockdown. The preferred architectural style today is minimalist: very different from the visual complexity of past generations, and this factor might contribute. How do we get some data on this possibility?

On 2021-08-27 22:08:03, user evasmagacz wrote:

To look at the data from a different perspective:

In your first dataset:

Model 1: n = 16000 <br /> In patients who were previously infected: <br /> There were 5 symptomatic re-infections per 10000;<br /> Less than one hospitalisation per 10000, and no deaths.

In patients who were previously vaccinated, <br /> There were 124 symptomatic re-infections per 10000;<br /> 5 hospitalisations per 10000 and no deaths.

In your second dataset:<br /> Model 2: n = 46000<br /> In patients who were previously infected: <br /> There were 15 symptomatic reinfections per 10000; <br /> Less than one hospitalisation per 10000, and no deaths.

In patients who were previously vaccinated, <br /> There were 105 symptomatic reinfections per 10000 <br /> 5 hospitalisations per 10000 and no deaths.

In your third dataset:<br /> Model 3: 14000<br /> In patients who were previously infected: <br /> There were 16 symptomatic reinfections per 10000 <br /> Less than one hospitalisation per 10000, and no deaths.

In patients who were previously infected and then vaccinated, <br /> There were 11 symptomatic reinfections per 10000 <br /> No hospitalisations per 10000 and no deaths.

On 2021-10-30 04:38:45, user Rn wrote:

The conclusions of this study stand in stark contrast to a report published today by the US CDC. https://www.cdc.gov/mmwr/vo...

Among COVID-19–like illness hospitalizations among adults aged >=18 years whose previous infection or vaccination occurred 90–179 days earlier, the adjusted odds of laboratory-confirmed COVID-19 among unvaccinated adults with previous SARS-CoV-2 infection were 5.49-fold higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine who had no previous documented infection (95% confidence interval = 2.75–10.99).

On 2021-08-29 20:54:09, user peter_wark wrote:

Thanks again Recovery trial.<br /> Participants admitted with COVID19; unable to maintain SpO2 <94% despite FiO2 0.4.<br /> Mean age 57yrs<br /> Primary outcome was intubation or mortality at d30.<br /> CPAP HR 0.72 (0.53-0.96) p=0.03<br /> HFO2 0.97 (0.73-1.23) p=0.85<br /> The number needed to treat for CPAP was 12 (95% CI, 7 to 105) and for HFNO was 151 (95% CI, number needed to treat 13 to number needed to harm 16).

On 2021-08-04 07:26:14, user oikoslibre wrote:

In the first chapter you talk about PCR.

I would like your opinion on the following document

https://www.fda.gov/media/1...

When I read this document , it becomes clear that this test is of no use at all

Positive results are indicative of active infection with SARS-CoV-2 but do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease

In this document I also read: Since no quantified virus isolates of the 2019-nCoV were available for CDC use at the time the test was developed and this study conducted, assays designed for detection of the 2019-nCoV RNA were tested with characterized stocks of in vitro transcribed full length RNA.

Is it possible to write an article on this virus without the use of PCR data?

Do you have the isolated virus?

On 2021-08-05 18:41:36, user Ultrafiltered wrote:

With the probability of a PCR match of 1 with any sample comparison to a reference given 8 billion genotypes against strands of 30 to 50 mRNA, as DNA is expressed in any and all cells, the study only shows how many in the population are expressing a gene similar to a COVID phenotype, thus why the CDC has pulled its support of the PCR tests and going back to the process of isolation and identifying cells discovered through patient exam, similar to current Influenza like analoques. The basis of this paper goes to show that if you're sick with disease, you are sick with the disease and shed components, just like any other virus. The idea this effect is novel in this paper is superceeded by years of virology and research.

On 2021-09-16 07:33:29, user Chaos_14 wrote:

This study doesn't mention how many vaccinated vs unvaccinated people were tested.

"Notably, 68% of individuals infected despite vaccination tested positive with Ct <25, including at least 8 who were asymptomatic at the time of testing." (68% of what number?)

Since we know immune response, even with vaccines, decreases with age, it would be helpful to know the ages of the people in both the vaccinated and unvaccinated groups.

It would also be helpful to know the Ct in the samples of asymptomatic, <br /> unvaccinated people if there were any.

While it's beneficial to know that it's possible for infected vaccinated people to carry a viral load similar to infected unvaccinated people, this study left me with a lot of unanswered questions.

On 2021-08-06 23:22:56, user disqus_92pIDbtuHj wrote:

Hey, where's the full description of method and limitations? I get that this was published in medRxiv, a free distribution server for unpublished preprints that haven't been peer reviewed. It even states preprints "should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information".

