6,062 Matching Annotations
  1. May 2026
    1. On 2020-04-25 05:20:18, user Alma Lopez wrote:

      Mexico also gives BCG vaccine and there is no evidence it helps. Early treatment with HCQ would help but they won't give it to you unless you are very ill. Second phase of disease anticoagulants and cortisone and antibiotics are working . But only some hospitals are doing it like INER

    2. On 2020-04-06 17:26:31, user Neha Dagaonkar wrote:

      The universal vaccination policy adopted in India is compulsory vaccination during the post-natal period. Any vaccines including BCG can provide immunity for 15-20 years thus reducing infant and adolescent mortality rate. <br /> The underlying assumption here is that the countries that stopped the universal vaccination policy or never had one, are at higher risk. Since the adult population is more at risk with SARS-CoV 2 infection with higher mortality as compared to younger population, so statistical correlation in this hypothesis lacks necessary biological correlation and age distribution for susceptible population by age group.

    1. On 2020-04-26 12:58:30, user FeatheryHen wrote:

      Interesting analysis, but I'm left wanting to know more about the source data. It would be good to see a summary of the different transmission events you analysed and what the characteristics were, other than enclosed or not. Is a link to source data available?

    1. On 2020-04-26 13:24:24, user Rosemary TATE wrote:

      Hi, <br /> I'm struggling to understand the results. Eyeballing the graphs in figure 2, the best fit appears to be with Nitrogen dioxide, yet the R (do you mean rho?) is the lowest. Ditto the R2. I assume you use linear regression to obtain the fitted lines, although no mention is made of this in the methods.

      Also, I would expect levels of pollution to be higher in regions with highest populations, which would similarly be expected to have more deaths. Did you think of controlling for this, or alternatively using the death rate rather than reported cases?

      It would be very helpful if you included a table with the number of deaths and pollution levels for each region - or at the very least label the graphs.

      What was the rationale for collapsing the 120 sites into only 7 regions - it would be much more useful if this was more fine grained.

      And yes, please can you send me your data<br /> Thanks

    1. On 2020-04-29 22:11:46, user Sinai Immunol Review Project wrote:

      We would also like to point out a brief report by Gioia et al. (2005; https://journals.sagepub.co... "https://journals.sagepub.com/doi/pdf/10.1177/039463200501800312)"), describing the existence of SARS-CoV-1 reactive T cells in healthy donors, an important observation that is very likely due to cross-reactivity with endemic coronaviruses and now seems to be confirmed by the findings in this current preprint.

    1. On 2020-04-30 19:23:08, user Pei-Hui Wang wrote:

      This work has been published on Journal of Medical Virology ( https://onlinelibrary.wiley... ). According to the findings in this paper, we propose that antibody-based COVID-19 “immunity passports” is unfeasible.

      We agree with the opinions of Jayakrishna Ambati, Balamurali Ambati, and Benjamin Fowler that “ Passport holders and society would have a false sense of security while non–passport holders would have their civil liberties and work opportunities unwarrantedly abridged. A passport policy would also endanger lives by undercutting good hygiene and healthy behavior; those desperate to return to work or re-integrate into society would risk exposure to the virus in attempt to develop antibodies.” From Scientific American https://blogs.scientificame...

    1. On 2025-09-06 14:48:49, user Jeffrey Rothstein wrote:

      Nicely done. But I'm surprised you didn't use the appropriate control group when one considers the differential diagnosis of ALS which would include myelopathy, inclusion body myositis, radiculopathy, multifocal motor neuropathy, Thyroid diseas. Controls such as Parkinson's and Alzheimer's any competent neurologist would easily separate from ALS and truly don't add to a diagnostic approach. But mimicking controls would be the most powerful as detailed above. For example, it's likely that muscle markers would also show up in some of those controlled diseases and therefore will be thrown out as providing any kind of disease specificity.

    1. On 2025-09-22 16:17:50, user practiCalfMRI wrote:

      The CSF in periventricular spaces and lateral ventricles moves considerably with the pulse pressure wave each heart beat. The edges of these spaces are thus ill-defined (or blurred) over the duration of an 8-sec image with 3-sec labeling period. Given that this is a difference method, I am concerned about a systematic motion difference which may be biasing the results in these regions. I would encourage the authors to either explain how motion cannot produce biases, or present experimental evidence to show that pulsatile motion does not cause inadvertent differences.

    1. On 2025-09-29 15:17:43, user Bryan Wilent wrote:

      I think this is great and as I read through it hit me how challenging this is to do. Kudos to the team.

      1. I would consider adding therapeutic impact to title and checklist. The distinction between diagnostic accuracy and therapeutic impact should be addressed head on and then can distinguish between the metrics in the checklist. I feel like this is often conflated in the literature at times and people using this checklist would benefit with a clear guideline

      2, I gather that this will be part of the checklist, but readers would benefit with clear list of all measures available and delineation of which metrics apply to diagnostic versus interventional domains (relative risk, odds ratios, probabilities) If getting into the latter, should also expound on nature of the intervention, like in Holdefer/Skinner structural causal model paper.

      3 How to handle suboptimal IONM planning (modalities/nerves/muscles used), e.g., a study found that IONM had low sensitivity for quadriceps pain/weakness after lateral fusions but the study used posterior tibial nerve SSEP for the LE and EMG only.

      4. How to handle dynamic and variable alert criteria (and not a hard threshold), which is consistent with current ISIN guidelines for SSEPs with variable reproducibility and guidelines for MEPs in diagnosing evolving nerve root v cord v brain dysfunction? I don’t have a great suggestion, but I think it needs to be addressed. Example. A case had a 60% change in SSEPs from a limb in context of stable of MEPs, so an alert was not called.

      5. Alert to what? Is it appropriate to analyze alerts specific to a pattern or injury? Example, how to report if some "alerts" had low specificity, but this alert pattern had both high sensitivity and specificity. Lieberman et al from 2019 on MEP patterns and foot drop is a an example thinking of that uses ROC curves for different muscle MEP change patterns.

    1. On 2020-04-06 06:00:12, user Sócrates Ufrb Menezes wrote:

      Is it possible that the anchoring and transmission of the SARS-CoV-2 (RNA) genetic material, is related to HYPERTONICITY AND OR HYPOTONICITY and the attraction to the target, as well as its replication, is related to Na levels in the cell gradient? Thanks and good work!

    1. On 2020-04-20 02:30:29, user Lei Liu wrote:

      I am a biostatistician. There is a problem with the false positive rate. As it was shown, the false positive rate is 2/401. If we assume all 3330 subjects were negative, then the p-value to get 50 false positives is 0.11 by Chi-square or Fisher exact test, which is not statistically significant. That is, even though the accuracy of the test is very high (99.5%), the low prevalence in the population makes the conclusion more likely due to false positive.

    2. On 2020-04-20 07:16:34, user JustDoublechecking wrote:

      Antibodies suppose to be detectable 11-12 days after onset of viral infection. If to take the study results at face value, it means 2.5-4.0 of population was actually sick by mid-March and on the day of the testing it was actually closer to 6% or more (even with very low viral doubling rate under quarantine). I saw no adjustment in the study as they compared directly to confirmed PRC tests on April 1st.

    3. On 2020-04-22 01:33:09, user peteolcott wrote:

      People on the internet are using this study to actively promote very risky behavior. Here is my analysis that rebuts this study:

      Conclusive proof that covid-19 is much more lethal than the flu is provided by the fact we already have more deaths than the seasonal flu even though we took unprecedented precautions to minimize these deaths.

      37,889 2020-04-18 USA covid-19 deaths<br /> 34,200 2018–2019 influenza season deaths

      If we reduce the number of human interactions 50-fold and still have more deaths than the seasonal flu this conclusively proves that covid-19 is 50-fold more deadly than the seasonal flu.

      This is true no matter what the per infection death rate is. If the per infection death rate of covid-19 is the same as the flu yet the unmitigated infection rate is 25-fold greater than the flu, then covid-19 is still 25-fold more deadly than the flu.

    4. On 2020-04-17 20:04:27, user jeffrey spence wrote:

      I have some concerns about the confidence intervals presented in this preprint and hence some of the conclusions. It is stated that there were 2 positive tests out of 371 + 30 tests of known negative samples. This suggests a point estimate of the false positive rate of 0.5%, but a confidence interval of [.06%, 1.79%]. This includes the point estimate of the proportion of positives in the sampled individuals from Santa Clara County (50/3349 = 1.5% ). This means that the data are consistent with there being 0 positive individuals in the sample. As such, claims of a 50-85 fold excess of cases over confirmed cases, are much too precise to the point of being potentially misleading.

      I'm not certain why the confidence intervals in Table 2 that account for the uncertainty in the false positive rate (1 - specificity) are so small, but I suspect that it may be due to using the delta method which is inappropriate for small sample sizes.

    5. On 2020-04-17 22:25:59, user LCMB wrote:

      So they test a bunch of very wealthy white women from Facebook and Palo Alto/Mt. View, and think that represents a real finding? Why was the socioeconomic characteristic not noted in this report? It goes without saying that this particular demographic likely was self-distancing and using precautionary measures, able to shelter at home, and had the financial means to stay home. If this many people tested positive for anti-bodies, imagine if a real cross-section had been tested. The numbers here are way lower than the actual prevalence of antibodies found in our community. Regardless if the researchers proclaim they were able to adjust/weight the under-represented demographics or not.

    6. On 2020-04-18 03:04:01, user Matt Durrant wrote:

      A study participant mentioned on Twitter that you asked all participants in a questionnaire whether they had COVID19-like symptoms previously. You could have used this to correct your ascertainment bias, but you don't mention this survey question in your paper. Why didn't you use it?

    7. On 2020-04-18 04:00:54, user We'll See What Happens wrote:

      "Participants were recruited using Facebook ads targeting a representative sample of the county by demographic and geographic characteristics"

      What about past symptom characteristics? The obvious volunteers for this study would be people that had symptoms and want to know if they have it. This is not random sample at all. Reporting two sigma confidence for prevalence in the general population is completely irresponsible. This is an embarrassment for Stanford University.

    8. On 2020-04-18 05:48:06, user Grace wrote:

      Dr. Bhattacharya, thank you for your groundbreaking CoVID19 prevalence study. Addressing the volunteer bias that is possible, have you considered comparing the survey's results on reported symptoms to Google's symptom tracker for the county? This would allow you to adjust for a potential enrichment of volunteers with previous disease.

    9. On 2020-04-18 17:22:02, user I.J. Frame wrote:

      You rightly point out that your estimates largely depend on the lateral flow test performance, including specificity. To what extent did you (or the test manufacturer) evaluate cross reactivity with serum positive for antibodies against coronaviruses OC43, NL63, 229E, or HKU-1? I think demonstrating that the assay does not cross react with these coronaviruses will help strengthen your work.

    10. On 2020-04-19 21:23:49, user figureitout1 wrote:

      I am not in the field and have no expertise but I think this study may have measured just the prevalence of the common cold in Santa Clara county. The ELISA assays for IgG and/or IgM antibodies are known to give false-positives due to the other Corona viruses that give us the common cold. It is known from European studies that the common cold in the winter time can cause roughly 3% positive Covid-19 ELISA tests – just about what was measured in this study. In order to get meaningful results a second test (neutralization test that is not sensitive to the common cold viruses) needed to be done on the positive samples. The scientifically correct conclusion of the study would be: the Covid-19 prevalence is between 0% and 4%. It seems irresponsible to put the study on the web and have people, including politicians, jump to hasty and possibly wrong conclusions.

