On 2020-04-14 10:56:53, user Prof Page wrote:

It would be good if there were parenthetical sample sizes noted for these studies. Some are exceedingly small.

On 2020-04-14 11:02:19, user Philip Davies wrote:

This is a very interesting pre-print. BUT, I think the data in table 3 has been mixed up (deaths for low v high dose are incorrect). The authors need to correct this and then ensure the tables are correct everywhere else. I have asked the authors to look at this and re-issue a corrected version (I also question whether the qSOFA results (table 1) were meant to be for values >2 rather than <2.

This is important. It could mean that lower dose chloroquine is not only safe but could prove to be statistically better than placebo (will need the full 28 days analysis to know that).

Dr Phil Davies

http://thevirus.uk

On 2020-04-15 11:35:12, user GP MD wrote:

Ceftriaxone and azithromycin have their own toxicities....including mitochondrial dysfunction and ROS over-production in mammalian cells. The dosing of all three agents means a much higher risk of oxidative damage to mammalian DNA, proteins and membrane lipids. This would be worsened in those with impaired production of glutathione or reduced glutathione levels due to acetaminophen dosing.

On 2020-04-15 18:47:50, user Y H wrote:

Over thirty years ago, we found that chloroquine and related chemicals block muscarinic agonist binding. Similar findings were reported afterwards. This effect may link to a cause for cardiac arrhythmia induced by chloroquine. YH

Antimuscarinic effects of chloroquine in rat pancreatic acini<br /> Yoshiaki Habara, John A Williams, Seth R Hootman<br /> Biochemical and biophysical research communications 137 (2), 664-669, 1986

On 2020-04-24 20:11:40, user Diego B. wrote:

This article has been posted on JAMA Network: https://jamanetwork.com/jou...

On 2020-04-24 20:18:46, user Diego B. wrote:

This article has been published on JAMA Network: <br /> https://jamanetwork.com/jou...

On 2020-04-14 17:58:53, user Badly Shaved Monkey wrote:

From a U.K. perspective:

My common sense reservation is that if Coronavirus was going to hit, say 60% of the U.K. population and 0.1% of those would die as suggested by Silverman and Washburne, that’d be about 40,000 deaths in total in the U.K. We’ve already hit 12,000 under the influence of a significant degree of social restriction over several weeks. While it is hard to predict the logistic asymptote from the exponential-like phase, it stretches credulity to suggest that the unmoderated U.K. epidemic would have burnt itself out with 40,000 deaths.

On 2020-04-14 19:47:35, user Sinai Immunol Review Project wrote:

Main findings:

The aim of this study was to assess an association between reduced blood lymphocyte counts at hospital admission and prognosis of COVID-19 patients (n=192). The authors found:<br /> - Patients with lymphopenia are more likely to progress to severe disease or succumb to COVID-19 (32.1% of COVID-19 patients with lymphocyte reduction died). <br /> - Reduction of lymphocytes mainly affects the elderly (> 70 years old). <br /> - Lymphocyte reduction is more prevalent in COVID-19 patients with cardiac disease and pulmonary disease, patients with increase in the chest CT score (key marker of lung injury) and a decrease in several respiratory function markers (PaCO2, SpO2, oxygenation index).

Limitations of the study:

Reduced blood lymphocyte counts with aging have been known (https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.03.08.20031229v2)") https://onlinelibrary.wiley... "https://onlinelibrary.wiley.com/doi/epdf/10.1111/sji.12413)"). Therefore, it is not unexpected that a larger fraction of COV ID-19 patients above 70 years old have lower lymphocytes counts. Since age has been reported to be a major factor that determines outcome for COVID-19, lymphocyte counts and prognosis should have been adjusted by age. Multivariate analysis to identify independent risk factors is lacking.

Relevance:

Previous studies demonstrated that SARS-CoV-2 infection leads to a decrease of the T cell count. This study confirms these results and shows that lymphocyte reduction mainly affects the elderly. Lymphopenia was associated with disease severity as well as worse prognosis. Future studies need to address if lymphopenia is a negative predictive factor independent from age.

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

On 2020-04-14 21:52:36, user Dr Eric Grossi Neurocirurgia wrote:

Is missing the intervals of age - 29.4 to 60 years only - Enormous Bias

On 2020-04-15 11:04:57, user Dr Eric Grossi Neurocirurgia wrote:

I would like to highlight a serious methodological error in this study. What we want for a drug treatment of COVID-19, only two objectives, to avoid and / or treat SARS and reduce contagion, therefore pragmatism in the selection of patients must be as close as possible to the clinical reality, which did NOT occur, since only patients between the ages of 29.4 to 60 years were analyzed. This alone invalidates any useful result, since the vast majority of human losses are over the age of 64.

