On 2021-03-14 17:30:22, user Vikingman wrote:

Hi<br /> Would there be an updated version of the table in page 7 of the PDF other than 29 January? Thanks. Keep up the amazing work.

On 2021-03-17 20:32:20, user Alessia Visconti wrote:

Now published in the British Journal of Dermatology (https://onlinelibrary.wiley... "https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.19807)")

On 2021-03-19 14:42:27, user NermeenHM wrote:

I am so impressed with the extent of effort exerted on this paper and how it was deployed on such a large number of participants in the Arab world! Frankly, I never expected anything to come out of our part of the world with this high level of proficiency and accuracy + all this amount of participation. That’s quite a big number to be disregarded or dismissed particularly when, being a part of the Arab world myself, I know that it reflects a great deal of what we see around us and hear from friends, neighbors, colleagues and relatives. These results explain so much about how people think in this part of the world, also a lot more about the “why?” and the “who?” which were missing from the blurred and (usually) foggy picture when it comes to accurate figures and surveys. We’ re always “undocumented” in so many ways even with a pandemic looming high above our heads! Indeed, the issue of Covid vaccination is not something to be trifled with or treated lightly! I would highly recommend two things:

First: I quote the conclusion, “With the highly dynamic nature of the pandemic and vaccine production process and the interplay of ever-changing factors that affect vaccine acceptance, our study needs to be replicated at a later time to measure the change in public acceptance.” Yes please, that would be something really beneficial + informative.

Second: Due to the great importance of the topic and the rapid impinging of Covid on the<br /> world map and our societies, you should accept this paper to help others make use of its findings.

On 2021-03-19 17:43:57, user Kebbiet wrote:

Wait.....what were the mother's antibody titres BEFORE the vaccination? "Covid naïve" could be asymptomatic natural antibody formation after a year of frontline care provided during the pandemic. As with PCR testing, a negative result is only good at the time the test sample was obtained. As soon as the patient leaves the testing site, they may be exposed and turn positive from that exposure. To establish true Covid naivety, we would need to know whether there were detectable maternal antibodies immediately before administration of the 1st shot. A negative antibody test 6 months prior is of no value in establishing a direct connection of neonatal antibodies to the vaccine. We already know that Covid+ mothers have given birth to babies with detectable antibodies. We are missing a correlation step in this analysis.

On 2021-04-05 00:50:51, user Brandon Grant wrote:

The authors conducted secondary analyses to examine the effect of study type on the outcome of mortality for the studies of SARS-CoV-2 that were included in the primary analysis. However, the authors do not mention conducting secondary analyses to examine the same correlative relationship for any of the studies of any other virus besides SARS-CoV-2. This lack of equivalent data analyses and resulting lack of homogeneous comparisons of outcomes renders any conclusion based on the aforementioned data null and void.

On 2021-04-09 01:13:34, user Patrick Palmieri wrote:

Did a large number of COVID-19 infected people seeking health services at EsSalud know they were not receiving evidence-based interventions? In addition, were EsSalud leaders aware there were five different 'treatment groups' as well as a ‘control’ group? Thanks to the researchers of this manuscript, we can now ask for more details to address previous 'rumors' about poor clinical management of people with COVID-19. This point is especially important as the EsSalud hospitals have been sealed to family and visitors. As such, patients are left in these hospitals without advocates for their safety and wellbeing.

Although the current study presents an ‘observational cohort’ design, we need to ask about the circumstances, structures and processes, that resulted in the original data reported in this manuscript. The researchers clearly stated they ‘compare[d] five treatment groups to the standard of care treatment regimen, as a control group....’ To this point we need to ask how could these six groups (with significant variations from the care standard) be organically organized from the existing patient population at EsSalud? In this regard, I am not claiming the researchers did anything wrong, but we need to understand how EsSalud ignored or facilitated the reported situation. In fact, we should thank the researchers for exposing some potential issues only believed to be unsubstantiated rumors in the previous months. Again, we need to recognize the vulnerability of patients as there were no family members present to be advocates in the EsSalud hospitals.

In explaining the possibility for five treatment groups and one control group at EsSalud, the researchers added ‘...decision to administer one of these treatment groups depended on clinician’s own criteria guided by the Ministry of Health recommendations, which was changing over time according to updated evidence-based reviews...’ Given the fact that EsSalud is the social security system for workers in Peru with separate clinical practice guidelines claimed to be based on evidence, this statement indicates the quality of care and standards of medical practice were not monitored by EsSalud. Again, this is concerning as the patients were vulnerable, without family advocates, and there is no statement in the manuscript about the normal informed consent process for clinical management.

The current observational study indicates there was a single ‘standard treatment’ authorized yet five alternative protocols were implemented as seemingly 'n of 1' studies. How were physicians in EsSalud able to clinically manage patients with unapproved protocols that significantly varied from the evidence? Were EsSalud leaders aware of the deficiencies in clinical management that probably contributed to the deaths of many patients? As a matter of normal clinical management did each patient consent to the treatment they received understanding there were more effective treatments available?

From the information reported in this manuscript, the clinical management of patients with COVID-19 at EsSalud needs to be reviewed by external authorities to determine the possibility of clinical negligence, medical malpractice, unethical conduct, unauthorized research, and/or illegal activities. Again, I want to emphasize these comments are in no way focused on the researchers. I sincerely appreciate the researchers exposing several serious ethical concerns that have only been rumors for months.

On 2021-08-01 07:53:29, user Dlya Truby wrote:

Folks read "Supplementary Appendix" page 12: Deaths: Vaccinated group - 15; Placebo (unvaccinated): - 14.

On 2021-07-29 16:28:46, user aep wrote:

link to competing interest statement broken

On 2021-07-31 09:03:45, user Eli Baied wrote:

Per abstract, vaccine efficacy at 6-months 97% for severe disease. It seems logical to me to vaccinate the unvaccinated globally in hope to better control this pandemic.

On 2021-08-01 00:45:40, user Michael Kowalik wrote:

18 deaths in the study group and 16 in the control group, so (at best) zero lives saved from Covid.

On 2021-08-06 22:27:57, user Ewin Barnett wrote:

Am I the only person wondering where the discussion of the autopsy results was published? In fact VAERS is now easily over 5,000 vaccine-related deaths yet zero autopsies.

On 2021-09-02 13:44:56, user ABO FAN wrote:

I do not understand the meaning of this paper at all.<br /> 1. There is no statistically significant difference between one and two corona deaths. This means that the vaccine is not effective.<br /> 2. The test period is until March 13, 2021, therefore the current mainstream delta strains were not tested.

On 2021-04-16 18:14:19, user Judy Hodge wrote:

I am curious what vaccine the mother that was tandem feeding received? Also am I reading your data correct that the Moderna elicited a higher IgA response in breastmilk?

On 2021-04-16 18:43:40, user Lee Rague wrote:

This paper has been published in the Journal of Nursing Management

https://doi.org/10.1111/jon...

On 2021-04-28 07:44:22, user Lee Rague wrote:

this paper is now published

https://onlinelibrary.wiley...

On 2021-04-17 17:36:18, user Mando Dido wrote:

This article available at:

https://www.mdpi.com/2076-3...

On 2021-04-22 18:18:59, user friidrottare wrote:

What about the protection against the variants, such as the South-African ?

On 2021-04-23 13:52:16, user Dijon Mustard wrote:

The title says "up to 12 months", the abstract says "at least 12 months". Please change the title to accurately reflect the paper's findings.

On 2021-04-24 20:59:22, user Mike wrote:

The study looked only at infected people, but many writing articles about this study fail to emphasise this properly. As a result, this study is misinterpreted by many as saying: "Instead of protecting you, being vaccinated increases the chance of being infected with the South African variant by a factor of eight." I think the study needs to be updated to warn against this possible misinterpretation, which is very common. Even I have fallen for it initially, and only reading the news article twice clarified for me that's not actually the case.

I'm getting tired of correcting people, and explaining that 100% of the people from the study were infected, so automatically if the vaccine protects better against some virus variants, the percentage of other virus variants in the sample will increase.

This quote from one of the authors doesn't help: "We found a disproportionately higher rate of the South African variant among people vaccinated with a second dose, compared to the unvaccinated group,” Tel Aviv University's Adi Stern said. “This means that the South African variant is able, to some extent, to break through the vaccine's protection.”

Even Dr. Fauci agrees with me: "Speaking directly to the Israeli study, Fauci said it was misleading and makes it sound like people who get two doses of the Pfizer vaccine have a higher chance of COVID infection than unvaccinated people."

On 2021-04-25 15:33:39, user Tam Hunt wrote:

This study is conflating deaths with covid with deaths caused by lockdown measures bc it employs the UK standard definition of a covid deaths as follows:

In the UK, all-cause death by 28-days post confirmation of SARS-CoV-2 infection is the standard definition of SARS-CoV-2 mortality,8 so we used death from any cause as the primary outcome. In sensitivity analysis restricted to people diagnosed with SARS-CoV-2 a minimum of 28-days prior to the censoring date, and logistic regression with deaths censored beyond 28-days the results were consistent.