    1. On 2020-04-20 08:28:13, user adrian wrote:

      Sorry I just don't buy this, this is a blatant example of cherry-picking. The paper states no-where how the regions were selected, and it is clear to anyone familiar with the data that in each country, 3 regions are specifically selected to demonstrate a clear relationship. Taking Italy as an example, there are several regions across the north with similar climates but very different growth rates of cases. Not to mention that the authors have not accounted for population correctly in their analysis. If I had reviewed this paper I would have recommended rejection.

    1. On 2020-04-21 23:28:15, user sammmy wrote:

      Hilarious abuse of statistics. Patients were NOT randomized between different treatment groups. It is very possible that patients in a grave condition selected hydroxychloroquine as the only available drug and their higher death rate is attributed to their condition not the drug. Observational studies like this one do NOT prove cause and effect. I hope the people that were criticizing the other studies that they were 'not randomized and double blind' will apply that critique to this study as well.

    2. On 2020-04-22 01:19:52, user stickler wrote:

      Every news media seems to be including this same sentence: "The nationwide study was not a rigorous experiment," which to trump supporters means that its conclusions are completely untrustworthy and it can be summarily disregarded as a politically motivated product of the deep state. In what way did this study lack rigor? Does there appear to be anything lacking in the design, methodology, data, analysis, interpretation or reporting of results, or is it more a matter of just awaiting peer review?.

    3. On 2020-04-22 10:40:37, user stylin19 wrote:

      Index dates range from March 9, 2020 to April 11, 2020, and patients were followed from index until hospital discharge or death. The period prior to index is designated as the baseline period and on or after index is designated the follow-up period.

      something is not quite right about this study.

      There were only 731 COVID-19 cases in the U.S. end of day 03/08/2020.

      Why did the VA start using hydroxychloroquine so early ?

      FDA "emergency use" edict wasn't approved until 03/29/2020.

      FDA already has a "compassionate use" for drugs. <br /> It's usually at end of life situations.

      Per your study:<br /> “However, hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease, as assessed by baseline ventilatory status and metabolic and hematologic parameters.”

      Is it possible this study may actually prove more of these Vets were saved because of hydroxychloroquine?

      You really need to provide more data regarding Hospitalization\treatment dates for each patient.

    4. On 2020-04-22 11:48:35, user Graham Senior-Milne wrote:

      'CONCLUSIONS: In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone.'

      What's missing? Yep, mortality with HC + AZ. In the text it says:

      'Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72).'

      In other words, and unless I can't read plain English, the risk of death is reduced by HC + AZ.

    5. On 2020-04-22 12:20:25, user Patrick Langer wrote:

      Chloroquinederivatives are highly likely to kill male, black patients, because a lot of them have Glucose-6-phosphate-dehydrogenase-deficits so it will cause hemolysis. It's a common fact and I don't get why it is still not widely discussed. Same with people or people with ancestry from other (previous) malaria-endemic areas like Brazil, Ecuador, northern Italy...

    1. On 2020-04-22 12:04:06, user Katri Jalava wrote:

      Nice. You could add a figure/map 1c with the current case load or prevalence. Also, would like to know the result of how your model fits to current data. Ie. has the beginning of the Covid-19 outbreak in Africa and India followed your conclusions, that cases to Africa came through airtraffic from Europe and in India transmission has been mostly within the country.

    1. On 2020-04-22 12:31:02, user rupesh chaturvedi wrote:

      Here is preprint.

      Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications

      Fan Wu, Aojie Wang, Mei Liu, Qimin Wang, Jun Chen, Shuai Xia, Yun Ling, Yuling Zhang, Jingna Xun, Lu Lu, Shibo Jiang, Hongzhou Lu, Yumei Wen, Jinghe Huang

      doi: https://doi.org/10.1101/202...

    1. On 2020-04-22 18:28:14, user Clarissa Damaso wrote:

      Hi, I'd like to know how you determined virus titter in order to calculate the MOI. It's not in Material and Methods. I'd also like to know why you opted to detect virus RNA during infection instead of checking the production of infectious particles. Thanks.

    1. On 2020-04-05 13:03:21, user Rosemary TATE wrote:

      Authors can you please upload the supplementary material. All I could find under supplementary materials are the figures that already appear at the end of the document. It would be very useful to see the list of your sources of data, and also details of the model used.

    1. On 2020-04-05 15:51:35, user Sinai Immunol Review Project wrote:

      Summary: Multiple studies reported the same level of infectiousness between symptomatic and asymptomatic carriers of SARS-CoV-2. Given that asymptomatic and undocumented carriers escape public health surveillance systems, a better mathematical model of transmission is needed to determine a more accurate estimate of the basic reproductive number (R0) of the virus to assess the contagiousness of virus. The authors developed a SEYAR dynamical model for transmission of the new coronavirus that takes into account asymptomatic and undocumented carriers. The model was validated using data reported from thirteen countries during the first three weeks of community transmission. While current studies estimate R0 to be around 3, this model indicates that the value could range between 5.5 to 25.4.

      Critical analysis: The SEYAR model realistically depicts transmission of the virus only during the initial stages of the disease. More data is necessary to better fit the model with current trends. In addition, multiple factors (e.g. behavioral patterns, surveillance capabilities, environmental and socioeconomic factors) affect transmission of the virus and so, these factors must be taken into consideration when estimating the R0.

      Significance: Public health authorities use the basic reproductive number to determine the severity of disease. An accurate estimate of R0 will inform intervention strategies. This model can be applied to different locations to assess the potential impact of COVID-19.

      Review by Tamar Plitt as part of a project of students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine at Mount Sinai.

    1. On 2020-04-06 17:25:08, user t Darroll wrote:

      Why wait to administer Chloroquine/hydroxychloroquine? My understanding of the initial studies of Chloroquine/hydroxychloroquine with azithromycin which was done by the Chinese and French showed that the most productive time to administer it was in the first 3-4 days of Covid-19. It seemed to work best given early in the disease process and then seemed to significantly shorten the disease time frame..

    1. On 2020-04-08 18:30:28, user JC wrote:

      This study fails to evaluate filter efficiency and potentially creates risk that hospitals improperly reprocess N95 respirators. Exposing N95 masks to extended periods of heat (autoclave) has been shown to reduce filter efficiency effectiveness (https://utrf.tennessee.edu/... "https://utrf.tennessee.edu/information-faqs-performance-protection-sterilization-of-face-mask-materials/)"). The article should not claim success unless filter efficiency is shown to be maintained.

    1. On 2020-04-10 07:15:55, user Chris Romo wrote:

      Wow, what a tough crowd this is.

      First, thank you for this intuitive tool! In less than an hour, I am better informed now, when compared to the collective several weeks of endless barrage of media getting the message out.

      To the tough crowd: <br /> I get it folks, you want to see different information. Might I recommend a "suggestion" over harsh criticism? When offering feedback, footnote the source from which you are referring to? Keep in mind, there is a great deal of underlying data that informs this tool. Imagine what that meaning had, how that probably had to be massaged to meet the abstract's intent.

    1. On 2020-04-11 07:57:42, user Jean Perron wrote:

      This paper appears to be a hoax. Most evidently, the data on Figure 5 is not at all from Reference 17 and does not correspond to the Covid-19 age association of any country. But the whole premise of the paper is flawed: CFR cannot be compared among countries without modeling test strategies (more tests lowers CFR both mathematically and as a management tool), and modeling the spread of the disease (for many reasons CFR increases as the disease spreads, e.g. people take time to die). Finally, among-country association between vitamin D defiency and CFR does not constitute evidence of causality: a lot of things differ between Germans and Italians. (Last: the paper is very poorly written and full of errors and typos).

    2. On 2020-11-06 03:35:38, user AliD wrote:

      The final version of the article has been published on the journal of Aging Clinical and Experimental Research in Sep 2020. Please use the following information to cite the article.

      Daneshkhah, Ali, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, and Vadim Backman. "Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients." Aging Clinical and Experimental Research 32, no. 10 (2020): 2141-2158.

    1. On 2020-04-11 15:25:20, user Sinai Immunol Review Project wrote:

      Title: Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients

      Summary:<br /> As hospitals around the world are being overwhelmed due the COVID-19 pandemic, it is of utmost urgency to identify biomarkers which would accurately predict patient outcome at an early stage. Severe COVID-19 complications often include acute respiratory distress syndrome.<br /> The authors analyse clinical and laboratory findings in 40 COVID-19 patients: 13 required mechanical ventilation, and 27 did not. Age, comorbidities, radiological findings, respiratory rate or qSofa score (mortality prediction score upon sepsis) did not discriminate between<br /> both groups. However, all patients requiring intubation were male, and the pulse as well as several laboratory parameters correlated with the risk of respiratory failure. The strongest correlation was found to be with serological IL-6. Elevated IL-6 was found to be associated with the risk of respiratory failure by a factor of 22.

      Critical analysis:<br /> The value of 80pg/mL of IL-6 was identified as decisive, as 92% of patients who reached this cut-off required intubation 0-4 days afterwards. The study must be extended to a larger cohort, however, to perhaps identify a more precise cut-off.<br /> Moreover, the causality between IL-6 and respiratory distress remains unclear. Understanding the mechanisms behind these correlations could pinpoint new therapies to prevent respiratory failure.

      Relevance to current epidemic:<br /> Foreseeing respiratory distress at an early stage in admitted COVID-19 patients could allow hospitals to better manage their resources, both human and material.

      By Maria Kuksin

    1. On 2020-04-12 19:24:03, user Ben Vitale wrote:

      Opinion: MIT grad students attempted to sanitize used n95 masks for reuse using Co 60 gamma radiation. The problem they reported was a loss in the ability to capture particles through electrostatic capture after radiation. <br /> Question… was a test for the used n95 masks electrostatic capture ability done before radiation? If so, could the loss of its ability to capture fine particles electrostatically be because of contamination rather than radiation. The problem may be compound and the masks may need to be washed before attempting to sanitize them for reuse. <br /> If the particle capture problem persists after cleaning and radiation, one might want to introduce some static electricity by rubbing a balloon with wool and placing the mask on top of it! This may work?

    1. On 2020-04-12 19:24:42, user Heriberto Prado wrote:

      In this study Diao et al show that there is a reduction in the number of T cells (both CD4+ and CD8+ subpopulations) in COVID-19 patients. This reduction correlated with increased levels of IL-16, IL-10 and TNF-alpha in sera. They propose that increased expression of the inhibitory receptors PD-1 and TIM-3 observed in these patients are indicative of T cell exhaustion. The observation that there is a dramatic reduction in T cells warrant further study. However, the data does not support that T cell exhaustion is involved. A technical concern is the panel of antibodies selected for the flow cytometric analysis. The authors employed two antibodies that were conjugated to bright fluorochromes (APC and PE) to identify CD8 molecule, which show a high expression on CD8+ T cells. However, to identify TIM3 (a less expressed antigen) they used FITC, which is a dim fluorochrome. No mention is made regarding what fluorochrome was used to discriminate viable cells nor the number of events acquired.