On 2020-04-15 15:04:27, user Mehee f wrote:

this is completely unscientific the US has a population of 335M on this basis it will have 4M cases and 100,000 fatalities by now. Also you did not compare figures with other countries there is a big variation of mortality rates between 0.5% in South Korea to 12% in Italy. It is very biased report based on all estimates and no data pure speculation.

On 2020-04-15 19:05:05, user disqus_NrkWMn1KOM wrote:

"collected data to emulate a target trial" - So, not a real study?

On 2020-04-15 19:07:06, user Gregory Armstong wrote:

Thanks for contributing this. It's a very important topic. There are few well controlled studies of risk factors for COVID-19.

My one comment--and I didn't read the entire manuscript: I'd strongly recommend removing vital signs and laboratory findings from the regression. Those are manifestations of severe disease, not risk factors for it. They're some of the main considerations in deciding whether to hospitalize and whether to admit to the ICU. They should correlate strongly with both, and including them in the model will severely dilute the impact of true risk factors and could completely hide them. They shouldn't be considered independent variables.

On 2020-04-15 20:48:45, user empiricist2 wrote:

According to the French study, the addition of Azithromycin cleared out the virus in 4 days, versus at least twice that without it. And others use zinc, considered a very important factor. So why just test HCQ alone? And what were the antivirals that hampered results? Certainly there are other studies to report on that include zinc etc. Even in China they had reported that IV Vit C helped significantly. One doctor takes 10g daily as preventative. Vit C has a long history of antiviral benefits in large doses.

On 2020-04-18 21:54:04, user Jim Trader wrote:

Kind of a useless study. With an average delay of 16 days from symptom onset to enrollment and treatment in this trial, those patients are pretty much past the viral phase of the disease, where an antiviral treatment would have the most value, and are well on their way to pneumonia and a cytokine storm problem, which is ultimately what kills. Even the subset analysis of patients with a 7 day delay from symptoms to enrollment is still too long. As the authors state, it is very difficult to do these kinds of trials when patients average 12 days from symptoms before they come into the hospital, and can be explored as trial participants. So unfortunately there is no signal here, and from a molecular biology viewpoint, that is exactly what I would expect with this trial design. HCQ therapy needs to start within 48 hrs of symptom onset, ideally 24.

On 2020-04-16 14:51:37, user agoraks wrote:

Quote: "The assays are sensitive and specific, allowing for screening and identification of COVID19 "

Question: what is the actual sensitivity and specificity of the assay for detecting active disease by IgM or convalescence IgG in Sars-CoV-2 infected patients ?

On 2020-04-16 19:48:56, user Stef Verlinden wrote:

It is troublesome that the article does not give the materials and the method used to derive/calculate the QTc. Formally a QTc can only be calculated from a signal derived from Lead II of V5 registered with a 12 lead ECG machine. QTc's calculated by a computer algorithm (unless it is specifically validated to do that job) are not to be trusted. This needs to be done by hand by a well-trained person.

Most importantly, the QTc calculation is not linear. A heart rate of 90 gives an overestimation of the QTc of 50 ms (when using the Bazett method). Did the authors correct for this? Based on this paper, it is not possible to establish whether the QTc's are truly prolonged or that these are false positive outcomes.

For reference check; QTc: how long is too long? https://www.ncbi.nlm.nih.go...

On 2020-04-17 07:35:29, user Mansour Tobaiqy wrote:

Thank you, the paper has bow been published at IPIP:

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

On 2020-04-17 20:43:16, user Drew Middlesworth wrote:

I was estimating the true infected numbers were 10-20x higher than the reported numbers based off the hospitalization rates, I wasn't expecting it to be this high. Although folding these numbers into NY infected counts would mean that over 100% were infected which can't be right. My estimate would show about 25-50% infected currently.

Although the other thing that would skew this, by using Facebook ads and not doing a random population pick, you would skew the results higher as people who were sick in Jan-Feb would be more likely to respond to the ad to get tested. They could easly be 2-3x too high which would be more inline with the numbers I was estimating based off hospitalization rates.

On 2020-04-18 00:16:22, user Rob Kuchta wrote:

I am very suspicious of the 50- to 85-fold difference in confirmed cases based on the NY (and NYC) infection rates. NY has a 1.2% infection rate as a whole, and for NYC it is 1,5%. Using these values, that would indicate that from 60-100% of the population have been infected in NY state, and infections should be dropping rapidly (also, I have never heard of a virus having this sort of infectivity). In NYC, the infection rate would be 75-100%. This suggests that either there is an unknown issue with the test or that the Ab generated by being infected by this virus do not prevent subsequent infection. This latter situation would be rather worrisome in terms of a vaccination strategy to prevent infection.

