On 2020-11-23 11:57:37, user Martin Kral wrote:

Will this method effect any of the antibodies that the immune may have developed. In other words, after the infection has subsided, will the natural immune system develop the necessary antibodies or will a vaccine still be necessary?

On 2020-12-01 22:15:47, user Pedro Emmanuel Alvarenga Ameri wrote:

Hello all, I just had a chance to read the preprint. The work is pretty cool. Im conducting an investigation to validate a few risk scores and Im interested to validate this one too at a Rio de Janeiro population. However, in order to do so, it would be necessary to have the model intercept in addition to the coefficients available at table 1. Additionally, it would be also necessary to have the predictors units not available in table 1, and the range of each predictor, to perform the same normalization informed at the methods section. Is it possible to inform these missing information? At last, the web calculator mentioned at the paper is an excellent way to show and use the results, however its web address is not informed in the manuscript. Where can I find this web calculator? Looking forward to see the final version of the manuscript. May the force be with you all.

On 2020-12-09 07:14:02, user JANAKI RAMANATHAN wrote:

this is interesting and is reinforcing the fact that the pandemic lockdown have created spaces for intervention of yoga therapy on digital spaces too. this is inevitable and may still continue even post covid i guess in different forms. pain is a corolllary in different spatial and socio economic and medical contexts.hope something substantial emerges

On 2020-12-12 04:13:41, user Hartmut Ziche wrote:

I am waiting impatiently for the publication of your second (late September/early October) seroprevalence study in French Guiana. I hope it confirms your model and possibly improves it's predictive capacity.

On 2020-12-14 15:13:45, user GH wrote:

The authors note that "The initial decrease in suicide rates during 1913-1918, with the lowest rate of 9.97 per 100 000 in 1918, was followed by an increase with the highest peak of 22.15 per 100 000 reached in 1970". Interestingly 1918 is the year before the spanish flu pandemic, and even more interestingly one of the mentioned peaks occurs in 1922 (15/100 000) (at the end of the pandemic). This is a 50% increase in 4 years, probably the biggest increase in the entire dataset. Doesn't this suggest a post/during-pandemic-effect at least for the spanish flu?

On 2020-12-17 23:14:59, user Rakshit Sidd wrote:

Hey Peter, Can you please let me know that which dataset you referred in to? I need the source.

On 2020-12-18 11:30:03, user Wendy Olsen wrote:

The paper is very useful.

It is informative about a free data source for India known as the covid19india website.

Since reading the paper, I explored this website. It has an API for data scientists to use the data. This paper by Vandana Tamraka, Ankita Srivastava, Mukesh C. Parmar, Sudheer Kumar Shukla, Shewli Shabnam, Bandita Boro, Apala Saha, Benjamin Debbarma, and Nandita Saikia is very useful in giving a summary of the age-sex-specific individual records in the database at a specific date in mid 2020. Since then, I believe the website Covid19india has now arranged to provide only District summaries which omits age-sex details.

The paper is also very useful in providing an analysis of cumulative cases, over time, from March to July 2020, with a spatial autocorrelation correction. This is impressive and helpful. On the other hand, the spatial autocorrelation variables are not causal mechanisms, and they can reduce the apparent impact of other variables that do represent background causes or events. Even so, apparently the social-group variables at the District level did have some correlation with the cases (ie with cumulative contagion) in the time-series model, even after the spatial correction.

I enjoyed the smoothly written conclusions of the paper.

Regards - Wendy Olsen - - @Sandhyamma is my Twitter name, or meet me alternatively using Facebook.

On 2020-12-20 22:03:54, user Sam Smith wrote:

Congratulations for publishing the research.<br /> Would any of the modern anti-allergy antihistamines probably work equally well? For example bilastine tablets? Then there is Azelastine nasal spray. So one could use both oral antihistamine and nasal antihistamine at the same time.<br /> And take it with famotidine = Pepcid of course.

On 2020-12-21 00:56:39, user RP Rannan-Eliya wrote:

These systematic review findings are largely consistent with the findings from our global ecological analysis of 172 territories just released in Health Affairs that controls for multiple interventions and factors during the first COVID-19 pandemic wave. The mask finding is buried in the paper, but when using daily mask usage as the intervention measure, we detected only a small beneficial impact of mask wearing, but it was not statistically significant.

RP Rannan-Eliya, N Wijemunige et al. 2021. Increased Intensity Of PCR Testing Reduced COVID-19 Transmission Within Countries During The First Pandemic Wave. Health Affairs.<br /> https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2020.01409

It seems very difficult to detect statistically significant benefits from mask wearing for COVID-19 in global analyses that adequately control for other interventions, suggesting that the benefit is likely to be small at population level. One possible reason is that this is because mask wearing in most contexts is only mandated outside the home, whilst most SARS-CoV-2 transmission occurs inside the home in most countries. Another could be that the transmission blocking is weak in practice owing to problems in how people wear masks, compliance, etc.

On 2020-12-27 18:54:51, user Travis Cesarone wrote:

This is odd, PN Medical has suggested cloth masks cause hyperventilation. <br /> This drastically lowers CO2, constricting blood vessels in the brain, leading to severe anxiety. N95s and surgical masks are associated with hypercapnia which can cause confusion and disorientation.

This should be interesting in peer-review.

https://www.pnmedical.com/b...

Individuals have a false sense of security that masks are protecting them. This 'security' has not been quantified in any study, so it is false. Therefore, there is a false increase in mental health due to a severe fear of the virus.

On 2020-12-28 08:48:28, user Disqus wrote:

The study design is somewhat confusing, a cross-sectional and prospective study that appears somewhat more similar to an ecological one than others. The authors crossed<br /> data from multiple sources including some known for their unreliability. Most surprising the authors states that they were unable to find a correlation between the opening of schools and the increase in Rt (par. "School closures did not alter the rate of Rt decline in Lombardy and Campania"), a statement that appears in stark contrast to the trend of Rt<br /> in Fig.6A and 6C showing a net increase after the opening of schools from an<br /> initial pre-opening value of approximately 1 for Lombardy and 1.5 for Campania,<br /> to a peak value of approximately 2.6 (Lombardy) and 1.9 (Campania).<br /> Curiously, the authors comment only on the descending part of the two curves but avoid<br /> commenting on the ascending phase following the opening of the schools.<br /> Finally, in spite of the medRxiv warning, one wonders why the authors decided to disseminate their unverified and not and not yest reviewed results, through the italian media (see for example the facebook pages of the authors for the links), suggesting the idea of a) somewhat solid and well establisehd general conclusions and b) the review process is a purely formal matter and not of substance.

On 2020-12-29 18:14:28, user Pablo Pablo wrote:

Students and young people are the same set , so this research shows that young people are safer than population.

By converse, teachers and people with age to work are not the same set, so this research shows that teachers are less safer than population.

On 2020-12-28 18:07:37, user Rogerio Atem wrote:

The 3 preprints of this series on COVID-19 epidemic cycles were <br /> condensed into a single article that summarizes our findings using the <br /> analytical framework we developed. The framework provides cycle pattern <br /> analysis, associated to the prediction of the number of cases, and <br /> calculation of the Rt (Effective Reproduction Number). In addition, it <br /> provides an analysis of the sub-notification impact estimates, a method <br /> for calculating the most likely Incubation Period, and a method for <br /> estimating the actual onset of the epidemic cycles.

We also offer an innovative model for estimating the "inventory" of infective people.

(Revised, not yet copy-edited)

https://doi.org/10.2196/22617

On 2020-12-29 15:21:15, user Claus R wrote:

Please make sure you review the Nov 5 Frontiers in Medicine commentary on the Flaxman paper, https://www.frontiersin.org.... In it, Kuhbandner & Homburg argue (for the UK) that Flaxman et al. ignored that R was already very low at the time when NPIs could have taken effect, something you seem to be confirming with your more extensive analysis here.

• Claus Rinner, Ryerson University, gis.blog.ryerson.ca

On 2021-01-15 21:12:09, user Florian wrote:

Hello, I can only tell it from an UK perspective, I think your hard date on Lockdown measures and that they only did apply on the date you mentioned is false. I recall in the week you are mentioning Social Distancing, I was cutting the business trip short to travel back home and from that point forward many people including me worked from home. Our client even sent everyone into the home office one week prior. Think this illustrates quite well that the policy wasn't in place the behaviour lol had to adapt a couple of weeks later was adapted by many at that point in time. So your interpretation of the data at least for parts of the UK where I can speak for is flawed.

On 2021-01-01 08:15:38, user Forrest Weghorst wrote:

Figure 7 would be more informative if the graphs showed symptom trajectories of Positive Tests vs. No Positive Tests (which is what all the statistical tests are comparing in the corresponding paragraph), not Positive Tests vs. Everyone (including Positive Tests).

On 2021-01-06 17:08:20, user Jeff Boris wrote:

I would be careful with your definition of POTS--it is not as rigorous as it should be. For adults, it really should be a relatively persistent increase of HR of at least 30 bpm in the first 10 minutes of standing after supine position, with symptoms of orthostatic intolerance, and with a history of symptoms for at least 3 to 6 months (depending on the reference). I do find the sex, race/ethnicity, and symptom distribution to be very similar to that of both our demographics article (Boris JR Cardiol Young 2018) and the Dysautonomia International-sponsored article (Shaw BH J Intern Med 2019).

On 2021-01-20 21:42:40, user Cort Johnson wrote:

Such close similarity to ME/CFS with some expected differences - such as shortness of breath, early fever, loss of taste and smell.Unrefreshing sleep and IBS-like symptoms are very common in ME/CFS and it might be useful to track those in future studies. Low body temperature has been reported for ME/CFS and it would be interesting to see if that shows up over time.

Very early studies of the ME/CFS or rather ME outbreaks described a heterogenous melange of symptoms specific to each outbreak which resolved into a familiar pattern of fatigue, cognitive problems, etc. The groundbreaking Dubbo studies demonstrated that a wide variety of infectious triggers can produce the same long term symptom set. The results, then, are not surprising but it is still startling to see them.

Congratulations Body Politic for getting this and the other study together. We are in your debt.

On 2021-01-06 09:58:19, user Martin Reijns wrote:

Many new variants of SARS-CoV-2 are now in circulation, including variants that are thought to have higher rates of transmission, such as B.1.1.7 (VOC-202012/01) first detected in the UK and 501_V2 first detected in South Africa. Some of the nucleotide changes impact on viral RNA detection by qRT-PCR (depending on the variant and on the assay used), with S and N gene assays affected most commonly.

Our N1E-RP and N2E-RP multiplex assays still detect all of the main reported variants, including: B.1.1.7, 501_V2, 20A.EU1 and 20A.EU2.

I put together an updated SnapGene file with primers and probes of commonly used qRT-PCR assays on the genome sequence of the original Wuhan-Hu-1 isolate, with mutations that occur in common variants indicated. This file can be found here:

https://www.researchgate.ne...

On 2021-01-06 18:36:37, user RT1C wrote:

In your discussion, I think you should distinguish between mechanisms proposed to work in vivo vs. those observed in vitro. For example, the high sugar concentration of honey may be antibacterial in in vitro tests/cultures, but when ingested, it will be diluted by other foods and liquids and irrelevant as a mechanism for antibacterial action. The same is true of the some the other suggested mechanisms.

On 2021-01-08 21:27:37, user Marek J wrote:

What type of honey was used? Was the cumin milled before use?

On 2021-01-07 14:02:12, user Meerwind7 wrote:

Household size (number of siblings) was not taken into account?<br /> If I understand correctly, the multi-variant analysis showed that population density has negligible, insignificant effect on its own, and what was perceived to be a density effect in the separate statistics for each veriable was just the result of positive correlation between social deprivation and density?<br /> It might be meaningful to perform multi-variable statistical tests once again for local prevalence, social deprivation and each of the other influences as third (possibly) independent variable.