      The phenomenon of exhaustion is antigen-specific, it is characterized by poor effector functions, sustained coinhibitory receptor expression, along with a distinct transcriptional state (Pauken and Wherry 2015). As opposed by the data reported by Dia et who show that total number of T cells are reduced, which suggest that COVID-19 induces T cell death in an antigen-independent manner. As it was mentioned before, the group COVID-19 patients and of healthy donors is small and is not age-controlled. PD-1 and TIM-3 coexpression should have been evaluated, as these markers might be expressed in different T cell subsets. In addition, Figure 3 shows that CD4+ T cells from COVID-19 patients expressed TIM-3 in a low percentage of cells (<1%). Thus, PD-1 expression might be dysregulated as consequence of the disease, the cytokine storm, or as mechanism that tries to limit the immunopathology observed in these patients.

    1. On 2020-04-14 10:07:38, user Rob wrote:

      Thank you for this paper, as usually there is plenty of time to consider and/or analyse all angles within the context of Covid-19 I acknowledge the challenges. Beside, solid suggesting already mentioned. Please consider this as influencing the effect seen in relation to smoking and Covid-19 severity. Age (65+) are most risk of severe covid-19. Often smoking rate in 65+ is well below the national average. In the US ~14% is the smoking prevalence whereas 8.4% for 65+, in the UK ~16.5% is the national smoking prevalence whereas 10% 65+ (figures from CDC and ONS). Life Smokers die younger or likely to have comorbidities especially if they have smoked. Combines with other factors e.g under reporting and other mentioned already in the comment. Finally the effect size may be further attenuated by air pollution often severe in cities where most Covid-19 cases are found. Even if the paper shows a real effect, this would def change the effect size. In any case, it would not neccesarily show that smoking is protective

    1. On 2020-04-14 11:29:44, user Andrea Nicoletto wrote:

      I am not sure whether I am commenting a scientific article, a political statement or something in between. This article came to my attention because, even if it has not been peer-reviewed yet, has already been referenced in a press release of Italy's central health agency (ISS), which comments the results as a matter of fact and calls them "published".

      Skimming the full text the following points came to my attention.

      1 - On page 4, you state that "Due to the high concordance (99%) among confirmation results with the engaged laboratories, thepolicy was then changed allowing selected Regions with demonstrated confirmation capacity to directly confirm COVID-19 cases (17)." Reference 17 contains only an internal note specifying what a "case" is, but does not contain the data supporting the statement that there is high concordance. Previous publications coming from ISS (e.g. [1]) state that "99% of the samples analized by the national reference lab of ISS result POSITIVE", which suggests a selection bias in sending samples to the central laboratory and completely invalidates the confirmation process. False positive/false negative rates of the cross-analysis has not been reported.

      2 - In your introduction, you state that "extensive contact tracing and testing of close contacts unveiled ongoing transmission in several municipalities of the Lombardia region". The difficulties in testing and tracking cases in Lombardia region is well known, with several papers (including your references) and statements from authorities highlighting the fact that (a) the number of tested people is little w.r.t. the number of potential cases; (b) the classification of potential case varies on a regional basis, and a potential case in any other Italian region might not qualify as a potential case in Lombardia region, thus not getting tested; (c) testing protocols in Lombardia region do not include the testing of people living within the same household of the confirmed case, thus it is unclear in which way the contact tracing has been "extensive"; (d) the delay between the collection of the swab and the communication of the result is long and with a high variance. All these facts shall be taken into account when analyzing statistical data.

      3 - In your conclusions (!), you state that "Further, we observe that as of March 8 2020, the Rt it is still abovethe epidemic threshold. The progressively harsh physical distancing measures enacted since then may have enhanced the decreasing trend in transmissibility as happened in China". You support this statement using a paper which analyses the transmission of Ebola in West Africa. This seems to me like a political statement which shall have no place in a scientific paper, let alone on its conclusions. You have no data to back this statement, since your analysis terminates on the 12th of March, i.e. three days later of the enacment of the lockdown. You even show that there is a decreasing trend in R_t starting in the last decade of February, which puts the R_t at the beginning of the national lockdown slightly above 1 with a strongly declining trend. While writing this sentence has no scientific value, of course, it allows the MoH and ISS to defend their decision-making because "science said that".

      I do not have the specific background to carry out a review of the quantitative data, but I cannot ignore the use of poorly-backed statements to dignify as "science" what are only political decisions. Unsurprisingly, these statements are those which will fit into press releases and official statements.

      [1] https://www.epicentro.iss.i...

    1. On 2020-04-14 22:16:56, user VWFeature wrote:

      Which just restates CDC's pandemic flu advice a different way. Assuming ~1/1000 mortality, this suggests that unrestricted spread which might infect 250-300 million people in the US would cause a peak of illnesses with 25 million hospitalizations and 250,000-300,000 deaths in the US over 1-3 months, well above what the health system can manage.

      This would cause a situation worse than Italy with many people dying from otherwise treatable conditions, a higher death rate, and thus 500,000-3 million deaths in the US, many of them health care workers who get higher exposure at work.

      US states responded late, but better late than not at all.

    1. On 2020-04-15 20:31:22, user Jim Thompson wrote:

      It will be interesting to see if they break out the degree of symptomatic improvement. Profound reduction of CRP suggests a substantial anti-inflammatory effect. Right now the data seems to be pointing toward early use with the positive endpoint being reduction in progression to more severe disease. That would be a powerful benefit. C19 is overwhelming us with the ones who get really sick; for the rest it's fairly trivial as diseases go...

    1. On 2020-04-15 20:57:05, user Christian Smith wrote:

      In the Discussion section, you write: "Should either those reported data or current global understanding of COVID-19 biology include substantial errors, those will become evident as a divergence between model predictions and Sweden’s public health situation"

      Why did you then decide to not compare your predicted results to the real-world observations we have access to so far? Current (April 15) Covid19-induced ICU cases are reported at approximately 500, current hospitalized cases at 2100, accumulated deaths at 1200, and accumulated detected cases at 12000. There seems to be something off with your predicted numbers. Your plots are not easy to get exact numbers from, but as far as I can tell, the following numbers pop out for April 15 (today):

      Figure 2A) ~20 000 hospitalized, 2B) ~10 000 hospitalized.<br /> Figure 3A) ~4000 ICU cases, 3B) 2500 ICU cases

      Your predictions are an order of magnitude off from actual observations.

      Minor point: Your assumptions on available ICU beds in Sweden are based on outdated sources. It is well known that the capacity has increased significantly in the last month.

    2. On 2020-04-16 21:48:19, user Kelsey Wood wrote:

      I'm curious as to how long the mandated social distancing would have to be to reduce deaths by 50% (the paper doesn't say how long this period would be) and what would happen to deaths when those measures are lifted

    1. On 2020-04-16 13:24:14, user Rachel Tipton wrote:

      2 hours of wear! People ate having to wear these for 10 and 12 hours at a time, "decontaminate", and wear for another 10-12 hour shift. This is a serious limitation in the study! You're putting people at risk by releasing this information because hospital administrators will then jump on this and preach it like doctrine while the providers have to wear the same mask for shift after shift. Please go back and redo this study with a longer wear time in between decontamination. Then this will truthfully be applicable to the work force.

    2. On 2020-04-16 21:42:14, user Gracie wrote:

      Critical language from the full report "Quantitative fit tests showed that the filtration performance of the N95 respirator was not markedly<br /> 30 reduced after a single decontamination for any of the four decontamination methods <br /> Subsequent rounds of decontamination caused sharp drops in filtration performance of the ethanol-treated masks, and to a slightly lesser degree, the heat-treated masks. The VHP- and treated masks retained comparable filtration performance to the control group after two rounds of decontamination, and maintained acceptable performance after three rounds." Ethanol is not an acceptable treatment method.

    3. On 2020-04-17 13:01:47, user Greg Blonder wrote:

      Two comments:

      1) Can you also test whether 7 days in say modest heat (120F) is effective? This would allow people to use a buffer stock protocol- in on Monday, out the next week, and would decontaminate PPE in general. Absolutely critical in preventing death in developing nations. Even if it does not kill all associated microbes, like MERS, any improvement is needed.

      https://1drv.ms/b/s!AkTaUk4...

      2) Can you please influence 3M to could create a heat decontamination grade mask, perhaps with a color changing use indicator for tracking number of cycles? Heat decontamination is faster, cheaper and has improved coverage compared to peroxide vapor .

    1. On 2020-04-16 18:03:55, user Sinai Immunol Review Project wrote:

      This retrospective study evaluated the use of intravenous methylprednisolone to treat severe COVID-19 pneumonia in a cohort of 46 patients. The severity of the disease was determined according to version 5 of the Coronavirus Pneumonia Diagnosis and Treatment Plan by the National Health Committee of the People's Republic of China. The percentage of patients with comorbidities was 32%, and it was reported similar between methylprednisolone treated and untreated groups. The results showed that the group of patients that received methylprednisolone (n=26) had a shorter number of days with fever than patients that did not received methylprednisolone (n=20); they also had a faster improvement of peripheral capillary oxygen saturation (SpO2), and better outcomes in follow-up CT scans of the lungs. The dosage of methylprednisolone was reported to be 1-2mg/kg/d for 5-7 days, although there is no information about the concrete dosages for each patient. From the 46 patients, 43 recovered and were discharged, while 3 cases were fatal. Patients without administration of methylprednisolone needed longer periods of supplemental oxygen therapy, though there is no reference to the number of patients requiring mechanical ventilation. Interestingly, there were no significant differences in leucocyte and lymphocyte counts nor in the levels of IL-2, IL-4, IL-6 or IL-10 after treatment with methylprednisolone.

      Some of our main criticisms to this study are also pointed-out by the authors themselves: it is a retrospective single-center study with no validation cohort and without mid- and long-term follow-ups. The reported mortality was 7% (3/46) and did not appear to be affected by corticosteroid treatment: one patient died in the group that did not receive methylprednisolone, while two patients died in the methylprednisolone treatment group. Additionally, although the authors mention that patients received cotreatments, such as antiviral therapy and antibiotics, there is no mention of differences between the prevalence of other medications between the two groups. Unfortunately, there is also no indication on whether the patients receiving methylprednisolone were discharged earlier; the authors merely refer that the symptoms and signs improved faster.

      Corticosteroid have been widely used as therapy for acute respiratory distress syndrome (ARDS), including in infections by SARS-CoV, so these findings in COVID-19 patients are not unexpected. The implications of this study for the current pandemic due to SARS-CoV-2 require evaluation in future clinical trials, especially in a randomized way and in combination with and comparison to other immunosuppressive and immunomodulatory agents, including hydroxychloroquine. Nevertheless, based on this report, the intravenous application of methylprednisolone with the intention of strengthening the immunosuppressive treatment and controlling the cytokine storm appears to be safe in COVID-19 patients, and it might successfully shorten the recovery period.

      This review was undertaken by Alvaro Moreira, MD as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai

    1. On 2020-04-17 16:39:15, user Thomas Clarke wrote:

      These results would be more useful with more complete description of the propensity score used here.

      The use of log(age) will I believe lead to very poor deconfounding of age-related group differences. The correlation between CFR and age varies as more like exp(age) - with an increasing effect as age increases. log(age) will make the difference between 40 and 80 the same as the difference between 20 and 40 - clearly wrong. Better (although still problematic) is to use just age, best to use a suitably fitted exponential of age. [Unless I've misunderstood what is meant here by log-transformed age, and the variable used in the analysis is actually the exponential of age].

      For example: two populations of ages {20,40,80} and {40,40,40} would be viewed as similar in age-related mortality risk with this treatment whereas that is far from true.