On 2021-04-26 14:10:09, user Peter wrote:

"…patients receiving these drugs should be prioritized for optimally timed second doses."

But what is the "optimal" timing for a second dose?

It takes time for the immune system to respond to the first dose. In general, extending the prime-boost interval leads to a greater eventual response.

This paper suggests that patients on TNF blockers may not respond as well to a single dose, so delaying the second dose may leave them at risk for longer.

Perhaps the answer may be that such patients are likely to benefit from an additional, early booster dose, followed by a third dose (a second booster dose) when their immune systems have had more time to respond to the first doses.

On 2021-04-28 13:32:34, user Huijghebaert Suzanne wrote:

This study poses a number of relevant questions to resolve, before concluding on efficacy. To start: calculating backwards, the number of PCR negative symptomatic subjects (31 in total) were comparable in both treatment groups, suggesting that all differences over the 21 days of treatment were accounted for solely by COVID-19, so strangely, the spray – in contrast to what is claimed – would not prevent other common colds....! So, how much analytical flaw, how much efficacy?<br /> 1) Calculating the % back in carrageenan+saline versus saline alone 7.6% corresponds to 15 and 8.6%<br /> to 17 subjects each respectively, totaling 32 instead of 31: where is the incorrect overlap, 1 person too<br /> much calculated as +?<br /> 2) Most importantly, which PCR test did you use and how did you assure that carrageenan did not interfere with the PCR assay? Cfr Ribeiro 18th Apr, 2013, asking for a safe way to remove carrageenan from RNA samples and reporting that after RNA extraction (by Trizol), reverse transcription and real time PCR, only the control group (saline injected, without carrageenan) had positive amplification, while carrageenan interfered<br /> with the reaction. <br /> 3) The impact of carrageenan may additionally also already interfere at the sampling stage by affecting/reducing the RNA loading, leading to less<br /> positive results (cfr Laurie et al.). Also that step should be validated.<br /> 4) As the difference moreover is very small, and the outbreaks in health care personal often concerns clusters within a same division, how do the individual data relate to different clusters within given departments?

Without proper profound validation the PCR test(s) in presence of various carrageenan concentrations, the findings may not translate in a true benefit, but possibly mask (so missed) viral positivity and so falsely hide transmission events. Unless validated in detail, the combination of already reported reduced PCR-response (due to carrageenan) in the nasal samples and case clustering may possibly annihilate all differences of significance.

Suzy Huijghebaert, Belgium

On 2021-04-29 16:16:17, user George Orwell wrote:

FYI these comments were posted to the previous version of this article:

BenSahn<br /> 2 days ago<br /> I'm one of those people. I had Rituximab infusions in November for IgG4-RD. In March I got the J&J COVID vaccine while on a low dose of prednisone. Last week, after a few weeks off prednisone, blood test showed I had no COVID anti-bodies.<br /> Reply<br /> –<br /> Avatar<br /> Risham S<br /> 22 days ago<br /> What about therapies like entyvio? Can anyone shed some light on that? Many thanks for the study , a great help for CID patients like me. Appreciate it.<br /> 1 <br /> Reply<br /> –<br /> Avatar<br /> David Rubin Risham S<br /> 20 days ago<br /> Entyvio (vedolizumab) is selective to a T cell subset and doesn't affect your B cell immune response. Early data in IBD show no difference in titers after mRNA vaccinations.

On 2021-05-07 12:57:59, user Melissa Y wrote:

As acknowledged by the authors, some of them are co-founders of a company that is developing a product based on this technology. After three months of use, there was no significant difference between the stimulation and control groups on any standard measure of cognitive function. There was a significant difference on a name-face association task for a very few subjects. There was no significant difference between the groups in hippocampal atrophy. The data reported in the paper appear to conflict with what is stated in the abstract. The mostly negative results are consistent with the negative results reported by the company. These are just facts.

On 2021-05-09 00:18:01, user Minga wrote:

The focus on a comparison between household vs non household contacts hide the lack of any comparison between schools, offices, or factories contacts vs non job-related contacts.

On 2021-05-09 20:43:42, user Tiago Pereira wrote:

Great work! Very very important piece of information. I would suggest to calculate the 95% predictive interval, the range of incidence expected in 95% of the populations. See: Ioannidis JPA, Rovers MM,. et al. Plea for routinely. presenting prediction. intervals in meta-analysis. BMJ Open 2016;6:e010247. I don't think the weights from the random-effects model are 100% appropriate. It would be nice to have a sensitivity analysis via a "fixed-effects" model with weights proportional to the (approximate) number of people in each of those populations.

On 2021-05-11 17:34:07, user Joe Smith wrote:

Table 2 is interesting. It looks like, compared to 'other cancer (non-ADT)', the ADT patients had higher rates of infection (raw data). Looks like the table S2 suggests men taking ADT are more likely to get tested than...all non-ADT? all other cancer (non-adt)? I don't know what the comparator is for S2. But I don't see an OR listed in S2 for 'all other cancer (non ADT). Hopefully that was used in the creation of the Table 2, but it wasn't presented in S2.

I'm no statistician, but it seems like some of the covariates would interact; eg african americans may be less likely to get tested than white people overall, but maybe african americans with cancer are just as likely to get tested as white people with cancer. Hopefully someone can add some detail on this point, I'd like to know more.

I also note table 2 has a lower n than table 3, meaning some ADT+, COVID tested patients didn't have matching controls so were not included in this analysis (62/295~20%). For all subjects, a much lower % (6.7%, 1666/25006) were excluded from Table 2 for not having 5 matching controls. I wonder why it was so much more difficult to find matches for the ADT patients, and if this could have affected the outcome.

Finally, Table S3 is very important, and I believe should be added to the body. This table "Association between ADT use and SARS-CoV-2 positivity and COVID-19 severity among prostate cancer patients".

The percent of severe disease cases is very similar (22% vs 23% unadjusted) p~0.9 (propensity matched). So, when you are directly comparing the outcomes in men with prostate cancer, ADT does NOT result in fewer cases of severe disease.

Appreciate the timely work and sharing the prepublished article!

On 2021-05-12 11:20:59, user Rajesh K. Pandey, MD wrote:

Our arsenal of treatment options against COVID-19 remains very limited. For this reason re-exploration of the use of anti-inflammatory medications is imperative. A case in point is the use of colchicine against COVID-19. There is abundant data demonstrating colchicine's effects on lowering hs-crp in turn lowering risk of ACS. As supported by LoDoCo2 and Colchicine-PCI trials, Colchicine halved the risk of CV events vs placebo. In the COLCOT trial we saw a decrease in the combined primary endpoint of stroke; MI; CV death, CV arrest and resuscitation. In the COPS study, a benefit was seen in patients within 3 days of an MI. Overall amongst the above studies colchicine showed a benefit in CV outcomes. Therefore we take issue regarding the claim that colchicine increases the risk of PE. In our combined 50-60 years in practice, we have not had any incidents of PE in our 100's of patients treated with colchicine. Dr. Tracy Hampton's publication on February 2nd, 2021 in JAMA described the phenomenon that autoantibodies may drive COVID-19 blood clots, similar to patients with Anti-phospholipid syndrome. The statistical analysis of the COLCORONA trial may have done an injustice to known benefits of colchicine. We should continue to remain open minded on colchicine's potential therapeutic applications. Thank you.

On 2021-08-10 14:49:04, user Dr. Chris Bird wrote:

This looks like very nice work. You have not, however, estimated "Total Immunity" as claimed. You have estimated how many people have been infected, which is very useful. To get "total immunity", you have to incorporate the growing body of literature on the probability of not being immune even if you have recovered (Cavanaugh et al 2021) or been vaccinated (Sheikh et al 2021 as one example). That will substantially decrease the estimate of immune and help to explain why the July-August 2021 surge is occurring.

On 2021-08-13 12:38:20, user TKREGER wrote:

This study relies on the PCR test, which has been proven to be flawed in regards to accessing Covid infection in individuals. Until we have a reliable testing procedure, this and other Covid studies relying on the PCR test, are of little real use.

On 2021-09-18 17:00:44, user Ruben wrote:

Would love to see events stratified by age. There are almost 700 more people age > 65 in the biontech group as compared to moderna. With total hospitalizations being only 43 and icu only 7 patients for pfizer vaccine, it makes you wonder how much of this is skewed by age.

On 2021-09-03 18:17:49, user Sam Wheeler wrote:

What if someone takes 30mcg Pfizer Comirnaty on left arm, and immediately goes to other vaccination site and takes 30mcg Pfizer also on right arm? 60mcg total.<br /> Could this be more efficient? Even better than 100mcg in the same arm?<br /> Or would it be even better to get 60mcg in the same arm, but separated by a small distance? Would the latter vaccinator notice it and refuse to vaccinate if she/he sees the arm?

Moderna has 100mcg of mRNA.

30mcg is ridiculously small amount, as I believe they are testing exactly this 30mcg Pfizer dose even for children who are 6 months or older.