Population density was just used as a digital property (less or above 500 /km2) in the multi-variable modeling, not the exact figure? <br /> As the density in built-up areas almost always exceeds 500 /km2 by far, it would appear to be more meaningful to distinguish at a higher cut-off level, for example >5000 /km2, which is more representative for multi-story housing. That will aso be representative for more extensive use of public transportation in the area other than for ways to school. It could also be plausible that quite low density leads to higher risk (due to longer distances to school spent in busses), and also high density, but medium density is associated with lower risks.<br /> The regional incidence seems to be taken into account with a logarithmic relation; I wonder if results would look different for a linear analysis.

On 2021-01-10 14:55:39, user Mmd wrote:

How Can I access the data?

On 2021-01-13 11:14:06, user Magnus Brink wrote:

Congratulations to a well conducted and highly interesting study. It seems out of doubt that IL-6 receptor inhibitors can save lives in covid-19. But what about time spent in the ICU? The headline in the prerelease by gov.uk reads: “NHS patients to receive life-saving COVID-19 treatments that could cut hospital time by 10 days”. I would say yes for saving lives but no for cutting time spent in ICU. Table 2 tell us that there are no differences in “Organ failure free days” (OSFD) in survivors; 14 days (IQR 7 to 17) for patients treated with tocilizumab compared to 13 days (IQR 4 to 17) for controls. The conclusion must be that tocilizumab will save lives but unfortunately not un-crowd our ICUs.

On 2021-01-15 10:11:06, user Martijn Weterings wrote:

This research shows an interesting significant difference between the groups. The contingency table <br /> 3, 2, 8, 1 <br /> 22, 23, 17, 24 <br /> is an indication for a significant dependency.

However this is likely caused by age differences (given the abundant information that indicates the relationship between age and risk of death). It is mostly the 3rd group with the highest number of deaths (8 deaths) and the highest estimated adjusted risk ratio (RR 2.18). This is also the group with the highest age.

It is very problematic that there is no clear dose response relationship.

Because this lack of a monotonic relationship between O3l and risk, it seems arbitrary to make a comparison between the 4th quartile and the first 3 quartiles. The observed effect is mainly due to the 3rd quartile having a high risk. One might just as well make a comparison between the 1st quartile and the last 3 quartiles and find a similar (though slightly less) significant result.

Besides other potential confounding variables it is the age distribution among the four quantiles which is remarkable and likely seems to be a strong influence on the statistical relationship. This means that the adjustment must be done with great care. I personally believe that currently the adjustment might be biased due to the binning of the continuous O3 levels into 4 quartiles and age might need to be included as a polynomial and not just a linear effect (it is actually unclear what sort of model has been used).

The problem with binning is that correlation between age and O3 levels might not be captured smoothly. The relationship is not linear (rather it is something exponential or logistic). For each increase 10 years increase in age there should be something like a 2 fold increase in risk of death (in this research the odds ratio is only 1.33 for a decade increase which is odd). This means that a group of 80 year olds and 60 year olds, with a mean of 70 years, are not comparable to a group of only 70 year olds. One might get peculiar results when the distribution of age in the different quartiles is not evenly distributed. (and possibly there could be some sort of Simpson's paradox due to the way that age is distributed within the 4 quartiles, if the 3rd quartile happens to have many people of 'very' old age then this might interact with the age effect, resulting in a reduced risk rate for the increase of age and an increased risk rate for the 3rd quartile)

I would suggest to provide a scatter plot of age versus O3l (along with some colour or markers for death vs no-death) which allows a more clear view of the structure in this data set and allows to see a more clear relationship with the O3l. It could also be interesting to see the output of a logistic model where O3l is treated as a continuous variable (potentially with some non-linear relationships like polynomials or interaction terms). Such a model would not have to treat the levels O3l levels as categorical, and would have less problems with non-homogeneous age distributions within the categories.

I would not be surprised to see some sort of clusters in the scatter plot of O3l versus age (and potentially deaths occur might occur more often in particular clusters). A more exploratory analysis of such structures might reveal more useful insights to generate hypotheses to be studied in future research.

On 2021-01-18 20:12:59, user ad4 wrote:

The authors state that "only national lockdown brought the reproduction number below 1 consistently". This appears true for the first lockdown (23 Mar), but I'm not sure the same claim can be made about the second lockdown (beginning 05 November). I would strongly suspect that if Figure 1I showed data for December and January, we would see an increase in R above 1, despite tiered lockdowns at the time.

On 2021-01-19 14:48:37, user Laura Green wrote:

The authors' inability to control for potentially important cofounders renders this paper's conclusions unreliable.

On 2021-01-19 21:13:39, user Richard Brown wrote:

Did the clinical data record the NSAID (particularly Ibuprofen and Naproxen) taken early (later less relevant). In our veterinary field early NSAID therapy (meloxicam, Flunixin, ketofen) is regarded as highly relevant in these situations.

On 2021-01-20 08:54:27, user Mariluz Boquera Ferrer wrote:

Congratulation from your work. <br /> Would you send an e.mail address from the corresponding author to ask you some questions regarding this article?

On 2021-01-22 14:40:19, user Tim Meyer wrote:

It is understandable that the issue of the Covid-19 incidence in football (soccer) players is of general (and scientific) interest. Also, it makes sense to compare this incidence to the general population of that age. However, such comparisons have to be made in a scientifically sound manner. One of such principles - also on pre-print servers or possibly even more so on such platforms which are not peer-reviewed in advance - is the meticulous description of the methods being used. Unfortunately, crucial information about this is lacking for the article from Andersen et al. entitled „Incidence and relative risk of infection with SARS-CoV-2 virus (Covid-19) in European soccer players“.

It is not described how the infection numbers for the 5 leagues have been obtained (i. e. uncertainty about the numerator for the incidence calculation). Also, we do not get sufficient information about how the (estimated) incidence in the general population has been assessed. In this regard, it is noteworthy that a frequently tested population like the one of the players potentially has a number of undetected infections close to zero. This is completely different in the general population where some studies point to numbers of undetected infections in the range of 75-90% with higher values in the young age groups where asymptomatic Covid-19 courses are more frequent. Due to the very short methods description it is not clear which calculations have been carried out for this study. Therefore, we have uncertainties about the numerators of both incidence calculations which makes results hard to interpret.

When we assume (in favour of the authors´ numbers) that the number of undetected infections has been taken into account appropriately by referring to an „infection fatality rate“ from a small area in Germany (a highly questionable method from our perspective) the message would be that hygiene protocols in Germany and England work well. However, studies based on procedures like the ones in this text appear methodologically unsound and should not be published – not even on pre-print servers. Even on such pre-print platforms more thorough descriptions as well as careful interpretations (including the limitations of one´s work) are needed because otherwise misinterpretations may enter the public domain.

Tim Meyer (Conflict of Interest: Chair of the German Task Force "Sports Medicine/Special Match Operations" which has been developing the hygiene protocol for the German football leagues; chair of the medical committees of the DFB and UEFA); Barbara Gärtner (Conflict of Interest: Member of the German Task Force "Sports Medicine/Special Match Operations" which has been developing the hygiene protocol for the German football leagues

On 2021-01-23 12:27:23, user Martin wrote:

Testing was forced and not voluntary. No ethical guidelines were followed. Slovak citizens were forced to go on testing sites to get tested otherwise they would get fine and can not go to job. Even prime minister Igor Matovic (who made people go to testing by force) said few weeks after testing in national TV, that testing was not voluntary.

There is a lot of sources online, even on Youtube (in Slovak language).

In these days, another forced testing is in progress with more severe penalties for people who not attend. For example - who did not attend this testing, from 27th January cant even go out to the nature alone (with no people around). Violation = 1000 eur fine (averege monthly salary in our country).

This goverment totally ignores rule of law and basic principles of law state.

On 2021-01-30 23:05:47, user disqus_uZtSLivn1O wrote:

CFR increases when the rate of unscreened infected individuals increases (you mention this yourself). The proportion of positive tests increased sharply in December; an indicator of a higher incidence of unreported cases. This is not an interesting finding in my opinion.

On 2021-02-07 11:26:26, user Luzia wrote:

Such precious excellent news! I am delighted that scientists are researching the benefits of natural remedies like propolis. This helps us to take more responsibility for our own health. Lets be grateful to the bees that they collect and process this natural substance and do all we can to protect them.

On 2021-02-15 13:07:34, user Guido wrote:

State, local governments & complicit media simply ignore this, as unions help shut down rank and file "health & Safety Committee" walkout/sickout strikes. Our Creative Class is speciously distracted by blatantly staged shock & awe by an autocratic duopoly as the most vulnerable are intentionally exposed to the mutated strains, before vaccination is properly evaluated.

On 2021-02-20 09:50:26, user Darren Brown; HIV Physiotherap wrote:

Thank you for this comprehensive study. In your methods you reference inclusion of 2 functioning/disability measurement tools; (a) World Health Organization Disability Assessment Schedule (WHODAS) 2.0; (b) Washington Group (WG) on Disability Statistics. Which WHODAS and WG questionnaires did you use as there are different versions? You have not reported any results from these measures of functioning/disability. Are you able to provide these results either in the main article or supplemental material, as they are very important data.

On 2021-03-04 05:40:34, user J Sato wrote:

I read this preprint paper and would like to ask if the authors can share the data of BCG vaccinated individuals and unvaccinated individuals.

I understand that this research divides the individual into BCG primed and control primed.<br /> I guess there are BCG vaccinated and unvaccinated individuals among both BCG primed and control primed groups.<br /> I would like to divide the individual into four groups; BCG primed & BCG vaccinated, BCG primed & BCG unvaccinated, control primed & BCG vaccinated, control primed & BCG unvaccinated.<br /> Can you share the data of those?

Kind regards,<br /> Jun Sato

On 2020-11-03 11:20:46, user Thomas de Broucker wrote:

one of my concerns is the validity of so little differences (although significant) of the SD values throughout the results knowing that the minimal pathological value admitted by neuropsychologists is -1,65 of the normal population tests results

On 2020-11-11 00:15:13, user kdrl nakle wrote:

This is not to be trusted, we have no idea how the patients were selected (if at all) for SORT <9 and >9 and there is no control group for either. For all we know the results could easily be because of the course of the disease than about remdesivir.

On 2020-11-18 16:11:06, user D Greenwood wrote:

Impressive work. But could the finding anti-S and NAbs declines faster in males than in females simply be regression to the mean? The conclusions sound like males end up with lower anti-S and NAbs than females, but the results you present do not show this - they show M3-6 results much the same for males and females. Maybe if you showed the full trajectory over all visits, and analysed these using multilevel models, this would give some support to your claim. As a second point, please update the manuscript to give all estimates and confidence intervals, regardless of statistical significance, e.g. table 2. This way policy makers can combine your results with those of others and you make a greater contribution to science.

On 2020-11-18 18:56:00, user Vincent wrote:

For the sake of science and public trust, it would be highly relevant that the authors of this study would do any of the following: 1) Withdraw their paper and address the comments below (that is the point of posting manuscripts to pre-print servers, allowing peer-review), 2) submit the manuscript to a peer-reviewed journal or 3) transparently state that their findings are erroneous due to errors in the analyses.

These actions would be important especially in the light new evidence (https://www.acpjournals.org... "https://www.acpjournals.org/doi/10.7326/M20-6817)") that, in line with previously conducted RCTs on other respiratory pathogens, shows that surgical facemasks are not effective (with 5% significance level) in preventing transmission to its wearer.