      More information about the treatment of other confounders - e.g. "admission data" which would appear to be an undefined scalar, and lesion area where the treatment of 0 is arbitrary and maybe problematic, would be appropriate.

      Finally, information about the relative matching of the different groups used would help determine the sensitivity of the results to these issues: the sensitivity analysis stated does not address this. The Hosmer-Lemeshow test is helpful but in view of possible extreme nonlinearity in confounding variables I think good results could be obtained from this when in fact they are not robust.

      This is an interesting analysis and it would be good to see how the results hold with more careful handling of age correlation to CFR. There may be similar issues with other parameters, but more information would be needed here to determine that, and the very strong nonlinearity of CFR with age stands out. All these concerns could be answered without additional test data, so it would be helpful if the authors could do this in more complete write-up.

    1. On 2020-04-17 18:53:10, user Frank Conijn wrote:

      A few matters should be noted:

      * This study was done with patients with "severe COVID-19". In patients with severe SARS Cov disease, the virus was found to have damaged the heart in 35% of cases, causing "cardiac disease including arrhythmias, sudden cardiac death, and systolic and diastolic dysfunction" (1). So, a fair portion of the patients in the Brazilian study probably already had poorly functioning hearts at the start of the study.

      * The dosage in the high-dosage arm was extremely high: 2 x 600 mg of chloroquine per day for 10 days. Chloroquine is stronger and has more side effects than hydroxychloroquine. In comparison, Gautret et al found a substantial beneficial effect with a much lower dosage: 3 x 200 mg of hydroxychloroquine per day for 10 days (2).

      * (Hydroxy)chloroquine has always been contraindicated for, or should be prescribed with extra caution to, patients with a cardiac arrythmia. (Which of the two differs per country.)

      * It furthermore has a pretty good safety profile. Even in long-term use by patients with diabetes II, who have a high chance of retinopathy (3).

      This suggests that (hydroxy)chloroquine could still be used in patients with mild symptoms that do not have a history of cardiac disease (the congenital Long QT Syndrome [LQTS] is a very rare disease). Even by family physicians/general practitioners, if you'd ask me.

      Patients with such a history should be referred to a hospital, in which there would be an alternative in the form of remdesivir.

      References:

      1. https://onlinelibrary.wiley...
      2. https://www.sciencedirect.c...
      3. https://pubmed.ncbi.nlm.nih...
    1. On 2020-04-19 01:39:26, user Constantine Daskalakis wrote:

      Where do the testing data for Germany and Spain come from (Fig2)? As far as I know, <br /> they don't report total number of tests performed.

    1. On 2020-07-16 12:04:36, user MT Foley wrote:

      Hi, The high seroprevalence results from Bergamo (57% infection rate by June 3) may present a counterfactual challenge to this model. I find it unconvincing that this busy district of northern Italy would have had little by way of previous exposure to the other four common corona viruses, or would experience much less cross-protection from such exposure to prevent infection rates climbing this high. Would welcome any clarification or thoughts, as the implications are substantial if on the back of such research public health policies or populations were to relax measures too soon.

    1. On 2020-07-16 18:54:38, user Marm Kilpatrick wrote:

      This is a fantastic dataset. Could you possibly show the data relative to date of onset of illness, both for SARS-COV-2 & for other viruses? Also will the raw data be shared when paper is published? This could help quite a bit in syntheses on several key topics. Thank you!

    2. On 2020-07-24 07:38:54, user Sally Anderson wrote:

      What volume of buffer/medium do you add to your swabs? Do you test the whole of the sample by RTPCR or do you only process a proportion of it? When you plot no. of copies / ml is this per ml of buffer/medium you initially place the swab in? Do you think you are just targetting virus particles or is there a contribution from infected cells?

    1. On 2020-07-16 20:34:30, user David Halvorson wrote:

      This paper should not be published in its present form. The following statement is totally without a factual basis; "Thus, it is not clear that the risk of getting infected during a flight is any higher than the risk associated with everyday activities during the pandemic." It is obvious to most of the air traveling population of the world that the risk associated with flying is much greater than the risk associated with everyday activities. The large number of people in close proximity violate two of the few tools available to us according to health professionals. On another note, it is obvious that emptying 1/3 of the seats would reduce the number of passengers and similarly reduce the risk.

    1. On 2020-07-17 04:24:05, user Bruce Conklin wrote:

      I wrote the authors on July 12, asking if they had data on troponin levels. The authors have not responded. I tried to download the supplementary data, but found none. Investigation into direct tissue effects of the virus on tissues would be warranted to back up the claim that the disease is only immunological.

    1. On 2020-12-05 11:14:49, user Robert Brown wrote:

      A very useful study, but more questions than answers surely? I respectfully suggest an alternative one-line summary might read:

      Administration of a significant single oral bolus of Vitamin D3 (200,000iu) in COVID-19 patients, close in timeline to onset of ARDs, with Baseline 25(OH)D values averages of 21.0ng/ml and 20.6ng/ml, where significant numbers are on Corticosteroids and or PPI (which reduce magnesium and zinc (via zinc fingers), both ‘D’ co-factors), when almost all established risk factors were skewed against the treatment arm, did not result in any benefit in hospital stay or mortality.but did show tendency to reduced oxygen requirement.

      See lower post for detail.<br /> Erratum reference 2 is a TCT and not RCT – apologies.

    1. On 2020-07-20 17:29:44, user Kamran Kadkhoda wrote:

      The following finding <br /> Using the pre-defined cutoffs, the sensitivity of IgG antibodies rose from 7% (<=7days) to<br /> 7% after 14 days of symptoms. The sensitivity of IgA and IgM rose to 91% and 81% 2-4 weeks<br /> post-symptom onset but dropped after 4 weeks to 57% and 40%, respectively.<br /> ...is classic for an anamnestic immune response especially given<br /> IgG showing up early similar to other studies and the half-life of<br /> IgG-plasmablasts suggesting response to previous response to common CoVs.

    1. On 2020-07-20 20:58:06, user Dan Elton wrote:

      This is classic p-hacking! Look at https://en.wikipedia.org/wi... and apply a correction (the simplest would be the Bonferroni correction, or dividing the p values by the number of comparisons done). I'm going to be really sad if a journal publishes this without a massive overhaul. Negative results are useful, but statistics have to be done correctly or you're doing everyone a big disservice!

    1. On 2020-07-20 23:49:35, user Joshua Santarpia wrote:

      Hi all,<br /> Several folks pointed out the high airborne concentrations noted in the original version of this manuscript. We appreciate the catch. The units should be in TCID50/m3, not cm3. A major difference. A corrected version should be available soon.

    1. On 2020-07-21 05:50:56, user Josh Lerman wrote:

      Super interesting. I also noticed this cycle just by eye browsing the CA data. If it is an artifact of data collection, that should maybe be fixed. Thanks for the analysis.

    1. On 2020-07-21 22:11:37, user BiotechObserver wrote:

      "Screened patients either had confirmed SARS-CoV-2 infections by PCR, or suspected disease, defined as being told by a physician that symptoms may be related to SARS-CoV-2 or exposure to someone with confirmed SARS-CoV-2 infection... In addition to screening potential donors, Mount Sinai also offered the Mount Sinai ELISA antibody test to all employees within our health system on a voluntary basis."

      It would be helpful to know what percentage of each of these 4 subsets of screened patients (out of the 51,829 total screened) were positive vs. negative on the ELISA test. <br /> Your sensible subsequent explanation on sensitivity findings notwithstanding, (it seems plausible you are detecting positive in the ELISA test >95% of those with a confirmed past infection), this breakdown would still be valuable from an epidemiology perspective.

      "The vast majority of symptomatic cases that were screened experienced mild-to-moderate disease, with less than 5% requiring emergency department evaluation or hospitalization."

      It would be helpful to visualize in a few additional figures the breakdown of various measures (titer ranges, decline/increase, neutralizing activity) stratified by severity of symptoms (asymptomatic vs. mild vs. moderate vs. hospitalized, or asymptomatic vs. mild/moderate vs. hospitalized).

      Thank you.

    1. On 2020-07-22 18:17:50, user Marm Kilpatrick wrote:

      Dear Authors,<br /> I'm confused about the methods used to recruit participants. The text seems to indicate that you posted a website to which people could volunteer and then selected randomly from those that volunteered. Is that correct? If so, this seems like a very biased set of people from which to select a random sample and would likely alter the resulting seroprevalence estimates. If I am misunderstanding how you recruited participants could you please clarify that part of the text? Thanks!<br /> marm

    1. On 2020-07-23 09:56:15, user Jonathan wrote:

      One has to hope for a vaccine and/or effective treatment before the colder northern hemisphere seasons. If not, a second wave is almost inevitable. Thank you for your vital and ongoing work.

    2. On 2020-07-23 13:47:00, user Gill Prager wrote:

      At what Baseline outside air temperature does the 15% change in mortality occur? For how long does that temperature need to remain constant pluS/minus each degree for each subsequent rise/fall in mortality?

    1. On 2020-07-24 10:17:10, user Paul McKeigue wrote:

      This revision includes changes made in response to the first stage of peer review: new material includes the passages highlighted in yellow and Supplementary Table S1.

    1. On 2020-07-24 16:23:32, user David Gagnon wrote:

      Was any data collected on the numbers for the ages of the people in the same household?This section was badly written, is missing something, or I just don't understand something in the language. 15.5% is the lowest of those numbers and that seems odd, since the I would guess the majority of 2 person households to be couples without kids, both young and old, and in the latter case the secondary infection should have been notably high, right?<br /> There are also three number in the section that correspond to three groups:<br /> "The secondary infection risk for study participants living in the same household increased from 15.5% to 43.6%, to 35.5% and to 18.3% for households with two, three or four people respectively (p<0.001). "<br /> Is the 18.3% for households with more than 4 people? Is it then 18% per person?

    1. On 2020-07-26 01:02:03, user JayTe wrote:

      Relatively simple to calculate the herd immunity threshold. Take the CDC figure for the infection fatality rate multiply by Covid-19 deaths to determine the infected population. Divide the infection population by the total population and you get the implied herd immunity threshold. Overall for the US it is 15%. There are some states that have not reached that level. Mainly Florida, Texas and Arizona. Does that give you a clue as to what is happening in those states?

    1. On 2020-07-26 06:33:24, user Aurora Fontanilla wrote:

      X-linked recessive gene carriers (mothers of G6PD deficient) should also be considered in the study as they may already be considered as immunocompromised. If so, they may easily spread the virus to their children G6PD deficiency.

    1. On 2020-07-29 06:02:10, user Marm Kilpatrick wrote:

      Thank you for this important work. It appears that the data in Table 1, include both the cases detected due to symptoms as well as those detected through contact tracing. If this is the case, then could you possibly also present the data (perhaps in a supplementary table) that only includes characteristics of cases from contact tracing? This way one can get a true sense of the fraction of cases for each age that are truly asymptomatic? The current presentation, if it includes cases detected due to their symptoms, would overestimate the fraction symptomatic. Thank you.<br /> marm

    1. On 2020-07-29 22:25:43, user P. J. wrote:

      When you download the PDF, you will see all relevant info. ALL patients also got hydroxychloroquine and 3/7 also got azithromycin. Interestingly no heart issues, no deaths, better outcomes. Is it the combo...maybe? Honestly, I don't care as long as it works, but let's be up front about it.

