On 2021-12-11 04:21:08, user dorothee von laer wrote:

This may be very different if Omicron takes over.

On 2021-08-28 16:03:15, user Grammymidge wrote:

Hate to say but with how the US political machine is working to push the vaccine and affecting the Medical research community and leaders (i.e., the Surgeon General) here I have suspect of any finding produced in a US study that is opposite of findings in other parts of the world (i.e., Isreal). The latest Israeli study is based on a higher population, ~46,000, then what was used in this. The metrics of the study show that natural immunity provides a higher protection then the vaccine. But it does indicate the natural immunity coupled with one does of vaccine provides the individual with slightly higher protection against Delta. I found it very informative and worth a read.

On 2021-12-13 17:29:17, user Nico wrote:

Thanks so much for this research! I work with people with missing periods (hypothalamic amenorrhea) and a common concern is whether vaccination might negatively impact the hypothalamus and period recovery. It is fantastic to be able to have some real data to share, not only on impact of vaccination but also impact of covid. One suggestion - in figure 6, perhaps consider changing the color scheme (or maybe truncating the color scale at -0.2 to 0.6?) so that it is easier to distinguish between the colors in the range in which most datapoints seem to be falling.

On 2021-12-13 22:59:33, user Just Because I can wrote:

Greetings RI team from Utah! I must begin with nicesties; "Go BRUNO"! My son graduated this past May 2021 from Brown. I am a speech and language pathologist with over 30 years of hospital, private and public school setting experiences. Over the past nine years, I have professionally focused on children ages 3-5 within the public preschool and private therapeutic settings. I service students and their parents with the most intensive and restrictive learning environments within our District due to cognitive, behavioral and communicative delays. I can't help but weigh in now, as I previously shared this article with my peers in August as I braced for the impact of the 2021 school year.

Given your single assessment tool (I professionally do not profess strong decisions based on a single evaluative instrument, even as widely accepted at the Mullen), I've found your results to be intriguing and frankly, just as we anticipated.

To compare to RI, our school district, closed schools for Remote Learning for only 3 mos. in the Spring of 2019 and returned to in person instruction with hybrid options in 2020. Of a caseload of 65 students, I had 3 that were online/virtual. In 2021, our District returned to essentially all in student learning.

My informal observations this school year in Utah has been as follows:

1. Increase in new referrals and eligible "older" 4+ year old children scoring remarkably delayed communication (Standard scores <50 given a typical range of 85-115) and no previous history of EI or preschool interventions. Our TIER 3, most restrictive preschool program has a marked influx of new referrals (e.g., total students in May was 24 and currently rises at 36 with 8 new referrals in Jan.)
2. Many declined or rarely attended virtual Early Intervention supports, skipped medical wellness visits including dentistry during the pandemic.
3. Increase in parent report of primary concerns with behavioral components.
4. Given the current timeframe, we are NOT seeing marked progress with an influx in discharges (no longer eligible due to more typical standard scores). We are seeing progress and we have continued to see progress through the pandemic (which at times surprised me) but the levels of improvement are not as remarkable or typical as years past.
5. Typical communication, fine/gross motor and even cognitive delays are still present but the comorbidity of exceptional delays in social/pragmatic and ultimately, behavioral skills combined make measured learning and ultimately IEP progress at a slower rate. Social/pragmatic delays are interfering with overall progress.
6. Parent involvement, participation, enthusiasm and grit appear markedly depressed. Educational teams walk a fine line between empathy, compassion and expecting parents and care givers to step in and "do hard things" in difficult times. The teams are using external motivators such as pizza cards to motivate parents to attempt, complete and turn in 2x monthly parent based home practice pages.
7. Increased rate of meeting attendance with Virtual options.

Where do we go from here? I agree, measuring student outcomes is critical but supporting the parents (in any evidence based manner) is to me, a critical and crucial element. I thought the kids, once exposed to typical learning/situations and with repetition, our inflated numbers would flatten in a year and they would bounce back into typical ranges but it's the apathetic, tired, depressed parents that are lacking resilience and grit currently. I do think another component that would be most valuable and continues to need funding is Preschool for All (or most).

Thank you to any cohort, parent, professional person interested in this dialogue, for reading my insights.

On 2021-08-12 19:48:21, user Pasco Fearon wrote:

Hi Sean, and colleagues. Fascinating paper, but the scores are so low I worry something might not be right. Could the testing have been affected by the pandemic measures directly - e.g., mask wearing during testing? I could imagine some impacts but these are extreme, which leads me to worry that it's an administration issue. Can this be checked or ruled out somehow? I get asked this question a lot (how much have babies been affected by the pandemic), hence why I'm keen to be pretty confident in what I say.... Thanks!

On 2021-12-15 18:08:42, user Gaute wrote:

Does the unvaccinated include people that are to fragile to receive the vaccine ???

On 2021-12-16 17:59:27, user rick wrote:

No discussion of side effects of non pharmocological interventions. It's like recommending coronary bypass without discussion of morbidity and mortality from the procedure.

On 2021-12-24 21:24:16, user Shannon Rowland wrote:

How much shorter was the duration in the vaxed group vs unvaxxed? And those who took something other than Moderna- can I assume that they didn’t have the same benefit?

On 2021-12-27 04:46:23, user Wes Higbee wrote:

So, if I get vaccinated, I markedly increase my chances of infection?

On 2021-12-28 04:07:37, user abworkshop wrote:

Epidemic is simultaneously 5% with symptoms or more of the population. We hardly have 1%.

On 2022-01-05 16:39:51, user Mike B wrote:

This is obsoleted by the Omicron variant.<br /> Publication of this data may be misleading due to the immune escape of Omicron being much higher than Delta.

On 2021-10-17 04:54:57, user Sameer Bhat wrote:

This systematic review and meta-analysis has now been peer-reviewed and published in the Journal of Trauma and Acute Care Surgery (accessed from: https://doi.org/10.1097/TA.0000000000003402)

On 2021-10-30 19:49:57, user Sanghyuk Shin wrote:

Congrats to the authors on this monumental effort. However, the paper will be much stronger by drawing from the extensive literature on racism and its impact on mistrust of health system among Black and other minoritized people as summarized in https://www.healthaffairs.o...

On 2021-11-01 21:20:05, user JS wrote:

Any plans of clinical efficacy trials regarding:<br /> 1) prevention<br /> 2) transmission (effect of index patient using the spray agains infecting contacts)<br /> 3) early treatment (efficacy of antibody spray started after infection against symptomatic illness)?

On 2021-11-07 06:10:27, user Ina wrote:

I haven't really understood what happens when a recovered subject is taking the vaccine. I mean there are already neutralising antibodies which will come in contact with the Spike protein leading to destruction of the cells that express it... right? Is that happening in the muscle or it has a more extensive degree? <br /> Those recovered from Covid are more likely to have adverse reactions after the jab, says a Harvard study... what is the explanation, what do we know about the molecular mechanisms ?<br /> I would love to know more about this and I would appreciate very much your opinion on this.

On 2021-11-09 17:19:35, user MrMinerUndercover wrote:

How exactly are you people criticizing CDC studies for their construction; when this study doesn't even tell you the number or nature of the test subjects.<br /> It just posits something without any actual data.<br /> Finally, the people whom the consider to have natural immunity caused from getting covid INCLUDES people who got covid, and 1 shot. Would this not stray the data?

On 2021-08-26 19:32:16, user Aubrey Bailey wrote:

A few problems:<br /> 1. The authors count single dose vaccine as "vaccinated". That's not anyone's accepted definition.

1. The authors include naturally infected individuals in the vaccinated group if <br /> they got vaccinated later. Why? Were there not 16K fully (double) vaccinated people<br /> in a giant medical database?

2. This is the big one - <br /> I admit to skimming, but I didn't see any control for time intervals since infection.<br /> This<br /> is absolutely critical because we know that the antibody response <br /> wanes over about 8 months. Since the vaccine has been around for more <br /> than 8 months, it makes sense that more people will be at the tail end <br /> of that. Thankfully many more people get vaccinated than infected.

In light of all of these and in light of the un-reproduced nature of these findings (which should have been observable since Februrary), we should consider the first sentence of the conclusions to be at best, strongly overreaching, and at worst irresponsible phrasing.

On 2021-08-27 10:52:36, user Sock Dollager wrote:

Please follow up on this comparing infectiousness / viral load of someone with two shots who gets breakthrough infected, vs infectiousness / viral load of prev infected/natural immunity patient who gets breakthrough infection.