This was a SMALL sample of 43 men... undergoing IVF and they served as their own self control. WHEN, was a sample after vaccination taken? WHEN was the baseline taken? HOW did they control for the effects of other variables... like the treatment recommendations these patients may have been following at the IVF clinic (especially since these were pulled Hospital IVF records)! They compared each man to his own baseline before and after vaccination, (14 men had male factor infertility, and 29 with normal spermogram results). Regardless all men were very likely receiving lifestyle, diet, or even medication recommendations! They also neglected to control season as a variable. Previous literature shows poorer sperm quality in Winter, and better quality in Spring. This design looked at two samples from each man somewhere between winter and spring. The same span of time for each man? No one knows!

On 2021-08-07 16:14:30, user Dmitry Pruss wrote:

Isn't it a time-of-testing confounding effect? In Israel, percent of positive tests increased from 0.1% in the beginning of the study period to 1.5% in its end, which would likely result in an artifactual increase of positive in those vaccinated (and tested) earlier...

On 2021-08-08 19:23:45, user Sam Wheeler wrote:

So against delta, 1 dose of The Moderna COVID-19 (mRNA-1273) vaccine seems much more efficient than 1 dose of Pfizer Biontech?<br /> And no data about how efficient is Moderna with 2 doses against delta?<br /> What do we know about Janssen = J&J? Janssen is very efficient if you take into account it is given as a single-dose, and one can boost it by taking a booster or primer with other covid vaccine.

On 2021-08-09 15:03:31, user Disha Agrawal wrote:

Figure 3b is surprising and difficult for me to understand. The Y-axis for all figure 3 results should be Geometric Mean of the ELISA tests, as per the text. Assuming that to be so, Figure 3b is Antibody to N protein, which should not be induced by Covishield. Yet most Covishield/Covishield samples seem positive, as shown, with no difference from Covaxin/Covaxin. A possibility I considered is that most people were already infected, but then the Covaxin/Covaxin group should have been strongly boosted. Clarification from authors or others who were able to figure it out is welcome.

On 2021-12-01 22:44:50, user Tom wrote:

The susceptibility of Chilrden was estimated by PCR-Testing alone and has a high variance in the 95-CI. I guess the numbers may be even lower.

On 2021-09-14 21:28:12, user Alberto wrote:

23 vaccinated individuals, samples collected 5.2 weeks (average) after the second dose of the vaccine. No information about age, health, etc... compared to 10 individuals infected one year prior to taking the blood samples and 7 infected less than 2 months prior to taking the blood samples. Again no information about age, health, etc...

Conclusion: "Hence, immune responses after vaccination are stronger compared to those<br /> after naturally occurring infection, pointing out the need of the vaccine to overcome the pandemic".

Isn't that conclusion going well over the possibilities of this study? When in real world studies with cohorts of > 25.000 individuals it has been proven that the immunity acquired from infection is vastly superior to that from vaccination, how should we take these results?

On 2021-12-15 06:52:55, user MD PhD wrote:

Although it's a small sample size still it would be worthwhile to know the antibody response to booster/third dose in 6 months vs 9 months group post-vaccination. Additionally whether these groups received first and second shots at 3-4 weeks or 7-8 weeks interval will offer pertinent information since this basic difference rendered more antibody response in the latter groups as per studies (the point being that boosters might turn out to an immediate requirement for the 3-4 weeks vaccination interval group while the 7-8 weeks interval group might potentially be able to put it off for a month or so in light of prior studies showing a robust antibody response with delayed vaccination)

On 2021-09-16 13:24:58, user Theo Sanderson wrote:

The apparent pattern of back mutations at position 142 is an experimental artefact due to errors in some Delta sequences. It emerges from the fact that Delta has SNPs in the primer binding site for ARTIC amplicon 72 (in a previous ARTIC scheme) which often result in the failure to amplify this amplicon, containing the G/D 142 locus, from Delta samples. Small amounts of contamination from other genotypes (e.g. B.1.1.7) that are amplified normally at this location can then lead to an amplicon here (typically with reduced depth). This results in a final sequence which appears to have a back-mutation at this position, and phylogenetic analyses can tend to group such samples together on trees.

T95I is in this same amplicon.

It is likely that the Ct correlations observed here reflect the fact that the correct G142D call is much more likely to be detected despite the low efficiency of amplification for samples with higher viral loads.