On 2021-08-14 13:55:30, user Don Elbert wrote:

Nice work. There is a typo saying that p < 0.5 is significant. Are there any barriers to applying a GLM with age and time elapsed from 2nd dose as continuous covariates (ANCOVA) on the whole dataset?

On 2021-08-19 17:13:00, user Frank Ploegman wrote:

Thank you for this excellent and extremely important study.

On 2021-08-21 21:15:54, user HarryT wrote:

Virus mutation frequency is somewhat constant. Vaccinated human hosts changed the outcome of the selection out of a pool of mutant viruses.

On 2021-07-03 09:59:14, user Steven Kelly wrote:

Useful results! The other SARS-CoV-2 vaccine effectiveness studies use +14 days after the second dose, so I'd suggest you extend to include that date too before publishing. The definition of 'infection' here seems to be 'positive result on test taken by subject based on own symptoms or known exposure' — so somewhere between 'symptomatic infection' and 'infection'. In other studies of Pfizer on the Alpha variant, VE for symptomatic infection [1] vs. infection [2] is 49% vs. 30% at 1 dose + 21 days, and 93% vs. 90% at 2 doses +14 days, so the exact definition can be quite important. <br /> [1] https://www.bbc.com/news/uk...<br /> [2] https://www.nejm.org/doi/fu...

On 2021-07-11 19:31:18, user geek49203 wrote:

Published reports state: "“The big takeaway was that if you are not vaccinated, and were not previously infected, one, you have a very high risk getting infected—24 percent of employees over a year tested positive." (Epoch times). But I see only 254 out of 4,313, which is 5.8%. Even allowing for a doubling of the timeline (to a full year?) that's around 11-12%, which is fairly in line with what the Brits published in May in The Lancet.<br /> SECOND - it's obvious to me that there is a likelihood that the number of infections are seasonal. IF those who got injections were vaccinated on the downward slope (ie, Feb 21 forward) instead of the upward slope of Dec 20-Jan 21, wouldn't the results be much different? So studying those who got the vaccine would have to take into account the prevailing non-study environment, correct? A non-vaccinated person wasn't very likely to get COVID in June of this year, or June of last year, correct?

On 2021-07-12 20:50:31, user David Epperly wrote:

Some good details. Should add diary info from each of the infected as available to include: recollection of interactions with patients 0a and 0b and 0b's recollection of all interactions with all infected. Each interaction should include distance, time, and environment. More info about tent structure, identity blurred photos of event wide-shots, and historical prevailing wind conditions for area. Help us understand how transmission likely occurred. Also state relationships of each infected (spouse, close friend, acquaintance, ...) to help understand likely interaction levels. It appears 0a and 0b are related. Tell us. Move info on Delta into a supplement and focus on details of the event. Create a supplement for additional event / relationship / transmission details. Capture more of what happened.

On 2021-07-13 11:53:38, user DflippinK wrote:

How many SARS Cov-2 genomes are isolated to a single strain?

On 2021-07-16 20:44:43, user temporalista wrote:

I reviewed the spreadhseet and replicated the computations in different software for both analysis (R) and visualisation (PowerBI, Tableau). In all cases the formulae seems correct and consistent.

I've been able to follow the modelling reasoning (is not complicated) and check the referenced sources. It seems consistent.

On 2021-07-16 22:51:17, user Leo G. wrote:

Another way to slow down immune escape might be prophylaxis (IVM or HCQ + Zinc), starting about a week before the first jab and ending (or calculated to end) when the person acquires maximum immunity.

On 2021-07-21 20:13:20, user Dean Karlen wrote:

The first claim in the title (vaccines dampen diversity) is not substantiated.

Linear entropy is a measure of how evenly spread are the lineages. As stated, if for one month all sequences are the same lineage (no diversity), then the measure is zero… on the other hand if the sequences are evenly distributed amongst all 1296 lineages, the value is about 7. When a VOC appears, it is labelled a VOC precisely because a large number of cases are seen of that lineage! So, of course, when VOCs begin to dominate the linear entropy decreases.

Figure 1 shows that starting in January 2021, just as alpha becomes dominant, linear entropy begins to decline as expected. January 2021 happens to be the time that mass vaccination gets underway - so it is not clear how much (or if any) of the reduced diversity is due to vaccination.

The second claim in the title (regarding breakthrough infections) is questionable. The sample size is small and no statistical test is presented that supports the claim of greater diversity in the unvaccinated compared to vaccinated.

On 2021-07-22 10:33:41, user David Simons wrote:

Hi,

Thanks for sharing this data, it may be interesting to include descriptives for those that were test negative for COVID-19.

Also in table 1 your numbers for smoking status do not appear to be accurate. You seem to be missing 2,610 smoking statuses for your COVID-19 positive sample.

On 2021-07-23 11:43:39, user andyround wrote:

Fascinating, thanks. What I can’t square between studies like yours and the one on cynomolgus monkeys on the one hand, and the range of estimates of sizes of droplets in respiratory exhalations on the other (as recently reviewed by Lydia Bourouiba for example), is how the quantity of viral RNA apparently scales with the *number* of droplets rather than their volume. It implies that the concentration of viruses per droplet is hugely dependent on the size of the droplet and I can’t think of a mechanism to achieve this - are viruses massively self-repelling? (over micron-scale distances?) Are they highly surface active? I wonder if you have thought about this.

On 2021-07-27 01:29:32, user Vaskor Basak wrote:

Thank you very much for sharing this paper. I am interested to know what lag time was assumed between infections and deaths when calculating or inferring the CFR figures. Was it possible to use a distribution of variable lag times, based on real life data, for more sophisticated modelling? Also, has the lag time increased and/or CFR decreased as new medical interventions have slowed down the rapid onset of Covid-19 for severe cases requiring hospitalisation, since the beginning of the pandemic?

On 2021-07-29 07:39:07, user ncn wrote:

Will this preprint be submitted to a peer-review journal? Wish the research team all the best.

On 2021-07-29 08:08:57, user Salvatore Chirumbolo wrote:

The evidence that acetaminophen (paracetamol) worsened the rate of hospitalization in COVID-19 patients respect to NSAIDs such as indomethacin, is the major highlight of this contribution. The Italian Ministry of Health (Nov 30th 2020) recommended only paracetamol and a watchful attitude during the early onset of COVID-19, to simply dampen fever and related pain (see https://www.bmj.com/content... "https://www.bmj.com/content/368/bmj.m1086/rr-18)"). So, NSAIDs are not dangerous for early and mild COVID-19 as initially believed, whereas paracetamol is. In this perspective, in Italy a wide community of citizens, professionals, physicians, caregivers, practitioners, attorneys and so on, joined together to promote the best COVID-19 home therapy at the earliest (within first three days from positive swab or symptoms), to reduce hospitalization (and mortality), as paracetamol exacerbates COVID-19 immuno-thrombosis, probably leading even to death (see Pandolfi S, Simonetti V, Ricevuti G, Chirumbolo S. Paracetamol in the <br /> home treatment of early COVID-19 symptoms: A possible foe rather than a <br /> friend for elderly patients? J Med Virol. 2021 Jun 25. doi: <br /> 10.1002/jmv.27158). Hoping that politics may take into account the evidence reported by the current medical science.

On 2021-07-29 12:52:04, user Erik Widen wrote:

Please note that the published version contains both corrected and more expansive information and supplants this preprint for all purposes. It is available through the link above or use https://doi.org/10.3390/gen....

On 2021-07-30 00:51:33, user Les Campbell wrote:

Your method seems insecure.<br /> Firstly there were no vaccinations during your “wild type “ period. There were during your alpha and delta periods. How have you controlled for this? Have you considered findings in USA and Israel that vaccine adverse reactions have influenced your results?<br /> Secondly just because you have defined periods when variants were of concern it does not follow that the women in your study had that variant without sequencing for each subject. <br /> Thirdly why do you recommend that pregnant women should get the vaccine? Women of child bearing age are at very small risk of death or severe complications. <br /> What were the cohort numbers? Especially for the delta variant? <br /> Why were no pregnant women treated with therapeutics or given simple vitamins and minerals or antibiotics (pneumonia) as they would be in many other countries?

On 2021-08-01 17:03:27, user imogen88 wrote:

Why didn’t they breakdown the vaccinated by specific vaccine formulation? It would be very helpful to see if there’s a significant difference in viral load by vaccines among different age and risk groups.

On 2021-08-03 21:39:28, user Fruit Gal 522 wrote:

Judging from how long ago this was published...June 1, and it's now Aug. 3, it's taking excessively long for this to be peer reviewed. Sources from a google search say it should take 3-4 weeks to review.

On 2021-08-03 23:09:01, user Ankita Bag wrote:

Hi,<br /> Can I get an access to this code.<br /> Thanks in advance.

On 2021-08-04 08:41:37, user ingokeck wrote:

Dear authors,

Thanks for this fascinating study! I am really surprised that you only found 6+3=9 cases in your sample.