Thank you.

On 2021-08-27 13:34:21, user Luke Bartelt wrote:

The authors should correct table 1a and 1b where group demographics appear identical.

On 2021-08-28 02:02:31, user Marxtinks wrote:

It is not surprising that natural infection elicits stronger immune responses than the current vaccines. Covid 19 encodes 24 individual proteins. In contrast, only a single protein, the Spike antigen used by both Moderna and Pfizer in their vaccines. Furthermore, it is likely that the large scale S antigen mRNA immunization will lead to development of mutant strains not neutralized by sera or T cells of people vaccinated by the S antigen. It would be wise to develop novel vaccine strategies

On 2021-08-28 08:55:21, user Martijn Weterings wrote:

In table 1a we see that the comorbidity factors correlate strongly with the main factor (vaccinated/natural). For instance the vaccinated group has two and a half times more immunocompromised people (420 Vs 164).

This means that there is high degree of multicollinearity which makes the coefficients of the fitted models meaningless. We see for example in table 2a several negative coeffients for factors like diabetes, COPD and immunosuppression. These coeffients have a large estimated error and are not 'significant' but they *do* influence the other coefficients in the entire model.

Errors that follow from this might also be increased due to the logistic function which 'pushes' coefficients to extreme values when the frequency in certain classes is close to 1 or 0.

https://stats.stackexchange...

https://stats.stackexchange...

Asside from the correlated variables and the influence of this on model coefficients... The correlation is also an indication that the matched groups are still very different from each other, despite the matching. This means that the experiment is prone to selection bias.

Despite these two facts these results are still very interesting. It would be nice if they could be presented in a more raw form such that the pattern may be better seen (e.g. do the cases all occur in the high risk group with comorbidities?), and not just the output of fitted coefficients from models.

On 2021-08-31 00:14:58, user chelsea wrote:

Yes figures and tables would be nice.. they do not provide what extra level of protection you get if you have had sars cov2 and then get vaccinate... is it measured in folds like the actual infected over the vaccinated or is it like 13%?

On 2021-11-14 09:40:17, user disqus_1lj0sBLhKD wrote:

No P values are given.

It would be very useful if the specific ARBs used and the various doses used were given, and correlate this with the risk of getting COVID-19 and dying. There was a study done in Argentina:<br /> https://www.dropbox.com/s/t...<br /> using 180 mg Telmisartan (80 mg BID) which showed excellent results. Another study, using Losartan at a dose of only 50 mg per day, did not show any advantage for Losartan. See: https://www.medrxiv.org/con...<br /> The people who did the Telmisartan study chose Telmisartan because of its reputed superior binding affinity, longest half life, high tissue concentrations, superior insurmountably, and superior activation of the PPAR gamma receptor. See page seven of the Argentina study.<br /> It would be very useful for the selection and design of future studies if any additional data could be shown that would shed light on this.

On 2021-11-15 00:40:35, user Smith James wrote:

Where can one purchase the device pictured item e, figure 1?<br /> xmedic9@gmail.com

On 2021-11-23 01:10:34, user Charles Warden wrote:

Hi,

Thank you very much for posting this preprint.

I have a couple questions:

1) Is it possible to add a bar for predictions made with clinical data alone (without genomic data) in Figure 3?

2) Is it possible to give some sense of the number of samples / SNPs affected by each of the criteria in Supplemental Figure S9?

Thanks again!

Sincerely,<br /> Charles

On 2021-11-26 15:30:32, user Pierre wrote:

Quite in opposition with the study published published last month by imperial college explaining "fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases" . I am lost ! https://www.thelancet.com/j...

On 2021-11-28 23:39:37, user Silje Nes wrote:

The study compares a group of PCR positive individuals to a group of PCR negative individuals, in order to find out what impact Covid infections have had on the use of healthcare services. The underlying assumption is that the PCR negative group is a representative selection of the general population that have not had Covid. This fails to acknowledge some important characteristics of the PCR negative group.

To distinguish between individuals who had Covid or not, the authors look at all positive and negative tests within a given time frame. As mentioned in the paper, there was limited testing capacity in Norway during the first 3 months of the pandemic. Only a minority (typically healthcare workers and close contacts of confirmed cases) had access to PCR testing at the time of their first symptoms. The study concludes that the limited testing «affects the groups with COVID-19 and no COVID-19 to an equal extent». This is not entirely correct. Individuals without access to testing in the early months who were to develop persistent symptoms, would typically be tested several weeks or even months after first symptoms. Most individuals with Long Covid from the first months would therefore have only a negative PCR test result, and consequently end up as part of the comparison group. According to FHI’s own numbers, 220 had been admitted to intensive care by 10 May 2020, and 471 by 1 Feb 2021, implying almost half of the Covid infections took place before testing was available to the general population.

Since we don’t know from the start what proportion of Covid infected people needed access to healthcare over an extended period of time, it is difficult to assert to what extent the outcome of the study is affected by these falsely negative individuals being part of the comparison group.

The consequences of having persistent Covid symptoms without a formal diagnosis, in regards to use of healthcare services, is not clear. Doctors could choose to thoroughly examine the patient in order to rule out other morbidity, or tell the patient that it would pass by itself, and to wait it out, with no further examination.

In addition to this, an unknown number of individuals will have had false negative PCR test results, and therefore be part of the «No Covid» comparison group despite having had Covid. <br /> Also significantly, the study fails to take into account the fact that many individuals would get tested because they were showing symptoms of Covid, and that this implies illness that could affect their use of healthcare services, regardless of cause. The selection in the comparison group is therefore skewed towards a part of the population who were sick.

Thus, in actuality the groups that are compared look like this: <br /> - PCR positive – Covid infected<br /> - PCR negative – Three subcategories (unknown ratio): <br /> –– No symptoms (close contacts, general population)<br /> –– Symptoms (other disease)<br /> –– (Long) Covid infected, tested while no virus present

On 2021-11-30 07:55:24, user Hartwig Zehentner wrote:

What a tremendous model to prove ones view of life. Models are great, if they do, what they are supposed to do. I have a completely different idea, about the situation: If you force unvaccinated people to do tests for daily procedures or as entry ticket for work. Even if they are asymptomatic. And on the other side estimate even symptomatic (sneezing, cough, etc.) vaccinated people as "negatively tested".. (Example: I had two patients lately with confirmed COVID 19 despite being "fully vaccinated"; if they hadn´t had severe symptoms needing to go to the hospital, they both could have shown their "Vaccinepassport" for a tour through discotheques all night, where unvaccinated people are restricted from entering). And maybe many vaccinated but infected people have only mild symptoms, they surely don´t get tested, because of the green pass...<br /> So i´m very sure you can´t compare the groups of vaccinated and unvaccinated in regard of amount of tetsting. And with the background of vaccinated people with breakthrough infections being at least as infectious as unvaccinated people, for me this blaming of unvaccinated people is only propaganda, reminding me of germays worst times.<br /> Dr. med Hartwig Zehentner DESA EDIC

On 2020-05-26 20:36:45, user C'est la même wrote:

A lack of sequencing data limits the conclusions of this study. Suggestion that individuals were reinfected by the same strain is not confirmed due to lack of specificity of the serological testing. There is far greater genetic diversity of these strains compared to SARS-2. Just like influenza, subsequent infections in the few years following an infection are due to exposure to different strains, or similar strains but with significant drift in key antigenic proteins.

Immunological memory is not dependent on high levels of circulating antibodies and hence the antibody kinetics do not tell us very much about long term immunity. The observed kinetics are similar to many other infections/vaccines and primarily reflect plasma cell kinetics, not memory-B-cell functions. So long as a small population of memory T-cells and B-cells are maintained, long term immunity will be maintained.

I strongly suggest that a strong worldwide vaccination approach will be effective, even if at worst, there is significant genetic variation that requires annual vaccinations.

On 2020-05-26 21:50:22, user Sam Wheeler wrote:

Good paper, I downloaded the pdf.

We still don't have the answer: what if an adult has taken the BCG shot very recently. There are clinical trials that will answer this question, hopefully soon.

In many countries, medical doctors refused to prescribe BCG vaccines to adults even before covid-19, and pharmacies don't stock the vaccine at all. In which countries can an adult easily buy a BCG vaccine, and in which countries it is nearly impossible?