On 2021-09-16 13:35:24, user David Brown wrote:

There is evidence that abdominal obesity in both humans and chickens is determined by the fatty acid profile of the diet; specifically, the linoleic acid content. Read pages 7-9 of this 2019 Master's Thesis. https://trace.tennessee.edu...<br /> For further comment regarding linoleic acid intake and vulnerability to COVID-19 complications, read these articles:<br /> https://www.medpagetoday.co...<br /> https://www.science.org/doi...

On 2021-09-17 17:04:42, user kdrl nakle wrote:

This would all be OK if we could rely on COVID reporting but we cannot. For example a continent of 1 billion people, Africa, on Wednesday reported 12,000+ cases while we have seropositivity in Kenya of 50%! Meaning, their numbers as reported, are a joke. India that reported some 33 million cases had more likely some 900 million cases. And similar things are happening throughout Asia, Latin America, and Eastern Europe. In other words, your statistics are a joke.

On 2021-09-19 12:46:53, user daan joubert wrote:

I rhink you are referring to the article entitled "Africa Dailye deaths.100k etc" showing the difference between the high incidence in the upper and lower parts of the continent compared to the equatorial region where Ivermectin is used against tropical parasites and there are few deaths. It seems to have been removed for some guessable reason.

On 2021-09-22 01:46:06, user jhick059 wrote:

Dear authors,

I believe your denominators (15,997 Moderna doses and 16,382 Pfizer doses) are off by more than a factor of 10.

Ottawa Public Health has 342,656 doses of Moderna and 485,178 doses of Pfizer between 2021-06-01 and 2021-07-31. Link: https://open.ottawa.ca/data...

You also state (pg. 6/20) that your data suggest a tenfold higher incidence than other papers estimating an incidence of 1/100,000. A tenfold higher incidence than 1/100,000 is 1/10,000, which is closer to the value you would obtain with the adjusted denominator.

Sincerely,<br /> Joseph Hickey

On 2021-09-22 03:14:20, user Norsksoul wrote:

It is a preprint article but they basically identified all vaccine recipients in Ottawa during the June 1 through July 31 study period. <br /> This was the denominator of the study group. <br /> Anyone from this study group that was admitted with Acute Myocarditis or Pericarditis within 1 month of a Moderna or Pfizer vaccine became the numerator. <br /> So 32 cases occurred in 32,379 vaccine recipients which comes out to a 1/1000 incidence. This study should be done in the 12-18 year old age range and the incidence would likely be even worse.<br /> But wait,....it gets even worse. <br /> That 1/1000 incidence is in a group of 32,000 men AND women. <br /> But out of 32 cases of myocarditis, 29 occurred in men. <br /> That’s 90%! <br /> They unfortunately don’t give the data on male/ female percentages in the study group denominator but if we assume a 50/50 split, then the male incidence is actually 29/16,189 or 1 in 558 males vaccinated. <br /> 1/558<br /> 1/558<br /> 1/558<br /> Let that sink in for a minute. <br /> This is reckless medical malpractice at its worst.

On 2021-09-23 06:52:46, user White Rabbit wrote:

There are several issues about the meta-analysis by Martinoli et al. for example they wrote they did a meta-regression in order to explain the the huge between-study heterogeneity affecting the results, but no meta-regression results appears anywhere. They observed a statistically significant publicaton bias ("We found an indication for publication bias (P=0.03)" ,page 10) a serious but unaddressed issue. Ther are also inconsistencies between the results and the conclusions, e.g. though they found that "Children and adults showed comparable SARS-CoV-2 positivity <br /> rates in most studies" (page 9)" the abstract reads "children are 43% less susceptible than adults".Furthermore in some tables and forest plots, they used as denominator the total of students and staff altogether instead of students only, to estimate the students incidence.

On 2021-09-23 15:49:33, user kdrl nakle wrote:

What is needed more is the distance between the shot and data collection. We need longer duration period for VE evaluation. Your time period is too short.

On 2021-09-23 18:14:58, user kdrl nakle wrote:

n-28, n=29, n=106 and no significant difference between 2.4x10^5 and 3x10^4? That is because your samples are small. I think that 8 fold increase would be significant if you got bigger samples.

On 2021-09-24 06:20:12, user Ella Lively wrote:

Where can I get the questionnaire for thus study please?

On 2021-09-28 15:09:49, user Tomas Maximus wrote:

Looks like the proportion of breakthroughs climbed dramatically as time went on, with breakthrough accounting for 17% of total new cases in July. Wonder what the August and September numbers showed.