Your sample corresponds to 60/330=18% of the population of the US. If we assume that it is representative, this means in the whole US there were only ca. 50 cases of myocarditis in 12-17y old in total. Using the estimation of the CDC that 37% of all kids were infected (see https://www.cdc.gov/coronav... Table 2), this is a rate of just 50 in 30,000,000*37%, thus 4.5 cases per million infected.

So, the risk of myocarditis from Covid-19 is 4.5 cases per million infected and factor 100 smaller than what you report in your result, probably because your cases in the dataset are mostly hospitalized which make only a very small subgroup (ca. 1%) of all cases in this age group.

Compared to the risk from the mRNA vaccines of 10 per million (your source) or rather 333 per million based on the results from Israel (1:3000), the risk from the vaccination is 2 to 100 times greater than the risk from a Covid-19 infection.

I would appreciate it very much if you could correct your calculation to the correct base infection rate as given by the CDC, and also discuss why you assume a smaller vaccine risk than the data from Israel suggests.

On 2021-08-04 15:55:17, user Hassan Rostam wrote:

The article has been publishet @ New Microbes and New Infections

https://www.sciencedirect.c...

On 2021-08-09 15:16:23, user VT wrote:

Please do not post docx-files. Some researchers will be unable to download those files due to security concerns.<br /> Thanks!

On 2021-09-12 05:30:50, user kdrl nakle wrote:

William Brooks talks nonsense. The increase in mg household secondary infections could easily be the result of prior infections (before lockdowns) as a source of infection. It could have easily happen, perhaps even worse without lockdown. And indeed the hospitals in NYC, Brkln and Qns were overflowing with patients. But when you have political slant it is hard to think, isn't it?

On 2021-09-12 13:38:28, user synchromystic wrote:

"As no vaccine is 100% effective".<br /> Really?<br /> I'd love to see the breakthrough cases of polio, small pox and many other viruses.

On 2021-09-12 21:59:19, user Swapnil Hiremath wrote:

<reposting with="" minor="" edits="" as="" disqus="" thought="" last="" one="" was="" spam="" for="" some="" reason=""><br /> The authors have undertaken an ambitious project: briefly, taking numerators from the VAERS database, denominators from vaccine numbers from elsewhere. They then perform a ‘harm-benefit’ analysis looking at COVID hospitalization as the only harm. The whole analysis is restricted to the 12-17 age group in whom the concern of myocarditis is admittedly higher.<br /> They report a risk which was anywhere from 1.5 to 6.1 times higher for vaccine associated myocarditis vs COVID causing hospitalization. Vaccines must be bad, surely.

However, several problems are quickly apparent.<br /> 1. The rate of myocarditis is much higher than the ones reported in Ontario: 160/million for 12-15 males compared to 72.5/million from Ontario (which includes Moderna as well - which has higher rates of myocarditis than the Pfizer/BioNTech). Why would this be so? There are many possible reasons, including the overestimation from VAERS being probable cause. On a perusal of the supplement, there are many which are other viral diseases which could be the reason; additionally many descriptions are quite vague (‘the doctor told us troponin was elevated’). It is very easy to submit cases to VAERS, so the numbers reported could be an overestimate - proper case ascertainment with source documents is necessary to be sure of the cases. Needless to say, simple arithmetic to derive 'rates' is also problematic. The VAERS website specifically suggests the numbers should *not* be used for estimating rates.

1. It was not clear why the authors chose Jan 1, when vaccines EUA for 16-17 started in March, and for 12-15 in May. In their database, there seems to be one case in March and most of the VAERS reports from May or later.

3.Next, the authors make many assumptions when it comes to who had comorbidities and who did not among the children, and multiply numbers to come up with some crude estimates. It would be useful for a pediatric diseases researcher to assess these assumptions. The 40% assumption of children hospitalized 'with COVID' and not due to COVID is a very crude untruth that the authors and others have needlessly perpetuated on social media with little foundation.

1. Most importantly, the authors assume that hospitalization is the only bad thing for children who develop COVID. Some 12-17 years olds have died due to COVID, and some may have had a 1 day hospital stay - their analysis treats these equally and incorrectly. Some teens developed MIS-C. Some developed longer term sequelae. To group them under ‘hospitalization’ seems overly simplistic. Similarly, from perusing some of the vaccine-myocarditis, many seem to have recovered with symptomatic care alone. The authors seem to be minimizing COVID and maximizing vaccine associated adverse events.

2. It should be noted that the involvement of children in the first two waves seems to be different than the one we have seen in the last 2 months with delta (for whatever reason - perhaps with lower immunization numbers in these).

3. Lastly, the pandemic is not yet done. Many more children are going to get COVID in the next few months and years. We are going to have many more hospitalization, morbidity and sadly many more deaths. There will be long term morbidity and sequalae. We do need better data to assess the risks and benefits. This study is not it.

Unfortunately this study has been picked up uncritically by media and will worsen vaccine hesitancy. This seems unwise in the face of an ongoing pandemic.

On 2021-09-13 21:04:36, user Thomas Mohr wrote:

If I review a paper, I start with the methods section. So let us do this:

Quote: "We searched the Vaccine Adverse Event Reporting System (VAERS) data for <br /> females and males ages 12-17 in reports processed from 1/1/2021 through <br /> 6/18/2021 with diagnoses of “myocarditis,” “pericarditis,” <br /> “myopericarditis” or “chest pain” in the symptom notes and required the <br /> term “troponin” in the laboratory data. We defined a CAE using the CDC <br /> working case definition for a probable case."

As others, and VAERs, have pointed out, the VAERs database can not be used to do this.

Quote: "Cases and hospitalizations with an unknown dose number were assigned to dose 1 or dose 2 in the same proportion as the known doses: 15% occurred following dose 1 and 85% occurred following dose 2."

Nope. That is not how it works. Incomplete data have to be excluded.

Where is the proper prior probability of myocarditis?

At this point latest I would stop reviewing and return the verdict: reject without encouragement to resubmit.

On 2021-09-10 19:50:39, user Roger Seheult wrote:

Were you able to exclude the subjects from VAERS based on SARS-CoV-2 positivity? Was it even known if they had tested positive for SARS-CoV-2?

On 2021-09-13 09:36:17, user Michal wrote:

Excellent work! The link to direct-diabetes as in:

The IMI-DIRECT data access policy is available from www.direct-diabetes.org

does not seem to work. Also, the metabolite names (both on the plots and in the supplementary information) seem to be malformatted by R, it would be wonderful if you could restore clean names (with correct punctuation instead of dots) for the final publication.

On 2021-09-14 17:21:09, user Auriel Willette wrote:

Hi everyone, I am the Corresponding Author. Please note that Sara A. Willette's author affiliation was incorrect in the pre-print version of this article, and a correction has been filed with the journal. Specifically, her correct affiliation was and is IAC Tracker Inc, Ames, IA, USA. I apologize for any inconvenience. Thank you.

On 2021-09-19 09:24:45, user Cengiz Kiliç wrote:

Dear Dr Swedo et al,

We read with enthusiasm your consensus paper. We are looking forward to its publication, since it is very timely and much needed. We believe such a consensus, reached at by an international panel of experts, and using rigorous criteria, will be very helpful to set the main principles for advancing research, in an area where little is known. Such a clinical guideline will limit the circulation of several existing diagnostic criteria sets that have little relevance with the clinical presentation of the disorder. We especially appreciate your (strongly) emphasizing the fact that misophonia is a sound-sensitivity disorder, and not a disturbance of any sensory input.

At our Stress Assessment and Research Center (STAR) of Hacettepe University, Ankara, we have been conducting research on misophonia (as well as other stress disorders) since 2015. Our first study*, which was just published last month, presented prevalence rates on a random population sample, using our own proposed diagnostic criteria (it is a pity that our study did not appear in time to be included in your literature search). Our second study was a treatment study comparing the effects of psychoeducation, filtered music and exposure in 60 misophonic outpatients, which we are preparing for publication. Our follow-up study (of the population-study sample) is still ongoing. We touched upon the limitations of the existing proposed diagnostic criteria sets in our BJPsych paper’s supplement, and would be happy to share our views in more detail (if requested).

Sincerely,

Cengiz Kiliç, Professor of psychiatry<br /> Gökhan Öz, psychiatrist <br /> Burcu Avanoglu, psychiatrist<br /> Songül Aksoy, Professor of audiology<br /> Misophonia Research Group, Stress Assessment and Research Centre (STAR)<br /> Hacettepe University, Ankara<br /> Email: star@hacettepe.edu.tr<br /> Phone: +90-312-3051874

* Kiliç C, Öz G, Avanoglu KB, Aksoy S. The prevalence and characteristics of misophonia in Ankara, Turkey: population-based study. BJPsych Open. 2021 Aug 6;7(5):e144. doi: 10.1192/bjo.2021.978. PMID: 34353403; PMCID: PMC8358974

•

On 2021-09-21 21:41:54, user tooearly wrote:

Did the authors mean to say 10 cases per 100,000?