On 2020-05-27 01:46:56, user Dario Palhares wrote:

I congratulate you from this preprint. Since 2014, in Bioethics, we have questioned quarantine measures as a simple excuse for the State to get absolutist; a State of Exception. Never in history has quarantine shown any effectiveness in reducing, modeling or preventing a single epidemics. I guess you´ve got interesting feedback here in order to aprimorate you work when published. Anyway, I would like to ask (if not beg) you to analyze data from some other European countries: Portugal, Greece, Netherlands, Belgium, and in USA, to split data by state/region: NY, NYC, Florida, California.

On 2020-05-27 02:53:57, user Divalent wrote:

Are case data the date that test results were reported to the public, or the date the lab determined the test result, or the date of test sample was taken, or the date of first symptoms? (I'm trying to get a handle on what sewage detection tells us, and how it can be used. I.E., how much of the 7 day offset is due to asympt shedding, vs test-processing delays vs test result reporting delay, vs time from sympts to time of test.)

On 2020-05-27 08:45:44, user Thomas Wieland wrote:

Thanks for your comment! Unfortunately, there is no explicit behavioral measurement that could be used. However, there are some other findings which imply behavorial changes before the German "lockdown" started: Surveys show an increasing awareness towards SARS-CoV-2/COVID-19 in February/first half of march (e.g. the Ipsos survey of February 2020). Moreover, the German Robert Koch Institute (RKI) documented an "abrupt" and "extremely unusual" decline of other respiratory diseases (with shorter incubation period, such as influenza) from the beginning of March (calendar week 10). See the corresponding RKI paper (EpidBull 16/2020, page 7-9). These findings imply a more cautious behavior (staying at home when sick, physical distancing to strangers e.g. in public transport, thorough hand washing, carefully cough and sneeze etc.). Well, also hoardings started in the middle of February, which is, of course, an indicator for awareness towards the Corona threat (though hoarding is not desirable or even "rational"...)

On 2020-05-29 08:49:02, user David Cadrecha wrote:

Similar study in Spain shows a 20% reduction in the number of deaths per day social distancing started earlier.

Looking at different countries and regions, a strong correlation between late intervention and number of fatalities is found.

It should work for any country and tells that every single day of anticipation reduces deaths by roughly 20-25% (in the absence of other preventive actions)

“LA PRÓXIMA VEZ DEBEMOS ACTUAR ANTES. Impacto de la precocidad de las intervenciones por Covid-19”

https://t.co/TWfpDklLfo

On 2020-05-29 10:12:28, user Alessio Notari wrote:

The evidence for Temperature dependence is actually statistically well established, see:<br /> https://www.medrxiv.org/con...

and also after taking into account many other factors it remains significant:<br /> https://www.medrxiv.org/con...

Moreover also laboratory evidence show inactivation of the virus due to sunlight:<br /> https://academic.oup.com/ji...

On 2020-05-30 07:08:15, user Greg Dropkin wrote:

a revised version of this has been published by Frontiers in Public Health:<br /> https://www.frontiersin.org...

On 2020-06-01 09:16:36, user ??? wrote:

Dear Colleague

I am Jaehun Jung, the corresponding author of the paper.

HIRA in Korea conducted a database update on May 15 that included 1,000 confirmed cases and over 150,000 controls. We will revise the manuscript based on a more detailed case definition and medication history.

Preliminary analysis showed that most of the drugs presented in our study did not show any statistically significant effects. If you are using our research results in systematic review or meta analysis, be sure to consider this.

Thank you

On 2020-06-01 14:51:31, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2020-06-02 10:57:42, user Bruce Nelson wrote:

The sample unit was the household. One person was tested per household. But SARS-CoV-2 is clustered by household, leading to possible underestimate of prevalence?

On 2020-06-04 00:53:02, user Bruce Zweig wrote:

The sentence ‘Our findings showed that only 4.22% of the overall population received 5ARI anti-androgen therapy’ should say ‘male patient population’ instead of ‘overall population.’

On 2020-06-04 08:18:20, user Abderrahim Oussalah wrote:

It could be insightful to have adjusted effect sizes for the GWAS after considering body-mass index and other potential risk factors (e.g., therapy with angiotensin-converting enzyme inhibitor / angiotensin receptor blocker) as covariates in the models?

On 2020-06-05 07:12:39, user Matthias Hübenthal wrote:

Thanks to Ellinghaus et al. for sharing these interesting results. The authors utilized rs8176747, rs41302905 and rs8176719 to predict ABO blood types. Combinations of the inferred blood types then have been used to predict case/control status employing logistic regression. Alternatively, one could base the prediction on a genetic risk score incorporating the ABO SNPs. Boxplots of the risk scores could then be used to illustrate group-wise differences. However, for completeness association results for the ABO SNPs should be reported and discussed.

On 2020-06-04 09:47:03, user Malcolm Semple wrote:

Dear Authors, Great paper, well written. Your reference Docherty et al as unpublished. This is now published in BMJ : Docherty Annemarie B, Harrison Ewen M, Green Christopher A, Hardwick Hayley E, Pius Riinu, Norman Lisa et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study BMJ 2020; 369 :m1985

Did you identify distinct symptom clusters as we did?

Wishing you well

Calum<br /> CI ISARIC4C & CO-CIN

On 2020-06-05 12:01:10, user Alimohamad Asghari wrote:

This article is published in this journal address:<br /> http://mjiri.iums.ac.ir<br /> Cite this article as: Bagheri SH, Asghari A, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, Jalessi M, Mohebbi A, Alizadeh R, Honarmand AA, Ghalehbaghi B, Salimi A, Dehghani Firouzabadi F. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Med J Islam Repub Iran. 2020 (15 Jun);34:62. https://doi.org/10.34171/mj...

On 2020-06-05 20:23:05, user Steve S wrote:

It is good to see this strange weekly cycle being addressed by the research community. The hypothesis that contracting on the weekend because human behavior changes on these days—set by our arbitrary definition of time (a week)—sets the trend of the weekly cycles in viral metrics (cases reported and deaths) is appealing. However, it seems a tad odd to me that the explanation of the death rate being weekly is completely dependent on it having a cycle that is divisible by a week, i.e., 14 days is two weeks. If say the death rate peaked at 10 days instead, then you would expect interference patterns between previous weeks to create something analogous to beat frequency in sound, where there would be several irregular peaks within in a week and the weeks could look different from each other. 14 days would therefore have to be a perfect coincidence, which just seems unlikely... but still possible I guess. I'm a neuroscientist not an epidemiologist, so forgive my ignorance, but are there examples of other infectious diseases that have weekly trends. Are the cases reported and death rates also weekly in these cases?

On 2020-06-06 12:39:13, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2020-06-06 12:41:48, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2020-06-06 15:24:15, user wbgrant wrote:

The analysis of data from European and perhaps other countries is problematic for a couple of reasons. One is that the 25OHD concentrations used may not be appropriate for those who develop COVID-19 due to age mismatch or not being for winter.<br /> Another is that life expectancy, an index for the fraction of the population that is elderly, has a stronger influence on COVID-19 rates than does 25OHD. See this preprint<br /> Kumar V, Srivastaa A. Spurious Correlation? A review of the relationship between Vitamin D and Covid-19 infection and mortality<br /> https://www.medrxiv.org/con...<br /> I verified their findings by using more recent case and death rate data.

On 2020-06-07 22:27:50, user TNT wrote:

Why did the doctors only administer 1000 IU/d? More serum vitamin D would have had greater immunoregulatory effect. Optimal immune regulation Is achieved at 100 nmol/L and many studies have demonstrated 4,000 IU/d is safe. Agree with the need of identifying patients’ serum content before the trial began

On 2020-06-08 02:08:18, user Simin wrote:

Hello from Istanbul, <br /> Not a science person but just a concerned human being. <br /> I have a question if I may. <br /> The water basin siphons mentioned in the article, are they only restroom siphons or does the research include the siphons of the kitchen basins too? <br /> The reason for my question is to figure out if the grocery cleaning habits maybe ended up any virus particles in the kitchen sinks.

Thank you for all your efforts and kind reply if possible.

Simin

On 2020-06-12 04:50:15, user Paul_Vaucher wrote:

Dear authors,

Thank you for this interesting article of major interest. I find the process and research question to be most relevant. I however have a few questions that remain open to understand how the study could come to the conclusion that aerosols and surfaces were not important vectors of covid-19.