On 2020-04-18 16:15:43, user spacecat56 wrote:

In reading the draft report of the study (pre-print, dated April 11, 2020) my predominant thought was, in choosing to respond to the invitation to the study participants are overwhelmingly likely to have self-selected based on their recent prior experience of symptoms that they suspect may have been due to COVID-19 infection.

The draft acknowledges the possibility of this bias but tosses it off as "hard to ascertain". But the draft also says that data on prior symptoms were collected; data which are entirely omitted both from the published analysis and from the published tables.

Because the analysis ignores this factor and because of the potential for this bias to totally dominate the analysis, in my opinion after reading the study draft, we still know effectively nothing at all about the prevalence of infection in the studied population. Accordingly I would expect to vigorously object to any attempt to incorporate the reported results into public policy and planning.

I would urge the study team to bend their efforts to addressing this deficiency. At a minimum, I suggest, the report should include the withheld prior-symptoms data. Preferably, some efforts should be made to deal with the difficulty of estimating the bias. Perhaps it would be helpful to subdivide the sample data based on yes/no prior symptoms and analyze each subset?

On 2020-04-18 16:27:11, user Zev Waldman MD wrote:

I agree with other commenters that people who suspected prior Covid infection (or exposure) are more likely to seek antibody testing than those who did not. While participants were asked about prior symptoms, it is not clear what was done with this information. The rate of symptoms/exposure could be reported, compared to the community rates, used as a risk factor for positive antibody testing, etc.

My other concern that has gone less discussed is their calculation of the case fatality rate. While they recognize that reported case numbers as of April 1 are an underestimate, it seems that they forget this skepticism when looking at reported deaths. They seem to take it as a given that 50 people died of Covid in the county as of April 10 as reported, and used this to project to deaths by April 22; however, like case counts, there are multiple reasons to suspect this number of deaths might be higher:

1. Reporting of deaths is well-known to be delayed - i.e., date of reporting does not equal date of death

2. People who actually died of Covid may never have been tested, and thus may not be included as cases or deaths

3. The doubling time of deaths used to project to April 22 is also based on reported deaths; if reporting of deaths is delayed, the doubling time may appear slower than it actually was.

If the death estimate due to illness before April 1 is too low, their corresponding CFR would be an underestimate as well. (This would be exacerbated if their case estimate is too high due to self-selection into the study, as seems possible.) At the very least, some sort of uncertainty around the death estimate should be provider, which in turn would increase the uncertainty around the final CFR.

I know CFR wasn't the main focus on the article, but worry that, because these results support their prior beliefs, some readers may take the results at face value and push them to policymakers before they have been more widely vetted by the scientific community.

On 2021-12-12 01:32:39, user Wild Bill, Jr. ????:????:?? wrote:

When I first read this paper, a year ago, I was skeptical about it. The alarmists presented what seemed to be some strong arguments against it

However, with the passing of time, infection-fatality rate statistics and deaths from all causes statistics support the Stanford team's hypothesis: The dreaded virus has turned out to be a lot less lethal than the alarmists claimed it was.

On 2020-04-23 15:59:44, user gmshedd wrote:

If we take the observed fatalities (by residence) in the Bronx (2258 as of 4-22) and Queens (3432), and apply the suggested infection fatality rates of 0.12% to 0.20%, we can infer that between 80% and 133% of Bronx residents have already been infected, and that between 76% and 127% of Queens residents have also been infected. Therefore, Bronx and Queens residents have achieved herd immunity, so they can re-open everything immediately. This is such great news! Oh, but you say, these populations aren't similar. OK, so I'll use Nassau County (Long Island)--median income $111k vs $116k in Santa Clara County. 1431 Nassau County residents have died, from which we would infer that between 53% and 88% of the 1,356,924 county residents have been infected. My point is that the suggested infection fatality rates don't pass the eye test, and, since they are derived from the infection rates that are at the center of the controversy, it would seem that the publication's Santa Clara County infection rates are higher than seems reasonable for the NYC area--unless California COVID-19 has a significantly lower infection fatality rate than New York COVID-19.

On 2020-04-24 05:58:27, user JM V wrote:

With 80 (1.7%) people dead in Castiglione d'Adda (Caveats: Old/Smoking/Unlucky/Collapse of Health care system/Some would have died anyway) this was already extremely unlikely. Now, with NYC 0.22% excess deaths and 21.2% of shoppers having antibodies, an IFR of 0.8% - 1.2% appears plausible.

On 2020-04-25 07:19:42, user John Smith wrote:

1. A local website (SFGate, I think) mentioned a person who emailed many friends about the free test and this selected wealthier people who might have more exposure to international travel. This would boost the percentage with antibodies above a population sample that had more poor people in the sample. It did mention the team tried to correct for this email by recruiting from other areas of the county. 2. Santa Clara county has more international travel than most other areas of the USA that have fewer immigrants, so people who are saying other areas of the USA might have the same higher level of recovered patients would be wrong.

