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 2021-10-06 17:29:33, user Trevor Madge wrote:

Forgive me I may have misunderstood the paper, but is the dataset only including those who where "sick" with COVID19? Does it exclude all asymptomatic infections?

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 2021-12-07 10:40:57, user S. von Jan wrote:

I feel that some of the assumption that go into the model calculation are overestimated, others are underestimated, and some important further information is not considered. I am referring specifically to v (vaccine uptake), s (susceptibility reduction) and b (relative increase in the recovery rate after a breakthrough infection).

The authors assume a vaccination rate of 65% for the period between 11.10 and 7.11. For the sake of transparency, I think it should be mentioned in the study that in Germany an underestimation of the vaccination rate of up to 5 percentage points is assumed (1), perhaps this should also be considered in the scenarios. Moreover, the recovered cases are not mentioned at all, do they not play a role for the model?

For s in the "upper bound" scenario, a 72% efficacy of the vaccination in Germany is assumed (2), this figure comes from the German Robert Koch Institute (RKI) and is calculated based on the vaccination breakthroughs in Germany, i.e., it only includes the number of symptomatic cases in Germany. The RKI writes on the estimated vaccine effectiveness: "The values listed here must therefore be interpreted with caution and serve primarily to classify vaccination breakthroughs and to provide an initial estimate of vaccine effectiveness" (3, own translation). The vaccine effectiveness estimated here refers to the effectiveness of vaccination against Covid 19 infections with clinical symptoms, not against infection in general. However, there are indications that infections are more often asymptomatic in vaccinated persons ("vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older"(4)), and vaccinated people in Germany must rarely participate in Covid 19 tests. The RKI points out that vaccination would considerably reduce transmission of the virus to other people but assumes that even asymptomatically infected vaccinated people can be infectious: "However, it must be assumed that people become PCR-positive after contact with SARS-CoV-2 despite vaccination and thereby are infectious and excrete viruses. In the process, these people can either develop symptoms of an illness (which is mostly rather mild) or no symptoms at all" (5, own translation). So is the effectiveness of vaccination against symptomatic infections in this setting relevant when it comes to the role of the vaccinated/unvaccinated to the infection incidence?

In the "lower efficacy" scenario, s is given as 50% to 60% based on an English study. This percentage corresponds to the data from another study, which estimates the effectiveness of the Biontech/Pfizer vaccination against infection as 53% after 4 months in the dominant delta variant (6). Would this number not be more plausible for the "upper bound" scenario? The "lower efficacy" scenario could then be calculated with an efficacy of 34%, for example, as suggested by another study on infection among household members (7).

If we consider b, "an average infectious period that is 2/3 as long as this of unvaccinated infecteds" is assumed. This figure seems reasonable based on the available information on the faster decline of the viral load in vaccinated persons. However, there are statements, for example by Prof. Christian Drosten in an interview with the newspaper “Die Zeit”, that make this effect seem less significant: "The viral load - and I mean the isolatable infectious viral load - is quite comparable in the first few days of infection. Then it drops faster in vaccinated people. The trouble is, this infection is transmitted right at the beginning. I'm convinced that we have little benefit from fully vaccinated adults who don't get boostered" (8, own translation). Moreover, there is another issue that is not mentioned in the paper at all, but which I think should be taken into account: Unvaccinated people in Germany have to test themselves much more frequently than vaccinated people (e.g., at the workplace) due to the 3G rules (9, this means vaccinated, recovered or tested). Children and adolescents have a testing frequency of 3 rapid tests a week (10). Even if the effectiveness of the rapid Covid 19 tests for asymptomatic infections should be 58% (i.e., only 58% of infected persons are correctly identified as positive) (11), a test rate of 2 to 3 tests per week would still reduce the duration during which an unvaccinated person is infectious and not in quarantine. This consideration is not included in the model calculation.