1. What is the external validity of the results for making inferences over infectiousity on the entire period people could be carriers of the disease? In this study, most participants had already been in quarantine for 5 days. Repeated sampling has shown viral load to be optimal in the upper airway system 2 days before and 2 days after symptoms appear. Viral load from nasal and throat swabs drop to a rate where viral culture becomes difficult from 8 days onwards. Most of the study participants were probably beyond that point and were therefore not expected to be very infectious in the first place. If existant, infection through secondary contact and aerosols are however more likely when viral loads are high. It therefore seems difficult from the collected data to infer that household infection through these vectors are unlikely at all times.<br /> 2) When comparing risks from different surface types, how do authors justify the use of chi2 statistics with a sample smaller than 200 and all positive cells with less than 5 cases? In this condition, type 2 errors are very high and this test should not be used under this condition. The number of positif tests are too low to be able to answer the question of whether different surface types are more or less potential vectors of the disease.<br /> 3) Statistical inference assumes independence between measures. This is clearly not the case as a median of 9 samples were taken from each household. Statistical methods should therefore account for these clustering effects. However, the sample size is probably too small for this and a pure descriptive approach without inference could be more relevant.<br /> 4) Could we have any indication on viral load from throat swabs in household cases? If their viral loads were low, we wouldn’t then expect contamination to happen anyway. In two of your 21 housholds, there were apparently not a single case with a positive PCR. This might suggest viral loads to have been too low for any form of infection to have occurred in these households. It seems important to document to what extent each household had at least one person who could infect the air and surfaces.<br /> 5) Likewise, to document risks of infecting the air, were any samples from direct breathing taken from cases Within each household? This seems important as we would theoretically not expect ambient aerosols to be present in aerosols if viruses were difficult to find from air breathed out from cases.

This study investigates an important question. I am however not convinced the method used truly answers the question as the public seems to understand it. Their is indeed room for misinterpretation and for the public to consider contact and air contamination not to occur at any time.

To avoid any overinterpretation, it seems important to clarify that this study only tests risks of air and surface contacts days after people have been placed in quarantine when we don’t suspect them to be very infectious anymore.

On 2020-06-08 09:03:15, user Paul McKeigue wrote:

All code used in the statistical analysis and the Rmarkdown source of this manuscript is available on a github repository (https://github.com/pmckeigu... "https://github.com/pmckeigue/covid-scotland_public)")

On 2020-06-08 11:15:58, user Rohit Bakshi wrote:

Interesting work. This is in line with our recent case series of COVID-19 in teriflunomide-treated patients with multiple sclerosis. All had self-limiting infection and remained on teriflunomide during their COVID-19 illness: https://link.springer.com/a...

On 2020-06-08 13:40:04, user bvwredux wrote:

Exine. The outer layer of the pollen, it is incredible stuff. Also the "remnants of the tapetal cells" found in the nooks and crannies of the exine layer. Either or both of them may be potently anti-viral for the corona virus -- that's my speculation. There is little pollen in bat caves. See https://www.ncbi.nlm.nih.go...

On 2020-06-08 20:18:31, user itdoesntaddup wrote:

I did my own empirical research along these lines for local authorities in England, finding a power law relationship between cases reported by Public Health England and population density, summarised in this chart, made before there was a change in the testing regime:

https://datawrapper.dwcdn.n...

I was inspired to put it together through being a long term observer of the output of the Santa Fé Institute (including some of the papers written by Luís Bettencourt under their aegis). I found that Geoffrey West had published a short note there on the same topic a few days later:

https://www.santafe.edu/new...

On 2020-06-08 21:45:38, user Paul Gordon wrote:

Nevermind, I see that it's in GISAID now as Thailand/Bangkok-CONI-0018/2020

On 2020-06-10 19:55:05, user Sebastian Rosemann wrote:

Dear authors,

this is an interesting overview-study. However, many questions concerning the quality of the data and a systematical question arise.

Systematical

How do the authors assure that the uniform reporting delay of ~10 days reflects the real pandemic curve by e.g. comparing published reproduction rates against the rates used to estimate the effects of NPIs? How do the authors deal with overestimating certain NPIs when comparing their impact rates to local observations?

For the german numbers we have the following discrepancy:<br /> The estimated reproduction number is based on reported cases using a delay of ~10 days from infection to confirmation. This seems not appropriate as a study from germany and the discussion around it shows.<br /> If simply using the reported cases curve one may get wrong drop rates for NPIs.<br /> This Science-study first used the reported cases:

https://science.sciencemag....

As stated by the authors in a technical note the drop-rates are quite different if one uses the real epi-curve with exact symptom-onset (if available):

https://github.com/Priesema...

Figure 19 shows a model based three-change-point approach and the impact.<br /> Figure 16 shows the same model fitting the curve with reported cases.<br /> Mind the drop rate of the first invention (which was cancellation of gatherings > 1000).

The reproduction numbers in this study lead to a totally different conclusion as changes in R are not correct and gatherings < 1000 as first NPI are not introduced correctly which gives the closing of schools an overestimated impact.

A closer look at the reproduction number of the netherlands reveals the same.<br /> Drops are visible but not in this intensity:<br /> https://www.rivm.nl/documen...

Data quality

A look around intervention dates in different countries brings up questions concerning the quality of these data. Some of the findings to discuss are the following:

Belgium:<br /> Large gatherings were effectively cancelled since around march 10th and 13th<br /> https://en.wikipedia.org/wi...

Bulgaria:<br /> 10 out of 28 regions closed on march 4th<br /> https://www.bnr.bg/en/post/...<br /> General closage happended on march 13th<br /> https://en.wikipedia.org/wi...

Germany:<br /> Gatherings > 1000 were effectively cancelled since march 9th, one week before closing schools.<br /> https://en.wikipedia.org/wi...<br /> Closing schools was announced on march 13th but startet on march 16th.

Finland:<br /> https://www.reuters.com/art...<br /> Mainly closed since march 18th.

This list is open and does only include a few finding that should be discussed or taken into account in the estimation. However, i know that inventions are not always clearly clear to categorize. But this should be more reflected by untercertainties in estimations.

On 2020-06-10 21:37:52, user La-Thijs Mokers wrote:

HCQ isn't even the active component in the andecdotal cases of succesful treatment. You have to administer the HCQ together with a zink-supplement, else nothing will happen for sure. Also you need to get the timing right; this suggested treatment will only work during the early stage of infection, when viral load is relatively low. Herein HCQ merely functions as ionophore for the Zn2+ ions ( https://www.ncbi.nlm.nih.go... ), so that they can easily pass the cellwall into the cell, where they will inhibit viral replication ( https://www.ncbi.nlm.nih.go... ). Nothing fancy to it if you know how to use freaking google. Ofcourse loads of misleading studies will be continued published - like the recent Lancet drama of Mehra et al -, leaving out zinc and testing ridiculously high dosage of HCQ on very ill patients with a sky high viral load. No wonder you get a negative result if your research setup is designed to fail like that.

On 2020-06-11 03:51:09, user kpfleger wrote:

I echo Helga Rein's request for data on vitamin D levels of COVID-19 patients in your data. I emailed Ben Goodacre and the OpenSafely team email address suggesting this on May 14 but have received no response. The data implicating low vitamin D levels as causally worsening severity of COVID-19 infection is now very compelling. For a 1-page summary of the facts with links to supporting sources see: http://agingbiotech.info/vi...

The world needs a dataset with n=10,000+ examining vitamin D levels in COVID-19 patients.

On 2020-06-11 18:36:28, user Ruth Kriz wrote:

This is consistent with my findings in other chronic infections that about 55% have PAI-1 or Leiden Factor V mutations that prevent them from up regulating their Thrombin/anti-thrombin complexes or elevated Lipoprotein (a) that binds with tPA when inflammation triggers the clotting pathway.

On 2020-06-12 15:42:05, user DFreddy wrote:

I miss mental health as risk factor. Every human also has a mind and a body. We know from piles of evidence that the mind impacts physical health too. I hope it will be included in a future analysis. Seems very elemental to do, no?

On 2020-06-14 12:52:28, user Nayo57 wrote:

Best recent seroprevalence studies from NYC and Bergamo yield roughly 1500 deaths/100k infections or a crude IFR of 1.5%. With Germany's crude IFR of about 4.5%, the total number of infected would be around 3 times the official estimate. We have to await age-stratified data to refine this estimate.

On the other hand, CFR for medical staff in Germany as reported by RKI is about 0.15% vs 0.2% for age-groups 20-60 years when adjusted to gender-mix in medical staff. This would put the underreported fraction of cases in the range of about 30%.