It simply cannot be acceptable that a study like the one by Ollila et al is published without peer-review, receives a lot of media attention, undermines the credibility of other researchers and then when confronted with criticism, no responses are given.

On 2021-05-28 15:56:20, user Paul Smeets wrote:

Impressive study that appears well done. However, I think the headline is overstated in the absence of information on which effect size of the 'brain health' measures is clinically/physiologically relevant; why couldn't there be a 'safe' level, like for many other substances? That might be below current recommendations but still... I.e., define 'safe' in this context. It would strengthen the paper and aid application of the outcomes in health policy if this, to my mind, crucial point were discussed.

On 2021-06-02 19:11:57, user Tim Winton wrote:

Would it be possible to have the Simulink and Matlab code + diagrams?

On 2021-06-03 01:36:26, user Ifonly wrote:

The count includes three outbreaks in Queensland. One was from a worker from a hotel, the other two were a doctor and nurse treating patients in hospital. Similarly, one case in NSW was a person transporting a patient to hospital. Regardless of where they are housed when they arrive, we can anticipate still needing to transport and treat the sick to hospitals.

I think it is reasonable to treat differently the best practice approach of current administrations and the the situation in Victoria at the beginning of hotel quarantine.

I believe Queensland had a policy of hospitalising all positive cases. From the Queensland experience, we can expect 2 breaches in hospital per 543 positive cases .37% or 1 in 271. It is not unreasonable to expect a similar figure for dedicated facilities.

In total there has been 3312 positive cases arrive in Australia (excluding the NT), From those there has been 14 breaches, 3 on the way to or in hospital, 2 in Victorian early days leaving 9 breaches for 3312 or .27% or 1 in 368. This of course is not entirely accurate as it includes the 543 in Queensland who spent part of their time in hotels before moving to hospital.

On 2021-06-07 20:43:55, user nicolasflamand wrote:

The data from this preprint has been peer reviewed and is now available under the form of a research article in the FASEB Journal. Link : https://faseb.onlinelibrary...

On 2021-06-09 12:56:25, user Tracii Kunkel wrote:

The key here - NOT PEER REVIEWED. It's been demonstrated that people who have been invfected have often changed their health-risk behaviors after recovery. How could the researchers have not assessed this factor? It's possible that the low rate of re-infection by those without the vaccine was heavily influenced by them taking precuautions much more seriously.

On 2021-06-18 15:27:12, user Matt Jolley wrote:

The study reports no reinfections. This recent UK PHE data shows 15,983 <br /> "possible reinfections". https://www.gov.uk/governme...

On 2021-06-22 21:23:31, user Jewbacca wrote:

FWIW, this was Israeli policy when we rolled out vaccines -- no vaccination for those previously infected and recovered --- as it was deemed both not needed and those that recovered from COVID were at somewhat higher risk of complications from the shot, such that the risk of side effects outweighed the risk of severe illness.

Glad you guys can catch up.

On 2021-06-10 09:09:08, user Mikko Heikkilä wrote:

The authors confirm in the Data Availability section that the data supporting the findings are available within the article. But in the article under the title Supplementary materials are mentioned R code for analysis and Values from original articles to use alongside the R code. These seem to be missing from the article nor there is a link to them on this preprint server.<br /> Would you please clarify and/or supply the material so that the Adjusted OR values can be verified?

On 2021-06-11 09:52:46, user Schupp wrote:

Over 56% of the test candidates involved had been vaccinated with BCG 12 months previously.<br /> Unfortunately, it is not clear from the study what the distribution of the reduced immune response to the previous vaccination is.<br /> A reduced response of the toll like receptors is even desired on certain time!<br /> For this reason it would be interesting, how it looks 2 or 3 months after the 2nd vaccination?<br /> Unfortunately, there is no data on this either.<br /> Therefore, as an absolute layman, I can not classify this study as very questionable.

On 2021-09-08 04:46:33, user Anni wrote:

Quite normal for any vaccine to affect immune responses to unrelated pathogens <br /> https://www.sciencedirect.c...<br /> ... not a bad thing, and Comirnaty has been shown to activate antibodies from past viral infections, all good signs.

Also, Don't forget to check the conflict of interest statement of the study we are commenting on.

The employer, "Trained Therapeutix and Discovery", with the motto "Don't fight the wave, ride it"!! is advertising their treatments to "dampen the ruinous hyperinflammation" in severely ill, hospitalized COVID patients.

It's clearly in their interest to reduce confidence in vaccines, as vaccinated individuals seldom need their treatments, vaccination mostly prevent the aforesaid ruinous hyperinflammation issue ...

Personally, unless you are a pharmaceutical company poised to profit off severely ill covid patients, I'd strongly suggest fighting the wave of infections with a good vaccine.

On 2021-06-11 18:53:43, user SemperCogitens wrote:

A couple of things people really need to note here:<br /> 1) This is PRE-publication. It hasn't been peer-reviewed. Everything on this website is such. It cannot be regarded the same as something which has gone through the full process with a respected journal.<br /> 2) This is an observational study (retrospective cohort). It is NOT a randomized, placebo-controlled clinical trial. Only the RCT can prove causation. This is hypothesis-generating research only. It does not PROVE HCQ works, merely suggests that.

3) If you dig in a bit, they define "treatment" to include only 37 of the advertised 250ish patients in the cohort, specifically those receiving >3,000mg HCQ and >1g azithromycin. Small sample sizes should always be viewed with extreme skepticism. Less than 30ish and your p-value is essentially meaningless.

4) The overall mortality rate of the total group was ~80%! These people were old, unhealthy to begin with, admitted to the hospital after nearly a week of progressing symptoms, required ICU care, intubation, and mechanical ventilation. These were very sick patients.

5) Clinically, we see a pattern for the treatment of ARDS and secondary pneumonia, not COVID. High dose corticosteroids work (we know this for ARDS), tocilizumab, a potent anti-inflammatory works (we have some data for this in ARDS as well). And azithromycin is a very common drug to treat bacterial pneumonias that often pop up secondary to lung disease like this.

So, please avoid jumping to unsupported conclusions. If we want real answers, we have to keep our skepticism, and be very careful in our analysis. The key here is we need corroborating studies. An April 2020 study at the VA showed exactly the opposite effect of HCQ in a similar patient population (though the VA obviously serves more males).

On 2021-06-12 06:21:09, user Maksim wrote:

By now the manuscript has been reviewed by three reviewers in two different journals. Opinion of one reviewer is mostly positive, two reviewers are very skeptical regarding methodological approach (per se) used in the manuscript. Regarding this skepticism I would like to mention that while ecological studies do have limitations, these are considered as useful and widely used in the field, in particular in relation to COVD-19 (e.g., Escobar et al., 2020 PNAS, https://www.pnas.org/conten... Urashima et al., 2020 IJERPH https://www.mdpi.com/1660-4... "https://www.mdpi.com/1660-4601/17/15/5589)").

On 2021-06-13 18:06:46, user Tough Love 2019 wrote:

This study confirms what people with a modicum of common sense already know: that, with very few exceptions, only those who ignorantly and stubbornly resist getting vaccinated are ending up in the ICU with COVID-19. At this point in the United States only those who don't want to avoid becoming gravely ill or dying of COVID will in fact get sick and die from it. In effect, getting sick with COVID, once a fate at least partially beyond one's control, is now a matter of personal choice, except for those with compromised immune systems that don't respond normally to vaccines. The United States now must avoid hoarding tens of millions of vaccine doses for those who haven't wanted them during the months that they have been available. It is morally imperative to make these vaccine doses available to poor countries where lots of people want to protect themselves from COVID but are unable to because of the lack of vaccines there.

On 2021-06-15 22:10:30, user Maurizio Rainisio wrote:

A major confounding factor, the referendum vote held on September 20-21 is dismissed as irrelevant. The voting sections were attended by 25 millions people, 57 % of those having the right to vote. Using the voting date in place of school opening in table 1 one can see a much better link, an average distance of a very reasonable 10 days and a much smaller variability, 16 of 21 regions being in the range 6-16 days.

Using the Google mobility estimate to measure workers' mobility is indeed inappropriate as in Italy most workers use public transportation that is not caught by Google, but this cannot justify the dismissal of the this covariate

Such a relevant policy decision like schools' closure deserves at least some confirmation. This is not provided by Sebastiani et al with their indeed poor paper, nor by some sensitivity analysis that could be performed by means of alternative methodology (eg by a deeper analysis of derivatives of the epidemic trendline that might help to better position inflexion points) or by by analyzing other similar events (eg the opposite event at the time of high schools closure in November or the school reopening in April).

On 2021-06-16 22:10:09, user Alberto wrote:

What the figures show is not well explained in the abstract or the text itself. Basically they show that people who were previously infected had a level of antibodies at baseline (prior to vaccination) which is roughly equal to those not previously infected after two doses. After one dose, they exceed that level.

Furthermore it also shows that most of the persons not previously infected don't benefit from a second dose, since the average is roughly the same after one and two doses. Only a small subset of the subjects seem to get some benefit from a second dose.

Therefor, it seems a more logical conclusion that persons previously infected should not need to take the vaccine and that people previously infected should take just one dose (with a few exceptions).

Always remember that in medicine, when you need to take something you should take it. But when you don't need to take it, you shouldn't take it.

On 2021-06-19 22:08:03, user Nabin Shrestha wrote:

The method used to calculate the vaccine effectiveness in this study was the same as in prior publications on the subject, including the Moderna and Pfizer vaccine efficacy studies published in the New England Journal of Medicine and the Astra-Zeneca vaccine efficacy study published in the Lancet. Are you saying that all these analyses were flawed? If so, you should specify exactly how you would do the calculation. Saying "Therefore the analysis is flawed" is not helpful feedback.

On 2021-06-19 22:33:09, user Mazda Sabouri wrote:

My initial thought is that the test group might possibly suffer from a bias towards having other non-Covid issues. While those infections detected through the REACT study were chosen at random, those detected through hospital and clinic data, including the asymptomatics, would have had a much higher likelihood of having other non-Covid issues when testing positive for Covid.

I would personally isolate out the infected who were detected through the REACT study and compare their aggregate results to the control group. Even then it's possible that the infected group might still be more prone to having non-Covid issues, but this bias would be much less pronounced.

On 2021-06-20 14:25:52, user Ricardo S R wrote:

Do you have data on which patients had anosmia? Since the primary olfactory cortex is involved, would be interesting to know if this volume loss is related to plasticity/wallerian degeneration-like phenomena.

On 2021-06-20 12:02:21, user ThaomasH wrote:

1. I wish the results were translated into unites that would permit estimation of the benefits of mask-wearing in terms of days of sickness and death.
2. I wish the results spoke to the issue of benefits to the wearer vs benefits to others.
3. I do understand the conclusion that mandates had zero effect on mask wearing.

On 2021-06-21 01:41:23, user Downtown-Pete wrote:

Just one question about this statement in your"Materials&Methods": .."between November 1, 2020 and March 5, 2020.." : I assume you mean March 2021? <br /> It would make a difference, if the statement as currently written (March 2020)<br /> is indeed correct.

On 2021-06-22 02:05:29, user GDY AirTech Enterprises wrote:

With recent developments in what we know about the current pandemic, information about the effectivity of air conditioning and ventilation systems are important. Easy access to papers like this is important for the sake of scientists and citizens alike. Knowledge should be accessible.

On 2021-06-22 12:20:41, user PattonWasRight wrote:

Is this a concern now? The CDC is now recommending a lower PCR threshold for testing vaccinated patients. Are vaccinated patients showing less or more severe symptoms than unvaccinated patients with VOC infections? If vaccinated patients are showing less symptoms, then there’s risk here as the entire world is operating under the idea that vaccinated persons can travel freely (air travel) while while unvaccinated cannot.