On 2021-09-29 04:15:27, user Nikki wrote:

I work as an account Escalation Specialist/call center supervisor who takes over Escalated calls. I've never had issues with missing small details which are required to do my job. I caught covid in mid July, had a horrible experience with two weeks worth of severe vertigo, nausea, fever spikes, tons of phlegm, panic attacks. <br /> One month and a half after recovery, I've had 4 major fails which may ultimately end up costing me my job. <br /> My pcp, therapist, and boss appear to disregard this when I try to explain to them about the fogginess. <br /> As a very detail oriented person, I just don't miss those things.... never in my 15 years in callcenter experience.

On 2021-09-29 11:30:07, user kdrl nakle wrote:

Good example of making a paper focused on useless graphics instead on self-explanatory data.

On 2021-10-02 14:59:26, user Alberto wrote:

Thanks for the detailed report. I'd only like to ask about the last sentence included in the abstract: "The beneficial and protective effects of the COVID-19 vaccines far <br /> outweigh the low potential risk of neurologic and psychiatric reactions. Going through the paper I haven't seen anything that attempts to estimate these rinks vs. benefits in any way (let alone a systematic way, by age, risk of severe disease in case of COVID-19, etc...). It seems like a statement that's been added there arbitrarily and does not belong to a scientific paper that not actually evaluating any risks associated with the disease itself or the vaccine efficacy to prevent them.

On 2021-10-03 07:19:18, user Ruth Berger wrote:

That age and male sex are major risk factors is well known; mortality associations with pandemic wave should not be reported without factoring in varying levels of underdiagnosis (to my knowledge, it was larger in the first wave than the second) and age-specific vaccination rates.

On 2021-10-04 06:54:30, user kdrl nakle wrote:

Simple yet important result, meaning we should definitely know Cp (Ct) value after getting tested. The next thing would be to investigate transmissibility but that is obviously much harder research.

On 2021-10-04 12:12:28, user LG27 wrote:

Why was there no stratification by prior infection? It's not even mentioned in the limitations.

On 2021-10-05 22:59:35, user MrMemeinator wrote:

So you're seeing the same thing we all saw in the UK and Israel months ago. Color me surprised...

On 2021-10-16 12:57:40, user gerryz wrote:

Can anyone tell me if there is evidence infection symptoms are milder in vaccinated? Articles?

On 2021-10-06 16:56:58, user zega wrote:

Baseline is 1/100000/365days https://www.myocarditisfoun... vast difference, they an be off by 8000times and still below...

On 2021-10-07 22:22:53, user Robyn Schofield wrote:

"As the devices do not meet medical device electrical safety standards (EN60601) they were operated at a distance of >=1.5metres from any patient." Can the authors please clarify - what wavelength the UV was operating at, and whether this device has been tested for ozone production / loss rates. I assume that the EN60601 requires ozone production to be tested for? If ozone is being produced (or destroyed to odd oxygen) that this would need testing before deployment in a medical setting. Ozone, a respiratory irritant gas, will easily travel more than 1.5m (so distance should not be seen as useful in setting safety protocols for electronic air cleaning devices in a medical setting).

Are hospital rooms with no ventilation in line with current infection prevention and control or hospital design / operational guidelines in the UK? In Australia this would be in breach of both our hospital design and operating guidelines which require a minimum of 6 ACH for all hospitals.

The effectiveness of UV with air high flow rates has to be questioned (because the exposure time for bio-aerosols is short) - are the authors able to separate the effectiveness of the filtration over the UV features? Most literature on this point shows that in real-world operation the HEPA provides 99.97% of the removal of bio-aerosols from air and the advantage of UV is untested / unproven (this is particularly true at 1000m3/h flow rates this device is operating at). I assume this device will be noisy >65dB - can this please be specified.

On 2021-10-11 18:40:32, user Andrew T Levin wrote:

Comment #1: Research in Context

1. Diamond Princess Cruise Ship. The manuscript makes no reference to any epidemiological analysis of this episode, which informed seminal assessments of the age-specific infection fatality rate (IFR) of COVID-19.[1-4] Nonetheless, that evidence is particularly relevant, because the cruise ship’s passengers included 1231 individuals ages 70+ who were not merely “community-dwelling” but healthy enough to embark on a multi-week grand tour of southeast Asia. Following extensive RT-PCR testing, 335 passengers ages 70+ were confirmed to have been infected with SARS-Cov-2, and 13 of those passengers died from COVID-19 – an IFR of about 4%. Moreover, the strong link to age is underscored by the even higher IFR of 8% for passengers ages 80+. Given the size of that sample (which meets the 1000+ threshold used here), this evidence should certainly be incorporated into this meta-analysis.