On 2020-06-17 20:50:32, user Serge wrote:

The<br /> effect of trained immunity resulting from an early-age vaccination <br /> proposed in the article is supported by a study at Bonn University (Dr. A. Schlitzer):

https://www.uni-bonn.de/new...

On 2020-06-18 07:05:58, user Anton De Spiegeleer wrote:

A revised version of this manuscript is available in pre-proof in the Journal of Post-Acute and Long-Term Care Medicine (JAMDA): https://doi.org/10.1016/j.j...<br /> This reference can be used for citations.

On 2020-06-19 06:18:19, user Kato Peterson K wrote:

This is an interesting study Nicholas, looking forward to you coming up with a harmonised country specific manual to guide nutrition education and counselling for T1DM in Uganda

On 2020-06-21 12:03:07, user Isaac Nault wrote:

I'd be interested to see this methodology applied to estimating the hospitalization rate.

On 2020-06-21 13:21:31, user OxImmuno Literature Initiative wrote:

https://www.immunology.ox.a...

On 2020-04-19 10:43:00, user n1oftheabove wrote:

Would you share the curated data publicly, e.g. via github?

On 2020-05-20 09:31:25, user Reks wrote:

Two comments and one question:<br /> 1. I think your reference 26 got mixed up? ( here: In a recent systematic review we concluded that the evidence in favour of face mask use outside of hospital was weak. 26)<br /> 2. The measures data are not entirely accurate: face masks were made mandatory in Poland on April 16th<br /> 3. Assume that countries tended to close down schools at roughly same epi stages. Your models, however sophisticated, would not be able to tease out the effects of school closures and any limiting factors that are inherent in the course of this epidemic, let's call them "natural" factors for want of a better term. Or would they? If not, should you mention that in the limitations? Can you perhaps check if this is likely to be the case (i.e. closures or other measures tending to be introduced at similar stages across quite a few countries)?

On 2020-05-20 12:50:05, user Neil Oxtoby wrote:

Minor correction to your text on page 5 "subtyping studies using longitudinal sMRI...": SuStaIn (PMID:30323170) uses cross-sectional sMRI.

On 2020-05-20 19:25:43, user Christian Gibbs wrote:

Please note the dislaimer at the top of the article:

This article is a preprint and has not been peer-reviewed. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

On 2020-05-22 22:54:11, user Snap wrote:

An updated version of this paper with 8 countries can be found here https://www.medrxiv.org/con...

On 2020-05-23 23:03:15, user Hilda Bastian wrote:

I have written a post that includes some criticisms of this preprint after brief review: http://hildabastian.net/ind...

On 2020-04-23 23:47:11, user Tesla Coil wrote:

In addition to the criticisms raised in other comments, I see a fatal flaw in the study's "Statistical Analysis" that I believe has not been raised (apologies if I have missed it).

The authors appear to first re-weight the sample by demographic factors, and only then adjust for test sensitivity and specificity. This appears to me to be the obviously incorrect order.

If, say, in the unweighted sample, true false positives of the test were 1.5% (which is within the 95% confidence interval of 0.1% to 1.7% calculated by the authors), and the authors only found 1.5% positive samples, the actual true positives would be 0%. So for the unweighted sample, the lower bound for prevalence of antibodies should be 0% true positives. Any further re-weighting of the sample cannot change this and the lower bound must remain 0%.

However, as the authors re-weight the sample first, they apply the false positive rate of 0.1% to 1.7% to their re-weighted estimate of 2.8% positive samples.

On 2020-04-24 16:22:33, user gfrenke wrote:

According to the CDC website their flu statistics are based solely on people who were symptomatic. The CDC doesn’t’ do antibody tests after the flu season to see how many were infected with a flu virus but never had symptoms.

On 2020-04-26 15:47:52, user DaveSezThings wrote:

The analysis has made a significant, basic error in handling the uncertainty associated with the specificity of the test. Leaving aside concerns regarding the applicability of the delta method, the mistake arises in that computing the standard error the values for Var(s) and Var(r) should be divided by the sample numbers used in the studies to establish these values, not the main study sample size n=3,330, which is used across all terms in the relevant equation in the appendix (it's on the middle of page 3). We can see this as the range of specificity (95% CI 98.3% to 100%) is sufficient to explain the observed data with zero genuinely positive cases.

Basically this destroys the conclusions which should now be along the lines of "unfortunately the test used for this study was not specific enough to support any conclusions beyond setting a maximum level of infection."

Stuff happens, time is short etc... the authors should just issue a correction. It'll be quick and easy and save a lot of irrelevant speculation,

On 2020-04-24 07:15:48, user Rajendra Kings Rayudoo wrote:

TO <br /> Yoann Madec,Rebecca Grant,

I have gone through your paper above <br /> i had a doubt that<br /> 1) the antibodies that are transferred from one person to another ,can have long-term effect on the fighting with the antigen.and

2) do the donor can increase the anti-sars antibodies continuously after donation.

thanking u <br /> with regards <br /> rajendra

On 2020-04-26 21:01:22, user reuns wrote:

Important study because it proves the outbreak came from the Highschool (15-18yr plus the teachers and workers)

On 2020-04-24 09:51:12, user Rajendra Kings Rayudoo wrote:

TO<br /> Kamalini Lokuge, Emily Banks, Stephanie Davis, Leslee Roberts, Tatum Street, Declan O'Donovan, Grazia Caleo, Kathryn Glass

I rea the above paper very happy to listen the decline of carona in Australia but as you mentioned the measures to take in the populous country likeindia which is 70 times bigger than Australia but the mathematical models and the way of finding asymptomatic carriers are fascinating

i request you to please explain the methods of conducting the efficient way to eradicate the asymptomatic carriers

thanking you <br /> with regards <br /> rajendra

On 2020-04-24 14:50:11, user BR wrote:

This study compares a group of patients with "more severe disease" that needed medication ("many times as a last resort"-VA) and where they "expected, increased mortality"----with a group with milder forms of the illness that didn't need medication. I'm not sure what the value is in making such a study.

On 2020-04-24 15:57:17, user Rajendra Kings Rayudoo wrote:

To<br /> Manisha mandal , shyamapada mandal

Every thing is ok but how come the analytics of asymptomatic carriers and presymptomatic carriers which are grave fmdanherous to spread

More over in india this is a stage which entering into community transmission

Regards<br /> ............................................. Rajendra

On 2020-04-25 14:04:04, user Rosemary TATE wrote:

Hi, I dont see the STROBE guidelines checklist (for observational studies) uploaded, although you ticked yes to this<br /> "I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. "<br /> A lot of people seem to ignore these but they are important and any good journal will require them.<br /> Can you please upload? Many thanks.

On 2020-04-25 20:17:25, user Pasquale Valente wrote:

The study show also extraordinary good news. Too bad that the <br /> authors do not underline them. So it is good, while we thank them for <br /> the work done, we make clear the positive numbers that can be glimpsed <br /> between the lines. So, as far as I intend to report, the study is based <br /> on two surveys conducted between 21 February and 7 March, which affected<br /> 85% (2812 people) and 71.5% (2343 people) of the population of Vo ' <br /> Euganeo (PD), the town of 3300 inhabitants where, on February 21, the <br /> first death from pneumonia occurred, which was attributed (by whom and <br /> on what basis?) to the SARS CoV-2 infection in Italy. The study not <br /> reported as a case of pneumonia has been defined, nothing regarding the <br /> clinical picture, nor anatomo-pathological disorders. It refers to the <br /> basis of a news item learned in the press (a man 78 years old, <br /> cardiopathic, who went through several shelters in intensive care died <br /> in that sad day. The study seems interested to elucidate, interestingly,<br /> the mechanisms of transmission of the virus and in particular the <br /> dynamics of its onward transmission, between symptomatic and <br /> asymptomatic subjects. The study produces also some useful data. The <br /> prevalence of Sars CoV-2 positive cases was 2.6% (73 positive tests / <br /> 2812 tests) in the first survey and 1.2% (29 positive tests / 2343 <br /> tests) in the second survey on 7 March. How many symptomatic cases with <br /> positive tests? The table show n. 43 symptomatic subjects/ 2812 subjects<br /> tested, equivalent to 0.015%. In the second survey 16/2343 symptomatic <br /> cases were found, that is equal to 0.0068%. Isn't this good news? Only 7<br /> -15 per 1000 inhabitants of Vo' Euganeo manifested fever or cough in <br /> the winter period in a town of Veneto. Meanwhile, the Schiavonia <br /> Hospital, where the man died, was first closed and then reopened as<br /> a COVID hospital. May be this is also a good new. We are preparing at <br /> the best, for the next pandemia. The study claims to have also collected<br /> data on the progression of symptoms and hospitalization of some <br /> subjects. Well, we will look forward to seeing them on a new <br /> paper. <br /> Best Regards

On 2020-04-26 00:39:15, user tsuyomiyakawa wrote:

There are two major issues that make the design of this study inappropriate for examining the BCG hypothesis.