On 2021-09-24 06:28:51, user gzuckier wrote:

I admit to not having perused either the comments here nor the blog sites listed above, however there is a viable alternative model for these results, other than the one posed in the conclusions.<br /> Firstly, from the small number of infections in either the vaccinated or the previously infected group, it's clear that we are looking at outliers here; not a general waning of immunity over the time period, but rather a minority of individuals in either group whose immune system did not respond fully for one reason or another.<br /> This highlights a rather striking conceptual difference between the two groups, however; a large proportion of any individuals with defective immune systems have already been eliminated from the previously infected group, by the initial Covid infection having killed them. This group as now tested would absolutely be expected to have fewer immune failures than the Covid-naive individuals making up the vaccinated, not previously infected group, and thus fewer infections and fewer hospitalizations.<br /> This interpretation, of course, also perfectly explains the reduction in infections and hospitalizations seen in the previously infected and vaccinated group, relative to those previously infected and not vaccinated.<br /> Unless some way can be found to eliminate the effect of this unintended selection bias, i.e. filtering out previously infected group members with persistent severe immune incompetence, this study can tell us nothing regarding the relative protections of vaccine vs "natural" immunity.

On 2021-09-01 06:52:27, user Jeffrey Bachant wrote:

The key model rests on ~260 total cases out of ~65,000 individuals between the cohorts. <br /> Cohort studies are biased towards statistical artifacts if the outcome of interest is rare. Thus, the main finding should be that delta infections in both cohorts is infrequent. The confidence intervals for the way cases bin between acquired immunity primed by viral infection vs vaxx is statistically only applicable to their cohort group. Whether it has predictive value in a larger setting is unexplored. It's clearly written in way that, just from what I've bumped into, has allowed it do be heavily talisman linked by the anti-vaxxer crowd. Its unfortunate.

On 2021-09-08 03:11:32, user TBonePickenz wrote:

Too much discussion for something that has ***not been peer reviewed*** <br /> Also bear in mind this is a retrospective study.<br /> The gist is vaccines < natural immunity < natural immunity + vaccine. It is unclear if the 3rd option is statistically significant in my read.

In the first part of the discussion, they say "Individuals who were previously infected with SARS-CoV-2 seem to gain additional protection from a subsequent single-dose vaccine regimen. Though this finding corresponds to previous reports, we could not demonstrate significance in our cohort." However, in the final paragraph of the discussion they say, "Notably, individuals who were previously infected with SARS-CoV-2 and given a single dose of the BNT162b2 vaccine gained additional protection against the Delta variant." <br /> This needs to be clarified in the peer review process.

What it does do (in the US which is swimming in unused vaccines) is open up the question of the necessity of vaccine mandates in those who have already had a natural infection.

• a vaccinated doctor

On 2021-09-08 20:11:56, user David H wrote:

This is an interesting and potentially important study that seems to be playing into a political narrative - 'natural infection' vs vaccination. But before going there we need to acknowledge that it has not been fully analysed and the potential sources of bias have not been fully explored. In observational studies time is a critical factor and it is not clear how it has been handled in the analysis. There are no Kalpan Meier curves. Potential baseline confounding is partly addressed, but not time varying confounding. I cant find information on person time at risk in the three cohorts and that is critical, because it determines the periods during which individuals are at risk of reinfection or breakthrough infection. Is there an immortal time bias in the naturally infected cohort? Additionally, I cant see information on testing rates in the 3 cohorts - most infections will have been mild so this is critical. If testing rates (hypothetically) are lower after natural infection then that could introduce a major ascertainment bias. The study doesn't seem to have measures (or proxies) of health protecting behaviors, which may also be different between the groups. I am not saying that the results are wrong, rather that I think the authors need to complete more detailed analyses to address confounding, temporal selection and ascertainment biases.

On 2021-08-26 19:01:49, user zlmark wrote:

Do your results change significantly, if you analyze different age groups separately?<br /> In other words, what happens if instead of using the age as a covariate, you limit your analysis to a particular age group?

On 2021-09-26 20:12:47, user kdrl nakle wrote:

Poorly written. Better paper:<br /> https://www.medrxiv.org/con...

On 2021-09-29 07:40:06, user Richard Stone wrote:

How many people are in the study? Human chemistry is very complex. Some markers work well with some people and not so well with others.

On 2021-10-03 07:08:57, user kdrl nakle wrote:

Midwestern state? Write South Dakota, what is the point of obfuscation? A lot of stuff in this paper, nothing usable.

On 2021-10-14 09:10:21, user J Hung Tran wrote:

They just measured virus load/Ct at one timepoint, I wonder how the Ct value progress over the course of infection between groups?

On 2021-11-14 14:59:17, user Martin Jezierski wrote:

If they can't isolate/purify it, how can they determine 'viral load', or show any spread (especially in the asymptomatic)?

On 2021-09-03 11:19:28, user Sam Wheeler wrote:

I noticed the main author Naaber worked at Synlab Eesti. <br /> Do you still use the same IgG spike test for customers of Synlab Eesti and Synlab Finland? It is difficult for customers to interpret as the only information Synlab tells that the reference value is below 50 AU/mL. I was tested at Synlab and got about 6000 AU in June 2021 and about 4000 AU in August after two vaccinations and no covid-19 disease. Perhaps I should take a third dose already in September for maximum protection? I got my second dose in June.

On 2021-09-06 06:07:04, user William Brooks wrote:

The author estimates that Tokyo contains 6 infectious people for each person who tests PCR positive, which is probably an underestimate since the test positivity rate was over 20% during most of August. But even if the ratio is 6:1, this means Tokyo's infection fatality ratio outside of healthcare settings is below 0.01%, which hardly justifies the author's desire to search the city for health people who might have enough SARS-Cov2 DNA in their nose to return a positive result on a 40-cycle PCR test.

Also, the author seemingly doesn't know that the first three states of emergency (SoE) started after infections were already falling [1], making all three not just ineffective but also unnecessary. Overestimating the effects of non-pharmaceutical interventions, he calls for the government to copy policies that have failed throughout the world based on a superficial understanding of a few cherry-picked examples: Taiwan has has a 5.2% case fatality rate, so there are obviously a lot of infected people who don't get tested, while Australia and New Zealand are back in lockdown again after failing to "control the virus." Since there are more cost-effective pharmaceutical interventions for actual Covid patients, they should be prioritized.

[1] https://doi.org/10.1101/202...

On 2021-09-08 03:23:50, user Tim Hinchliff wrote:

This is such a great natural experiment to test lockdown efficacy. One wonders why it hasn't been published yet?

On 2021-09-10 07:18:16, user Michael Gardner wrote:

JimmyJoe6000, I have the same question. If you, or anyone else, has the answer please post it.

On 2021-09-10 18:07:48, user dm wrote:

After watching the delta varient spread effectively between vaccinated individuals it would be irresponsible to not cite the following from the study:

"This study has several limitations that must be considered. First, the study cohort size is small, thus making it hard to draw firm quantitative conclusions. Second, our study cohort is biased towards breakthrough infections that were detected in our on-campus screening programs (saliva-based RTqPCR at UIUC, nasal swab-based LAMP assay at NU). Finally, enrollment in this study concluded before the arrival of the Delta variant at either study site. It remains unclear how well the effects of vaccination on viral infection dynamics that we describe apply to Delta variant breakthrough infections, given the unique features12 and enhanced transmissibility13 of this variant relative to the viruses we captured here."

On 2021-11-30 12:53:37, user BSTL wrote:

This represents the first publication of data to support the use of closed system device components in pharmacy technical services such as dose banding in the UK where compliance with the NHS yellow cover document (YCD) guidelines is required.

On 2021-11-30 20:32:11, user Toa_Greening wrote:

Based upon MoH data 30/11/2021 Unvaccinated are 3.5x (8.21/2.35) likely to be hospitalised from a case of Covid not 25x.

No doses received prior to being reported as a case <br /> Cases 3518 Hospitalised 289 Hospitalisation rate 8.21%

Fully vaccinated at least 7 days before reported as a case <br /> Cases 1194 Hospitalised 28 Hospitalisation rate 2.35%

On 2021-12-01 11:23:59, user Drago Varsas wrote:

Common sense will do. "No matter the causes of death ( like being killed by a truck driving over you ) if covid ( a test run at 35-45 cycles never meant to be used for diagnostics ) it counts as covid" The test does not exclude other corona viruses or influenza and most people had serious chronic illnesses and died from them after a very questionable covid positive test. People will other illnesses were also falsely labeled as covid and not treated for their actual illness and often consequently died. It's a crime against humanity and no hair splitting talk will change this.

On 2021-12-01 21:39:22, user Heinrich Schweizer wrote:

The Title of this paper is very misleading. It is evident, and the authors explicitly state it in the discussion section that: (citation: "The analyses performed here represent model-based estimations that are limited by data quality..."). So I think the title would rather have to be formulated as a question than as the firm statement (lending itself to propagandistic abuse).