On 2020-11-19 18:22:04, user Ivan Ivanov wrote:

Impressive work. It is probably misunderstanding but the authors use 10mM KCl/10mM NH4SO4 in the buffer for Bst 2.0 and they call it 1x Isothermal Buffer which infact is the commonly known ThermoPol buffer (optimal for Bst LF, not for Bst 2.0). NEB sells Bst 2.0 with Isothermal buffer containng 50mM KCl/10mM NH4SO4.

On 2020-11-20 02:26:46, user Prasad Kasibhatla wrote:

Interesting.. scaling reported median risk (2e-6) for individual touches by average touches per day (336), gives a transmission risk by fomites of 10-12% over a 6 month period (roughly length of pandemic ). Seems high .. so my scaling must not be appropriate. Any thoughts?

On 2020-11-23 23:12:54, user Louis Rossouw wrote:

Why does this paper compare mortality July 2019 to June 2020 to try and determine the impact "after" COVID-19 when the pandemic started in Feb-March 2020? So the "after COVID-19" of the title of the paper includes more time before COVID-19 than after the epidemic started?

The authors also do not allow for any changes in age distribution / popualtion mix that may be affecting observed mortality trends.

On 2020-11-25 07:42:20, user Carol Shadford wrote:

When you say 'continual sensation of having had a “nasal douche”' are you referring to a feeling that the sinuses have been cleared out and are now empty or is that referring to the rushing feeling you get when chlorinated water accidentally goes up your nose -- a wasabi-like feeling?

On 2020-11-26 05:48:46, user Community Medicine with velz wrote:

Re-infection can be defined only by viral genome sequencing. The implication of these results can be mis-leading as re-infection has been defined by RT-PCR in this study.

On 2020-11-27 19:21:54, user Jackie A wrote:

This work is useful because it is the first modeling paper reckoning IFN role in the disease - and an early administration of it could be beneficial, which is consistent with recent RTC for IFN-beta. However, it is built on rodents and the extrapolation to humans is not clear and not validated by tissue data extracted from humans. The authors assume that tissue viral loads correlate with organ failure which has not been demonstrated.

On 2020-11-27 21:02:26, user Robert Brown wrote:

Vitamin D, Magnesium, Steroids, PPI and COVID-19; Interactions and Outcomes - Response to ‘Effect of Vitamin D3 Supplementation vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-blind, Randomized Controlled Trial’ [Preprint] [1]

Thank you and congratulations on your important and significant paper. This is only the fourth[2] [3] [4] reported RCT examining vitamin D supplementation as a therapeutic intervention for COVID-19. Biology provides multiple pathways by which vitamin D hydroxylated-derivatives[5] may impact Covid-19 risks [including via; ACE2 receptors; airway-epithelial-cell tight-junction-function, immune responses [affecting lymphocytes, macrophages T cells, T helper cells, Th1, -17; Tregs; cytokine secretion IL-1, -2, -4, -5, -6 -10,-12; IFN-beta, TNF-alpha; defensins and cathelicidin, and receptors HLA-DR, CD4, CD8, CD14, CD38. Vitamin D also regulates; mitochondrial respiratory, inflammatory, oxidative and other functions; RXR and other receptor links between steroids, retinoids, hormonal vitamin D, thyroid hormone, oxidised lipids and peroxisomal pathway immune responses.][6]

Significant evidence [40+ patient-papers[7]] suggests higher Vitamin D status [serum/plasma 25(OH)D concentration] is associated with diminished COVID-19 infection rates,and reduced severity [including ICU admission and mortality].[2 3 4]

Thus, it is crucial, to consider if the preprint’s broad-based conclusion “Vitamin D3 supplementation does not confer therapeutic benefits among hospitalized patients with severe COVID-19”, [time to discharge as well as lack of observed ICU and mortality rate benefits], stands scrutiny when any one, or combination of, the following factors are considered: -

Delay in vitamin D administration after severe symptoms onset

Patients presented “10.2 days after symptoms”, thus were already verging on serious outcomes at admission; “89.6% required supplemental oxygen at baseline [183 oxygen therapy; 32 non-invasive ventilation] and 59.6% had computed tomography<br /> scan findings suggestive of COVID-19.” [Days to dyspnoea from overt infection average 7-8, and acute-respiratory-distress-syndrome [ARDS] develops after median 2.5 days.[8]]

Further, the timing of vitamin D supplementation, at or after <br /> hospitalisation, was not specified, despite timing clearly being an important factor, given the advanced stage of illness at admission.