Overall, it appears that several central parameters were underestimated or overestimated in the model calculation: The vaccination rate is actually higher, the effectiveness of vaccination against infection is certainly lower than the figure given in the “upper bound” scenario, and the period in which infected persons infect others is shortened for unvaccinated persons by 3G regulations, since they have to go into quarantine if they test positive. As a result, the contribution of the unvaccinated to the infection incidence in Germany is likely to be strongly overestimated in the model calculation, especially in the “upper bound” scenario.

(1) https://www.rki.de/DE/Conte... <br /> (2) For adolescents, s is even estimated at 92%, without explicit data being available here.<br /> (3) https://www.rki.de/DE/Conte.... <br /> (4) https://www.thelancet.com/j...<br /> (5) https://www.rki.de/SharedDo... <br /> (6) https://www.thelancet.com/j... <br /> (7) https://www.thelancet.com/j... <br /> (8) https://www.zeit.de/2021/46... <br /> (9) https://www.bundesregierung... <br /> (10) https://taz.de/Schulen-in-d... <br /> (11) https://www.cochrane.de/de/... This overview work does not yet refer to the delta variant.

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 2021-12-03 00:34:25, user Sulev Koks wrote:

This manuscript is under review at Experimental Biology and Medicine.

On 2020-05-30 07:55:21, user Irene Petersen wrote:

You seem to conflate the risk of getting exposed (and thereby infected) and the risk of dying with covid19. However, these risks may vary substantially and therefore we would need a two-step approach to obtain meaningful predictions. For example, age and ethnicity are strong predictors for exposure while diabetes and obesity are strong predictors of mortality once you are infected.

On 2020-06-23 13:30:40, user Ralph Hawkins wrote:

Analysis of the RECOVERY trial pre-print data, looking only at non-ventilated patients together, not stratified by oxygen use. There is NO DEMONSTRABLE TREATMENT BENEFIT.<br /> Dex treated 360/1780 (20.2%) vs standard care 787/3836 (21.6%) p=0.2427

On 2020-06-23 19:20:17, user addie wrote:

The article states that patients receiving mechanical ventilation were ten years younger than those not receiving respiratory support - this implies that ventilators were being rationed? Can the authors speak to this.

Thank you.

On 2020-06-25 15:01:25, user Kirielson wrote:

I think this paper is fine, my question I would have for the authors: Did you attempt to evaluate if the patient could relay back those risks to you through any metric? Finding a way to see if a patient understands it by evaluation may see how effective one is over the other while looking at their preferneces.

On 2020-06-05 13:21:52, user Arnar Palsson wrote:

Reference 6. Falconer D, M.T. Introduction to Quantitative Genetics, (London, 1996).

Has two authors, Douglas S. Falconer and Trudy F.C. Mackay

On 2020-06-26 16:13:44, user Veli VU wrote:

the authors do not detect SARS-CoV-2 in samples from 2019 March. Rather, they do detect IP2/IP4 resembling SARS-CoV-2. Whatever virus it is it does not have the E and N1/N2 of SARS-CoV-2. Fluctuations in qRT-PCRs even in 2020 samples -different sewers- are way too high to trust the reliability of the RT-PCRs. However, their approach is amazing. I hope they use a metagenomic approach to sequence to sewers rather than doing an RT-PCR assay, which doesn't look very rigorous.

On 2021-06-04 13:42:50, user fauxnombre1 wrote:

Help me understand. The cumulative dose is not a product of the duration of treatment? Patients receiving treatment longer have a better survival rate?

On 2020-06-06 05:51:49, user Tim Lee wrote:

The possible relationship between A blood type and COVID-19 progressive respiratory failure.

Endemen et al (2020) found that progressive respiratory failure in COVID-19 is linked to hypercoagulability.21 This conclusion is supported by cohort studies that found hypercoagulability and a severe inflammatory state in COVID-19 patients 22,23 . Type A blood increases the risk for thromboembolic events.25 Viral infections activate the blood coagulation system.29

It may be that all factors that increase your risk for hypercoagulation increase the risk for progressive respiratory failure in COVID-19. One factor that has caught my attention is mercury. It is ubiquitous and known to cause hypercoagulation. (26-28) For more info please read my note on the topic https://www.qeios.com/read/...