2. Comprehensive Tracing Programs. The manuscript makes no reference to countries that succeeded in containing the first wave of the pandemic in spring 2020 through systematic tracing and testing of all contacts of infected individuals.[5] Such evidence is particularly relevant here, because the virus was contained within the “community-dwelling” populations of those locations and never spread to any elderly care facilities. For example, in the case of New Zealand, there were 256 infections and 19 deaths among adults ages 70+ -- an IFR of about 7%.

3. Hospitalized Patients. The manuscript cites a single study (published in July 2020) that examined the association between comorbidities and mortality risk of COVID-19.[6] However, that study was not able to distinguish whether comorbidities were linked to greater prevalence (the probability of getting infected) or to a higher IFR (the risk of mortality conditional on infection). Unfortunately, the manuscript makes no reference to any subsequent studies on this issue. In particular, a large-scale study of U.K. BioBank participants found that measures of frailty were indeed associated with higher mortality rates in the overall panel but not linked to mortality within the subset of hospitalized COVID-19 patients.[7] In effect, the prevalence of COVID-19 was markedly higher among residents of U.K. nursing homes compared to individuals of similar age living in the community, but the IFR was not significantly different. Those findings directly contradict a key assertion made at the start of this manuscript.

4. Prior Meta-Analysis of Community-Dwelling Populations. The introduction of this manuscript neglects to mention that an existing meta-analysis study (published in Nature in November 2020) was specifically focused on assessing IFRs excluding deaths in nursing homes.[8] That study estimated the link between age and IFR using seroprevalence and fatality data for adults less than 65 years old, and then showed that the model predictiions were consistent with data on fatalities among community-dwelling adults ages 65+. Moreover, that study used seroprevalence data adjusted for assay characteristics, and the results were obtained using a rigorous Bayesian statistical model that incorporated random variations in the time lags between infection, seropositivity, and fatal outcomes – a striking contrast to this manuscript, which uses rudimentary assumptions to address those issues.

5. Other Meta-Analyses. The introduction of this manuscript briefly refers to two other meta-analysis studies of the link between age and IFR.[5, 9] However, the manuscript then asserts: “Importantly, the vast majority of seroprevalence studies include very few elderly people.” (p.5) That assertion is supported by a single citation to the SeroTracker database, which provides comprehensive coverage of all existing national, regional, and local seroprevalence studies across the globe.[10] However, this assertion is completely incorrect as a characterization of the preceding meta-analysis of age-specific IFRs. As indicated in Levin et al. (2020, figure 5), that meta-analysis study included seroprevalence data on older adults (including narrow brackets for ages 60-69, 65-74, 70-79, and 75-84 as well as open-ended brackets for ages 60+, 65+, 70+, 80+, and 85+) from nine national studies (Belgium, France, Hungary, Italy, Netherlands, Portugal, Spain, Sweden, and the U.K.) and eight regional locations (Ontario, Canada; Geneva, Switzerland; Connecticut, Indiana, Louisiana, Miami, Missouri, and San Francisco, USA).[5]

On 2021-10-14 17:12:39, user lbaustin wrote:

Has this been submitted to any of the MEDLINE indexed journals who publish on this topic?

On 2021-10-22 17:10:09, user Jeremy M Bartels wrote:

Can you clarify if Ct values decrease, does viral load go up or down?

On 2021-10-31 02:14:19, user Peter Jaji wrote:

So this shows vaccinated people spread the virus as much if not more then unvaccinated?<br /> Please enlighten

On 2020-04-03 17:14:59, user Paula Thompson wrote:

OK. While I do like to look at data, I don't understand comments abt this being too simplistic. Are the data too simple, and not fitting reality well, or are they good? Thanks for help.

On 2022-12-15 21:37:06, user Yiwen Zhu wrote:

This paper has now been published in Neuroscience & Biobehavioral Reviews Volume 143, December 2022, 104954 (doi: 10.1016/j.neubiorev.2022.104954). Please update the link if possible, thank you! <br /> - Yiwen Zhu

On 2020-04-06 01:21:26, user iggy wrote:

TLDR; Does Coronavirus lower the testosterone of those who survived it, long term? <br /> What percentage of men who had Covid-19 is affected by lowered testosterone? <br /> How much is it lowered?

On 2020-04-23 17:59:14, user El Ray wrote:

You can only measure what makes it into a sample. Comparing different assays on the same samples is the most informative approach.

On 2023-06-21 18:28:21, user Wim van Drongelen wrote:

Now published in Communications Biology doi: 10.1038/s42003-023-04696-3

On 2020-07-23 11:59:38, user Mr C S Mence wrote:

All the researchers seem to be north of the equator. Is there any data from countries south of the equator who have experience of the pandemic through their winter months

On 2020-04-24 05:20:43, user Olexiy Buyanskyy wrote:

Where is the zinc? Zelenko pointed that zinc is required!