On 2021-12-01 22:33:29, user Volker wrote:

I estimate (from the text) that vaccinated individuals are involved in 5-6 out of 10 new infections. Which is more than half of all new infections. Seems not to be minor.<br /> Why is it not mentioned in the text ?!? Any reason, why this is not an important information, taken from the same graphics as the estimation about unvaccinated individuals ?!

The model used does not look like the real world in October and November. 2G, 3G, (no) testing have significantly different impact on the contact behaviour of vaccinated individuals, and even more on unvaccinated individuals. The contact model seems not to be realistic at all.

Is there any verification for the (contact) model with actual real data, instead of using static parameter for getting "some" results out of the model? How good (or bad) does the model match with the real world ? Do the results match anyway with increasing number of infected vaccinated individuals, and vaccinated individuals in hospitals ?

Looks like the model does not consider the absence of testing for vaccinated individuals, but this should have an impact on the number of known infections.

On 2021-12-02 12:45:22, user drummy_b wrote:

The Study worked with a effectiveness of the vaccines against <br /> transmission between 70% and 40%. Do we have any evidence for these <br /> assumptions? Furthermore, the effectiveness against transmission and <br /> against disease is not clearly separated in the text. The study should <br /> also provide a modelling with 0% effectiveness against transmission, <br /> then we could see, what matches best with the numbers we have in the real<br /> world.

On 2021-12-03 00:07:08, user Nils S wrote:

If it was true that unvaccinated were responsible for 90% of the infections, the incidences in Denmark would not be possible. Denmark’s share of unvaccinated in the population is roughly 1/3 lower compared to Germany. Following the results of the paper, the growth-rate in the exponential function for spreading the virus would be much smaller in DK, which would theoretically lead to much lower infections in DK compared to DE – if the analysis was correct.<br /> However, the incidences (7-day incidence per 100.000) in DE and DK started October 20th at the same level, close to 90. On November 28th Germany peaked with 482 while DK reached 505 and continued to increase. The Danish numbers do not fit to the results of this paper. The incidences should be much smaller due to higher vaccination rates in DK. Thus, the share of unvaccinated does not explain the growth of infections. It rather looks like, vaccinated and unvaccinated spread the virus similarly.<br /> I strongly recommend to test your hypothesis with data from other countries. And furthermore, I have strong concerns with respect to the RKI data used as input for your analysis. Due to the German regulations vaccinated do not test at all – except for a few exemptions. The entire data is heavily biased. UK for example provided much more reliable data. <br /> Best regards<br /> By the way, have a look at this Nature articel: <br /> https://www.nature.com/arti...

On 2021-12-04 10:54:27, user Martin Backhaus wrote:

Competing Interest Statement

The authors have declared no competing interest.

3 random checks on the authors and 3 times it is RKI staff. And no one identifies themselves.

• Benjamin Maier (Representative P4) - Employee at the RKI
• Marc Wiedermann - PostDoc / Data Scientist at RKI
• Mirjam Jenny - senior scientist of the science communication project group at the RKI

On 2022-03-20 18:28:48, user SB wrote:

First, in Table I there is an error for the RKI report of elderly. RKI printed 60.9 %!

On 2021-12-02 13:07:03, user Max Daigle wrote:

Is this Peer Reviewed?

On 2021-12-03 04:03:08, user Srinivasa Kakkilaya wrote:

This is completely misleading. There is no proof about the so called re-infections as being due to omicron variant, yet the authors seem to blame and speculate further that omicron is causing and can cause re-infections.

On 2021-12-21 00:17:11, user lbaustin wrote:

Were the "reinfections" in people who were symptomatic both times, or is it possible that one or both of the tests were false positives? It could well be that people are being tested more now, or that the cycle threshold has been raised, either of which results in more false positives.

On 2021-12-05 07:06:49, user Robert Thompson wrote:

This is another paper with undisclosed PCR Ct values. Diagnostic confidence is thus limited. There should also be some discussion of the kinetics of the serology tests- Nucleocapsid antibodies decay over time. There were a high number (12 of 20) apparently asymptomatic infections, but due to the assays used it would be difficult to identify those who had previous infection and recovery. As well, there is a time function, both seasonal and position in the epidemic wave, which complicates the analysis. A similar geographic uncertainty exists, as the timing of wave peaks varied through 2020 from region to region.

On 2021-12-05 14:19:41, user J Sato wrote:

Where can I see the hospitalization result by vaccination status for "Hospitalisation for COVID-19 was unchanged."?

On 2021-12-06 09:49:29, user Johan Auwerx wrote:

Interesting that you pull out ZIC1/4 as potential candidate genes for MSA. In our analysis focused on mouse aging, ZIC family members, in particular ZIC1, was also a top candidate involved in mediating age-associated changes in gene expression - see PMID 32997995 - Maroun Bou Sleiman & Johan Auwerx

On 2021-12-12 23:59:14, user tobydelamo wrote:

78% of cases were in males. As a trangender man, I own and recognize my responsibility to correct historical health inequities that favored men. I'm proud to be vaxxed and boosted, and I urge all men to do the same. Myocarditis is extremely rare. Folks, let's not use these few cases as an excuse to not get vaxxed and keep current with boosters.

On 2021-12-14 16:32:02, user Ole K. Fostad wrote:

What is the rationale for excluding 154 patients vaccinated with one dose <21 days before positive test? If they are hospitalized they shoud be counted as they have to be dealt with in the hospital-system too. There is no discussion nor justification for the exclution, it looks like this omission would result in survivorship bias.

On 2021-12-16 21:14:55, user Spaceman3 wrote:

What's with the P-value of 0.41 in Table 7? Isn't that the key data upon which the conclusions are drawn?

On 2021-12-17 11:01:11, user Ctina wrote:

Considering that those with natural immunity have antibodies against other proteins in the virus than just the spike, wouldn’t making conclusions on effectiveness of natural immunity on Omicron based on a pseudotype containing only the highly mutated spike protein be problematic?

On 2021-12-18 12:52:58, user DeshanPerera wrote:

Published version:<br /> https://journals.plos.org/p...

On 2021-12-24 17:48:21, user BernardP wrote:

Looking at the graphs, I see both vaccines lose all effectiveness at 90 days, but worse, actually drop into strong negative effectiveness after that time.

This would mean that these vaccines *increase* one's chances of infection after the initial 90 days "honeymoon" period.

Am I getting this right?

If so, why are governments pushing third doses as Omicron is becoming dominant?

On 2021-12-25 21:50:03, user Daniel Song wrote:

This is just a poor quality paper

On 2021-12-29 00:28:31, user madmathemagician wrote:

Why were Liechtenstein and Iceland excluded from the article? They're part of the ECDC dataset studied in the article. Such study should not exclude samples without appropriate motivation!

On 2021-12-30 12:02:04, user madmathemagician wrote:

Small whole numbers, like "daily new cases and deaths", can not even be expected to obey Benford's distribution.

Zeroes can even not occur in a Benford's distribution, but are numerous in the source data set.

On 2022-01-02 23:31:07, user Florian Binder wrote:

Very interesting hypotheses and analyses.<br /> Did you also check for an effect of absolute humidity?<br /> As the air is quickly warned up when breathed in, this might influence the amount of virus material breathed out.

On 2022-01-04 18:56:26, user Thomas Barlow wrote:

Did you account for pre-existing T-Cell immunity (pre-2020) which was known in 30 to 50% of the population in year 2020?<br /> Did you account for the fact that most people have had covid (most without even noticing) and will have developed T-Cell immunity naturally? How did you control for that? It's not a static measure and is more expressed and less expressed at different times of month, year.

Studies on INFECTION FATALITY RATE (IFR) - peer-reviewed studies [Studies conducted long before any vaccine] :

(notice the one confirmed for publication by the W.H.O. in September 2020 [published Oct. 2020] - A 0.23% IFR...about the same as flu).

MARCH 2021<br /> “the available evidence suggests average global IFR of ~0.15%”<br /> https://onlinelibrary.wiley...

FEB. 2021<br /> “The infection fatality rate for both the Bureau of Prisons and U.S. was 0.7%. Among institutions that tested >=85% of inmates, the combined infection fatality rate was 0.8%”<br /> https://www.ncbi.nlm.nih.go...

JAN 2021<br /> “The overall non-institutionalized IFR was 0.26%.”<br /> - https://www.acpjournals.org...

DEC 2020<br /> “This rate varied from place to place, with a lower range of 0.17% and a highest estimate of 1.7%.”<br /> https://www.sciencedirect.c...

DEC. 2020<br /> “Results show a fatality ratio of about 0.9%, which is lower than previous findings.”<br /> https://www.mdpi.com/1660-4...

NOV. 2020<br /> “The overall infection fatality risk was 0.8%”<br /> https://www.bmj.com/content...

NOV 2020<br /> “In the United States, COVID-19 now kills about 0.6% of people infected with the virus, compared with around 0.9% early in the pandemic, IHME Director Dr. Christopher Murray told Reuters.”<br /> https://www.reuters.com/art...

NOV. 2020<br /> “The estimated IFR was 0.36% (95% CI:[0.29%; 0.45%]) for the community and 0.35% [0.28%; 0.45%] when age-standardized to the population of the community.”<br /> https://www.nature.com/arti...