I’m seeing a scenario where vaccinated are more likely to be spreading more virulent strains - especially if the vaccine keeps them from developing more severe symptoms and the new lower CDC threshold is missing positive cases -although I think the lower threshold should have been used this entire time because of false positives (false negatives are probably more rare).

On 2021-06-22 15:51:54, user Amit Kumar wrote:

The paper has been accepted in Journal of Industrial Textiles.

On 2021-06-30 07:27:50, user AF wrote:

Also, neither loss of taste or loss of smell (both also mentally extremely burdensome symptoms) were not accounted for, although the prevalence of this symptoms is in the top 10 symptoms in the ONS study (https://www.ons.gov.uk/peop... "https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/4june2021)")

On 2021-07-01 12:29:35, user ad4 wrote:

Very interesting study.

One thing that must be considered is whether passports/certificates will push groups in high outbreak probability regions further away from vaccinating. That seems to be the case for the UK: see below for a study I recently conducted in the UK.

https://www.medrxiv.org/con...

On 2021-07-01 15:31:12, user David Gurwitz wrote:

This study may potentially allow better prognostics in Covid-19. If validated by further studies, it may even indicate that clinical trials of testosterone supplementation in male Covid-19 patients with low serum testosterone levels are warranted.

A recent study by Peruzzo et al. 2021 (Front Pharmacol. 2021 May 13;12:683529), titled “Synergy Between Vitamin D and Sex Hormones in Respiratory Functionality of Patients Affected by COVID-19” seems supportive for this preprint (and should be cited by the preprint authors). Peruzzo et al. observed “a significantly positive correlation between 17?-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men”. As Vitamin D is a well-established immune enhancer, it could be that the positive effects of higher serum testosterone reported in this preprint reflect higher serum vitamin D. This aspect of their findings should be examined.

The authors of this preprint discuss the role of hyper-coagulation in severe Covid-19 as a key risk for fatal outcome. In this context, it is noteworthy that a recent meta-analysis of 13 clinical trials (Ayele et al. 2021; Thrombosis Research; PMID: 33486321) indicated that testosterone replacement therapy in men was not associated with increased risk of venous thromboembolism.

Taken together, the authors suggestions that testosterone may be beneficial for male Covid-19 patients with low serum testosterone definitely warrants further research.

David Gurwitz, Faculty of Medicine, Tel Aviv University, Israel

On 2021-07-02 16:40:01, user Andrew Carey wrote:

a healthful plant-based diet score<br /> I read the text and couldn't find any further information about what this meant. There is much discussion of hPDI on the internet, but no publicly available calculator for it, and now I learn that there are a number of ways of working out a score for this and your team of researchers has chosen one of them based on your choice of phrase.<br /> I'm being harsh but unless this diet scoring system chosen was declared in advance of or independently of collecting the data, then this does not deserve to pass peer review.<br /> Make it public please.

On 2021-07-05 12:11:26, user Meerwind7 wrote:

Data from the US in 2020 showed a clear increase of cases in the southern states during summer, i.e. when and where air conditioning was the most widespread. After the summer heat, cases started to increase from North to South. Therefore, it seems quite obvious to me that air exchange is the main culprit of temperature- or weather-related changes.

Too complicated: "A further complication is that temperature, humidity, and UV radiation plausibly affect transmission and incidence through a range of biological and epidemiological mechanisms"

My theory could be further assessed by looking at regions or in sociological groups where installations of air conditioning are less widespread, so that people spend more time with open windows or outdoors in summer. A heatwave in temperate Europe (where air conditioning is rare in residential buildings) or in poor quarters of the US thus should not lead to increased infections, while a heat wave in US suburbs with widespread availability of air conditioning would have that effect (as long as people do not met outdoors anyway, in consideration of Covid-19). In southern Europe, air conditioning may be more widespread in urban centers, whih form heat islands, than in rural areas, so that would also drive differences,

On 2021-07-06 06:18:28, user Pavel Nesmiyanov wrote:

This is a one of the first articles providing direct link between quantitative IgG assay results and risk of disease. However, given the limited applicability (only one vaccine studied, wide confidence intervals, limited time frames, limited vaccine effectiveness) the results should be interpreted with a high degree of caution to avoid excessive antibody test prescription. Results of these test could provide a false sense of security in some patients or, vice versa, a false sense of low vaccine effectiveness.

On 2021-07-07 00:18:31, user itellu3times wrote:

For gosh sakes please mention the size of the current standard dose! Current standard for Moderna is 100 micrograms, study here is 25 micrograms? In both cases, two doses.

On 2021-07-09 08:48:07, user JN wrote:

"We defined admissions resulting in death as the last admission for each CYP that occur within 28 days of death identified through ONS or NCMD. "

ONS puts no such 28-day limit on deaths involving Covid (or any condition) so why does the study?

On 2021-07-10 05:28:04, user Cmharper wrote:

So would the likelihood of having or not having loss of taste and smell be a genre of mutation or an inheritable trait - if it is through inheritance, and if the referenced ‘p’ value is the likelihood of having loss of taste and smell, what is the difference in the ‘p’ value and the ‘q’ value for the recessive phenotype?

On 2021-07-14 02:01:48, user Direk Limmathurotsakul wrote:

The manuscript has been peer-reviewed and is now published at PLoS NTD. https://doi.org/10.1371/jou...

On 2021-07-21 20:55:48, user Meditate wrote:

Is anyone able to share what time period this study covered, I notice that the median followup was 258 days, and from the supplementary data. the serosurvey they are talking about is the one performed in August 2020. When did the study followup period end? April-May 2021? If this covered a reasonable time period of the second wave in Odisha, this would be great news for immunity against Delta.

On 2021-07-27 10:22:10, user Colin_Brown wrote:

Striking confirmation of 2020 OCT:<br /> "The use of Indomethacin… in hospitalised Covid-19 patients, was associated with marked symptomatic relief... There were no adverse effects. <br /> Indomethacin, instead of paracetamol, should be a preferred drug for the treatment of SARS-CoV-2”

On 2021-07-27 14:19:13, user Marco Biraghi wrote:

I think there's a mistake in the year: <br /> (data were collected in the period September 1st-November 30 2021).

On 2022-10-26 14:42:42, user Barbara Arch wrote:

Following peer review, the results and conclusions presented in this paper are currently under review. Further analysis is being undertaken and we will update the paper on completion of this additional work. <br /> Barbara Arch (lead author) & Prof MG Semple (Senior author and Study Sponsor CI)

On 2022-11-14 11:51:31, user Baral Nischit wrote:

The full manuscript is published and the PMCID is PMC9620387

On 2020-07-16 20:57:09, user Kate Webb wrote:

Really interesting- are the samples from MIS-C all before IVIG?

On 2020-07-18 17:50:20, user Matthew Almario wrote:

Who is the manufacturer of the UV light?

On 2023-05-15 01:46:49, user japhetk wrote:

This report is being used to promote the anti-vaccine movement.<br /> If the actual content is certain, it is indeed a concern and should be reported, but this study shows serious concerns.

First, this study does not take into account the number of tests. Given that the relationship between the number of vaccinations and the number of tests has been reported in many areas, this is the most serious flaw in this type of study and should be noted.<br /> Second, the results in Figure 2, which anti-vaccine activists focus on, is an inappropriate analysis that, as far as the methodology is concerned, only excludes uninfected persons from the unvaccinated population. We point out that this is one of the most serious problem of the study where the intent is clear and inappropriate.<br /> Furthermore, it is an attempt to statistically separate the effect of vaccination from the effect of previous infection, but this is not an appropriate method because many studies have reported that hybrid immunization does not show additive effects.<br /> The analysis in Figure 2 should have taken into account the history of infection and vaccination in the analysis comparing those with and without bivalent booster vaccination, but there should be no bivalent booster vaccination among the unvaccinated, which means that certain variables occurred only in one group. In this sense, this analysis is inappropriate.<br /> The raw data should be presented to show how many positives occurred among the unvaccinated, 3-dose uninfected, unvaccinated infected, 3-dose infected, etc. during the study period.<br /> Finally, this study cites a study that is convenient for cherry-picking and does not control for the number of tests, but the effect of vaccination history during this period is<br /> reported in Korea, Singapore, Japan, Luxembourg, and elsewhere, consistently contradicting the authors' results. The author's study is also inconsistent with the number of positive vaccine reports from Washington State and the CDC, which likewise do not take into account the number of tests.<br /> Bejko, Dritan, et al. "Effects of bivalent Omicron-containing vaccine boosters and prior infection against SARS-CoV-2 Omicron infections in Luxembourg, September-December 2022." Population Medicine 5.Supplement (2023).<br /> Tay, Matthew Zirui, et al. "Heterologous mRNA vaccine boosters induce a stronger and longer-lasting antibody response against Omicron XBB variant." The Lancet Regional Health–Western Pacific 33 (2023).<br /> Jang, Eun Jung, et al. "Estimated Effectiveness of Prior SARS-CoV-2 BA. 1 or BA. 2 Infection and Booster Vaccination Against Omicron BA. 5 Subvariant Infection." JAMA Network Open 6.3 (2023): e232578-e232578.<br /> https://covid.cdc.gov/covid...

All of the above make this study problematic and raise the concerns of improper statistical analysis for use in the anti-vaccine movement. We request that raw data by number of vaccinations and number of previous infections be presented. The study appears to have been published in a low impact factor journal, and if there is data on number of tests, that should also be presented.

On 2023-06-07 15:49:25, user Donald R. Forsdyke wrote:

These results are supported by a case history currently available at the Qeios preprint server<br /> Preprint

On 2023-06-20 09:28:49, user Matt Hodgkinson wrote:

The problem with this study, as others have noted on PubPeer, is that the authors are proposing a heuristic for identifying paper mill articles that fails under closer examination.

Prof Gigerenzer works on 'simple heuristics' and 'gut feelings' as a good approach to being smart: it seems that the authors thought this assessment was 'good enough' without thinking through the consequences of labelling so many authors as having committed misconduct with the wave of a hand.

It is possible that some journal editors will adopt such crude screening techniques and reject submissions that lack institutional email addresses and international authors, putting a further barrier in the way of authors from lower-income countries - and incentivising gift authorship. This would go against the spirit of the recent World Conferences on Research Integrity (WCRI) Cape Town Statement, including that "Barriers to ‘open science’ participation by researchers working in low-resource settings need to be identified and addressed by publishers, and other appropriate national and global stakeholders, such as science councils, funders, and similar institutions."

On 2024-01-05 11:17:42, user William Cawthorn wrote:

The peer-reviewed manuscript based on this preprint has now been published here: https://doi.org/10.1016/j.c...

On 2020-06-14 16:39:26, user David Curtis wrote:

It is very important to realise that this is not a study of patients with COVID-19 - it is a study of patients who are hospitalised with COVID-19. Only a small fraction of patients with COVID-19 are hospitalised so this may be telling us something important about who ends up being hospitalised. You have this sentence: "Some researchers have postulated that ethnicity may be associated with decreased symptom recognition and poor health literacy resulting in delayed presentation for care-something that could contribute to the greater illness-severity we observed(30). " I would like to see much more attention devoted to this and related topics. What your data seem to show is that, of patients admitted with COVID-19, BAME patients are more likely to require ICU admission and are more likely to die. So an obvious question arises. Are BAME patients more unwell when they are admitted? Or, are white and BAME patients fairly similar at the time of admission but then the BAME patients are more likely to deteriorate? I do not see anything in your data which clearly answers this question. I feel that some aspects of the clinical assessment on admission would illuminate this but I don't know how easy it is to pull them out from the ECR.