On 2020-04-28 03:05:27, user algebra wrote:

What was the dosage given? Too little might not work, too much could be toxic

On 2020-04-21 23:43:04, user docmeehan wrote:

I'm not sure VA database born retrospective cohort analysis that declines to reveal drug dosing protocols contributes much to the science. Let's have those drug dosing protocols.

On 2020-06-08 21:08:42, user Paul Gordon wrote:

Hi, nice work. I notice that NRW-11 is reported in the supplementary tables, but is the only genome missing in GISAID. Was it withdrawn due to quality or was there an oversight in the submission? Thanks!

On 2021-12-27 21:14:28, user Danes wrote:

Any comment on the huge discrepancy in pre-risk between vaccine and COVID groups in Table 1? Does not seem to be appropriate for this type of comparison.

On 2022-01-01 14:56:50, user Jeffrey_S_Morris wrote:

Nice study! For completeness, it would be nice if table 3 included the transmissibility odds ratios for vaccination statuses stratified by variant

On 2020-06-15 02:32:20, user Sinai Immunol Review Project wrote:

Main findings<br /> Sex-based differences in the immune response have been reported for various types of infections. There is a growing body of epidemiological evidence that supports the finding that men experience more severe COVID-19 disease than women do, but the immune mechanisms underscoring such a difference remain unknown.

Here, Takahashi et al. analyze PBMCs, plasma, and nasopharyngeal swabs or saliva from 93 mild-to-moderate COVID-19 patients (n=93), comprised of 48 women (n=48) and 45 men (n=45), to characterize potential sex-based differences in the immune response to SARS-CoV-2 infection. It is important to note that patients on hydroxychloroquine and Remdesivir were not excluded from a sub-cohort of patients (n=39) evaluated as baseline measures for untampered immune responses to SARS-CoV-2 (these patients were not treated prior to first sample collection). In a second sub-cohort, 54 patients were assessed longitudinally for an undisclosed amount of time. Samples from uninfected healthcare workers were used as controls.

Viral Load (nasopharyngeal or saliva samples)<br /> No significant differences were identified between male and female patients. Still, median viral RNA was higher in male patients at first sample collection and generally throughout disease course.

Antibody production (plasma samples)<br /> Anti-SARS-CoV-2 S1 protein-specific IgG and IgM antibodies were measured in the plasma of male and female patients. Though anti-S1-IgG antibodies were higher in female patients, compared to male patients, no significant differences could be identified either in the baseline cohort or in longitudinal patients.

Cytokine analysis (plasma samples)<br /> Among baseline patients, who had not received immunomodulatory therapy prior to sample collection (except hydroxychloroquine), type I/II/III IFN levels were not significantly different between male and female patients. However, IL-8 was significantly higher in male than in female patients. Of note, among longitudinally evaluated patients, CCL5 levels were significantly higher in male than in female patients. CXCL10 levels show a similar trend, though this was not significant.

Immune cell landscape (PBMCs)<br /> Both male and female patients exhibited a reduction among T cells and an increase in B cells. No significant differences in T cell subtypes (naïve, central/effector memory, follicular, regulatory) were observed between male and female patients. Of note, however, female patients showed (1) a significantly greater proportion of CD38+HLA-DR+ activated CD8+ T cells and (2) a concomitant enrichment of PD-1+TIM-3+ terminally differentiated T cells, compared to male patients. Otherwise, no other significant differences were identified between male and female patients.

The authors subsequently interrogated the peripheral myeloid compartment. Female patients showed a greater increase in CD14+CD16+ intermediate monocytes than male patients, while both patients exhibited a marked increase in total monocytes, compared to the controls. However, male patients showed higher levels of CD14loCD16+ non-classical monocytes than female patients and their uninfected, healthy counterparts. The authors noted that this enrichment of non-classical monocytes was correlated with CCL5 levels only in male patients.

Clinical comparison<br /> Clinical outcomes were tracked for both male and female patients. Clinical scoring was used to separate each group into two sub-groups: patients that had remained stable throughout hospital stay (stabilized) and patients that had worsened since the first sample collection (deteriorated). Deteriorated male patients were significantly older than stabilized male patients; there was no significant difference in age between stabilized and deteriorated female patients. In terms of BMI, both deteriorated male and female patients tended to be higher in BMI than their respective stabilized counterparts. Interestingly, anti-S1-IgG antibodies were higher in stabilized female patients than their deteriorated counterparts, though this trend was not seen with male patients. Otherwise, no other significant differences in clinical parameters were observed.