OCT 2020<br /> “We know that antibody tests are not perfect, and there may be a considerable number of people who do not mount a detectable antibody response to SARS-CoV-2. However, even when this uncertainty is taken into account, we still find that COVID-19 has a high fatality rate - on the order of 1% for a typical high-income country.”<br /> https://www.imperial.ac.uk/...

SEPT 2020<br /> The W.H.O. posted a heavily peer-reviewed & critiqued study from May 2020, showing the deaths per cases are 0.23% overall, and going up to 0.5% in the worst hit cities. 0.05% for under 70s - The W.H.O. reviewed it again, then published it in September:<br /> - https://www.who.int/bulleti...<br /> - https://apps.who.int/iris/h...

AUG 2020<br /> The medical journal 'Nature' had an analysis and stated that:<br /> "This result was used to calculate an overall IFR for England of 0.9%”<br /> https://www.nature.com/arti...<br /> ________________

On 2022-01-13 14:10:25, user Hans wrote:

Why is only the infectivity of the virus in droplets 5-10µm mearured? Droplets > 10 µm can stay in the air for minutes and contain (much) more virus..

On 2022-01-27 00:09:31, user Autofan1 wrote:

Something seems to be fundamentally wrong with this study - because empirical observations tell exactly the opposite story: much more people have been infected in low relative humidity environments.

The best examples are...<br /> 1) ...the large Covid-19 outbreaks in meat producing companies in Germany (cold and dry air = very low RH).

2) ...the typical spread of the annual flu virus, where most people are infected in spaces with dry air (offices, public transport...) which is dominant indoors during European winter time.

And vice versa the rate of infections in high humidity environments has been negligible.

E.g. public swimming halls and SPAs are high RH and no mass infection events have been recorded in these areas at all, although people are not wearing masks and are regularly talking to each other with little distance.

So either the interpretation of the measurements are wrong - or there is a mechanism in human air intake that causes low RH environments to be more infectious.

Since this study has the potential to influence the behaviour of a large population (with potentially negative consequences) it would be a good idea of the authors to once again verify the interpretation of their findings.

On 2022-01-14 21:37:58, user Rich Condit wrote:

Authors: Please include controls in which negative NP samples are spiked with different amounts of virus and processed for quantification of FFU. In this way you can determine a limit of detection for the assay, and report negatives as "less than xxx FFU/ml"

LIsten to TWiV 854.

On 2022-04-15 03:46:27, user the paper link wrote:

P values from multiple comparison post ANOVA, should be adjusted

On 2021-10-16 13:49:08, user crippapy wrote:

The high viral load of Delta makes it already very pathological if an unvaccinated person catches it and has that initial viral load they will feel sick, thus most likely isolate, mass vaccination leads to people carrying groundbreaking viral loads and asymptomatically spreading it. The suggestions you’re making are based on a narrow research, which in itself already doesn’t adequately support the idea of universal vaccination.

On 2021-10-22 04:59:41, user Dave wrote:

The conclusions do not support the results. Excluding patients with CT > 35 was done post-hoc and this subgroup analysis should be secondary to the ITT population when analyzing the primary endpoint. Twice as many patients in the control group were excluded based on this criteria than in the IVM group which means there is no favorable outcome on viral negativity when you look at all the randomized patients.

If you look at how the clinical trial was registered, there were many exclusion criteria but the CT > 35 for the first 2 tests were not one of them. It seems suspicious to me that the authors would come up with this arbitrary threshold, which conveniently resulted in a positive result. This doesn't make sense either because the authors mentioned 3 definitions of covid negativity: a CT > 30, CT > 35, and CT > 40. You would think that the authors would exclude patients with CT levels 31-35 if they would later define those patients as being covid-negative, but they did not for unknown reasons.

Finally, the diagnostic test the investigators used defined a negative covid test as CT > 40. Not 30 or 35 but 40. You can see this from the EUA documents the company submitted to the FDA. It's also important to understand that the diagnostic test was validated as a limit test, meaning that it could only precisely and accurately tell whether a sample was covid-positive or negative. The test could not accurately and precisely distinguish between a CT of 35 and a CT of 36.

Hopefully the authors will address these points during peer review.

On 2021-10-26 03:31:17, user Y S wrote:

I don’t understand: do they follow people vaccinated in February for the month of March, April etc. and compared with unvaccinated. Or make correlations with Cox method including people vaccinated in each month. In the latter case for vaccinated in March, outcome for people in April somehow has to be translated to the month of March, as the first month after vaccination?

On 2021-10-29 19:58:57, user Taylor wrote:

This paper was peer-reviewed and published in PLOS Medicine on 8/31/21: https://journals.plos.org/p...

NIH press release: https://www.nih.gov/news-events/news-releases/common-genetic-disorder-blood-test-reveals-when-benign-tumors-turn-cancerous

WUSTL press release: https://medicine.wustl.edu/news/liquid-biopsies-may-aid-diagnosis-treatment-of-bladder-nerve-tumors/

Journal commentary: https://journals.plos.org/p...

On 2021-11-03 00:28:57, user Josh wrote:

65% chance of ending up with at least one symptom of long Covid, and still rising significantly 6 months out? That seems extremely high. Is there a reason why the risk of developing long Covid appears so much higher in your study than in others, many of which report numbers in the 30-35% range? Also, is there a reason why your study shows virtually no reduction in the chances of developing long Covid in breakthrough vs. non-breakthrough cases, whereas an earlier British study shows a roughly 50% reduction?

On 2021-11-05 19:59:20, user Sergio Kas wrote:

So does this study say,

"Fully vaccinated were more likely than unvaccinated persons to be infected by variants carrying mutations"? Thats not good.

On 2021-11-06 19:21:58, user Eleutherodactylus Sciagraphus wrote:

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

References supporting this statement (both in English and in Portuguese):

https://brazilian.report/li...

https://www.emergency-live....

https://www.dire.it/14-10-2...

https://www.matinaljornalis...

https://g1.globo.com/rs/rio...

On 2021-11-15 08:01:21, user kdrl nakle wrote:

Interesting but your mothers in the sample are a bit older than usual "mother" population. How comes?

On 2021-11-15 21:17:25, user Mando Dido wrote:

This paper has been peer-reviewed and published now at;

https://www.mdpi.com/2076-3...

On 2021-11-18 19:38:56, user Fredrik Nyberg wrote:

Thank you for the comment!<br /> We state clearly already in the abstract that this is "...before the start of vaccinations" and specifically in 2020, which is before global and Swedish vaccinations started (some countries started in December 2020, Sweden had a handful of vaccinations in the last days of December 2020). So these obviously cannot be vaccine effects. Still, we can make it even more obvious in an extended updated version which we are working on.<br /> To be crystal clear - these rates are to show how common these conditions are WITHOUT vaccinations, so that in a world of vaccination it will become a little easier to evaluate if such conditions increase after vaccination or just occur as expected.

On 2021-11-23 11:21:00, user Zacharias Fögen wrote:

"Among fully vaccinated household contacts, the crude SAR was similar for fully vaccinated index cases compared to unvaccinated index cases (11% vs. 12%), but this was confounded by age of the index – both SAR and proportion of vaccinated index cases are higher in the oldest age groups (Supplementary Table S1)"

This is not counfounding. You are introducing a bias.<br /> Among age groups 50+, SAR between two vaccinated V-V (21.5%) is the same or less compared to U-V (22.22%, n.s.) or V-U (18.25%, n.s.) which clearly makes no sense if the vaccination had any benefit.<br /> There is an equal age distribution, about 10% over 75.<br /> (I used data from table S1).

Also, among age groups 30+, Vaccinated Index cases are significantly (p=0.01) less likely to infect an unvaccinated (12.55%) than a vaccinated person (18.15%) clearly indicating that a vaccinated person is more careful when interacting with an unvaccinated Person.

So, there is insufficient Control for confounding, as you did not control for risk avoiding behaviour. Risk Avoiding behaviour influences both likelihood of being vaccinated as well as compliance to social distancing and other infection-avoiding behaviour. So vaccinated people are less likely to be infected because they avoid it more through social distancing, which seems to decrease with age, as the analysis of age group 30+ and 50+ combined demonstrates.

On 2021-11-28 19:40:54, user Robert van Loo wrote:

44 relevant new variants up till now and on average some 2 per 10 million cases. Did we only see 220 million cases globally? I would think more with over 5 million deaths and an IFR of 0.6 %. I have papers and also WHO stating the reported 260 million cases is factors lower than the real number of infections. With over 5 million reported deaths and an IFR of 0.6 % the real number of infections would be over 800 million cases. The number of relevant new variants per 10 million cases would then be about 4 times lower. Of course if reported cases always underreport to the same extent the extrapolation of reported cases to new variants would not change. Still important to make the distinction as the underreporting factor is hugely variable.

On 2021-11-29 12:50:35, user Eleutherodactylus Sciagraphus wrote:

BMJ has further information regarding this case: https://www.bmj.com/content...