1. Endeman H, Zee P van der, Genderen ME van, Akker JPC van den, Gommers D. Progressive respiratory failure in COVID-19: a hypothesis. Lancet Infect Dis. 2020;0(0). doi:10.1016/S1473-3099(20)30366-2

2. Panigada M, Bottino N, Tagliabue P, et al. Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis. J Thromb Haemost JTH. Published online April 17, 2020. doi:10.1111/jth.14850

3. Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. Published online April 21, 2020. doi:10.1055/s-0040-1710018

4. Ellinghaus D, Degenhardt F, Bujanda L, et al. The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. medRxiv. Published online June 2, 2020:2020.05.31.20114991. doi:10.1101/2020.05.31.20114991

5. Groot Hilde E., Villegas Sierra Laura E., Said M. Abdullah, Lipsic Erik, Karper Jacco C., van der Harst Pim. Genetically Determined ABO Blood Group and its Associations With Health and Disease. Arterioscler Thromb Vasc Biol. 2020;40(3):830-838. doi:10.1161/ATVBAHA.119.313658

6. Worowski K. The Hypercoagulability in Mercury Chloride Intoxicated Dogs. Thromb Haemost. 1968;19(1/2):236-241. doi:10.1055/s-0038-1651201

7. Lim K-M, Kim S, Noh J-Y, et al. Low-Level Mercury Can Enhance Procoagulant Activity of Erythrocytes: A New Contributing Factor for Mercury-Related Thrombotic Disease. Environ Health Perspect. 2010;118(7):928-935. doi:10.1289/ehp.0901473

8. Song Y. [Effects of chronic mercury poisoning on blood coagulation and fibrinolysis systems]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi Zhonghua Laodong Weisheng Zhiyebing Zazhi Chin J Ind Hyg Occup Dis. 2005;23(6):405-407.

9. Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost. 2018;2(3):549-557. doi:10.1002/rth2.12109

On 2020-06-07 21:50:15, user Wei Gu wrote:

Peer reviewed version at Clinical Infectious Diseases:

Clinical Infectious Diseases, ciaa599, https://doi.org/10.1093/cid...<br /> Published: 21 May 2020<br /> https://academic.oup.com/ci...

On 2021-06-08 17:43:19, user Jan Zo wrote:

The article was published recently in Mol Cell Ped https://doi.org/10.1186/s40...

On 2020-04-10 15:16:29, user Guilherme Araujo Lima da Silva wrote:

Hi, Do you have the code available? Is it R, Python or Julia?

On 2020-06-09 16:22:37, user Sinai Immunol Review Project wrote:

Title <br /> Eosinopenia Phenotype in Patients with Coronavirus Disease 2019: A Multi-center Retrospective Study from Anhui, China

Keywords<br /> • Lymphopenia<br /> • Covid-19 severity<br /> Main Findings<br /> It was previously shown that more than 80% of severe COVID-19 cases presented eosinopenia, in a cohort of Wuhan [1]. In this preprint Cheng et al. aim to describe the clinical characteristics of COVID-19 patients with eosinopenia. In this retrospective and multicenter study, the COVID-19 patients were stratified in three groups: mild (n=5), moderate (n=46) and severe (n=8). All patients received inhalation of recombinant interferon and antiviral drugs, 50% of the eosinopenia patients received corticosteroids therapy compared to 13.8% of the non-eosinopenia patients according to the patients’ clinical presentation. The median age of eosinopenia patients was significantly higher than the non-eosinopenia ones (47 vs 36 years old) as well as body temperature (not significant). Eosinopenia patients had higher proportions of dyspnea, gastrointestinal symptoms, and comorbidities. Eosinopenia patients presented more common COVID-19 symptoms, such as cough, sputum, fatigue, than non-eosinopenia patients (33.3% vs 17.2%). Interestingly lymphocytes counts (median: 101 cells/ul) in eosinopenia patients were significantly less than in non-eosinopenia patients (median: 167 cells/ul, p<0.001). All patients within the severe group recovered and presented with similar numbers of eosinophils and lymphocytes compared with healthy individuals upon resolution of infection and symptoms. The results showed by Cheng et al. are similar to another study involving MERS-Cov [2], but is contradictory to the previous observation with infants infected with respiratory syncytial virus, where high amounts of eosinophils were found in the respiratory tract of patients [3].