Baseline vitamin D status [serum 25(OH)D concentrations] were relatively ‘good’

Baseline 25(OH)D values averaged 21.0ng/ml and 20.6ng/ml in the treatment and control groups respectively, i.e. they were relatively ‘good’, and above levels reported as being associated with the greatest COVID-19 risks.[9] [10]Sub-analysis of patients < 10ngml +/-Dexamethasone would be instructive. Further, deficiencies such as magnesium (an essential ‘D’ enzyme co-factor) might factor more in the lack of observed benefits for Covid-19 severity, than vitamin D status itself.

Corticosteroids

COVID-19 related corticosteroid vitamin ‘D’ interactions require<br /> investigation. 64.2%(Treatment) and 60.8%(Control) group patients respectively, were treated with Corticosteroids (Dexamethasone?), and mortality was somewhat higher in the Treatment than Control arm. Interactions between vitamin D and steroids including dexamethasone are observed[11], including “decreased synthesis of active vitamin D, and impairment of biological action at tissue level.”[12] However these potential effects have not been investigated in COVID-19 patients treated with both vitamin D and dexamethasone.

It would be most useful to know therefore, at what stage corticosteroid treatment began, and at what dosages, what other treatments were given [and at what dosage], and when such treatments were stopped, so that potential interactions between vitamin D, corticosteroids and other treatments for COVID-19<br /> patients could be elucidated.

In particular, any negative or neutralising effect of corticosteroids on<br /> ‘D’-derivatives and pathways, could account for the lack of reduction in risks of ICU and mortality outcomes, including slightly higher mortality, in those given vitamin D, a matter of importance, since dexamethasone, given before onset of serious ARDS, was reported in Oxford[13] to increase, not reduce, mortality.

Proton pump inhibitors.

PPI are known to lower serum magnesium,[14] an essential ‘D’ hydroxylase-enzyme co-factor. 47/120-(39%)[Treatment] and 49/120-40%[Control] used PPI, compared to 9.2% population usage in USA.[15] PPI-induced related serum magnesium reduction, +/- dietary insufficiency, is a reported COVID-19 risk factor,[16] thus possibly helping account, for D3 treatment, failing to reduce Brazilian Covid-19 mortality. Thought-provokingly a Brazilian paper reported “There is chronic latent magnesium deficiency in apparently healthy university students”, which deficiency is potentially more widespread.[17]

Conversely, RCT administration of magnesium with vitamin D reduced COVID-19 in-patient mortality.2

Rate of increase of Serum 25(OH)D

It is unclear when blood was sampled for determination of serum 25(OH)D concentrations, or if this was standardised for all patients.

A large bolus will increase 25(OH)D values in the healthy, “Oral D2 and D3 (100,000 to 600,000 IU) significantly increased serum 25(OH)D from baseline in all reviewed studies” . . . “peak levels were measured at 3 days (34) and 7 days following dosing,”[18]

However, timing matters, because hepatic hydroxylation5 to form 25(OH)D (Calcifediol) is likely reduced by; severe illness, as well as by obesity diabetes, and possibly hypertension,[19] conditions already recognised as risk factors for covid-19 severity.[20]

The Cordoba study[3] suggests that 25(OH)D [Calcifediol, that could be given together with vitamin D3, cholecalciferol], may be key to effective treatment of severe COVID-19 illness. There is no suggestion Cordoba patients were treated with corticosteroids. Cordoba patients were administered calcifediol on admission-day, but the period between overt infection and hospital admission <br /> was not reported.

Risk-factor Differentials in Patient Groups

A skew in risk factors favouring the control?

Control-Placebo to Treatment-D3:

Increased risk factors - Overweight (31/37, 0,84); Obesity (58/63, 0,92); Hypertension (58/68, 0,74); Diabetes II 35/49, 0,71); COPD (5/7,0,71); Asthma (7/8, 0,88); Chronic Kidney Disease (0/2, 0,0); Rheumatic Disease (10/13, 0,77)[21]; Black (14/20) Male 965/70).

Decreased factors - White (79/62) Female (55-50)

Improved oxygen parameters are not reflected in conclusion

“Despite the D3 group being at a greater risk, including due to hypertension, COPD and diabetes, known risk factors, significant differences in oxygen supplementation favour the D3 treatment group“.21

Oxygen supplementation (%) Placebo No. (%) D3 <br /> No oxygen therapy 9 (7.5) 16 (13.3)<br /> Oxygen therapy 97 (80.8) 86 (71.7)<br /> Non-invasive ventilation 14 (11.7) 18 (15.0)

Conclusion requires Caveats?

Thus, the un-caveated conclusion “Vitamin D3 supplementation does not confer therapeutic benefits among hospitalized patients with severe COVID-19”, likely requires caveats about possible effects of the several factors discussed above.

Further, the reported finding cannot be extrapolated to care of all Covid-19 patients, since the above- mentioned-potential interactions require further investigation, including; as to effects of; magnesium

status; treatment with PPI inhibitors, impact of corticosteroids in severe Covid-19 illness on vitamin D biology and outcomes, and consideration of pre-existing vitamin D status.