On 2021-11-29 13:55:01, user Valentin Klamka wrote:

I looked at "rem_burden_output.RDS" on your github. In the "S" column (which I think means suspectible?) there are zeros in some age groups for some countries. Is this intended? Looks like a bug. You should look into that, otherwise the plots in 3B are very misleading.

On 2021-05-25 20:30:08, user Marek J wrote:

You have wrong data in the mortality analysis for Niaee study. You swaped IVM for Control. According to the study, 4 deaths from 116 occured in IVM and 11/49 occured in Control.

Looking forward to your recalculation.

On 2020-04-23 14:14:16, user Pasquale Valente wrote:

How was the case of pneumonia defined?<br /> How was the causal link with SARS CoV-2 demonstrated?

On 2020-06-23 21:57:17, user Dr. D. Miyazawa MD wrote:

Please give me your opinion or point out any problems with this article.

On 2020-06-24 10:51:55, user Alev Kiziltas wrote:

Artificial intelligence has an important potential in healthcare. Not only the Dermatologist, all healthcare professionals can use TzancNet with less margin of error in the cytology of erosive-vesiculobullous diseases

On 2020-06-28 15:37:33, user Rakshanda Razi wrote:

TzanckNet seems like a promising tool for cost-effective diagnosis of erosive vesicobullous and granulomatous diseases.All the best to the researchers for their endeavours.

On 2020-06-26 08:49:57, user Christian Schultze-Florey wrote:

This article has been accepted for publication in EBioMedicine: https://info.thelancet.com/...

On 2020-06-27 10:57:04, user Filipe Pereira wrote:

Could be false positives. Some of the primers have similarities to the genome of other coronaviruses, which may be in circulation at the time.

http://covid.portugene.com/cgi-bin/COVid_primersandprobes_otherCoV.cgi

Could be contamination, it is crucial to sequence the amplicons to see which lineage was there (if any).

On 2021-12-22 16:54:13, user AndyUpNorth wrote:

Could there be a control population who were hospitalized for anything but COVID in order to rule out convalescence?

On 2020-06-28 15:15:20, user Norman wrote:

Thank you very much for your important article. There is an emerging “unseen “ epidemic of COVID-19 induced chronic fatigue syndrome. Do you have any information regarding this ?

On 2020-06-29 08:48:39, user Dr Mubarak Muhamed khan wrote:

RE: can creating new vaccine everytime is solution for new mutating viruses?

We published our view as e letter regarding old vaccine and it’s Possible use In present menace in science and C&E News<br /> Link:

https://science.sciencemag....

The e letter

(2 June 2020)<br /> Thank you very much for excellent update in new vaccines. We appreciate every efforts towards betterment of human life and fighting with new menace. Still Certain questions need to be asked while trying new vaccines everytime for Every new virus or any microbe mutation?<br /> Although we are Not immunologists, still certain questions haunts our mind. We hope that these queries and questions will ignite the minds of researchers and immunologists. With open minds we must ask these questions to ourselves in today’s tough time instead of getting rattled by situation<br /> 1. Does every new virus create specific antibodies? And for how long it works?<br /> 2. Is there any limit of immune response for any healthy Homo Sapien?<br /> 3. Whether body immune response of Homo Sapien get fatigued with every new challenges by new viruses?<br /> 4. Whether after multiple challenges by new viruses , body try saving Homo Sapien by cross immunity?<br /> 5. Although with new challenges by new virus, body may try responding by creating initial IgM .... And then IgG for certain time period, but whether memory is created for long time for such mutating viruses?<br /> 6. Why not to boost immunity with booster doses of existing vaccines and check cross immunity for fighting with new mutating viruses ?<br /> 7. When new vaccines are in development, why not to give a chance of revaccinations with existing proved vaccines (BCG, MMR, and many more) to masses??<br /> 8. Is there any harm in starting booster doses to children’s and adults of existing vaccines?<br /> 9. Till the new vaccines are developed for SARS Cov 2, good ample amount of time one will get to test boosting immunity with current vaccines and checking cross immunity for fighting corona?<br /> 10. We must continue searching new vaccines for every new virus. But what’s harm repurposing existing proved vaccine for strong cross immunity to neutralise many new menace?

Still Many more new mutated viruses will arrive and try to attack us in different ways in future. Why not to boost sustainable existing immunity with booster doses of existing well tested vaccines in vaccination programmes?

Sincere Regards<br /> Dr Mubarak khan<br /> Dr Sapna Parab<br /> Director & Consultant<br /> Sushrut ENT Hospital & Dr Khan’s Research Centre, Talegaon Danhade, Pune, India

On 2020-07-02 20:38:30, user Aiman Tulaimat wrote:

Another aspect of this study that I am still pondering is the decreasing response from high in ventilated patient, to moderate with some respiratory support, to none on no oxygen. Could the observed effect of dexa be limited to its ability to reduce ventilator induced lung injury (PMID: 27383928, PMID: 23451215, PMID: 24439582), especially that dexa is the least effective steroid in reversing the genetic activation in patients with viral pneumonia (https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.05.06.20076687v1.full.pdf)"). The study has not reported much of the ventilator data, particularly adherence with low tidal volume-low plateau pressure strategy.

Aiman Tulaimat<br /> Pulmonary, Critical Care, and Sleep Medicine<br /> Cook County Health<br /> Chicago, IL USA

On 2020-07-09 09:39:14, user ABCD2020 wrote:

Can Dexamethasone be used alongwith Remdesivir?

On 2020-04-12 12:44:15, user Clive Bates wrote:

Thank you for an extremely interesting and informative paper. I have a few suggestions about one aspect of the paper - tobacco use.

1. The paper alternates between use of 'smoking status' (the body) and 'tobacco use' (tables). It would be helpful to know which is appropriate and how the data on tobacco status was gathered. Tobacco use could include smokeless tobacco and, if FDA definitions are applied, it could include vaping.

2. The proportion of tobacco users assessed, hospitalised and developing critical conditions is substantially below the tobacco use prevalence for New York, even when age is considered. Is this worth mentioning?

3. The multivariate analysis shows an apparent protective effect against hospitalisation for current and former tobacco use as reported (OR = 0.71, 95% CI 0.57-0.87 p=0.001). This is a striking finding, but consistent with findings from CDC's summary of US data (MMWR (April 3, 2020 / 69(13);382–386)) and China (Farsalinos et al - pre-print) in which smoking appears to be underrepresented in the population with progression to more severe symptoms.

4. A weaker (non-significant) apparent protective effect of current or former tobacco use (OR = 0.89 95% CI 0.65-1.21, P=0.452) of was found in the progression from hospitalisation to critical condition. Hospitals generally impose smoking cessation and nicotine withdrawal at the point of hospitalisation.

5. Would it be possible for the authors to rerun the multivariate analysis with current tobacco use and former tobacco use as separate variables? It is possible that former use is masking a stronger effect from current use. Current and former tobacco use may have quite different effects on progression of the disease and former use can include people who quit smoking decades ago. The merging of current and former tobacco use may be obscuring valuable information in the data.

6. There are many possible explanations for an apparent protective effect. It is possible the tobacco use status has been underreported, or current and former users are overrepresented in the 'unknown' status. It is possible that patients fear disclosure of tobacco use will lead to discrimination in treatment or they may feel guilty about their 'contributory negligence'. However, it is also possible that there is a real protective effect from either smoking or nicotine use. This is not implausible: nicotine interacts with the same receptor that is responsible for development of the disease following exposure to the virus. This paper could yield useful supportive or falsifying insights into that hypothesis.

7. Even if such findings are disconcerting, we should be led by the data. It is not possible to rule out a protective effect at this point and this paper adds to the reasons to take the idea seriously. There could be significant implications for the population impact of COVID-19, implications for advice to tobacco users, and implications for practice in hospitals.

8. I have no conflicts of interest with respect to tobacco, nicotine or pharmaceutical industries.

On 2020-06-11 23:05:21, user hoipoloi wrote:

Why was the famotidine given in to the patients? If it was solely for treatment of acid/indigestion etc, have you ruled out the patients' physiological(digestive) makeup as the relevant factor ..... as opposed to the treatment of it?

On 2020-06-14 18:47:53, user Apratim Guha wrote:

k= p^{-1/2} is actually a very old and well known result. See Finucan (1964) or Samuels (1978).

On 2020-06-16 17:01:12, user Dr Jim Porter wrote:

Is there a fractal structure linking a "second wave" of spread with "second phase" of disease progression?

On 2020-06-17 16:13:35, user Naama Geva-Zatorsky wrote:

This paper is under review in Experimental Biology and Medicine

On 2020-04-16 01:21:40, user Bobenheimer wrote:

No more updates of the projections? Data tracking stops on 4/12.

On 2020-08-22 06:12:18, user Manal Said wrote:

It has been published in PLOS ONE:<br /> https://doi.org/10.1371/jou...

On 2020-08-25 16:15:15, user kagamiiii wrote:

Should have done leronlimab