To be blunt, let me state why I see this as an important issue. If BAME patients are more unwell when they are admitted then it points to problems with ensuring fair and equitable access to health interventions, here admission. You suggest that the fault might lie with the patients themselves - that their poor health literacy might result in delayed presentation. Maybe. But maybe this is victim-blaming. Maybe there are issues in the way healthcare is delivered and decisions about admission are made which make it harder for BAME people to get into hospital. I am not suggesting any deliberate racism on the part of health care professionals (though we should not completely discount this possibility). However we could consider that the way the gate-keeping around access to in-patient care is implemented results in a system which de facto disadvantages BAME patients. Obvious issues would be around language and ability to negotiate the 111 system. Perhaps there are issues with differential quality of services in primary care and the practices which BAME patients tend to be registered with. Perhaps there are communications issues with ambulance staff and 111 staff who are very influential regarding whether and when a patient gets to hospital to be assessed for admission.

This is a critical issue for our society and I hope you can somehow use the data you have to explore it. Have we created a system where it is harder for BAME patients to be admitted than white patients?

On 2020-06-17 11:54:35, user Dr. D. Miyazawa MD wrote:

Possible reason for why in multivariable analysis with BMI >=30, diabetes, hypertension, was outside the limits of standard statistical significance in Black patients.<br /> Obesity correlates with hypertension, diabetes, and is more prevalent in Black people.<br /> https://doi.org/10.22541/au...

On 2020-04-28 15:32:51, user Sinai Immunol Review Project wrote:

Main findings<br /> In this manuscript, the authors describe direct complement system activation through the SARS-CoV-2-N-protein as a common denominator of coronavirus-induced lung injury.

The authors refer to previous evidence on SARS-CoV and MERS-CoV in which they showed that the nucleocapsid (N-) protein binds to a variant of MBL-associated serine protease-2 (MASP-2) that under physiologic conditions initiates the lectin pathway of the complement cascade. The authors hypothesized that SARS-CoV-2 activates the complement cascade in severely ill patients through viral N-protein-mediated dimerization and activating auto-cleavage of MASP-2 leading to respiratory failure in some patients.

Following confirmation of MASP-2 binding to the N protein of SARS-CoV, MERS-CoV and SARS-CoV2, the authors show that MASP-2/MBL binding is enhanced and subsequently demonstrate enhanced complement activation in vitro as measured by C4b deposition in a complement deposition assay and enhanced phagocyte activity. Translating these findings into an in vivo model, the authors pre-infected mice with an adenovirus expressing SARS CoV, MERS-CoV and control virus and challenged the animals with LPS to activate the lectin pathway. This effect was abolished when the N-protein was truncated or anti-MASP-2 antibodies or C1 esterase inhibitor (dissociates MASP from MBL) were used. In mice infected with SARS- or MERS-CoV, the authors found significantly higher C4b and C4 deposits in the lungs and showed tremendously worse survival. However, when MASP-2 knockout mice were challenged with the above-mentioned viruses (or C1 esterase inhibitor given), survival was substantially better as compared to virus-infected wildtype mice.

The authors next analyzed lung tissues from deceased COVID-19 patients and found strong IHC stainings of complement components. In the final step, the authors treated two critically ill COVID-19 patients with a monoclonal antibody that binds C5a (differs from the C5 convertase inhibitor eculizumab) as a part of a clinical trial. Both patients showed clinical improvement of their severe pneumoniae.

Limitations<br /> The question if and in how far coronaviruses are capable of activating the complement system has been controversial so far with conflicting data published.

However, the authors performed a thorough and convincing analysis with well-designed in vitro an in vivo experiments showing the ability of the nucleocapsid to enhance MBL initiated complement activation.

The authors performed key experiments using adenoviruses only containing SARS-CoV and MERS-CoV but not SARS-CoV-2. While the assumption that due to the high sequence homology in the N-protein-binding motif and the proven binding of the SARS-CoV-2 N-protein to MASP-2 strongly suggests that the N-protein in SARS-CoV-2 also plays a major role in complement activation in vivo remains to be proven.

MBL induced complement activation is likely to increase C3a and C3b formation as well as C5a and MAC complex deposition. The finding that anti C5a has some clinical benefit is of interest but does not directly support the MBL mechanism shown here (C5a production could occur via alternative or classical pathway activation)

Significance<br /> Anti-inflammatory treatment in patients with severe viral pneumonia is established as a clinical standard procedure. However, most pathophysiologic aspects of immune hyperreactivity in these patients remains unclear. The study reviewed here shows one mechanism by which coronaviruses activate the complement cascade causing or at least aggravating inflammation in the lung. Showing the successful treatment of two patients with a anti-C5a mAb (not available in the US) is promising and supportive of ongoing or planned trials of a cyclic peptide C3 inhibitor or a C5 convertase inhibiting monoclonal antibody (eculizumab) in severely ill COVID-19 patients.

Reviewed by C. Matthias Wilk, MD as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai. Edited by Professor P. S. Heeger, MD

References:<br /> doi: 10.1038/emi.2015.28. Epub 2015 May 6.<br /> doi: 10.1128/mBio.01753-18

On 2025-02-15 00:44:43, user HLA.Fan wrote:

The authors should not make up nomenclatures for discussing HLA alleles. "HLA-DQB1*57" is not a valid way of describing variation at amino acid position 57 of the DQB1 gene. Similarly, "DRB1*13", confuses the appropriate 1-field descriptor for all DRB1*13 alleles with variation at amino acid position 13 of the DRB1 gene. No where in this preprint do the actual amino-acid variants seem to be discussed.

Further, the authors refer to "two- and four-digit HLA alleles". The digit-based HLA nomenclature has not been in use for almost 15 years (see: DOI: 10.1111/j.1399-0039.2010.01466.x). The authors should familiarize themselves with and use, modern, field-based HLA nomenclature.

Finally, when the authors do use HLA allele names, the names must be used consistently. When one is referring to an allelic HLA gene variant, the entire allele name is italicized. When one is referring to a specific HLA protein variant, the allele name is not italicized. There is no situation in which, e.g., "HLA-DQB1" should be italicized when "*02:01" is not italicized.

On 2019-07-18 18:38:41, user Guyguy wrote:

EVOLUTION OF THE EBOLA EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI

Show solidarity with the Congolese people in the 10th Ebola outbreak declared a health emergency of international concern: understand a qualitative study of variables of hospital activities on infection control practices in Kinshasa city

Wednesday, July 17, 2019

Statement Ebola outbreak in DRC as a health emergency of international concern

Following the recommendations of the international expert committee, WHO declared on Wednesday, July 17, 2019, that the Ebola epidemic in the DRC was a health emergency of international concern.<br /> The Ministry of Health accepts the evaluation of the expert committee. The ministry hopes that this decision is not the result of the many pressures from different stakeholder groups who wanted to use this statement as an opportunity to raise funds for humanitarian actors despite the potentially harmful and unforeseen consequences for the affected communities that depend on them. greatly from cross-border trade for their survival.<br /> While the Government continues to openly share with partners and donors the way in which it uses the funds received, we hope that there will be greater transparency and accountability of humanitarian actors in their use of funds to respond. to this Ebola outbreak.<br /> The Ebola epidemic is above all a public health crisis that requires a response by actors with real technical expertise. However, the main difficulty is that this epidemic occurs in an environment characterized by problems of development and shortcomings of the health system.<br /> Furthermore, we regret that after spending almost a year in this epidemic, certain groups of people in the community continue to adopt irresponsible behavior that causes the geographical spread of the virus. It is important to remember that in the cases of Goma and Uganda, the patients knew that they were at risk but refused to respect the health recommendations and deliberately traveled to another area. The Government will consider what steps need to be taken to prevent these high-risk groups from continuing to spread the epidemic in the region.

Follow-up of the situation of the pastor's contacts who traveled to Goma<br /> Vaccination around the confirmed Goma case continues at the Afia Himbi Health Center in the Goma Health Zone. All contacts in the city were found in less than 72 hours, including the motorcycle taxi driver that the pastor had used to get to the health center. The response teams from Beni and Butembo continue the investigations to trace the pastor's journey and identify his contacts in these two cities.

The epidemiological situation of the Ebola Virus Disease dated 16 July 2019:<br /> Since the beginning of the epidemic, the cumulative number of cases is 2,522, 2,428 confirmed and 94 probable. In total, there were 1,698 deaths (1,604 confirmed and 94 probable) and 717 people cured.<br /> 374 suspected cases under investigation;<br /> 10 new confirmed cases, including 6 in Beni, 2 in Mabalako, 1 in Katwa and 1 in Mangurujipa;<br /> 10 new confirmed cases deaths:<br /> 5 community deaths, including 3 in Beni, 1 in Mabalako and 1 in Mangurujipa;<br /> 5 deaths at Ebola Treatment Center (ETC) including 4 in Beni and 1 in Katwa;<br /> 7 people cured out of Mabalako Ebola Treatment Center.

No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 136 (5% of all confirmed / probable cases), including 41 deaths.

Deaths and cures data recorded in ETCs for the period 9-11 July 2019 are now available and have been added to the summary table.<br /> In total, 12 deaths were recorded in ETC during this period:<br /> 7 deaths at the ETC de Beni<br /> 3 deaths at Butembo ETC<br /> 2 deaths at Katwa ETC<br /> In total, 7 cures were discharged from ETC during this period:<br /> 5 cured at Butembo ETC<br /> 1 cured at the ETC of Beni<br /> 1 cured at Katwa ETC

75,697,081 Controlled people<br /> 80 entry points (PoE) and operational health checkpoints (PoC).

Source: Ministry of Health press team on the state of the response to the Ebola epidemic in the Democratic Republic of the Congo

On 2022-01-30 16:41:48, user Mary Beth Baker wrote:

Am a non-medical, non-math lay person, but in the comparison with the influenza pandemic of 1918/1919, it says that 1/4 of the US population was infected whereas 1/5 has been infected with Covid-19. Doesn't that make influenza worse, so far anyway? 6 in every 1,000 died of the spanish flu in US. How many per 1,000 of Covid so far?

On 2022-02-05 13:03:59, user GregoryGG wrote:

Hello,<br /> Unless I misunderstood, <br /> How do you know that the behaviour of people, the transmission prevention measures and the testing entry rules were the same between delta and omicron; and between vaccinated and unvaccinated ?

Also, since we know that immunity against a single variant may lower down over time, can we still consider single- and double-dosed people as being vaccinated? (they could be considered as non vaccinated over time).

Thank you.

On 2020-03-16 16:32:43, user Bill Keevil wrote:

Although not peer reviewed yet, this work is not surprising because we showed long term survival of the similar coronavirus 229E on plastics, ceramics, stainless steel and glass for 4-5 days; the virus was inactivated on copper in just minutes and its RNA destroyedhttps://mbio.asm.o.... Another group showed SARS survived 5 days on stainless steel. We and others also showed flu survives several days. Implications are that in a closed environment a potentially infectious aerosol of small particle size can remain suspended in air for some time before landing on surfaces – hence being outdoors or opening windows is probably a good thing. It might question whether the 2 metre gap between people is sufficient in a confined space. As I have said before, survival of coronaviruses for days on touch surfaces (not the 2 hours cited by some advisers) is a hygiene risk, and it is difficult to avoid touching door handles, stair rails, public touch screens etc. It re-emphasises the need for good personal hygiene such as washing hands rigorously throughout the day, or using an alcohol hand gel, and avoid touching the eyes, nose and mouth.