Further public health policy directed at reducing vitamin D, and other nutrient deficiencies for mitigation of COVID-19 risks at population levels, should not be conflated with clinical optimisation of vitamin D and metabolites for treatment of severe COVID-19 illness.

[1] Murai,I., Fernandes, A., Sales, L., Pinto, A., Goessler, K., et. al. 17th November 2020). Effect of Vitamin D3 Supplementation vs placebo on Hospital Length of Stay in Patients with Severe COVID-19 A Multicenter, Double-blind, Randomized Controlled Trial. medRxiv 2020.11.16.20232397; doi: https://doi.org/10.1101 /2020.11.16.20232397 Available at: https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1<br /> [2] Tan, C., Ho, L., Kalimuddin, S., Cherng, B., Teh, Y., et.al. (10th June 2020). A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients. doi: https://doi.org/10.1101/202... Available at: https://www.medrxiv.org/content/10.1101/2020.06.01.20112334v2<br /> Now published in Nutrition doi:10.1016/j.nut.2020.111017 <br /> [3] Entrenas Castillo, M., Entrenas Costa, L., Vaquero Barrios, J., Alcalá Díaz, J., López Miranda, J., Bouillon, R., & Quesada Gomez, J. (29th August 2020). Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of steroid biochemistry and molecular biology, 203, 105751. https://doi.org/10.1016/j.j... Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456194/<br /> [4] Rastogi, A., Bhansali, A., Khare, N., et. Al. (12th November 2020).<br /> Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgraduate Medical Journal Published Online First:. doi: 10.1136/postgradmedj-2020-139065 Available at: https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-2020-139065<br /> [5] Bouillon, R., & Bikle, D. (2019). Vitamin D Metabolism Revised: Fall of Dogmas. J Bone Miner Res. 2019 Nov;34(11):1985-1992. doi:<br /> 10.1002/jbmr.3884. Epub 2019 Oct 29. PMID: 31589774. Available at: https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.3884<br /> [6] Brown, R., Rhein, H., Alipio, M., Annweiler, C., Gnaiger, E., Holick M., Boucher, B., Duque, G., Feron, F., Kenny, R., Montero-Odasso, M., Minisola, M., Rhodes, J.,Haq., A, Bejerot, S., Reiss, L., Zgaga, L., Crawford, M., Fricker, R., Cobbold, P., Lahore, H., Humble, M., Sarkar, A., Karras, S., Iglesias-Gonzalez, J.,Gezen-Ak, D., Dursun E., Cooper, I., Grimes, D. & de Voil C. (April 20, 2020). COVID-19 ’ICU’ risk – 20-fold greater in the Vitamin D Deficient. BAME, African Americans, the Older, Institutionalised and Obese, are at greatest<br /> risk. Sun and ‘D’-supplementation – Game-changers? Research urgently required’: ‘Rapid response re: Is ethnicity linked to incidence or outcomes of COVID-19?’: BMJ, 369(m1548). DOI: 10.1136/bmj.m1548. Available at: https://www.bmj.com/content... (Accessed: 24 November2020. - Alipio study<br /> now in question – rest stands)<br /> [7] Brown R. (15 Oct 2020). Vitamin D Mitigates COVID-19, Say 40+ Patient Studies (listed below) – Yet BAME, Elderly, Care-homers, and Obese are still ‘D’ deficient, thus at greater COVID-19 risk - WHY? BMJ 2020;371:m3872 Available at https://www.bmj.com/content/371/bmj.m3872/rr-5 (Retrieved 24 Nov 2020) <br /> [8] Cohen, P., Blau, J., Eds: Elmore, J., Kunins, L., & Bloom, A. (2020). MD disease 2019 (COVID-19): Outpatient evaluation and management in adults. Literature review. Wolters Kluwner. Available at: https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19-outpatient-evaluation-and-management-in-adults/print<br /> (retrieved 25th November 2020)<br /> [9] Jain, A., Chaurasia, R., Sengar, N., Singh, M., Mahor, S., & Narain, S. (19th Nov 2020). Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep. 2020 Nov 19;10(1):20191. doi: 10.1038/s41598-020-77093-z. PMID: 33214648; PMCID: PMC7677378. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677378/<br /> [10] Radujkovic, A., Hippchen, T., Tiwari-Heckler, S., Dreher, S., Boxberger, M., & Merle, U. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients 2020, 12, 2757. Available at https://www.mdpi.com/2072-6643/12/9/2757 <br /> [11] Hidalgo, A. A., Trump, D. L., & Johnson, C. S. (2010). Glucocorticoid regulation of the vitamin D receptor. The Journal of steroid biochemistry and molecular biology, 121(1-2), 372–375. https://doi.org/10.1016/j.j... Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907065/<br /> [12] Giustina, A., Bilezikian, J. (eds) (2018). Vitamin D and Glucocorticoid-Induced Osteoporosis. Vitamin D in Clinical Medicine. Front Horm Res. Basel, Karger, 2018, vol 50, pp 149-160 (DOI:10.1159/000486078) Available at https://www.karger.com/Article/Pdf/486078<br /> [13] The RECOVERY Collaborative Group. (17th July 2020). Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. J New England Journal of Medicine R10.1056/NEJMoa2021436 https://www.nejm.org/doi/fu... Available at https://www.nejm.org/doi/full/10.1056/NEJMoa2021436<br /> [13] FDA. (8th Apr 2017). FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs) https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-low-magnesium-levels-can-be-associated-long-term-use-proton-pump (Accessed 25th November 2020)<br /> [14] Hughes, J., Chiu, D., Kalra, P., & Green, D. (2018). Prevalence and outcomes of proton pump inhibitor associated hypomagnesemia in chronic kidney disease. PLoS ONE 13(5): e0197400. https://doi.org/10.1371/jou... Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197400<br /> [15] Lee, S., Ha, E., Yeniova, A., et. al. (30th July 2020). Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut Published Online First: 30 July 2020. doi: <br /> 10.1136/gutjnl-2020-322248 Available at: <br /> https://gut.bmj.com/content/early/2020/07/30/gutjnl-2020-322248<br /> [17] Hermes Sales, C., Azevedo Nascimento, D., Queiroz Medeiros, A., Costa Lima, K., Campos Pedrosa, L., & Colli, C. (2014). There is chronic latent magnesium deficiency in apparently healthy university students. Nutr Hosp. 2014 Jul 1;30(1):200-4. doi: 10.3305/nh.2014.30.1.7510. PMID: 25137281. Available at: http://www.aulamedica.es/nh/pdf/7510.pdf<br /> [18] Kearns, M., Alvarez, J., & Tangpricha, V. (2014). Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review. Endocrine practice: official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 20(4), 341–351. https://doi.org/10.4158/EP1... Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128480/<br /> [19] Kheiri,B., Abdalla, A., Osman, M. et al. (2018) Vitamin D deficiency and risk of cardiovascular diseases: a narrative review. Clin Hypertens 24, 9 (2018). https://doi.org/10.1186 /s40885-018-0094-4 Available at https://clinicalhypertension.biomedcentral.com/articles/10.1186/s40885-018-0094-4 <br /> [20] Kruglikov, L,. Shah, M., Scherer, E. (Sept 2020). Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral-bacterial interactions. Elife. 2020 Sep 5;9:e61330. doi: 10.7554/eLife.61330. PMID: 32930095; PMCID: PMC7492082.<br /> [21] Borsche L. Private email 19.11.20