Limitations<br /> The sample size of this study (n=59) is very narrow and could bias the observations described. The authors did not thoroughly measure potential confounding effects of or control for type of treatments, which were different across the patients. <br /> It is still unclear if SARS-COV-2 infection induces eosinopenia or eosinophilia in the respiratory tract, since all reports so far showed peripheral eosinophil counts. As eosinophils antiviral response to respiratory viral infections has been shown [4], it would be important have discussed if the high inflammatory response produced by eosinophils could contribute to the lung pathology during COVID-19, especially when vaccine candidates have been tested and could induce increased amounts of eosinophils.

Significance<br /> This study suggests that eosinophilia may be a clinical phenotype of COVID-19 that distinguishes eosinopenia patients from non-eosinopenia patients. The contribution of the present study is relevant and calls for experimental analysis to reveal the importance of eosinopenia in COVID-19.

Credit<br /> Reviewed by Alessandra Soares-Schanoski as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.

1. Du, Y., et al., Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study. Am J Respir Crit Care Med, 2020.
2. Hwang, S.M., et al., Clinical and Laboratory Findings of Middle East Respiratory Syndrome Coronavirus Infection. Jpn J Infect Dis, 2019. 72(3): p. 160-167.
3. Harrison, A.M., et al., Respiratory syncytical virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation. Am J Respir Crit Care Med, 1999. 159(6): p. 1918-24.
4. Lindsley, A.W., J.T. Schwartz, and M.E. Rothenberg, Eosinophil responses during COVID-19 infections and coronavirus vaccination. J Allergy Clin Immunol, 2020.

On 2020-07-01 18:36:55, user SPARK wrote:

Reference 10 typo in pdf

On 2020-07-02 16:54:49, user Garganta Thiago Umberto Pereir wrote:

Federal Brazilian government ordered a nationa lockdown? When? It never happened!

On 2020-07-02 23:29:56, user Sergey wrote:

This pre-print does not have a Methods section- how did the medRxiv QC miss this?

On 2020-04-14 05:46:51, user Alexander wrote:

The same results: d-dimer>2500 (OR 6.9, 95% CI, 3.2-15.2), ferritin >2500 (OR 6.9, 95% CI, 3.2-15.2). Is it correct?

On 2020-07-12 14:20:35, user Knut M. Wittkowski wrote:

Herd immunity is not a "strategy", it's nature's way of dealing with influenza-like illnesses. Once the data is in, the models become obsolete. Herd immunity is already established in many places, including the northeast of the US (NYC) and most of Europe. Proof: There is no rebound in spite of widespread "reopening". QED

On 2020-07-13 09:29:08, user OxImmuno Literature Initiative wrote:

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

On 2021-01-28 19:31:33, user Maciek Boni wrote:

The public Github repo has been renamed: https://github.com/bonilab/...

On 2020-07-15 07:10:13, user Dr Ahmed Sayeed wrote:

Section Review comments and notes Abstract, title and references The study appears to be new and promising in the current scenario of COVID pandemic In the objectives, the authors have the aim to describe the bronchoscopic findings in COVID patients but in the method, they have forgotten to mention how the bronchoscopic findings will be studied What is the meaning of COVID19 patients? Is suspected covid19 or confirmed COVID 19 with Nasopharyngeal swab(PCR or serology or Nuclear acid amplification test) The references are recent and relevant with the inclusion of appropriate study