1. The efficacy of the BCG is supposed to wane over time and so the most of the protective effects of BCG in aged people, is any, is supposed to be mediated largely by herd immunity. Herd immunity would occlude the discontinuity.

2. BCG is a weakened version of tuberculosis (TB) and TB infection would exert equivalent or even stronger protective effects with the BCG hypothesis. Before implementation of BCG policy, most of the countries were high tuberculosis burden countries. So aged people in those countries are expected to be protected by their experience of TB infection in a similar way BCG protects, under the BCG hypothesis. Note that Vietnam and Thailand are still high TB burden countries.

Also, there are a few minor issues that I'd like to point out.

1. In Czech, it is interesting that there are some children under 10 years old who were tested positive and are not covered by BCG. In other countries, few children, who are covered by BCG, were tested positive.

2. In Figure 1 or in Supp. Figures, similar panels for the other analyzed countries should be also shown.

3. The raw data on which Fig 2 should be made available. Apparent positive correlation between BCG coverage and "the log cases per thousands" is interesting but it is likely to be a spurious correlation. Trying to identify the factor underlying such correlation would be important.

On 2021-05-29 03:44:48, user You Know you thought the same. wrote:

But the CDC has known this for years.<br /> https://wwwnc.cdc.gov/eid/a...

On 2021-01-24 19:40:01, user Han-Kwang Nienhuys wrote:

I have further analyzed the data in fig. 2; the odds ratios (frequency ratio B.1.1.7 / other) grow exponentially with daily growth factors between 1.06 and 1.09 between 6 weeks and 1 week before the of the data (only considering the UK regions where the error bars in Fig. 4 were reasonably small: EE, EMid, London, NEE, SEE, SWE, WMid). For this I need to assume that a fraction of the SGTF cases are 'false positive', since most regions show a constant SGTF rate in October, before taking off with exponential growth.

Also notable, genomic analysis in UK SEE, Denmark, Netherlands, and Portugal show consistently growth rates between 7 %/d and 9.4 %/d with only Denmark showing a slowdown (from 12 %/d to 7 %/d).

Also, one would expect the odds ratio to grow exponentially over time if there are just two competing variants, each with their own transmissibility or reproduction number. However, the other strains that make up everything else than B.1.1.7 are likely to have slightly different transmissibilities. Over time, one would expect the transmissibility to drift to higher values, also among those other strains. The fact that the odds ratio growth rate is decreasing does not necessarily mean that the B.1.1.7 is getting less infectious; rather, the mixture of other strains could be getting more infectious over time, just because the contributions of the less infectious ones in the mix gradually decreases.

Summarizing: I believe that 6 %/d is an estimate that is significantly too low.

For graphs of my analysis, please see https://twitter.com/hk_nien... .

On 2021-01-25 14:58:28, user ad4 wrote:

There is also a study by Simon Wood that also suggests that lighter NPIs were having a noticeable impact on R before lockdown. https://arxiv.org/pdf/2005....

On 2021-01-26 07:48:38, user Oliver Kumpf wrote:

This is an interesting study. Regarding some analyses I would be interested in the distribution of organ dysfunction. Were vasopressor-free days and pulmonary-support-free days equally distributed in the therapy vs control cohorts? What were the age groups who profited most? Younger patients were much more likely to survive as is represented in the suplementary material. The Kaplan-Meier curves were without statiscal analysis. Was there a statistically significant difference between pooled IL-6Ra treated patients and controls? What is the number needed to treat. This therapy is expensive and especially in countries with restricted ressources it would almost be impossible to use such treatment.

On 2021-01-27 06:24:26, user Michael wrote:

DL+DiReCT including the trained model of DeepSCAN is also available on github: https://github.com/SCAN-NRA...

This method for cortical thickness estimation is mentioned in the manuscript and refers to https://doi.org/10.1002/hbm...

On 2021-01-29 18:20:06, user Neal wrote:

I think it's worth looking at institutional conflict-the possibility that the institution that they work for has received major donations from interests that have some potential financial gain possible from negative results for Ivermectin. That would explain the strange results and methodologies of this study, such as 1. Including large studies as having "no data" 2. Selective negative individual outcomes from trials which did have positive results 3. Meta-analysis showing the exact opposite conclusion.

In an age when medical science may be highly corrupted by financial inducements, this needs to be scrutinized carefully. There are all too many "studies" or "Meta-analyses" that seem to have strange data, especially when an inexpensive treatment or prophylaxis threatens an expensive one.

On 2021-02-24 19:02:08, user George Orwell wrote:

The findings of this review are an outlier, in stark contrast to the rest - those produced by the WHO, FLCCC, EBM-C, and @CovidAnalysis. This pre-print says the studies considered had "7412 participants" but only reported mortality data on under two hundred of them. Even then, it shows Ivermectin reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04), but reported Ivermectin was "not associated" with reduced mortality.<br /> It excluded the vast majority of the FORTY-ONE clinical trials with results, 18 published, the rest in preprint, .<br /> So even though the authors reported on a small fraction of a small fraction of the results, they still found significant improvement in the most important and elusive metric of all to show improvement in, mortality. But nonetheless, they reported this as a negative finding.<br /> As is widely reported, "The probability that an ineffective treatment generated results as positive as the 41 studies to date is estimated to be 1 in 2 trillion (p = 0.00000000000045)."

On 2021-01-29 22:05:04, user José Raymond Herrera wrote:

It's about the predictable anti-inflammatory effect of Colchicine. I don't know if it's better than Dexamethasone already proved useful in those cases. In any event, we're talking about cheap drugs not promoted by big pharma...

On 2021-01-30 17:36:26, user Olga Rebrova wrote:

For the primary outcome P=0.0492 (Yates corrected Chi-sq.), authors do not mention which Chi-sq. test they used. Odds ratio is unappropriate measure for RCT. RR have to be used instead, and it's upper limit of 95% CI is 0.999. Adding 1 patient dramatically changes the conclusion.

On 2021-01-29 22:20:14, user Britt-Marie Halvarsson wrote:

Hi!

Very interesting paper and I am very grateful of your transparency with code and data!

However, I find it a bit problematic that the corrected R0's are not very normally distributed. Do you have a comment on that?

Best Regards,<br /> Britt-Marie Halvarsson

On 2021-01-31 17:34:25, user Paul Hunter wrote:

Very misleading analyses in this paper and the conclusions and recommendations that the authors make are not supprted by their data. How can the say “The decrement in<br /> incidence was evident from day 18 after first dose” and then estimate efficacy using data from days when they know that vaccine was not yet working. What they have shown is by three weeks after injection a single dose of Pfizer gives about 80 to 90% protection

On 2021-06-19 15:42:33, user TB wrote:

The data in Figure one is duplicated. The 'left orbitofrontal cortex (thickness)' data is the exact same at the 'left superior insula' data.

On 2021-02-03 07:20:39, user Bildung Aber Sicher CH wrote:

This study failed to mention school autumn holidays. The data they have is, in reality, from a period of low community transmission (not high as they mention) because the 2 weeks holidays coincide with the start of the second wave in the canton. <br /> The sampling starts a week after school resumed, therefore too early to for cluster build up in schools/classes, especially when looking at antibodies which will only appear some weeks after infection.

It also didn't consider any new studies as references, when plenty was available that contradicts their assumptions and conclusions at the time of publication.

On 2021-02-06 06:55:29, user kdrl nakle wrote:

Non-randomized comparison of apples to oranges (dosages, numerous differences in groups etc). Too small samples for so many variables.

On 2021-02-09 15:58:51, user David Curtis wrote:

I don't get it. Mendelian randomisation is supposed to test a causal relationship between two phenotypes. Here, you seem to be saying that your results demonstrate that smoking has a causal effect on depression and that depression has a causal effect on smoking. I don't see how you distinguish this from the alternative explanation - that there are genetic variants which increase risk of both smoking and depression. How do you distinguish causal effects from a simple genetic correlation?