Because this is a pre-print it is difficult to know exactly what they have done. Clearly they are using a different virus and culturing in Vero-E6 kidney cells while we used MRC-5 lung cells. An important difference may be that in their 2003 MERS paper they used 100ul culture onto unspecified size surfaces (“washers”) –McMaster-Carr, USA); for the new paper where they say they used 50ul of virus then we know that this can take a long time to dry out. Copper alloys kill bacteria and viruses when dry due to the inactivation mechanisms we have published. Our method to simulate hand contact uses 20ul onto 1 square cm, spread over the surface and then dries out in several minutes; sometimes we use 1ul when we have high concentrations of pathogen available.

Perhaps more importantly, our cells were maintained in minimal essential medium (MEM) supplemented with 1mM GlutaMax-1*, nonessential amino acids, and 5% fetal calf serum and incubated at 37°C and 5% CO2. Their cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM; Sigma) supplemented with 2% fetal calf serum (Logan), 1 mM L-glutamine (Lonza), 50 U/ml penicillin and 50 µg/ml streptomycin (Gibco).

*(GlutaMAX™-1 (Gibco), L-alanyl-L-glutamine, is a dipeptide substitute for L-glutamine. GlutaMAX™-1 can be used as a direct substitute for L-glutamine at equimolar concentrations in both adherent and suspension mammalian cell cultures with minimal or no adaptation. GlutaMAX™-1 is highly soluble, heat-stable, and improves growth efficiency and performance of mammalian cell culture systems. GlutaMAX™-1 eliminates problems associated with thespontaneous breakdown of L-glutamine into ammonia during incubation, allowing for longer lasting cultures. )

Importantly, glutamine binds copper while it also spontaneously breakdowns at physiological pH to ammonia which reacts with copper to precipitate light blue Cu(OH)2. This would give a partial passivation effect, making the copper surfaces less antiviral while our GlutaMAX-1 would not; hence explaining their longer time for copper inactivation.

This is one of the reasons we decided GlutaMAX-1 was the better option to avoid subsequent potential copper binding problems in the surface contact experiments.

On 2022-02-09 20:37:04, user anon wrote:

This is completely nonsensical after a population wide study by Patone et al. showed the pooled risk of developing myocarditis to be higher after any mrna vaccine series compared to covid infection for males <40. Yet 1000x higher from covid? I have to say, even among covid long hauler communities, compared to communities with vaccine side effects, the prevalence is much higher in the vaccine communities. Where am I missing the extra 1000 people for every extra person in the vaccine communities?

On 2022-02-16 16:01:22, user Matthias Bruhn wrote:

The ELISAs in Fig. 1 are saturated at OD 3.0, this “swallows” any differences between the variants. The conclusion that vaccinated + omicron infected makes antibodies equally strong against all variants should not be drawn based on saturated measurements

On 2022-02-21 12:44:14, user Amador Goodridge wrote:

This work have been complemente with a video reagarding all findings. Please see authors explaning the research here https://youtu.be/Z2X306wc-JU

On 2025-11-30 16:49:17, user Cyril Burke wrote:

[Note: This is the first of several reviews of an earlier version of our combined manuscript that aims to reduce ‘racial’ disparity in kidney disease. The comments were kindly offered by nephrologists, through a medical journal, and we remain grateful to them for the time and care they gave to improve our manuscript.

We removed identifying features and will include our responses in a subsequent comment. The changing title and line numbers refer to versions prior to our medRxiv preprints.]

April 1, 2022<br /> Screening for early kidney disease and population health using longitudinal serum creatinine

Dear Dr. Burke III,

REDACTED.

Reviewer #1: Burke et al submit a somewhat unusual paper, devoted to a topic of potential major clinical relevance, and as yet understudied.

General comments

1. The thesis of the authors, that using the baseline serum creatinine of a given patient would potentially improve the earlier diagnosis of kidney disease, even in the normal range, is in line with the experience of this reviewer, who always retrieves , whatever the difficulty of reaching that goal, past results of blood tests, and uses them as a way to date the onset of kidney disease, sometimes with important prognostic implications.

2. Yet, the authors do not provide data strongly supporting their thesis. For instance, when looking at case 2, should the last point (the most recent one) be omitted, there would be very little evidence supporting progressive early kidney disease.

3. The claim that the statistics fit the data better when all points are used (page 9,11) should not come as a surprise. Using thresholds instead of the full range of values has long been known to be more powerful for statistical analysis. But fitting the data does not equal to a high positive predictive value!

4. A key question is whether in a real world context, the earlier diagnosis of kidney disease would be possible, without too much background noise from intercurrent illness (functional), drugs (NSAIDS, etc..). In other words, would the specificity (or PPV) of the suspicion of early kidney disease be reasonable enough to catch the attention of clinicians

5. Even though there has been improvement in the standardization of measurement of serum creatinine (IDMS), the comparability of results measured by different labs remains suboptimal, at least in the experience of this reviewer, and medical shopping is not uncommon, making the availability of all previous results in the same graph a logistical challenge.

Specific comments

1. The authors should mention that the USPTFS decided a month ago to revisit the question of screening for kidney disease in high risk groups (page …)

2. Even though ESRD has a legal meaning in the USA, not very relevant to the topic of this paper about early kidney disease, the authors should stick to the nomenclature proposed by a recent KDIGO consensus conference (see Levey et al. Nature Reviews in Nephrology ). In particular, use kidney failure instead of ESRD/ESKD. When the topic is glomerular filtration, use that wording instead of kidney function (page…)

3. The authors allude to the concepts of prediabetes and prehypertension. But this reviewer points to the fact that the levels used to define those entities are currently “generic” , rather than based on previous values in an individual subject. Please discuss.

4. The authors repeatedly mention in the discussion section evidence that even small increases in serum creatinine have prognostic significance. This has indeed been known for decades but is a different topic: AKI . Admittedly, there is growing evidence that AKI and CKD are linked. But that the stability of a biological parameter is prognostically best is all except surprising: the same is true for body weight, mood, blood pressure etc…

Reviewer #2: Thank-you for the opportunity to review this work which highlights the importance of monitoring serum creatinine over time and how this can be a useful tool in detecting possible CKD. This is an important topic as the use of sCr on its own is certainly under-utilised and changes are often missed because they don’t fall into a predefined category.

MAJOR CONCERNS

“Choi- rates of ESRD in Black and White Veterans” doesn’t fit with the rest of the paper including the title; the introduction and conclusion also don’t adequately address this portion of the paper. It feels disjointed from the main point of discussion which is the use of sCr in screening “pre-CKD”. This section and discussion should be removed and possibly considered for another type of publication.

Cases 1 - 3, (lines 93 – 122): where are these cases from? There is no mention of ethics to publish these patient results, which appears to be a clear ethics violation. If so, these cases should be removed and patient consent and ethical approval obtained to publish them.<br /> The authors describe the reasons for not obtaining an ethics waiver for this secondary data analysis. Despite this, the relative ease of obtaining an ethics waiver for secondary data analysis usually means that this is done regardless.

The message of the article and data representation is unclear: do the authors wish to show that sCr is superior to eGFR in this “pre-CKD” stage, should both be used together? Do the authors wish to convey that a “creatinine blind range” does not exist? Or is the aim to demonstrate that continuous variables should not be interpreted in a categorical manner?

MINOR CONCERNS

ABSTRACT<br /> Vague<br /> Doesn’t give a clear picture of the study

INTRODUCTION<br /> 51 – 57: needs to state that these stats are from e.g. the US. The authors should consider adding international statistics to complement those from the US.

68: reference KDIGO guidelines, state year

75 – 77: is this reference of the New York Times the most appropriate?

82: within-individual variation not changes (this is repetition of the point made in lines 425 – 427, but should match the language)

82 – 84: reference? If this is a question it should be presented as such

84: “normal GFR above 60” = guidelines (including KDIGO) do not refer to 60 as normal GFR, 60 – 89 is mildly decreased. (see line 126)

93: avoid the use of emotive words such as apparently (also in line 428)

94: “Not meeting KDIGO guidelines”: KDIGO 2.1.3 includes a drop in category (including those with GFR >90). This would appear to include some of the cases listed. Additionally, albuminuria should have been measured for case 2 and 3.

97: “progressive loss of nephrons equivalent to one kidney”: this is based on a single creatinine measurement.

93 – 122: Could any of these shifts be explained by changes in creatinine methodology or standardisation of assays, especially over 15 – 20 years (major differences between assays existed before standardisation and arguably still exist with certain methods).<br /> It would be useful to see a comparison between serial sCr and eGFR measurements on the same figure. There appears to be significant (possibly more pronounced) changes when eGFR is used. As line 87 mentions changes in eGFR may be as useful (and in some situations more useful) than changes in sCr alone.

127 – 142: should there be separate charts for males and females, the differences in creatinine between males and females needs to be discussed somewhere in the paper. Similarly, is this suitable for all ages?

162 – 163: rephrase

METHODS<br /> 185 – 193: aim belongs in the introduction, can be adjusted to complement paragraph 178 – 182.

196 – 205: reference sources

224 – 247: not in keeping with the rest of the article or title and conclusion

RESULTS<br /> If eGFR is treated as a continuous variable does inverted sCr still have higher accuracy?

As mentioned, the section on ESRD in black and white veterans doesn’t fit in with the rest of the article.

DISCUSSION<br /> As mentioned, section 4.1 doesn’t fit in with the rest of the article. As the authors note the correlation between illiteracy and CKD is likely not causal.

387: erroneous creatinine blind range. The data presented does not show this is erroneous there is still a relative blind range. A distinction must be made between a population level “blind range” and an individual patient’s serial results. The data and figure 4 in particular demonstrate the lack of predictive ability of sCr above 40ml/min compared to below 40ml/min at a population level. For an individual patient this “blind range” is more relative, and a change in sCr even within the normal range may be predictive. (Note: the terminology “blind range” is problematic).

399 – 400: “rose slowly at first and then more rapidly as mGFR decreased below 60” this refers to a relative blind range. Whether these slow initial changes can be distinguished from analytical and intra-individual variation is the question that needs to be answered before we can say a “blind-range” doesn’t exist for an individual patient.

425 - 432: sCr is indeed very useful when baseline measurements are available. eGFR remains useful when baseline sCr is not available or when large intervals between measurements are found.

425: low analytical variation- if enzymatic methods are used

428: avoid the use of “apparently”

430: reference 56 compares sCr and sCysC with creatinine clearance NOT with mGFR, this does not prove that mGFR has greater physiologic variability. Creatinine clearance is known to be highly variable (partially due to two sources of variability in the measurements of creatinine: serum and urine).

The limitations of sCr for screening should also be discussed: differences in performance and acceptability between enzymatic and Jaffe methods (still widely used in certain parts of the world), the effect of standardizing creatinine assays (an important initiative but one that could also produce shifts in results around the time of standardization- see cases), low InIx means that once-off values are exceedingly difficult to interpret, is a single raised creatinine value predictive (or should there be evidence of chronicity): similarly are there effects from protein rich meals, etc (The influence of a cooked-meat meal on estimated glomerular filtration rate. Annals of Clinical Biochemistry. 2007;44(1):35-42. doi:10.1258/000456307779595995)

CONCLUSION<br /> The discussion recommends using SCr above eGFR while the conclusion recommends the NKF-ASN eGFR for use in pre-CKD and ASC charts. While the use of both together in a complementary fashion is understandable- this needs to be congruent with the discussion, aims and results.

On 2022-03-05 07:28:21, user Kaiser Stobbertus wrote:

A good study!<br /> I just wonder, though, why PEM (Post-Exertional Malaise) was not taken into account - especially given the expectable long-term suffering in patients who might get prescribed excercise?<br /> On topic, see, e.g.:<br /> https://www.ncbi.nlm.nih.go...