Introduction/background In introduction line 4, the term bronchial alveolar lavage would be more appropriate than bronchial culture The author uses the term culture repeatedly which excludes other methods like PCR, grams stain, KOH stain, AFB and would be advised to use the broader term to include other methods of detection of organisms The limitations of the study are not mentioned Methods The study subjects The age group of the patients should be mentioned and the site of covid infection? lung also needs to be mentioned The variables are defined and measured Yes the study appears to valid and reliable

Results My knowledge of statistics is very limited and it is difficult for me to comment

Discussion and Conclusions<br /> There is a grammatical error in line 2 and 5 of the discussion Suggest difficult to do suction In paragraph 3 of the discussion the reference 18 is written twice The reference in the discussion are not quoted in serial order The limitations of the study need to be explained more

Overall The study design was appropriate This study added the to the scarcity of the novel virus literature and it showed that more hospital acquired infections are common in patients with covid I did not find any major flaws in the article

full review:

Overall statement or summary of the article and its findings

The article needs some correction and rewriting with some of my suggestion<br /> Some more literature needs to be done and added to the discussion with some new references

Overall strengths of the article and what impact it might have in the respiratory field

The article appears to be promising and will definitely add to the literature of BAL in COVID which not frequently performed in fear of spreading the infection to the health care staff Culture and sensitivity will make a difference in the management of COVID ventilated patients

Specific comments on the weaknesses of the article and what could be done to improve it Major points in the article which need clarification, refinement, reanalysis, rewrites and/or additional information and suggestions for what could be done to improve the article.

More literature review<br /> More references need to be added<br /> Minor points like figures/tables not being mentioned in the text, a missing reference, typos, and other inconsistencies.

English and grammar

On 2020-05-01 04:18:35, user Dr. Anthony Burnetti wrote:

The proposed mechanism is blocking the import of accessory proteins into the nucleus that suppress the innate immune response. The dose needed to block viral replication in vitro is possibly higher than a dose that could have a positive impact on the immune response. It is still quite possible that the approved dose could have stronger effects in animals than in tissue culture.

On 2021-06-20 08:07:15, user Stephen Smith wrote:

note bottom-left panel in Fig1 needs replacing with the correct scatterplot; have tweeted the corrected sub-panel and will update PDF here shortly.

On 2020-04-16 23:17:24, user Samantha Grist wrote:

We appreciate the authors’ urgency in addressing SARS-CoV-2 decontamination for reuse of N95 filtering facepiece respirators (FFRs). In the spirit of that urgency and health impacts, we note two concerns with the current preprint that could (unintentionally) cause confusion: (1) likely mismatch between the wavelength range to which the reported UVA/B light meter is sensitive and the viral-killing UV-C wavelengths emitted by the LED High Power UV Germicidal Lamp, as highlighted by other commenters, and (2) omission of a direct comparison between the UV-C doses applied in this study and the minimally acceptable UV-C dose understood to be needed for efficacy (e.g., CDC Guidance).

We have contacted the authors Fischer and Munster via separate email suggesting that they:

1. Please check a potential mismatch between the UVGI light needed for viral inactivation and the UVA/B light meter used: The LED High Power UV Germicidal Lamp described in the Methods emits in the 260-285 nm range, as is appropriate to inactivate virus by damaging DNA and RNA. However, the UVA/B light meter (General Tools) mentioned in the Methods section is not suited to detect the virus-killing light from the LED High Power UV Germicidal Lamp. Further supporting the possibility of a sensor-source mismatch is the reported irradiance of 5 µW/cm^2, which is ~1000x lower than typically reported for effective N95 FFR decontamination [Lore et al., 2012 (1.6-2.2 mW/cm^2); Heimbuch & Harnish, 2019 (4.2-18 mW/cm^2), Mills et al., 2018 (17 mW/cm^2)].