On 2021-02-11 03:05:16, user Another Concerned Resident wrote:

Interesting study! Where can we find the supplementary materials? I'd like to check the ITT Table 1 because the PP Table 1 shows significant baseline differences.

A few questions:<br /> - Could you explain why you did not opt for placebo control and double blind?<br /> - What were the serology results performed at day 28?<br /> - You mention "COVID-19 infection occurred in 94% measured by RT-PCR". How were the extra 6% diagnosed?<br /> - Do you have any data on adverse events?<br /> - For the primary outcome: do you have any information on the reasons for admission?

Thanks

On 2021-02-11 19:05:46, user Dr John Tal wrote:

Eagerly awaiting the results of the trials using ciclesonide. Has been shown to slow down SARS CoV2 replication in vitro and seemed to be effective in a couple of case studies. https://jvi.asm.org/content...

On 2021-02-11 15:28:29, user Robert Olinski wrote:

You are speaking about Ct values that are not part of clinical diagnostics. What were clinical symptoms of people post-vaccination with decreased viral load? Does it mean that the vaccination did not prevent infection?

On 2021-02-20 15:56:24, user Howard Gu wrote:

It is surprising that vaccination only reduces the viral load by 4 folds. However, this could be due to the research design. Only the high viral loads are detectable and thus included in the calculation of viral load reduction. Vaccinated people might get infected but have good immune responses effectively suppressing the viral replication. This could result in 400 or 4000 folds lower viral loads which may not be detectable and thus considered not infected and not included in the calculation of viral load reduction.

On 2021-02-13 17:35:22, user Scott Aberegg wrote:

Where is the supplementary appendix? I would like to see the prior distributions upon which this analysis was based

On 2021-02-14 11:49:33, user Rafael Green wrote:

Hi,<br /> I looked at world_mortality.csv, summed the deaths by year and got this result:<br /> 2015 15747474<br /> 2016 17246133<br /> 2017 17689889<br /> 2018 16674370<br /> 2019 18004246<br /> 2020 20926842<br /> How are you explaining the decreasing in the number of deaths in 2018?<br /> Thanks,

On 2021-02-15 16:30:09, user Vana Sypsa wrote:

The paper appears now in Emerging Infectious Diseases

https://wwwnc.cdc.gov/eid/a...

On 2021-02-15 20:44:04, user Ro H wrote:

South Asians as a group, especially first generation (citizens or immigrants), regardless of income level, are less likely to voluntarily get tested or go to the doctor unless theyre really sick. People with mild to moderate disease are unlikely to get tested but will self isolate and quarantine. This is a cultural thing observed in great Britain also. This means that their positivity rates will be higher as only the really sick get tested and a higher percentage will be hospitalized. Its interesting that their death rates are lower though. Im a part of this south Asian community in New York and this is what I've experienced with family and friends.

On 2021-03-26 15:52:44, user MHR wrote:

Has this paper been published???

On 2021-02-16 09:06:27, user Raul Sanchez-Lopez wrote:

An updated version of this preprint has been accepted for publication in mdpi Audiology Research<br /> https://doi.org/10.3390/aud...

On 2021-02-17 17:12:29, user Tim Pollington wrote:

Dear Epke and colleagues,

I would like to share some comments following reading your (v. relevant) paper on impact of COVID on VL in India at the country level. This is the second time I've commented on a preprint like this on medrxiv, and shared an 'open review' so I hope you receive it in the spirit it was intended. As I'm interested in doing similar studies your manuscript was relevant to me. And since I am funded by BMGF I thought it would be a waste of my funded time if I do not share these thoughts with you too, especially since you're at the preprint/pre-accepted stage.

I thought the paper could benefit from an additional author who has field experience of the IRS/ACD activities occurring there to back-up your assumption that "no IRS and ACD take place and that only passive case detection" during an interruption.

Given that the role of Asx in infecting others is still debated (some say recent xeno shows near zero contribution while ours last year did fit estimates consistently when relative Asx infectiousness of 0,1 or 2% were used), your use of the models E1 & E0 is a smart move to err on the cautious side.

Model structure and quantification section<br /> Thanks for much for following best practice and using PRIME-NTD. It is the first time I have seen it and I definitely plan to use it in my next modelling publication and also when initially planning a model re engagement with policymakers.

Given that the model runs for 30 years has population growth been taken into account?

Impact assessment section<br /> Although adding incidence rates in the same period is acceptable, as events share the same 'person time at risk' denominator (and if the events are mutually exclusive), I'm not sure if epidemiologically it's a correct calculation to sum up rates over the 30 years since the population will be changing in this time and thus the denominators are changing. Perhaps one can convert it into absolute cases in each year and then sum those up?

Discussion section - First paragraph<br /> It may help the reader if more emphasis was made on how a 1-year impacted delay by describing how it is amplified. ie How just one year interruption causes growth which needs to be curtailed before it turns over and falls, and the excess cases this generates. This concept of amplification could be strengthened.

Second paragraph<br /> "80% of [VL-endemic???] sub-districts..." Did this cover just Bihar or all 4/5? endemic states.

Third paragraph<br /> I think mortality rates are really relevant but can understand your caution re scant data. I think it's so important now considering the 1%CFR 2021-2030 target. Could this independent review help provide some rough estimates from pages 12-15 & 40? <br /> Even rough estimates from your model on excess VL cases and when they would likely be seen in the coming years, could be a useful starting place for resource planning of drugs.

I think a caveat needs to be noted that this analysis is country-level whereas the threshold targets are at the block-level, to avoid the reader making an ecological fallacy.

I hope that helps and also encourage you to comment on my work if I get to that stage!

All the best, Tim.

On 2021-02-22 23:08:15, user Meg Beller wrote:

HOW do I get a neutralizing antibody titer test post Pfizer vaccine to see how my immune suppressed body responded?

On 2021-02-24 01:18:23, user algebra wrote:

Anecdotes of people who had Covid months ago and got the vaccine are alarming. Acquaintances report the side effects of the second shot were worse than the disease itself. Are these people reporting their reactions? No they just tough it out. They were told to expect side effects. How many of them are out there? Does anybody know? <br /> My own physician has been hearing some of these stories and suggests waiting.

On 2021-02-24 03:55:43, user kdrl nakle wrote:

Your samples are too small and IQR are too much overlapping to derive any conclusions. Go for bigger samples and perhaps you'll get something of it.

On 2021-02-26 11:58:34, user Magda Bucholc wrote:

The published version of the manuscript is available here: https://alz-journals.online...

On 2021-02-28 21:19:31, user Ana Christoff wrote:

Now published in PLOS ONE<br /> Swab pooling: A new method for large-scale RT-qPCR screening of SARS-CoV-2 avoiding sample dilution.<br /> https://doi.org/10.1371/jou...

On 2021-03-02 08:33:10, user Miroslava Zeliznakova wrote:

I am so disgusted how this research was done. The ethical principles were not followed. People didnt know that research is taking place, they were not informed about it. They were forced to test otherwise they have been threatened by government that they can't come out of their house, go to work, post office etc... I am from Slovakia and so many people suffered in hands of the government and i am surprised this study states the participants consent was gained. You should now do another study about how situation is in Slovakia now. Many people had got infected during mass antigen testing actually.

On 2021-03-07 09:48:53, user Pencroft wrote:

• voluntary? Yes, it was voluntary testing. As it is described in the article itself. There were (and there are) restrictions applied regarding the COVID pandemic as they are applied elsewhere in the world. Those who preferred somehow reduced level of them were required to prove that they are not infected. This type of the test or PCR one were accepted.<br /> There was no punishment by law for not taking part in this type of testing.
• written consent?<br /> As long as the researchers evaluate output and other public data and are not the ones who performs the test on their own as a part of their research, what is the base for requiring written consent? Those are 2 separate activities.

On 2021-03-03 22:58:04, user Dan Elton wrote:

The data from Phase, I, II, and III and our prior scientific knowledge on vaccines like this one indicate this vaccine is very safe and effective. It also appears to be our best weapon against the B.1.351 variant. US taxpayers have already footed the bill for 110 million doses and it's very likely millions of doses have already been produced. The US FDA should ask Novavax to submit all the data they have collected so far and their EUA application immediately and then the FDA should work overtime to approve it within a week in order to save lives. The FDA should also allow the vaccine to be pre-distributed to ensure the vaccine gets to at-risk groups as quickly as possibe. With 1,000+ people dying every day, we must act quickly to save lives! The status-quo is dangerous - the vaccine by contrast is very safe and will save lives!