Additional comparisons between deteriorated and stabilized patients of each sex revealed that certain innate cytokine mediators (TNFSF10 and IL-15) associated with worse outcome in female patients but not in male patients. In contrast, the proportion of CD38+HLA-DR+ activated CD8+ T cells was significantly reduced in deteriorated male patients compared to their stable counterparts, but this was not true for female patients. Indeed, poor CD8+ T cell activation and IFN? production were both negatively correlated with age in male patients, but not in female patients.

Limitations<br /> • A significant number of patients were diagnosed with underlying chronic conditions that have been previously described to associate with poorer COVID-19 outcomes or with a compromised immune system. <br /> • Approximately two-thirds of each group (men and women) were treated with tocilizumab, and nearly a sixth of each group were treated with corticosteroids. While these patients were excluded from the baseline cohort, it is unclear whether or not these patients contributed to the second cohort that was longitudinally examined.<br /> • The mean age for patients is notably higher than the mean age for the HCW control group.<br /> • Duration of hospital stay was not considered, so it is unclear how quickly certain subsets of male and female patients deteriorated. This may be a confounding variable, or at the very least, the kinetics of disease course in male and female patients is a parameter that warrants investigation.

Significance<br /> In summary, Takahashi et al. provide the first report-to-date that delineates immunological differences between male and female patients with mild-to-moderate COVID-19 disease during the initial stages of infection. For example, male patients deteriorate due to less robust T cell-mediated antiviral immunity, compared to their female counterparts. Several of the other findings substantiate previous reports, such as those of significant neutrophil chemotaxis in the lung of COVID-19 patients (and its association with poorer prognosis). This study, therefore, provides an important platform for additional inquiries into key signaling pathways and transcriptional programs that are differentially regulated between male and female COVID-19 patients by specific cell types (i.e. intermediate and non-classical monocytes, CD38+HLA-DR+ CD8+ T cells) identified in this report. These studies, alongside others, are warranted to better tailor therapies for male and female COVID-19 patients.

This review was undertaken by Matthew D. Park as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.

On 2020-07-11 04:42:51, user Tom Jarman wrote:

the authors reached the conclusion that masks do not have a significant difference in person-to-person transmission for influenza-like illnesses, yet they still recommend use of masks. What am I missing here?

On 2022-01-06 23:28:48, user Greg Nelson wrote:

This is encouraging, would love to see another paper comparing to the PCR negative population (2346 respondees - 951 with PCR positive (study population) = 1395 people) to see baseline frequency of symptoms

On 2020-08-24 05:59:23, user Jala Painter wrote:

If hydroxychloroquine is dangerous as a treatment for COVID19 will a lupus patient have to go off his Plaquenil medication if he contracts COVID19?

On 2020-08-24 17:50:51, user Puvvada Rahul krishna wrote:

We would like to withdraw the article from MedRxiv. The reason for withdrawal was plagiarism issue while publishing to other journal's

On 2020-08-25 20:28:59, user Jean Sanders wrote:

this is very valuable information; I am trying to process the data so I will be informed when we have meetings this week on school re-opening... Thank you for this fine work and the many references

On 2020-09-05 11:35:05, user Tricia Young wrote:

Thank you for providing statistics that are more consistent with what is really happening. Will this article be published?

On 2020-05-13 03:36:31, user Annalisse Mayer wrote:

But what about the people who died suddenly at home and never made it to the hospital? How many of them were smokers? Maybe being able to get to the hospital means one is better at resisting the infection

On 2022-02-12 20:26:12, user Jan Lakota wrote:

This paper is in concert with the presented findings:<br /> New diagnosis of multiple sclerosis in the setting of mRNA COVID-19 vaccine exposure

J Neuroimmunol. 2022 Jan 15;362:577785. doi: 10.1016/j.jneuroim.2021.577785.

On 2020-03-25 22:19:11, user Sinai Immunol Review Project wrote:

Title

Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Keywords

ARDS; interleukin-6 (IL-6); procalcitonin (PCT); pro-inflammatory cytokines; SARS-CoV-2 RNAaemia