Being designed for germicidal function, the LED High Power UV Germicidal Lamp would have significant output in the UV-C range and would not be expected to have significant output in the UVA/B range (280-400 nm). Put another way, the UVA/B light meter used would not be able to accurately assess the germicidal function of the LED High Power UV Germicidal Lamp, which stems from the UV-C light. It is the UV-C-specific dose that is relevant to viral inactivation, with UV-B (280-320 nm) dose providing significantly lower germicidal efficacy, and UV-A (320-400 nm) considered very minimally germicidal [Kowalski et al., 2009; Lytle and Sagripanti 2005; EPA].

1. Please clarify the total UV-C dose delivered in Figure 1, as the peer-reviewed literature points to UV-C dose of > 1.0 J/cm2 as the critical factor in N95 FFR viral inactivation treatment. Although UV-C dose governs viral inactivation, the preprint does not clearly state the germicidal UV-C dose delivered to the N95 coupons for the Figure 1 treatment times. While germicidal UV dose is the product of the UV-C irradiance and exposure time, comparison to the minimally acceptable UV-C dose of 1.0 J/cm^2 is needed. UV-C irradiance varies significantly both between and within systems, so treatment time is not an accurate characterization metric for understanding UV-C germicidal efficacy (especially when translating to a different dosing system); dose needs to be quantified directly with a NIST-traceable, calibrated radiometer matched to the germicidal wavelength range of the source. At the reported 5 µW/cm^2 irradiance, the total dose delivered during a 60 min treatment period is only 18 mJ/cm^2, greater than an order of magnitude lower than the effective 1.0 J/cm^2 UV-C dose reported in the literature for similar viruses [Lore et al., 2012; Heimbuch & Harnish, 2019, Mills et al., 2018] and current CDC guidelines for UVGI decontamination of N95s [CDC]. A UV-C dose of 1.0 J/cm^2 across all N95 FFR surfaces is understood from the literature as the minimum acceptable for N95 decontamination.

Without these clarifications we are concerned that this important study may be misconstrued by readers as indicating that either (i) very low UV-C doses are sufficient for N95 decontamination (the peer-reviewed evidence suggests that they are not), (ii) a certain UV exposure time is sufficient for N95 decontamination (dose, not time, is the critical factor) or (iii) that UV-A or UV-B are effective decontamination wavelength ranges (they are not). In the spirit of the authors’ study, our #1 concern is for the health of our heroic healthcare professionals. For additional detail from the peer-reviewed literature, please see the 2020 scientific consensus summaries on N95 FFR decontamination at: n95decon.org.

On 2020-05-02 21:19:54, user Javier Mancilla-Galindo wrote:

This study could have a great impact in policy making. However, even when the authors have acknowledged that serological studies will be of great importance in order to take any decisions, the authors have not commented on the impact that having non-neutralizing antibodies, especially for the persons undergoing asymptomatic or mild disease, could have on this model. Also, a sufficient and efficient cellular immune response would be granted for this model to hold true. A third factor which could affect this model is the ability of the virus to mutate into an antigenically different strain.

Even when the initial intention of the model was not to take into account these factors, it would be important to clarify that a 100% effective adaptive immune response is being assumed and that no viral antigenic variability is being considered. The authors could address what is known up to this date on these topics to strengthen the discussion and conclusions of this study and for successful publication.

On 2021-02-09 15:49:22, user Rhonda Witwer wrote:

Great study! What was the source of your Type 3 resistant starch? Different sources have been shown to have different effects, making it important to disclose the RS source.

On 2019-11-09 20:30:28, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT 07 NOVEMBER 2019<br /> Friday, November 08, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,286, of which 3,168 are confirmed and 118 are probable. In total, there were 2,192 deaths (2074 confirmed and 118 probable) and 1064 people healed.<br /> • 560 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • No new confirmed deaths have been recorded;<br /> • 1 person cured out of the CTE of Butembo;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths;

NEWS

End of tour of the general coordinator of the Ebola response in North Kivu and Ituri

• The Epidemic Response Coordinator for Ebola Virus Disease, Prof. Steve Ahuka Mundeke, was on mission from 05 to 07 November 2019 in a few areas affected by Ebola Virus Disease in North Kivu and Ituri, to inquire about the epidemiological and security evolution of the response. During this mission, he visited some sites of the response to Beni in North Kivu, including the Mangango camp where the vaccination of pygmies took place;