On 2021-03-05 23:06:05, user Minga wrote:

Several authors omitted to declare known links of interest with pharmaceutical firms. <br /> One of them declare not least than 24 pages of links with pharmaceutical firms on this official website : https://transparence.sante...., and nothing here. Such an offense to integrity put serious doubts about this pre-print.

On 2021-03-06 11:40:17, user Patti wrote:

I had Covid back in October 2020, I still hane no smell or little to no taste. The feeling in my nose is driving me nuts - I call it a vortex or the feeling I have when I take a breath is like a upside down tornado - it feels like clean air and yet sometimes burns. I have used nasal saline but doesn’t seem to do anything. Also slight blood when I blow my nose.

On 2021-03-08 08:44:37, user CD wrote:

"Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition ..."

The statement above makes it appear as if the SARS-cov-2 chooses where to mutate to escape host immunity, which is not the case. The pressure is put on the virus and mutations occur randomly, resulting in escape variants and some resulting in weaker variants

On 2021-03-14 10:34:35, user KalleMP wrote:

There are a number of data errors in this report. Having looked at 5 of the original 25 papers listed here I find that errors that are significant have been made in at least 4 of them.

The Turkey values are 75.5% deficient and 16.61nmol/l median instead of the listed 70nmol/l.

Bosnia reads 24.4% and should be 60.6% (their mean is 48.25nmol/l)

Italy reads 33.3% but a weighted average is closer to 30.7%<br /> Italy has used values from the highest performing Vitamin-D region and compared them to the national CoViD-19 figures which are accepted to be low.

Finland has used the native Finnish values and compared them to the national CoViD-19 figures which include immigrants who are more deficient yet represent a larger portion of the CoViD-19 figures.

On 2021-03-17 10:44:27, user Krisantha Weerasuriya wrote:

If there was the opportunity, a small simultaneous blood sample from the mother to measure the COVID19 antibodies would have provided further useful information.

Would it be possible with covering permission from the Ethical Committee to do a simultaneous blood sample for COVID 19 antibodies from mother and baby at 3 months (or the most appropriate time)?

On 2021-03-17 10:51:20, user D Greenwood wrote:

The trials registry protocol suggests n=507 symptomatic cases would be recruited and followed up, to "characterise prevalence and severity of organ volume change and damage in patients recovering from COVID-19 disease". Yet the preprint appears to focus on n=201 individuals still "symptomatic after recovery" and it is therefore not surprising that nearly 100% of them report symptoms, as this appears to be the eligibility criteria for the paper. Either that, or a substantial deviation from the published protocol. I therefore agree with previous comments on the importance of clarifying the recruitment process and inclusion/exclusion criteria so we know what the denominator is here. There is some benefit in knowing what the % of organ damage is in people with continuing symptoms, but the crucial question that health services and strategic leaders need to know is what this is as a % of all cases, or at least as a % of symptomatic cases. I hope that a revised version of this paper will make that clearer.

On 2021-03-18 09:12:13, user Bernhard Brodowicz wrote:

The summary in the last paragraph of discussion states: 'On the contrary, we found a significant, slightly increased risk of SARS-CoV-2 infection, which, however, was attenuated when taking account of older children in the same household.' The first paragraph of the discussion however is stating 'The risk of infection was amplified with increasing number of young children living in the household, but the overall association was attenuated when excluding households with older children.' and figure one, shows an increased risk associated with increasing number of children and increasing age of children.<br /> The wording in the summary (last paragraph of discussion) might be a bit misleading.

On 2021-03-23 18:30:37, user Moshe Elitzur wrote:

To CL: <br /> Do lockdowns work??

They certainly do, but we could not prove that decisively because lockdowns were implemented, on average, just before "flattening of the curve" was already occuring. So lockdowns were not put to the test during the first wave.

On 2021-03-23 20:14:18, user Gustavo Bellini wrote:

Great article, congratulations to everyone involved in this research!

Could you replicate the tests by adding sufficient levels of vitamin D to these cells? I believe that the behavior of macrophages in this case can be changed from the pro-inflammatory pathway to the anti-inflammatory pathway, thus avoiding the "storm of inflammatory cytokines" and restoring (?) their "normal" phagocytosis behavior.

Vitamin D has an immunomodulatory action that affects both the innate and the adaptive system.

Sufficient levels of vitamin D are needed for immune cells to produce IFN-y:<br /> - Vitamin D Is Required for IFN-? – Mediated Antimicrobial Activity of Human Macrophages<br /> https://stm.sciencemag.org/...

A 2010 study showed that sufficient levels of vitamin D are also necessary for T lymphocytes to be activated correctly:<br /> - Vitamin D crucial to activating immune defenses<br /> https://www.sciencedaily.co...

Macrophages and dentritic cells have the CYP27b1 gene and are able to transform 25OHD into Calcitriol (the active hormone).

All immune cells have VDR and are subject to the biological actions of the active form of vitamin D.

Here are two great recent reviews on the action of vitamin D on immune cells:<br /> - Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory<br /> https://doi.org/10.1002/jbm...

• MECHANISMS IN ENDOCRINOLOGY: Vitamin D and COVID-19<br /> https://doi.org/10.1530/eje...

Many studies are showing a significant correlation between vitamin D deficiency and the increased risk for severe symptoms / mortality from Covid. This website lists some of these studies: https://vitamin-d-covid.sho...

I hope this comment is useful in some way.<br /> Thanks.

On 2021-03-29 21:57:10, user Carl Steinbeisser wrote:

Great work. Really minor comment: In the acknowledgement only the Grant Agreement number is mentioned not the name of the project. Many IMI projects (and H2020 projects) do mention the name of the project too. Suggest to add the project name EHDEN.

On 2021-03-30 17:34:43, user Gustavo Bellini wrote:

Dr. Alex Vasquez published a critical analysis in relation to that study. He is demanding a retraction from JAMA:

https://youtu.be/_sfGV_xz0_Q

On 2021-04-06 09:29:36, user gerardencinallamas wrote:

The peer-reviewed published version of this pre-print can be found here: https://www.nature.com/arti...

On 2021-04-09 12:25:07, user Keish Gonzalez Acosta wrote:

Hi. I am a breastfeeding mother. I took the JJ vaccine 4 days ago. I am pumping milk. If your team is interested in collecting milk samples after JJ vaccine I would like to participate.

On 2021-04-14 16:38:58, user Anke Huels wrote:

This work has been published in The Lancet's EClinical Medicine: https://www.thelancet.com/j... (open access)

On 2021-04-20 02:03:34, user Hector Moises Chip / Micro Chi wrote:

By "reasoning" - that is according to Kant's a priori approach - to keep schools open would be a source of virus transmission. Basically because in spite of gathering "in bubbles", it breaks the gold epidemiologic principle of social distancing, particularly difficult in youngsters besides the fact that they wander (usually) in several unchecked other bubbles... Also there are on the empiric side, cases of intra school viral circulation that the present article has not searched . The whole script is therefore incomplete enough to draw firm conclusions. In any case, it would mean to stay in the prudent side, which is do not open school if the sanitary system is on crisis.

On 2021-04-20 11:46:33, user Sahithi Reddy wrote:

may i know where can i get the source code of this article

On 2021-05-10 06:59:28, user Maria Ban wrote:

The 42% protection after first dose is not a very good protection. How about protection from severe Covid after first dose, is it higher? The reason for my question is that I am not allowed to have a second dose (due to severe allergic reaction) and I fear that I will have to avoid other people for ever.

On 2021-05-12 14:47:48, user Rebecca Grant wrote:

This study has now been published in Eurosurveillance: https://www.eurosurveillanc...

On 2021-05-14 10:40:29, user NABIL ABID wrote:

i am really happy to be part of this project, including more than 100 African researchers. Thanks to all collaborators to provide high quality paper.

On 2021-05-14 15:19:36, user Misha Kogan wrote:

First controlled trial! Excellent news. Our real life experience with no funding is not so far off. At GWCIM over last 3 years 15 patients who stayed with program demonstrated 70% response rate with 4 patients showing very significant improvement. Funding is a key. Of 44 patients who came through out clinic most dropped out due to cost and logistics.