Key findings

48 adult patients diagnosed with Covid19 according to Chinese guidelines for Covid19 diagnosis and treatment version 6 were included in this study. Patients were further sub-divided into three groups based on clinical symptoms and disease severity: (1) mild, positive Covid19 qPCR with no or mild clinical symptoms (fever; respiratory; radiological abnormalities); (2) severe, at least one of the following: shortness of breath/respiratory rate >30/min, oxygen saturation SaO2<93%, Horowitz index paO2/FiO2 < 300 mmHg (indicating moderate pulmonary damage); and (3) critically ill, at least one additional complicating factor: respiratory failure with need for mechanical ventilation; systemic shock; multi-organ failure and transfer to ICU. Serum samples and throat-swaps were collected from all 48 patients enrolled. SARS-CoV-2 RNA was assessed by qPCR with positive results being defined as Ct values < 40, and serum interleukin-6 (IL-6) was quantified using a commercially available detection kit. Briefly, patient characteristics in this study confirm previous reports suggesting that higher age and comorbidities are significant risk factors of clinical severity. Of note, 5 out of 48 of patients (10.41%), all in the critically ill category, were found to have detectable serum SARS-CoV-2 RNA levels, so-called RNAaemia. Moreover, serum IL-6 levels in these patients were found to be substantially higher and this correlated with the presence of detectable SARS-CoV-2 RNA levels. The authors hypothesize that viral RNA might be released from acutely damages tissues in moribund patients during the course of Covid19 and that RNaemia along with IL-6 could potentially be used as a prognostic marker.

Potential limitations

While this group’s report generally confirms some of the major findings of a more extensive study, published in early February 2020, (Huang C et al, Lancet 2020; 395:497-506; https://www.thelancet.com/a... "https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930183-5)"), there are limitations that should be taken into account. First, the number of patients enrolled is relatively small; second, interpretation of these data would benefit from inclusion of information about study specifics as well as providing relevant data on the clinical course of these patients other than the fact that some were admitted to ICU (i.e. demographics on how many patients needed respiratory support, dialysis, APACHE Ii/III or other standard ICU scores as robust prognostic markers for mortality etc). It also remains unclear at which time point the serum samples were taken, i.e. whether at admission, when the diagnosis was made or during the course of the hospital stay (and potentially after onset of therapy, which could have affected both IL-6 and RNA levels). The methods section lacks important information on the qPCR protocol employed, including primers and cycling conditions used. From a technical point of view, Ct values >35 seem somewhat non-specific (although Ct <40 was defined as the CDC cutoff as well) indicating that serum RNA levels are probably very low, therefore stressing the need for highly specific primers and high qPCR efficiency. In addition, the statistical tests used (t-tests, according to the methods section) do not seem appropriate as the organ-specific data such as BUN and troponin T values seem to be not normally distributed across groups (n= 5 RNAaemia+ vs. n= 43 RNAaemia-). Given the range of standard deviations and the differences in patient sample size, it is difficult to believe that these data are statistically significantly different.

Overall relevance for the field

This study is very rudimentary and lacks a lot of relevant clinical details. However, it corroborates some previously published observations regarding RNAemia and IL-6 by another group. Generally, regarding future studies, it would be important to address the question of IL-6 and other inflammatory cytokine dynamics in relation to Covid19 disease kinetics (high levels of IL-6, IL-8 and plasma leukotriene were shown to have prognostic value at the onset of ARDS ; serum IL-2 and IL-15 have been associated with mortality; reviewed by Chen W & Ware L, Clin Transl Med. 2015).

Reviewed as part of a project by students, postdoctoral fellows and faculty at the Immunology Institute of the Icahn School of Medicine at Mount Sinai

On 2020-10-22 15:04:33, user BB_Aragon wrote:

Table 6 in the supplementary material appears to be another copy of the text. Could the author please replace this with the actual Table 6?

On 2020-04-22 11:58:50, user Hans-Ulrich ISELIN wrote:

Has anybody found a reference for the definition of the SOC (Standard of Care) applied in this study?

On 2022-10-13 01:38:32, user Renier Mendoza wrote:

Now published in the Journal of Korean Medical Science

https://doi.org/10.3346/jkm...

On 2023-12-21 15:35:25, user OJ Watson wrote:

Now published at: https://www.science.org/doi...

On 2024-02-05 08:06:08, user Sydney Paltra wrote:

A peer-reviewed version of this preprint is now available under: https://doi.org/10.3390/arm...

On 2020-04-28 09:20:22, user Carlos Gaspar Reis wrote:

What hydrogen peroxide concentration was used, 3%?

On 2020-04-28 11:01:19, user Henry Lahore wrote:

I do not understand the author's matrix pool testing process..

On 2022-05-03 19:26:37, user Carol Taccetta, MD, FCAP wrote:

The MMIA assay used here comes from the same institution as the authors--the reference states it is under a provisional patent.

On 2022-06-24 22:44:55, user S. W. wrote:

This preprint has been published in Emerging Infectious <br /> Diseases at https://doi.org/10.3201/eid2808.220617.