On 2020-12-01 21:23:17, user NubOfTheMatter wrote:

This trial appears to have been a wasted opportunity.

It is unclear why Vitamin D3 was orally administered to severely ill C-19 patients. It can take a fortnight to be metabolised into Calcifediol, the active, metabolised form required to trigger an immune response. A most unhelpful delay to the effective treatment of severely ill COVID-19 patients.

The RCT conducted at the teaching hospital in Cordoba used Calcifediol, with dramatic results. Compared to the untreated ‘control group’ there was a 96% reduction in the need for Intensive Care Unit admission, and a commensurate reduction in deaths.

One has to ask, therefore, why, in Sao Paulo, it was decided to administer un-metabolised Vitamin D3 rather than Calcifediol to severely ill C-19 patients for whom every day of non-treatment reduces the chance of a good outcome if not survival? Indeed, an experienced physician could have forecast the results obtained without the need for a trial.

On 2020-12-07 13:02:33, user Fernando wrote:

Good morning, I have some comments: I couldn’t find the final D level at 7 and 10 days (hospital discharge), this information is crucial to establish the effectiveness of the ministered dose. <br /> At a first glance, considering the patients were mostly deficient in vitamin D and obese (slow D absorption) the dose provided seamed too low to produce results in such a short time (7-10 days), specially as it was vitamin D in its over the counter form (not calcifediol).<br /> Also not clear how many days after testing positive did the patients take vitamin D. It seems that in Brazil people are only hospitalized after aggravation.<br /> Thank You!

On 2020-12-01 14:30:16, user Peter Griffiths wrote:

Published as: Griffiths, P., Saville, C., Ball, J., Culliford, D., Pattison, N., Monks, T., 2020. Performance of the Safer Nursing Care Tool to measure nurse staffing requirements in acute hospitals: a multicentre observational study. BMJ Open 10 (5), e035828.10.1136/bmjopen-2019-035828

On 2020-12-01 17:48:06, user Pandora wrote:

Interesting. Did you take into account regular medication taken for each group. Studies have been done on Ace2 inhibitors and blockers. There's also studies on proton-pump inhibitors and Sarscov2. They seem inconclusive too, but it may skew your results. Interestingly, a lot of these drugs and a diabetes drug are under recall for NDMA contamination at present.