      Seven patients out of 7 received at least one dose of the study drug?? Only 3/7 even got the full treatment? (It looks like with an average length of stay of 14-24.5 days, there was plenty of time to complete a 14 day course, assuming treatment began on the first day.)

      They do not give any breakdown of the drug group vs control as far as co-morbidities so they will need to do that going forward.

      In the end, there were 5 patients. Not sure if all those were on HCQ, as they leave that out. Were any of the five on azithromycin? Who knows? It says "overall" 3 patients received the full course of the study drug. Ok, is that overall of the 7 that started, or the five little patients that remained? Let's ASSUME 3 of the final 5 got the full 14 days, plus maybe HCQ and maybe AZ? There was no statistical significance in the length of time weaning from HFNC to NC 02. Time to room air was about 1.5 days sooner...so 36 hours.

      " Six patients in the control<br /> group (33%) required mechanical ventilation (p value compared with opaganib groups=0.13), 2(11%) required ECMO, and one required tracheostomy"

      The drug group also had better D-dimer results and higher baseline lymphocytes going into the study which are both markers seen in patients who tend to have better outcomes, drugs or not. There was no difference in the rate of CRP improvement between the control and drug group. They couldn't measure true normalization of lymphocyte count because the control group received steroids.

      Am I the only person routinely disappointed by the quietly buried info on HCQ? I think it was the RECOVERY remdesivir arm where patients weren't randomized until day 10-12 (well past the point where an antiviral would be of significant benefit) and 85% received HCQ up until starting remdesivir...and some even while taking it. A good number in the severely ill group were already maintaining O2 sats of 94% on room air when started on Remdesivir...in nursing, as far as oxygenation, we call that "stable." I don't know..maybe it's just me.

      The results of this amazing new drug just aren't impressive when this sentence is included by the authors:

      "In total, seven patients received at least one dose of opaganib since April 2, 2020. All<br /> patients received hydroxychloroquine (HCQ), however one stopped HCQ prior to opaganib<br /> treatment due to borderline Q-T interval in ECG. Three patients received azithromycin as well. One patient, who received both HCQ and azithromycin, developed diarrhea after two doses of opaganib, and the treating physicians decided to stop all his medications. A second patient who deemed to be in severe condition, was weaned to low flow oxygen within hours, and was discharged on RA (how long had he been on HCQ? Was he also on Azithromycin?) after receiving two doses of opaganib. Therefore, five patients were included<br /> in this analysis. Overall, 3 received the full 14-day course of opaganib, and 2 patients received 11 and 7 days respectively, before being discharged."

      2/5 received 11 and 7 days of study drugs before being discharged. Were they discharged on the last day of treatment? I don't think so since discharges were from 14-24.5 days in the treatment group. Why was therapy discontinued before discharge? 15.2-29.5 days until discharge in control group. Not sure who fell where so hard to know if that was statistically significant or not. But, the rate of decline as far as needing ECMO or mechanical ventilation were good...maybe, I mean with better D-dimer (not sure how much better...no info there) And higher lymphocyte count at the onset of the study, (Again, not sure how much higher) It's hard to know if the drug helped, if the other drugs helped, or if those patients were more stable going in and would have recovered either way. It just feels like another non-study study. I also have no idea how big the control group was. OH wait, there's a table. I missed it. The control group is over 3x the size of the trial group...come on guys. The control group had 3-4x the comorbidities..so a stacked control group in number and chronic disease manifestation. Mean lymphocyte count in the control group was 850 vs. 1100 in the drug group. Other labs as listed in Table one when you click on the PDF, but overall, the control group was sicker.

      I would be interested to know how the drug group (that got HCQ, study drug, and AZ) did vs the control group patients who got HCQ and AZ) That would actually be a more fair comparison...well maybe. I can't be sure since the control group was sicker and had more comorbidities to begin with.

      I started this analysis wondering if there was an exciting new drug that could really help and I finish still wondering the same thing. I am beginning to question if any of these studies have people familiar with research standards running them. No randomization, no blinding, no real placebo control group, (I understand the ethics of having a "no treatment" group that truly gets "no treatment" and respect that all patients deserve treatment so placebo will always be a treatment group.)

      Doctors on the drug company payroll or affiliated financially with the drug company, data analysis of trials and studies done by the sponsoring drug companies, writiing of studies by drug companies and or their employees rather than doctors without bias....I just find it all questionable.

      I keep reading studies that leave out randomization, control group, blinding, etc. The inclusion of gold standard research methods could give us real scientific data. Why does the scientific community routinely fail to integrate the known gold standards in their studies? Do they feel their drugs wouldn't stand up to such rigor?

    1. On 2020-07-30 04:05:03, user Martijn Hoogeveen wrote:

      In the v5 update: results of medical findings explaining the effects of allergens/allergies on influenza/COVID-19 are included. Methodological sensitivity analyses are added by including bootstrapped correlations and controlling for autumn. Outcomes are similar and conclusions are the same.

    1. On 2020-06-30 12:20:05, user Dude Dujmovic wrote:

      Nothing about filtration other than saying use multiple layers to improve filtration? How many layers? That is the most important aspect of mask. Hydrophobic property is important but you cannot recommend something that you did not do basic filtration research about.

    1. On 2020-06-30 14:50:33, user Munir Hazbun wrote:

      Congratulations with your results . We have published in Critical Care Exploration very encouraging results with a higher dose of MP. We learned early that at high dose MP work very well for rescue we have not have any prone position need and outcome are about 10% mortality in about 60 patients so far. Certainly optimal nursing and respiratory strategies are necessary for example we are not using propofol and use recruitment lung strategies

    1. On 2020-08-01 16:36:24, user Dude Dujmovic wrote:

      Term "loss expansion" deserves definition, it sounds like oxymoron. The table 2 is unreadable, you need to separate weeks into separate graphs to make sense of that.

    1. On 2020-08-09 20:47:59, user med sci wrote:

      Perhaps this topic "Seroprevalence of COVID-19 in Niger State" may be modified to reflect that the study was conducted only on small population of Niger state.

    1. On 2020-08-12 06:05:43, user Christian Heebøll-Nielsen wrote:

      It seems most of the differences between groups could be explained by the difference in time since symptoms onset. Have you made any effort to control for that?

    1. On 2020-08-12 17:28:58, user Lee Rague wrote:

      This study has been recently published as follow:

      Labrague, L. J., & de los Santos, J. (2020). COVID-19 anxiety among frontline nurses: predictive role of organisational support, personal resilience and social support. Journal of Nursing Management.

    1. On 2020-07-08 16:50:14, user tyler wrote:

      It is not possible to evaluate the merits of this "research" based upon an abstract which reports — using unspecified estimates and models, and unspecified methods to eliminate confounders — that this spring's unprecedented surge of first-time interest in exercising Second Amendment rights in the US has a significant causal link to the 0.00037 additional "fatal and nonfatal" injuries correlated with each additional firearms purchase.

      But, really...? Doesn't it also seem likely that the 0.000 additional injury associated with each additional gun purchase might be "caused" by pandemic panics and leadership failures? Or institutional racism? Or a divisive President inflaming a constituency of intolerance and fear? Or a surge in off-premises alcohol consumption? Or George Floyd, police misconduct, and cosmic rays?

      I hope that disclosure and review of data and methods might clarify any strengths or weaknesses of this work.

    1. On 2020-07-09 21:41:42, user kpfleger wrote:

      Thank you for this study! Suggestions to improve the manuscript:<br /> (1) In the PDF version linked here from medRxiv (as of 2020/7/9), p.1 states the multivariate infection OR as 1.45 but p.5 & table 3 list it is 1.50. Minor discrepancy but good to get the p.1 results summary correct.<br /> (2) You imply in the conclusion that most of the 25OHD test results were recent, such as upon presentation to health services for illness, but it would be helpful for you to characterize the dates of the 25OHD tests in your cohort. (Eg, so we know they aren't as old as the 10+ year old UK Biobank results.)<br /> (3) It would be helpful to have the descriptive statistics for demographic and clinical characteristics for the hospitalized vs. non-hospitalized COVID-19-P patients---analogs of tables 1 & 2 stratified by hospitalized or not. I'm not even sure you say how many were hospitalized.<br /> (4) You gave the multivariate adjusted OR for infection and the OR for hospitalization given infection. It would be nice to state the adjusted OR for absolute risk of hospitalization (not specifically given infection) as this is perhaps more meaningful for public policy.

      I look forward to a couple more analyses like this from other large HMOs or government insurers around the world. I also look forward to data on post-hospitalization measures of severity (eg, ICU/ITU admission, fatality) in population cohorts this large.

    1. On 2020-08-17 06:39:53, user Jesper Markmann wrote:

      A big difference between Sweden and Danmark, and the UK, US, and southern Europe is labor market rules and culture. In Denmark and Sweden people would stay at home, if they have the slightest symptoms. In the latter group of countries, more people would be inclined to go to work, in spite of symptoms in fear of loosing their source of income.

    1. On 2020-08-18 03:13:47, user Bashar Emon wrote:

      The paper has been peer-reviewed and published in a reputed journal- Extreme Mechanics Letters.

      Onur Aydin, Bashar Emon, Shyuan Cheng, Liu Hong, Leonardo P. Chamorro, M. Taher A. Saif,<br /> Performance of fabrics for home-made masks against the spread of COVID-19 through droplets: A quantitative mechanistic study,<br /> Extreme Mechanics Letters,<br /> Volume 40,<br /> 2020,<br /> 100924,<br /> ISSN 2352-4316,<br /> https://doi.org/10.1016/j.e....<br /> (http://www.sciencedirect.co... "http://www.sciencedirect.com/science/article/pii/S2352431620301802)")

    1. On 2020-08-19 17:04:00, user Pat Tokarz wrote:

      Thank you for this important information in such a timely fashion. It will be interesting to compare your experience with other institutions<br /> over time.

    1. On 2020-08-19 21:20:12, user Sissy Lona Moxley Skaggs wrote:

      Since this is dated in May as there been any additional information in your news base on antibodies or the length of the contagion in carriers that could be reviewed?

    1. On 2020-07-15 16:36:55, user Peter Ellis wrote:

      Death data for the UK (and its constituent nations) show a very pronounced weekend effect when analysed according to the day of reporting - see for example the graph at the bottom of this page:<br /> https://coronavirus.data.go...

      However, in England the "weekend effect" almost entirely disappears when data are analysed according to the actual date of death rather than the date of reporting - see for example the daily data files reported here:<br /> https://www.england.nhs.uk/...

      This therefore appears to be an entirely artefactual phenomenon driven by reduced reporting at weekends. The authors dismiss this possibility and assert that "one would expect for the pooled world data to be averaged rather than this almost weekly periodicity". Unfortunately for their hypothesis, Saturdays and Sundays fall on the same date everywhere in the world.

    1. On 2020-08-28 07:43:07, user Hilda Bastian wrote:

      At several points, the authors rely on what's described as the "historical efficacy of passive antibody therapy for infectious diseases". This is based on a small amount of data, much of it from the pre-intensive care era, and none from a publication later than 2010. As a result, no randomized trial is included, as they were published after 2010: 2 NIH randomized trials of convalescent plasma in influenza and 2 randomized trials of IVIG for influenza. Meta-analysis shows no benefit. [1] This also fails to consider the post-2010 ebola outbreak, and the failure of convalescent plasma to improve mortality from that disease. [1] Thus, there is no historically proof of efficacy of convalescent plasma, and what randomized data exists, does not suggest there has been important benefit in the past.