• In Ituri, Prof Ahuka traveled to Biakato Mines in Mandima, Mambasa Territory, where he first reinserted three of the four cured patients he had discharged well into the Mangina Ebola Treatment Center in the area. Mabalako health center in North Kivu. He also comforted the family of the retaliating agent and journalist, murdered on the night of Saturday, November 2, 2019 in Lwemba in Mambasa territory in Ituri;

• He also chaired the daily meeting on the activities of the response in the sub-coordination of Biakato Mines;

• On his way back, the general coordinator of the riposte went to the Mangina Subcommittee, where he chaired under the trees the morning meeting in Mangina. He also visited the Health Center "Case of Salvation" which collaborates with the response and to whom he handed over a large batch of mattresses in the presence of the WHO coordinator of Mangina's sub-coordination. He again visited the Mangango camp, where the pygmies who have joined the activities of the riposte live to help the response reach all the other pygmies;

• He closed his tour of North Kivu and Ituri with a visit to the Ebola Treatment Center in Beni.

VACCINATION

• Pygmy vaccination continues in Mabalako at Mangango camp, 19/19 vaccinated pygmies;<br /> • Continuation of vaccination in expanded ring, around 3 confirmed cases on 04/11/2019 and 2 cases confirmed on 05/11/2019 and the vaccination of the biker as contacts, in Beni in five (5) areas health care, including in Butsili, Ngongolio, Tamende, mandrandele and Kasabinyole;<br /> • Since vaccination began on August 8, 2018, 248,460 people have been vaccinated;<br /> • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 114,626,335 ;<br /> • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

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

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

On 2019-11-10 21:15:52, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT 08 NOVEMBER 2019<br /> Saturday, November 09, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,286, of which 3,168 are confirmed and 118 are probable. In total, there were 2,192 deaths (2074 confirmed and 118 probable) and 1064 people healed.<br /> • 501 suspected cases under investigation;

THE LIST OF NO:

• No new cases have been confirmed;<br /> • No new confirmed deaths have been recorded;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths;

NEWS

NOTHING TO REPORT

VACCINATION<br /> • Since vaccination began on August 8, 2018, 249,290 people have been vaccinated;<br /> • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 115.036.328 ;<br /> • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

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

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

On 2019-11-27 15:46:04, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT 25 NOVEMBER 2019<br /> Tuesday, November 26, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,304, of which 3,186 are confirmed and 118 are probable. In total, there were 2,199 deaths (2081 confirmed and 118 probable) and 1077 people cured.<br /> • 392 suspected cases under investigation;<br /> • 1 new case confirmed in North Kivu in Mabalako;<br /> • No new deaths among confirmed cases;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths;

NEWS

NOTHING TO REPORT

VACCINATION

• Despite the tense situation of the city of Beni, a vaccination ring was opened around the confirmed case of 24 October 2019 in the Kanzulinzuli Health Area of the General Reference Hospital;<br /> • 724 people were vaccinated with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two Health Zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 255,215 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine is in addition to the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. has recently been pre-qualified for registration.

MONITORING AT ENTRY POINTS

• Sanitary control activities are disrupted in the towns of Beni and Butembo in North Kivu province following demonstrations by the population which decries killings of civilians;<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 120,825,670 ;<br /> • To date, a total of 109 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

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

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

On 2020-04-18 16:52:45, user novictim wrote:

Also worth considering is the timeline for treatment. HCQ proposed mode of action is not just its anit-inflammatory properties but its ability to act as a zinc ionophore. Zinc ions then interfere in viral replication. So you have to use Hydroxychloroquine early in the infection to see the maximum benefit. If you give it after lung epithelium and T-cells are already compromised, the benefit is less significant.<br /> I look forward to the trial results involving prophylaxis with HCQ and the use of it at the first signs of COVID-19.