On 2020-04-20 17:17:34, user Andy wrote:

On the self-selection, non-random bias, participants were asked about "prior clinical symptoms".

But even that is not enough to correct the bias. People are more likely to participate if they think they have been exposed, not just because they had symptoms.

So the result is still going to be wrong after accounting for "prior clinical symptoms", because participants were self-selected for exposure.

On 2020-05-24 07:09:29, user Animesh Ray wrote:

Once again, this study uses previous studies' data (by the kit manufacturers) to estimate CL of their specificity estimate. This is flawed--a classic Type I error. In other words, the authors use "meta-analysis" of other studies data to establish the bounds of their own data interpretation. Meta-analysis requires very careful calibration of admissible data using several well-known metrics. None of that has been done here. These results will remain flawed until the authors use their kits under their own experimental conditions to determine the true negative frequencies using sufficient (at least 200) pre-COVID19 samples. Even then I will be worried because these samplings will be conducted non-contemporaneously with their main study. In other words, these studies have little hope of being salvaged because of their fundamentally flawed study design.

On 2022-04-20 20:37:11, user Mark Czeisler wrote:

Note from the authors:

This paper was published in Sleep Health on 20 April 2022 following peer review. Below is a link to the article.

DOI: https://dx.doi.org/10.1016/...

Mark É Czeisler, Emily R Capodilupo, Matthew D Weaver, Charles A Czeisler, Mark E Howard, Shantha MW Rajaratnam. “Prior sleep-wake behaviors are associated with mental health outcomes during the COVID-19 pandemic among adult users of a wearable device in the United States.” Sleep Health. 2022. DOI: 10.1016/j.sleh.2022.03.001

On 2022-05-22 17:15:49, user Teresa Moreno wrote:

UPDATE MAY 2022: lessons for the monkeypox viral outbreak?

According to the Johns Hopkins data repository (updated in Dong et al 2020), case numbers of COVID-19 in Spain rose steadily and rapidly after the early December 2021 holiday to an omicron-driven post-Christmas peak far higher than any other during the SARS-CoV-2 pandemic. On 8th December 26,412 new cases were recorded, whereas by 11th January 2022 this figure had risen an order of magnitude to 292,394. The entirely predictable threat of a countrywide viral superspreading event boosted by Christmas celebrations, many in poorly ventilated indoor environments, had become real, with deaths from the disease peaking in late February 2022.

In May 2022 cases of monkeypox suddenly emerged in several countries worldwide. The pathogen responsible for this enzootic disease is belongs to the Orthopoxvirus genus which includes the virus causing smallpox. How is this global outbreak of monkeypox being transmitted? As in the early days of the emergence of COVID-19, initial public health statements are emphasising personal hygiene and avoidance of close physical contact with the saliva or lesions of infected individuals (ECDC 2022; Koslov 2022). The World Health Organisation states that "monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding" (WHO 2022). This initial reaction to a new pattern of infectious disease is familiar (Moreno and Gibbons 2021). The spread of the now-eradicated smallpox virus was similarly considered to have been transmitted primarily by fomites and close contact, until the classic nosocomial outbreak in the German town of Meschede. Study of this event concluded that cases spread inside the hospital were infected by virus particles disseminated by air over a considerable distance (Wehrle et al., 1970, see also Gelfand and Posch 1971; Fenner et al., 1988; Tellier et al., 2019). Reviewing the history of this disease, Milton (2012) concluded that "the weight of evidence suggests that fine particle aerosols were the most frequent and effective mode of smallpox transmission". Given our precautionary recent experience and slow start with SARS-CoV-2, we argue that we should be treating this unexpected new zoonotic poxvirus outbreak as likely being driven at least in part by viraerosol transmission. It is another wakeup call for treating indoor air ventilation issues more seriously.

References<br /> Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 May;20(5):533-534. doi: 10.1016/S1473-3099(20)30120-1. Epub 2020 Feb 19. Erratum in: Lancet Infect Dis. 2020 Sep;20(9):e215. PMID: 32087114; PMCID: PMC7159018.<br /> European Centre for Disease prevention and Control. Epidemiological update: Monkeypox outbreak. 20 May 2022. <br /> Fenner, F., D.A. Henderson, I. Arita, Z. Jezek, I.D. Ladnyi. Smallpox and its eradication. WHO, Geneva (1988), p. 1460p<br /> Gelfand, H.M., J. Posch. The recent outbreak of smallpox in Meschede. West Germany. Am. J. Epidemiol., 93 (4) (1971), pp. 234-340, 10.1093/oxfordjournals.aje.a121251<br /> Moreno, T., Gibbons, W. 2021. Aerosol transmission of human pathogens: From miasmata to modern viral pandemics and their preservation potential in the Anthropocene record. Geoscience Frontiers. DOI:10.1016/j.gsf.2021.101282<br /> Kozlov, M. 2022: https://www.nature.com/arti... "https://www.nature.com/articles/d41586-022-01421-8)")<br /> Milton, D.K.. What was the primary mode of smallpox transmission? Implications for biodefense. Front. Cell Infect. Microbiol, 2 (2012), p. 150, 10.3389/fcimb.2012.00150<br /> Tellier, R. Aerosol transmission of influenza A virus: a review of new studies. J. R. Soc. Interface, 6 (2009), pp. S783-S790, 10.1098/rsif.2009.0302.focus<br /> Wehrle, P.F., J. Posch, K.H. Richter, D.A. Henderson. An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bull. World Health Organ., 43 (5) (1970), pp. 669-679<br /> World Health Organisation. Multi-country monkeypox outbreak in non-endemic countries. May 21 2022. https

On 2022-05-23 11:58:04, user Jakub Fronczek, MD wrote:

Brilliant paper, congratulations - great to see net benefit assessment. The only part I found confusing is: "In sub-2% decision thresholds there is no net benefit in using our system, but these patients are not a subject of interest in this analysis and should always undergo a biopsy". Since the analysis includes BI-RADS 4 patients, shouldn't a probability <2% be of interest as a criterion for downgrading a patient to a lower risk category? Perhaps I'm missing something! Kind regards, Jakub Fronczek.

On 2022-06-13 15:40:35, user Myia Mcmillian wrote:

While an interesting study, I would be very curious about the number of subjects involved who were truly Covid-naive. The CDC claims that only 1 in 4 Covid infections are reported: https://www.cdc.gov/coronav..., and by the time of the Omicron wave, supposedly producing breakthrough infections in both vaccinated and previously Covid-infected, most Americans had likely been infected with Covid at least once. Does that confound the study?<br /> Additionally the median age of death from Covid is >80 years old, and most serious cases are in the Elderly and seriously ill. Younger people generally fight off Covid, variably.<br /> As the Danish researchers recently showed in a re-evaluation of mRNA Covid vaccines: https://papers.ssrn.com/sol...<br /> there was no significant protection from Covid death by the Pfizer and Moderna vaccines in their initial clinical trials, probably due to poor trial design, and these trials had a combined 37,000 subjects in both vax and placebo groups.

On 2022-07-08 01:11:17, user Sun Yeop Lee wrote:

"(ii) the sclerostin reducing alleles of the genetic variants were associated with increased BMD level"<br /> what is the rationale for applying this criterion for choosing genetic IVs? Is this because it is already known fact taht lowering sclerostin increases BMD?

just wondering what are the variants that lowers the sclerostin but decrease BMD

On 2022-07-20 17:40:27, user Elle Tigre wrote:

You suggest that, “In only a few cases, the presence of S1 or spike may be correlated with vaccination, however according to our previous findings, S1 is only detected within the first two weeks after the first dose and spike is rarely detected.”

An important takeaway from the study you referenced in your point is that none of the participants in that study had previous covid infection. So, it’s not that vaccination and boosters aren’t correlated with PASC or “Long covid” but, perhaps, previous infection, either before and/or after vaccination as well as an unvaccinated cohort, may be worthy of exploration? Especially considering your acknowledgement of non-PASC hospitalized participants having S1 and N, but no detectable full length spike protein, which is indicative of a typical “natural infection.” That should’ve flagged your suspicions. When exosomes can carry spike protein *at least* up to 4 months(though many have found it circulating much, much longer), don’t you think vaccination and boosting would prolong that circulation of spike protein? If spike protein, on its own, can cause pathogenesis, why don’t you suspect it can also cause, or at the very least, prolong PASC? At this point, your team should have more follow-up questions and reasonable suspicions from your study results than answers.

On 2022-08-10 17:46:53, user Prajwal Mani Pradhan wrote:

Thank you for all the comments and reviews. We have updated and <br /> published the study in a peer-reviewed journal. The updated study can be

accessed here at no extra cost:

https://pubs.lib.umn.edu/in...

On 2022-08-22 03:33:38, user BGThree wrote:

In Section 2.1 "Cell culture system to express SC2 proteins from synthetic mRNA-1273" the authors disclose incubation of mouse and human cells with 200uL vaccine, but do not disclose corresponding controls. Specifically, mouse and human cells should be incubated WITHOUT addition of vaccine. This control is needed to demonstrate the proteins extracted from lysed cells are transcribed from vaccine mRNA not innate mouse or human mRNA.

On 2020-04-02 13:15:38, user Sinai Immunol Review Project wrote:

COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome<br /> doi: https://doi.org/10.1101/202...

SUMMARY: This study is based on flow cytometry immunophenotyping of PBMCs from 28 patients diagnosed positive for SARS-Cov2 (COVID19). The authors identify a population of abnormally large (FSC-hi) monocytes, present in COVID19 patients, but absent in PBMCs of healthy volunteers (n=16) or patients with different infections (AIDS, malaria, TB). This FSC-hi monocytic population contains classical, intermediate and non-classical (monocytes (based on CD14 and CD16 expression) that produce inflammatory cytokines (IL-6, TNF and IL-10). The authors suggest an association of FSC-hi monocytes with poor outcome and correlate a high percentage of FSC-low monocytes, or higher ratio of FSC-low/hi monocytes, with faster hospital discharge.

LIMITATIONS: While identification of the monocytic population based on FSC is rather robust, the characterization of these cells remains weak. A comprehensive comparison of FSC-hi monocytes with FSC-low monocytes from patients and healthy controls would be of high value. It is unclear if percentages in blood are among CD45+ cells. Furthermore, it would have been important to include absolute numbers of different monocytic populations (in table 1 there are not enough samples and it is unclear what the authors show).<br /> The authors show expression of the ACE2 receptor on the surface of the monocytes, and highlight these cells as potential targets of SARS-Cov2. However, appropriate controls are needed. CD16 has high affinity to rabbit IgG and it is unclear whether the authors considered unspecific binding of rabbit anti-ACE2 to Fc receptors. Gene expression of ACE-2 on monocytes needs to be assessed. Furthermore, it would be important to confirm infection of monocytes by presence of viral proteins or viral particles by microscopy.<br /> Considering the predictive role of FSC-hi monocytes on the development of the disease and its severity, some data expected at this level are neither present nor addressed. Although the cohort is small, it does include 3 ICU patients. What about their ratio of FSC-low vs FSC-hi monocytes in comparison to other patients? Was this apparent early in the disease course? Does this population of FSC-hi monocytes differ between ICU patients and others in terms of frequency, phenotype or cytokine secretion? <br /> In general, figures need to revised to make the data clear. For example, in Fig. 5, according to the legend it seems that patients with FSC-high monocytes are discharged faster from the hospital. However according to description in the text, patients were grouped in high or low levels of FSC-low monocytes.