      In addition to relying on this biased assessment of historical evidence to support a conclusion of effectiveness in this study, the authors cite this claim as a reason for not conducting a randomized trial: "Many COVID-19 patients would likely have been distrustful of being randomized to a placebo based on historical precedent". However, if they were accurately informed, prospective participants would be told there was no evidence of benefit. In a randomized trial in the Netherlands stopped because it was determined no benefit was likely in the study as designed, the authors reported that only 1 in 4 eligible patients declined, and that was typically because of fear of adverse events. [2] The requirement for adequate trial recruitment has more to do with doctors and patients in outbreaks not being misled about the state of uncertainty of this treatment.

      The authors argue that the patients in the Expanded Access Program are diverse. However, it is important to point out that their diversity is not representative of the people severely ill with Covid-19 and at risk of dying. For example, 19% of the group are Black, whereas the CDC reports that they are over 30% of those hospitalized with Covid-19 and twice as likely to die. [3,4]

      In respect of the representativeness of the small non-random sample described as "pseudo-randomized" in this preprint, no data is provided on the hospitals providing those samples.

      In addition, as others have already pointed out in a discussion linked here, [5] critical information on timing of deaths is not provided. Those transfused earlier in the "epochs" have far longer follow-up for deaths than the larger number more recently. Given that since early in the outbreak, it's been observed that deaths occur across 2 to 8 weeks from the onset of symptoms, [6] the impact of this could be substantial, as participation in the EAP was higher later. In the group on the Diamond Princess cruise, for example, per Wikipedia's tallying, half the deaths may have occurred in that second month [7], and assessment of mortality appropriately included censoring for this. [8] Case series in the US typically report substantial proportions of people still in intensive care at study's end.

      The authors' interpretation of their subgroup analysis based on a non-random set of blood samples preserved for blood bank quality assurance proceeds as though the safety of convalescent plasma for Covid-19 has been established, based on the data of their own uncontrolled study. However, controlled study is required to be certain, for example, whether plasma with lower levels of antibodies trigger antibody dependent disease enhancement. [5] As the FDA's memorandum reports that the results are also dependent on which assay results are used, this should be reported in any discussion of this subgroup analysis. [9]

      In the absence of adequate controlled study of convalescent plasma establishing that it does more good than harm in infectious respiratory disease generally in contemporary medical settings, and Covid-19 in particular, the authors' claim that their uncontrolled study provides "strong evidence" is unjustified.

      Disclosure: I have written about this study for the general public at WIRED, and am in the process of doing so at PLOS Blogs.

      [1] Devasenapathy (2020). https://www.cmaj.ca/content...

      [2] Gharbharan (2020). https://www.medrxiv.org/con...

      [3] CDC COVID-Net (2020). https://gis.cdc.gov/grasp/C...

      [4] CDC surveillance data (2020). https://www.cdc.gov/coronav...

      [5] Harrell (2020). https://discourse.datametho...

      [6] WHO (2020). https://www.who.int/docs/de...

      [7] Wikipedia (2020). https://en.wikipedia.org/wi...

      [8] Russell (2020). https://www.medrxiv.org/con...

      [9] FDA Clinical Memorandum (2020). https://www.fda.gov/media/1...

    1. On 2020-11-23 09:17:17, user Brenda Penton wrote:

      I don't see how the data can be used if it only included 4 months of pandemic data? If Sweden had had a decreased mortality rate pre-pandemic and after the first wave, wouldn't that mean they would have had a decreased annual mortality rate otherwise or the assumed trajectory? I'm not sure if after wave data can be used since people still distanced, I'd assume. I can see if they used data next year comparing the two from March 2020 to March 2021. I still don't see the relevance of the study...even though Sweden had thousands of deaths from a pandemic..they would have died anyways, so no biggie? Is that it? It seems that people are using this data for proof that Sweden didn't do so bad or some kind of excuse? It's a little messed up to me.

    1. On 2020-12-01 11:33:46, user S Cook wrote:

      While all their theories and calculations may seem exact, it is a proven fact that people in room, house, building, etc. will spread Covid 19 much faster than the model indicates.

    1. On 2020-12-03 17:33:21, user Nikita Mehta wrote:

      Hello, I was wondering if RNA sequencing data for intronic variants (both canonical and non-canonical) was discussed in regards to PS3. Or at least adjusting PVS1's strength for canonical sites if possible?

    1. On 2020-12-05 01:38:02, user ACE NYPD wrote:

      I have been using Betadine Gargle (.05% Povidine Iodine) as a gargle & nasal spray for months at 3 or 4 times a day. My wife, who has comorbidities also uses it. I have been exposed to Covid at least 4 times by others at work, and have always come back negative. Since I am in Tech Support, I have used keyboards and mice of infected persons. I am currently working from home until my latest exposure is 14 days since exposure. I took a rapid test that came back negative 6 days after the exposure, but I am still waiting on the PCR test I took the same day.

      I also take a vitamin D supplement.

      Do I think that the Betadine Gargle is preventing me from getting Covid, yes I do, but of course talk to your physician first. I have found these articles about Povidine Iodine and Covid:

      https://www.pulmonologyadvi...

      https://doi.org/10.1177/014...

      https://www.thailandmedical...

      Stay safe and informed.

    1. On 2020-12-10 22:13:25, user Lincoln Sheets wrote:

      This is a fascinating and somewhat counter-intuitive, but plausible, finding that could have important implications for practice and policy worldwide. This study deserves wider publication.

    1. On 2020-12-11 00:01:06, user lbaustin wrote:

      Has this article been submitted to a journal yet? If not, please add to the conclusion the point that for people living in modern settings, dietary sources and sunlight rarely provide adequate amounts of vitamin D, which is why the authors of the papers reviewed here generally support universal supplementation with vitamin D3.

      Also, excluding RCTs is so unusual in a review of the evidence that this decision needs to be justified.

      And, Hastie, et al., did not have a true sample size of 348,598. Only 1474 of the individuals in the UK Biobank database had Covid-19 test results. Of these, 449 had at least one positive test, and the remaining 1025 had only negative results. Similar sample size adjustments should be made for the other studies (Merzon and Kaufman) using "big data."

    2. On 2020-12-11 00:47:38, user lbaustin wrote:

      This Basic Review could provide you with the information you need to add to this article about biological plausibility (page 7 and following). https://www.frontiersin.org...

      It also includes two causal inference studies (page 12).

      The recent RCTs and quasi-experimental studies (Castillo, Rastogi, Afshar, and two by Annweiler) should further bolster the argument that vitamin D supplementation is a causal factor in improved Covid-19 outcomes.

    1. On 2020-12-13 20:05:53, user Peter Hodgkinson wrote:

      The paper advocates an age-based priority system but then gives top priority to care homes - not the same thing! In several places it claims that this approach yields the best benefits based on the QALY method....and yet it provides no supporting math. I'll try to help out. Care home residents survive an average of 30 months from arrival so, those being immunized now will, on average survive 15 months. So the year factor equals 1.25. This figure then needs to be multiplied by a quality factor ranging from zero (no life quality restored) to one (full quality of life restored). I would like to know what figure was used?<br /> R is hovering around '1' and the ensuing lockdowns have had an awful effect on the quality of life on the rest of the 68,000,000 population. So let's work out a QALY figure for the loss of quality life over the last 9 months. The math is obvious. The vaccines should be targeted at keeping R below '1' by targeting the main 'mixers'. These are generally the people going about their daily work and this would benefit everyone. They've done this for healthcare staff - no problem with that. But why not all the many trades that are necessarily visiting peoples houses on a continuous basis?

    1. On 2020-12-17 13:40:29, user Dr Anand Lakshman wrote:

      Can the proportion of active infections found be compared to proportion found through routine testing for same period? <br /> Since we have samples collected over 14 days, can we look at RT PCR positivity for each day and calculate incidence over the study period?<br /> How did we account for various socio economic groups? The sampling appears biased towards lower socio economic groups as the settings are largely public hospitals. How was the sampling for the elderly and co- morbidities done, as that is only one which is truly community based random sampling?<br /> The active infection rate in Ballari district is an outlier. Needs to be verified.

    1. On 2020-12-23 13:11:08, user Sheena Ricarte wrote:

      I want to emphasize on the basic human need for employment. Indeed, work gives people dignity, pride, and a sense that they are important since they are a component of an organization meant to serve a key purpose in society. As French Enlightenment writer and philosopher, Voltaire wisely remarked, "Work spares us from three evils: boredom, vice, and need."

      These past few months, I found news articles about people committing suicide due to joblessness caused by the coronavirus or COVID-19 pandemic very common. The reports involved people in desperate scenarios from around the world: Canada, the United States, Thailand, India, the United Kingdom, South Korea, Japan, and so forth. This dismal reality shows that chronic unemployment caused by the COVID-19 pandemic is an international problem severely affecting mainly the most vulnerable and the indigents.

      Workers whose jobs are on the brink of becoming irrelevant and obsolete due to technology revolutionizing the way we work and live worldwide are also susceptible to joblessness and severe mental health issues. I believe the articles and news reports I read highlight the strong correlation between the significance of JOBS, the apparent viciousness of the COVID-19 PANDEMIC, and the severity of SUICIDE committed by people unemployed for long periods and in abject poverty.

      COVID-19 adversely impacted human survival. It immensely deprived the people around the world of their important need to earn a living, provide for their families' needs, basically survive, and live decently. I believe COVID-19 is a great and notorious human rights "violator." Moreover, I believe worklessness is lethal. Having a job basically translates to having food on the dining table and being able to pay one's essential household bills. People who are unemployed for a long period can surely get inconvenienced by its devastating effects on their overall wellness, quality of life, and family's survival.

      I think one of the ways to resolve the COVID-19 and unemployment-related suicides is education with a different focus. The world's governments should stress to the people that we live in changing times and educate them on the things that matter the most today and possibly in the future. We live in a changing world and coexist with people from different generations and with different beliefs. As a millennial, I believe WORK and MONEY are LIFE.

      Governments and schools worldwide should educate the people about the relevant life and workplace skills and jobs they believe would be important today and in the future. In this way, young people can equip themselves well skills-wise and become smart and adaptable. They can also find employment that can be future-proof. Schools should also emphasize offering helpful financial education and the significance of being financially stable, if not financially secure in the long run, to prevent people from suffering from poverty when they lose their jobs.

    1. On 2020-12-23 21:55:19, user Marc wrote:

      Were you able to compare these antibody types/quantities results against those resulting from other strongly immune-provocative respiratory viral infections such as type A flu?

      And were these autoimmune antibodies rapidly declining post-infection or did they demonstrate high persistence?

    1. On 2020-12-25 09:54:49, user DrAnurag Patidar wrote:

      The review is providing insight about the impact of mhealth intervention on ante and postnatal care in low and middle income countries. It's a unique meta analysis which is very well undertaken and articulated. It will help the policy makers to make appropriate decision with regards to antenatal and postnatal care. The analysis is focused on middle and low income countries where the MMR and IMR is in bad situation. The result may impact to improve upon the same.

    1. On 2020-12-26 04:26:03, user Peter Tomasi wrote:

      The authors of this study (Corona-Ciao) https://www.medrxiv.org/con... draw conclusions from the results of serologic testing for a still ongoing extremely high-exposure environment in the study area.

      They suggest these conclusions also to be valid in a general way for schools that apply preventive measures in high exposure environments.

      Serologic tests only get positiv after a certain period of latency post onset of symptoms (POS).

      The collection of samples started October 26, when case numbers in the general population of the study area just had very rapidly risen to an extremely high level and continued until November 19.

      The rise started suddenly September 30 and was most massive from October 14 till October 30. After the described sharp and fast rise case numbers remained more or less at the very high level ever since. <br /> https://www.zh.ch/de/gesund...

      In the discussion of the conclusions it is important to know in which exact extent serum sample collection respected the necessary POS-latency for them to be truly representative of the very high exposure environment the authors draw their conclusions for.

      The Study used the ABCORA 2.0 binding assay of the Institute of Medical Virology (IMV) of the University of Zurich (Ref. 22). The publicly available document describing the test gives no information about the latency.<br /> https://www.virology.uzh.ch...

      It nevertheless refers to the following study: Seow, J., et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. medRxiv, 2020.2007.2009.20148429 (2020). https://www.medrxiv.org/con...

      This document states the mean time to seroconversion from POS against at least 1 antigen to be 12.6 days (Line 117).

      The authors of Corona-Ciao specify samples in their assay (ABCORA 2.0) were defined as seropositive for SARS-CoV-2 if at least two of the 12 parameters were above the cut-off (Line 172).

      As a rough estimate I therefore suppose the usual latency of the test to get positive to be somewhat longer than 12.6 days, maybe 14 to 21 days? If we ad 7 more days for safety, we have 28 days.

      I suppose the Institute of Medical Virology of the University of Zürich has validation data for its ABCORA 2.0 Test that specify latency from POS. It would be interesting to have validation data for children, if they exist.

      If we assume a latency of 28 days, a substantial amount of samples could have been collected while the level of the exposure environment was not yet as high as the one the authors draw their conclusions for.

      To clarify this worry, it is important, that the authors release complete information about when exactly collection of the samples occurred for all study participants and which exact latency from POS they assume on which validation data of the used ABCORA 2.0 Test.

    1. On 2020-12-28 18:04:37, user Rogerio Atem wrote:

      The 3 preprints of this series on COVID-19 epidemic cycles were condensed into a single article that summarizes our findings using the analytical framework we developed. The framework provides cycle pattern analysis, associated to the prediction of the number of cases, and calculation of the Rt (Effective Reproduction Number). In addition, it provides an analysis of the sub-notification impact estimates, a method for calculating the most likely Incubation Period, and a method for estimating the actual onset of the epidemic cycles. <br /> We also offer an innovative model for estimating the "inventory" of infective people.<br /> (Revised, not yet copy-edited)<br /> https://doi.org/10.2196/22617

    1. On 2020-12-29 00:33:03, user Olga Matveeva wrote:

      Several recent preprints support some of this manuscript findings.<br /> 1. Authors from Sweden and China in a study entitled “Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death” demonstrated that “The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelial, pericytes or stromal cells. doi: https://doi.org/10.1101/202...<br /> 2. Researchers in China concluded that “Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue-resident CD169+ macrophages.” They published a preprint entitled “The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Node” doi: https://doi.org/10.1101/202...<br /> 3. Researchers in France demonstrated “that SARS-CoV-2 efficiently infects monocytes and macrophages without any cytopathic effect.” Their findings are reported in the preprint entitled “Monocytes and macrophages, targets of SARS-CoV-2: the clue for Covid-19 immunoparalysis” doi: https://doi.org/10.1101/202...<br /> 4. Researchers in Brasil investigated SARS-CoV-2 infection of PBMCs and found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. They also found that “SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4+T lymphocytes” The preprint is entitled “Infection of human lymphomononuclear cells by SARS-CoV-2”. <br /> doi: https://doi.org/10.1101/202...

    1. On 2020-12-29 21:21:46, user Meerwind7 wrote:

      Is this modelling for an isolated "island state"? If there is exchange with other regions, where infection rates are assumed constant or independant of the regional approach, the advantage of "vaccines for the young" may set in at a little later, as the inward movement of infections could affect the older people stronger (if not yet vaccinated) and the effect of dampening infections by vaccines over time is disturbed. But not necessarily so or just a little, if imports affect the young first and spread (and either multiply or are dampened) among them for a while before affecting older people.

    1. On 2020-12-31 16:42:18, user R Pressinger wrote:

      One drawback with this study is it investigates only two parameters of lymphocyte counts - comparing individuals below 900 per cu/mm with those above this range. Normal lymphocyte count is approximately 1,100 to 3,100 for the middle 95% population. 2.5% of us score below this range and 2.5% above. Therefore, the majority of Covid-19 deaths could very well be in the bottom 5-10% range but we would not know if this was occurring from the current study design. Other published studies have shown asymptomatic Covid-19 patients average upwards of approximately 1,700 lymphocytes, which is interesting as this is still in the bottom 1/4th to 1/3rd of the general population. It would be intriguing and far more enlightening to add additional parameters for comparison. For example, comparing Covid-19 fatality rates for those with absolute lymphocytes below 900 to those in the "healthy normal range" (roughly between 1,800 and 2,400). Extrapolating from current findings, this information could possibly result in a dramatic difference in fatality rates. If this was the case, it would identify individuals at near zero risk of severe health outcome for this and future outbreaks and imply these individuals could be at the front line without risk of injury. This would be invaluable information for workers in many professions including medical, nursing home staff and teachers involved in the education of our children.

    1. On 2021-01-05 13:45:57, user Rogerblack wrote:

      The authors claimed case is at best flawed as they are implicitly assuming by use of the GHQ12 that people with covid are otherwise healthy.

      "The General Health Questionnaire (GHQ) is a screening device for identifying minor psychiatric disorders in the general population".

      It is not designed for those with severe fatiguing illnesses.

      https://oxfordbrc.nihr.ac.u... for example found many physical symptoms persisting.

      Endorsing 'Felt constantly under strain', 'felt you couldn't overcome your difficulties' when facing a disabling illness that may make you unable to complete normal activities, and has an unclear prognosis is not a clear measure of depression/anxiety.

      At best, each question needs to be investigated carefuly for contamination with physical health issues of the patient before a more detailed claim can be made than 'patient scores on the GHQ12'.

    1. On 2021-01-06 10:52:36, user Erik Hogh-Sorensen wrote:

      Regardless of the outcome, I am extremely happy that some scientists like Kasper Kepp & co. still dare make independent research and review potential government failures in the official response to covid19. Only through knowledge does mankind improve. Thanks Kasper Kepp!

    1. On 2021-01-07 22:48:33, user Adesuyi Ajayi wrote:

      What role will ivermectin play before or after vaccination for Covid 19? -No role or adjunctive ?<br /> Will viral mutations such as the B1,17 affect efficacy of ivermectin or vaccines ? <br /> These are questions to be answered for ivermectin and its possible use before any widespread chemoprophylactic use can be advocated.<br /> Will ivermectin be useful for future RNA respiratory viruses.

    1. On 2021-01-08 15:40:35, user lbaustin wrote:

      Nicely done! I especially appreciate the fact that the JBI's standards were used to determine that the studies were at low risk for bias.

      I am looking forward to seeing this published in a MEDLINE indexed journal so that it can easily be picked up by other researchers.

    1. On 2021-01-12 21:06:13, user Ca Doctorj wrote:

      @Wayne, 14 days after dose one, vaccine efficacy is >90% compared to placebo. How high do the antibody titres need to be to prevent infection? No one knows, but one dose appear to be enough.

    1. On 2021-01-13 16:49:11, user Ezequiel Petrillo wrote:

      Suppl. Table 2 has an error. Where it says that the Custom-made qPCR mix has 8 ul of MgCl2, it should say 4 ul (4mM final concentration), adding the extra volume with ultrapure water. We will fix this error in an updated version soon.

    1. On 2021-01-15 14:45:01, user mary wrote:

      It is proven that links of interest have a massive influence on the results of such studies.<br /> Please take the prevailing legislation into account and list any link of interests of the persons involved in this study. Thank you.

    1. On 2021-01-16 15:28:40, user Julie Courraud wrote:

      Our article has been accepted for publication in Journal of Molecular Neuroscience! Soon you will be able to see the latest improved version. We thank our reviewers for their constructive feedback.

    1. On 2021-01-19 14:10:34, user Curbina wrote:

      It is very sobering to finally be presented with a study that gives statistical dimensions to what has been already suspected: that surviving COVID-19 is not the end of it, and that the sequelae can be life altering, and even lethal. May this open the eyes to those that insist that there’s no justification to strict measures, but above all, that those who oppose the measures finally realize that this is not a game and that the personal responsibility to stay healthy is also for the sake of keeping your personal sphere of relations healthy.

    1. On 2021-01-21 12:22:19, user Michael A wrote:

      Thank you for this important trial. Please include specific data on what ‘usual care’ was given to patients. Comparing dexamethasone use between treatment and placebo groups would be important. If those rates were similar your conclusion would be even stronger.

    1. On 2021-01-22 19:01:20, user Alberto wrote:

      I hardly see any recommendation about measures to remove pathogens from indoor air. Good to see someone recommending it. I hope people take note and use methods, especially in public places, work places, schools, etc... The other big missing part is that to prevent upper respiratory tract infections (both to get them and to spread them), washing your hands often is good, but washing your upper respiratory tract often is fundamental. And yet, few advises about it. Pity.

      An article for anyone interested in measures for both of the above: https://clo2info.wordpress....

    1. On 2021-01-25 18:59:34, user janomila wrote:

      None of the citizens of Slovakia was informed about this research.<br /> - nobody signed the informed consent.<br /> - no voluntariness - blackmail under the threat of lost labor.<br /> Are anyone interested in the Nuremberg Codex???<br /> No, money are money. <br /> Who cares about human rights?

    1. On 2021-01-28 11:39:12, user Ronaldo Wieselberg wrote:

      There is a serious question in the paper. While there is a similarity in the two groups accordingly to comorbidities, there is no information about similarity of time of symptoms between the two groups. This may lead to uneven groups, in which, for example, the intervention group had a longer time of symptoms, thus, receiving a late diagnosis with PCR, after the period in which they could evolve in a worse condition, then providing a selecting bias in the paper.

      If the groups had similarity in this condition, this should be put clearly. Otherwise, it may be interesting to review the data.

    1. On 2021-01-31 20:05:06, user Gareth Hill wrote:

      What happens if you assume that the vaccines gave a very high efficacy 99%+, against death and hospitalization , as found in the trials

    1. On 2021-02-03 11:01:36, user Stig Mangschau wrote:

      "Risk" and "current findings" is not the same. If the rain is approaching you are indeed at high risk of becoming wet, even though you are currently dry.<br /> Yet in Norway this study is now being used as an argument for keeping schools open without keeping 1 meter distance. Schools are now reopening, and as a teacher, I feel very unsafe!

    1. On 2021-02-03 22:22:54, user Francisco Sánchez Jiménez wrote:

      But let's see, here the crucial test is missing, let's leave the apriorisms, that the antibody titers are in higher quantities does not ensure greater efficiency, or effectiveness, that remains to be demonstrated

    1. On 2021-02-13 15:15:13, user Rick Phelps wrote:

      It was noted that high degrees of in and ex leakage rates were typically observed. Were added filtration control measures taken to reduce and or control this variable. ? Others have published means by which the public can increase overall FFE using many techniques and materials.