RELEVANCE : Despite the limitations of this study, the discovery of a FSC-high monocyte population in COVID-19 patients is of great interest. With similar implication, a the recent study by Zhou et al (https://www.biorxiv.org/con... "https://www.biorxiv.org/content/10.1101/2020.02.12.945576v1)") identified a connection between an inflammatory CD14+CD16+ monocyte population and pulmonary immunopathology leading to deleterious clinical manifestations and even acute mortality after SARS-CoV-2 infections. Although the presence of these monocytes in the lungs has yet to be demonstrated, such results support the importance of monocytes in the critical inflammation observed in some COVID19 patients.

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

On 2022-09-08 10:01:58, user Virgínia da Conceição wrote:

Published in the Health and Quality of Life Outcomes journal, DOI: 10.1186/s12955-022-01945-7

On 2022-09-27 14:27:59, user C. Downs wrote:

The published version can be accessed at Scientific Reports 10.1038/s41598-022-20214-7

On 2020-05-26 17:04:01, user Eva Raschke wrote:

Could you please specify how the samples for Table 5 were collected, which criteria etc.?

On 2020-05-28 23:39:32, user Gerard Pujadas Anguiano wrote:

We have found that Celecoxib is also an inhibitor of the main protease (M-pro) of the SARS-CoV-2 virus. This result is published at IJMS. Find the PDF for the paper here https://www.mdpi.com/1422-0067/21/11/3793

On 2020-05-30 01:02:55, user Maxim Sheinin wrote:

Timely analysis. I'm curious if it's worth showing relationship between positive test rates and case fatality rates. Here's a blog post on the topic from a few weeks ago: https://medium.com/@maxbel1...

On 2020-05-30 01:10:44, user ajaxthegreat wrote:

This should be the final nail in the coffin for lockdowns. In a nutshell, lockdowns don't work, and especially belated ones are in fact worse than useless compared to more moderate NPIs applied earlier in the curve. Thus, ending stay-home orders and reopening most non-essential businesses can and should be done *yesterday* with practically no risk of resurgence of the disease. Higher-risk businesses like restaurants, bars, and nightclubs, as well as other amusements, should be reopened a bit more gradually of course, but once a country is at least two weeks post-peak (almost every country) they can begin reopening those as well, albeit with restrictions.

For masks, they probably do work well (just ask Japan and Taiwan) but confounding may have hampered the finding of any good signal in the noise for these policies beyond the first two weeks, especially since these policies were applied belatedly.

As for schools, closing them (even very briefly and locally like Taiwan did) likely worked in the short term, but more recent data show that reopening them does not seem to carry much if any risk of resurgence. For this particular virus, unlike with influenza, children are not superspreaders, in fact they are far less susceptible and infectious compared with adults, but school closures likely prevented at least some adults from infecting each other, both at school and by effectively forcing parents to work from home temporarily at a critical point in the epidemic curve.

On 2020-05-30 02:40:13, user M Del wrote:

If you look at the data table from the study of NY Columbia university the mortality rate is higher for blood type O+ median age 54.8 was 12.4% of the infected and for blood type A+ median age 61.8 it was 12% of the infected , type O has less positive cases compared to the representation of percentage of population but mortality was a little higher even when they were younger.

On 2020-05-31 07:59:11, user ashkan homayuni wrote:

I have noticed a preprint entitled "covid-19 in iran, a comprehensive investigation from exposure to treatment outcomes" <br /> I have read the article and noticed authors mentioned that during 22 feb to 5 march, 100 patients with covid-19 were included; however I working as an internist physician in YAS hospital (where study has noted to be consucted in) have to report you that we had only 46 cases during above mentioned period of time. I am so concerned about reliability and honesty of the data presented by authors and I am afraid that it may subject to data falsification or data duplication.

On 2020-06-01 15:30:23, user Nathan Goodman wrote:

Regarding RJones1’s question about the data: WA Dept of Health provides downloads updated weekly https://www.doh.wa.gov/Emer.... The download is near the bottom of the page.

Timothy Siegel’s comment about the validity of using positive test results as a proxy for prevalence is absolutely correct. Sadly it’s the only data available. Various models use the data to estimate actual prevalence, eg, https://covid19-projections..., and more specifically. the WA estimate at https://covid19-projections...

For what it’s worth, weekly case counts (meaning the number of positive tests) has declined steadily in WA from 2,555 week of Mar 22 to 1,256 week of May 17 (the last week for which the DOH download is reasonably complete). Over the same period, case counts for the youngest group (age 0-19) have increased from 65 to 180.

The pressing question is whether this increase is real or an artifact of testing strategy. Are more kids getting sick, or is it simply that more kids are getting tested.

Dr. Malmgren’s preprint is silent on this question.

On 2020-06-02 19:09:27, user Irene Petersen wrote:

There are two key issues with this study.

1) The majority of people in this study (about 16 million) are NOT at risk of the outcome (dying from COVID19) as they will not have been infected.

2) Dying from COVID19 is a two-stage process - A) Risk of getting infected B) Risk of dying once infected. This study conflates the two. Thus you can't tell whether an elevated risk is due to A or B.

On 2020-06-03 04:00:14, user ??????? ??????? wrote:

You can not trust the testimony of patients who are admitted to hospitals with a serious illness. Currently, the entire public health system is anti-smoking. For example, insurance companies may apply certain restrictions for smokers. Therefore, patients hide the fact of smoking. In connection with the above, the fact of smoking should be documented by objective methods.

On 2020-07-24 14:22:28, user Rosemary TATE wrote:

So where is the EQUATOR checklist that you say you have uploaded?

On 2020-06-04 09:38:49, user Rosemary TATE wrote:

This is very interesting. However, the most recent report by ICNARC, which is based on 9347 UK patients, suggests that ethnicity is associated with worse outcome in hospital and also with increased hospital admissions.<br /> https://www.icnarc.org/Our-...<br /> They are preparing a manuscript - hopefully it will be out soon.

On 2020-07-27 21:49:29, user Dude Dujmovic wrote:

94% in the abstract, 92% in the body of text?

On 2020-06-06 13:59:32, user Nayo57 wrote:

While the result of this interesting and meaningful analysis may be statistically correct: a reduction of R of 0.04 with 10% mobility reduction does not explain the vast reductions from R = 3-4 at outbreak to below 1. A rough analysis of WHO reported case data and Google mobility data gave a similar result e.g. for time to reach R<1 or cumulative cases per population, measures one would expect to be impacted by effective social distancing. The best conclusion may be that mobility index as provided is not a suitable measure to assess or guide policies to contain COVID-19: Fig1 (Germany: increase in mobiilty index while R stays <1), Fig. 2(USA: decrease in mobility by further increase in R) and the scatter in Fig 3 support this view.

The interpretation would rather be that BEHAVIOUR during mobility activities matter much more than the QUANTITY of mobility. Alternatively, more focussed indexes (restaurants/bars; cinemas/theaters..) may be worth while to examine if they could be useful.

On 2020-06-07 12:40:21, user OxImmuno Literature Initiative wrote:

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

On 2020-06-08 10:42:04, user J Sato wrote:

Thanks for the detailed analysis. Here is a similar and simpler one. Hope you can work on the other countries as well.<br /> https://www.jsatonotes.com/...

On 2020-06-08 10:58:42, user ReviewNinja wrote:

Nice and very useful work! Saliva could be a great diagnostic tool! It would fix some problems about NP swab shortages and the necessity of accurate sampling by skilled personnel.

I was wondering about some details:<br /> 1.) The Ct values that you observe are lower for saliva compared to NP swabs. Could this (sometimes) be a matrix effect? Did you run standard curves of positive controls in a constant negative background of human RNA obtained as well from saliva as from NP swabs? A swab might sometimes just lead to more PCR inhibition? NP swabs and saliva might just have different Cqs for their LOD. Another way to assess this is with digital PCR.

2.) Just out of interest: What if you normalize the viral values for RNAseP expression (as a surrogate for sampling efficiency)? Are the values comparable then? Or is there really just more virus present in saliva? (I know, for diagnostics, this does not matter.)

3.)The RNAseP results indicate that sampling with NP swabs can indeed be an issue. <br /> It would have been nicer to also take standard curves here and plot RNAseP values, as Cq's on itself can be quite variable in between runs due to run-to-run variability.

3.) Just a last question, maybe for another paper;): are you also working on extraction free detection in saliva?

On 2020-07-24 03:22:06, user Paul McGehee wrote:

Any updates on where this is in the peer review process and when and in which journal it may be published?

On 2020-06-08 21:16:33, user Christian Lehmann wrote:

nice article - the problem is the communication in by the public media - The authors show a ASSOCIATION - this is something completely different from a causality - so please be careful, having a certain blood group does not tell you something about your possible disease outcome.

On 2020-06-09 20:00:05, user Anne Smith wrote:

I'm blood group O. That should require two of the same allele. The article reports an association between ARDS and a specific SNP, but all of the discussion in the paper is about the relationship between major blood group and chance of ARDS. At 23andme, for rs657152, on a ABO gene, my genotype is A/C. My first question is how is that even possible, since if this SNP determines blood group and I'm type O I should have either two A's or two C's. Second, I and many others would really think you to present the odds of specific variants on rs657142 and ARDS! For two A's, two C's, and one of each.

On 2020-06-10 00:22:53, user Michael Jolley wrote:

From Fig. 3A, it would seem that rs11385942 sits in the LZTFL1 gene, which the authors did not mention. This gene is highly expressed in lung epithelial cells (and is mutated in many lung cancers). Since LZTFL1 protein is involved in regulating ciliary trafficking and controlling ?-catenin nuclear signaling, might not this be an important clue as to how the virus operates (which the authors missed)? https://www.nature.com/arti...

On 2020-06-09 18:29:42, user Chris Winchester wrote:

Would it be possible to study in your data set the quality of RCTs from different funders (e.g. commercial funders vs governmental funders, charities and NGOs)?

On 2020-06-10 08:42:20, user Rita Van Dingenen wrote:

Although more confounding factors have been taken into account in the revised version, I am not convinced that they can capture the specific dynamics of the COVID-19 epidemic where the spreading seems to be strongly driven by sparse super-spreading events, taking place under specific circumstances (e.g. relatively crowded social/cultural/sports events involving shouting, singing, strong breathing). The number and frequency of such events (or infrastructure) could be an important determinant of which PM2.5 may just be a proxy. Further, in stead of mortality rate, case fatality rate would be the more appropriate indicator to establish a possible impact of air pollution, removing a lot of noise from confounding factors.

On 2020-06-10 13:38:42, user trochurozvahy wrote:

Is the Physical Oceanography background sufficient for this type of epidemiological analysis? Just curious.

On 2020-06-13 03:34:34, user kpfleger wrote:

Why are the 25(OH)D levels reported here (43 or 44 nmol/L w/ IQRs of 32 or 31 respectively for the n=580 C19+ and n=723 C19- UK Biobank cases) so much higher than those reported in Hastie et al, "Vitamin D concentrations and COVID-19 infection..." Diabetes Metab Syndr., 2020: https://pubmed.ncbi.nlm.nih...<br /> which reported median 25(OH)D of 29nmol/L w/ IQR 10-44 for C19+ & 33 IQR 10-47.<br /> This is a huge difference for 2 papers with online publication dates 2 days apart both pulling data from the same source.

See also D'Avolio et al, "25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2", Nutrients, 2020 and Meltzer et al, “Association of vitamin D deficiency and treatment with COVID-19 incidence”, medRxiv, 2020 for 2 different studies that found in contrast to the top level conclusion here, that low D was associated with higher C19 incidence. Discussion of all 4 paper of these papers in the "D deficiency might be associated with higher infection risk" of the review: "Low vitamin D worsens COVID-19": http://agingbiotech.info/vi...