    1. On 2021-02-23 20:17:28, user AJ wrote:

      Regarding public health measures selecting for mutations-<br /> the effect is nil; those mutations must exist in order to perpetuate, and if a mutation confers a transmissibility advantage it will outcompete according to this relativity regardless of the mitigations in place. This is a virus transmitted through lungs and by air- we are not going to start growing gills and swimming and neither will it. It is bound by the laws of physics.

      The daily survivorship/ incubation period is also long. In order for a mutation to reduce transmissibility by affecting/incapacitating the host the effect would need to be massive.

      The S strain, the relatively slow one that was not as virulent is gone. It had a lower R and was not as virulent. The tendency of these mutations is clear, and is shown by the Weizmann institute.

    1. On 2021-02-26 03:39:12, user Larisa Tereshchenko wrote:

      Now published in JACC: Heart Failure: JACC Heart Fail. 2021 Feb;9(2):100-111. doi: 10.1016/j.jchf.2020.09.006. Epub 2020 Nov 11. PubMed PMID: 33189627

    1. On 2021-03-01 19:08:36, user Rainald Koch wrote:

      The model ignores delays. If tracing and testing is not much faster than the transmission itself, the effectiveness of backward contact tracing is largely overestimated. Compliance with quarantine is another weakness. What works in SE Asia won't work in most other cultures.

    1. On 2021-03-02 21:59:38, user cybericius wrote:

      For a year already I have dry nose and every morning dry flat parts with dry blood come out when blowing. Never had this before, and very hard to breath through nose before blowing it out. The mucus during the day feels more stickier than ever before.<br /> Inside the tip of the nose I feel a sensitive area. Sometimes I smell iron (blood?). Humidifier doesn't help, I keep the air on 55%. Would be great to know how to find a way back to have normal nose state again.

    1. On 2021-03-10 06:06:36, user Robin Whittle wrote:

      These researcher's ability to actually discern the 25OHD levels of real people seems to be very limited, since they are relying on analysis of genetic variations which supposedly account for only 4.3% of the observed variation in 25OHD levels.

      Their fealty to actual observations is questionable since they represent the Cordoba calcifediol trial [Castillo et al. 15] as involving "high dose vitamin D" and "less intensive care unit admissions". In this trial, oral 0.532mg calcifediol (25OHD) was given at the earliest opportunity, and can be expected to have raised circulating 25OHD levels within four hours or so to 60ng/ml or more, according to the patent for the same capsules, https://patents.google.com/... - although these levels were with young, healthy and presumably non-obese subjects. The outcomes were ICU admissions 50% to 2% and deaths 8% to zero. This is an extraordinarily successful outcome, well explained by the promptness with which 25OHD levels were repleted. Criticisms of randomisation etc. were countered by Jungreis and Kellis doi.org/10.1101/2020.11.08.....

      The Murai et al. [16] trial in Brazil did use high dose vitamin D3 - which takes days to a week or so to be converted to circulating 25OHD - and which was given much later in the patient's disease progression. So it is not surprising that it produced no clinical improvement.

      The shallow and unreasonably dim analysis this article gives of RCTs, and the limited ability of the researchers ability to actually discern 25OHD levels in actual people, does not seem to give the authors a reasonable basis for their pronouncement "These findings, together with recent randomized controlled trial data, suggest that other therapies should be prioritized for COVID-19 trials.".

      A more informed analysis of current research would point to articles such as McGregor et al. "An autocrine Vitamin D-driven Th1 shutdown program can be exploited for COVID-19" https://www.biorxiv.org/con... in which Th1 lymphocytes from the lungs of severe COVID-19 patients are found to be stuck in their pro-inflammatory program, unable to enter their anti-inflammatory shutdown program, as they should after complement levels rise, because their vitamin D autocrine (internal) and paracrine (nearby cells) signaling systems are not working. The sole cause of this failure - which arguably causes severe COVID-19 via endothelial damage driving hypercoagulative blood - is lack of 25OHD.

      Such an analysis would concern the question of what levels of 25OHD are sufficient to ensure rapid, complete, vitamin D based autocrine/paracrine signaling in all immune cells generally, for instance by reference to the graphs of hospital-acquired and surgical wound infection rates vs. 25OHD levels in Quraishi et al. 2014 https://jamanetwork.com/jou... . These indicate continuing benefits to immune function up to 50 or 55ng/ml.

      A proper account of 25OHD levels and their relation to the hyper-inflammatory immune system dysregulation which drives severe COVID-19 would also cite Stagi et al. 2015 https://sci-hub.se/10.1007/... in which children suffering from Kawasaki disease had 25OHD levels averaging just 9.2ng/ml and in which those with coronary artery abnormalities averaged a disastrously low 4.9ng/ml. This research - with such obvious clinical implications for KD, Multisystem Inflammatory Syndrome, sepsis and severe COVID-19 - should be well known to all clinicians.

    1. On 2021-04-15 00:06:12, user fra setch wrote:

      Anti-spike IgG glycoprotein for Covaxin in Phase 2 trial was 65%. And this trial was done on only 96 Covaxin participants. Something doesn't seem right about this.

    1. On 2020-11-04 22:10:53, user stephan walrand wrote:

      it is not an issue of quickly decline, it is a question of crossing down a certain blood level: it is a threshold triggering effect. <br /> When enough people cross down the threshold, when positive they become more contagious as their respiratory track is more invaded, and they contamine other people being under the threshold, who also become more contagious.<br /> It is similar to a nuclear chain reaction: under a critical neutron rate production you can control the reactor, a little bit above it is an explosion.<br /> But I will be happy to consider any other explanation for the correlation with the latitude.

    1. On 2020-11-18 00:52:30, user Peter James wrote:

      I am very much concern with ethics of this research. The authors stated that the local authorities approved the study. Although it is good to have a local buy in in such research, I believe that it would have been prudent and ethically appropriate to seek proper ethics approval from a recognised body either from a university or from the national ethics committee. There are ethics committees or IRB. The most popular one is the one in the ministry of health and sanitation (Sierra Leone ethics review and scientific committee). I believe that those local authorities, many of which are less educated and have little or no idea about research ethics and so getting their consent does not equate to addressing the ethics concerns of such study. I think this research should not published given that the authors did not adhere to the tenets of good research ethics. As a Sierra Leonean researcher, I have observed such issues, especially during the Ebola outbreak where western researchers disguising as NGO workers tend to exploit our system or take advantage of the weak quality assurance system when conducting research in Sierra Leone. I believe such cannot be done in Italy.

    1. On 2021-05-30 17:20:05, user Badger Vanamburgh wrote:

      It’s astonishing that anyone thinks that this study is in any way scientific, controlled, with conclusions based on anything but bias. It’s alarming that such nonsense writings like these are even taken seriously enough for someone to decide to publish it, spread it around the internet. The times of truth, fact and reality ruling the day, are behind us. They are destroying science and destroying our democracy. That is very sad indeed.

    2. On 2021-06-10 02:33:11, user baby drumf wrote:

      How come countries like Taiwan and South Korea have such low rates of transmission? they are all wearing melt blown polypropylene masks (KF94 & N95 Respirators). Respirators work much better than cloth or surgical type procedure masks.

    1. On 2021-06-01 00:21:43, user Pat Frank wrote:

      "We show here that the mRNA from anti-COVID BNT162b2 (Pfizer) and <br /> mRNA-1273 (Moderna) vaccines is not detected in human breast milk <br /> samples collected 4-48 hours post-vaccine"

      Nice, but irrelevant. The worry has been that the mRNA encoded spike protein gets into breast milk (and other tissues).

      There does not appear to be any concern that the mRNA itself appears in breast milk. So the paper of Golan, et al., is irrelevant to the concern.

    2. On 2021-06-10 10:53:46, user Soshay wrote:

      Of course BNT162b2 (Pfizer) and mRNA-1273 (Moderna) would not be detected in breastmilk 4-48 hrs post injection. The biodistribution study follows the lipid nano particle envelope still covering the mrna up to 48 hrs post injection. Follow the ALC - 0315 and ALC - 0159.

    1. On 2021-06-11 09:20:26, user WayneGao TMU wrote:

      Taiwanese government may soon authorize EUA to a protein subunit vaccine by Medigenvac which just de-blind their phase 2 clinical trial results (about 3800 participants) on June 10, 2021. The results shows credible safety and good immunity response( for instance, GMT 662, compared to AZ's 370). Like many other countries, Taiwan has struggled with securing enough vaccines. My question, if the vaccine receive its EUA, is Taiwan going to be the first country to issue an EUA based post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccine? Thanks, Wayne

    1. On 2021-06-11 09:54:15, user Patrik D'haeseleer wrote:

      How did you deal with correcting for multiple hypothesis testing in this study? It sounds like you focused on one sub-population of 255 out of >1200 patients. How many different sub-populations did you wind up testing, how many different medications, and how many different tests per medication?

    2. On 2021-06-11 13:44:12, user Jay Alan Erdman wrote:

      Where to begin? 1) This is an abstract; not yet peer reviewed; so it's just four guys saying this. 2)They don't say how they got their population. 3) They provide no data. 4) There is no control group either randomized, case control, or cohort. 5) They really do not specify their methods. 6) There is no treatment protocol so we don't know what additional treatment they may have received. Overall this doesn't meet any scientific standard. But even if it had been well done; these patients presented in the Spring of 2020 when treatment protocols were very different and outcomes much worse. This study says nothing about whether HCQ would be of any benefit to patients receiving treatment in Spring 2021.

    1. On 2021-06-12 13:48:28, user Igor M. wrote:

      What was the rationale for using different metrics in figure 2? One talks about "% inhibition" and another about "optical density"- comparing apples and oranges? Secondly, I could not for the life of me find the justification for the seemingly arbitrary definition of "positive" and "negative" thresholds.

    2. On 2021-06-15 11:03:19, user camel faizal wrote:

      It seems the participants are quite elderly with the mean age at 40.4 (+-12. 2) years and just a small group of 15.

      Also the study should include data from both doses administered instead of just the first dose. Otherwise , this study just adds to more hesistancy.

      Would it not be better if there are more participants ( at least 10,000 or more ) and are in the younger age group , something like having participants between the ages of 18-40 years ?

      Thanks for the hard work and effort.

      Greatly appreciated and all the other comments need to be addressed too.

      People's lives hang in the balance.

    1. On 2021-06-12 19:20:03, user brycenesbittt wrote:

      The missing matching is individuals who "continue to take covid precautions" such as distancing, masking indoors, and limiting exposure in indoor crowds. Matching people just by zip code, age and gender misses this not-so-subtle point.

    1. On 2021-06-13 01:39:10, user cathyx wrote:

      You are using relative risk reduction instead of absolute risk reduction in your calculations. <br /> Therefore, your analysis is flawed.

    1. On 2021-06-19 13:31:53, user globus999 wrote:

      I read with interest the article. However, the conclusion does not seem<br /> to be supported by the evidence. If you look closely at all the plots, <br /> there seems to be no impact below 10 units. This would therefore <br /> indicate that yes indeed, there seems to be a safe level.

    1. On 2021-06-19 21:00:25, user Elisabeth Bik wrote:

      As pointed out on Twitter by @seqwave, in Figure 1, the 'Left orbitofrontal cortex (thickness)' and the 'Left superior insula (thickness)' plots are identical. Could the authors please check?

    1. On 2021-06-19 23:50:30, user Gabriel Rodrigues Couto wrote:

      This study was made with >70 year old patients. The interpretation should contain this information, right? It doesn't. In brazil a lot of midia is announcing this article as " the vaccine does not work".