On 2020-10-30 18:25:19, user gatwood wrote:

I suspect there could be a strong corellation between vaccination status<br /> and following a strict adherence to all COVID anti-infection <br /> guidelines, PPE etc... Experienced and medically trained Drs and nurses<br /> more likely have been vaccinated and also are more likely to follow PPE<br /> wearing and careful anti-infection routines. Support staff (food <br /> service, assistants and claening staff) with less formal medical <br /> training and understanding of infection are probably less likely to be <br /> vacinnated and also may be less likely to carefully employ all technical<br /> anti-infection measures. Would this account for the vaccinated folks <br /> having less COVID infection?

On 2020-12-03 15:34:00, user joetanic wrote:

Quite interesting data. I'm wondering whether anyone knows why France does not perform these tests?

Or the US? It seems a broad study, especially in France which seems to be bucking the trend, so to speak, would make clear what the future holds in many places.

On 2020-12-09 15:46:15, user Laura wrote:

This preprint has been published in The Journal of Immunology. You can read the latest version here: https://doi.org/10.4049/jim...

On 2020-12-11 16:21:41, user Fred wrote:

Disappointing study. I would not expect that antivirals are of any use if started when patients are already hospitalized. I would recommend to start with antivirals as soon as possible regardless wheter the patient has symptoms or not. But in this case we need studies comprising many more patients than in this small study

On 2020-12-11 18:07:58, user Thierry Grenet wrote:

Another discussion of the trajectories is given here : https://bmcmedresmethodol.b....

On 2020-12-12 17:48:59, user Patrick Karas wrote:

Congratulations on this excellent work. Molecular subtyping for meningioma is much needed to help develop future therapies, and your work pushes this forward. How do you think your subtypes A, B and C compare to the meningioma molecular types similarly labeled type A, B, and C published last year in PNAS by Patel et al (doi: 10.1073/pnas.1912858116)? It seems like there is a lot of overlap (group A with intact NF2; group B and C with NF2 loss; group C with increased FOXM1 expression and high copy number variation). This is a great step forward validating these subtypes through a different approach.

On 2020-12-12 23:20:04, user Omid Jahanian wrote:

This is an original manuscript of an article published by Taylor & Francis in the Journal of Spinal Cord Medicine on 09 Nov 2020, available online: https://www.tandfonline.com....

On 2020-12-13 04:57:43, user Haitham kussaibi wrote:

Dear valuable readers,

The current manuscript has been peer reviewed and published by <br /> Karger, Acta cytologica<br /> DOI:10.1159/000509669<br /> Thank you for your interest.<br /> The Authors

On 2020-12-16 20:05:03, user Wolfgang Lins wrote:

the authors discuss "anterior nasal (AN)" swabs, and on page 4 refer to this as:

Participants first underwent collection of the AN-sample, using the specific nasal swab provided in the test kit of the manufacturer, according to the instructions for use, which also correspond to the U.S. CDC instructions [4]. Briefly, while tilting the patient’s head back 70 degrees, the swab was inserted about 2cm into each nostril, parallel to the palate until resistance was met at turbinates, then rotated 3-4 times against the nasal walls on each side

First, the collection procedure described here in act matches to one in that CDC manual [4], however not to the AN collection but to the collection of Nasal mid-turbinate (NMT) specimen. That is a floppy usage of the terms AN versus NMT, and should at least been detailled when defining AN in this paper.

Second, the paper refers to a "specific nasal swab provided in the test kit of the manufacturer" for AN collection. Three lines later they write "a separate NP-swab (provided in the manufacturer test kit) for the Ag-RDT". <br /> As of my knowledge, the "STANDARD Q COVID-19 Ag Test" of SD Biosensor/Roche comes with a single kit - a NFS-1 from Noble Biosciences Inc., which is a swab for NP.

I think it would help this paper to identify the particular "specific nasal swab" used here to obtain the AN/NMT swab - since the conclusions of this paper make a claim that "using a professional AN-sampling kit is at least equal to....". Reference 5 with a link to a sdbiosensor IFU that refers to NP swab only does not put any more light into this.

Such a finding without properly identifying the particular kit unnecessarily reduces the value of this work.

On 2020-12-25 14:25:32, user muthu venkat wrote:

The Systematic Review and Meta-Analysis is interesting to read and need of the time to compile such an evidence particularly for middle and low income country. The authors have made sure that there is no bias in selection and reporting the evidences through use of appropriate software and methods.

On 2020-12-26 19:56:50, user Dr S K Maheshwari wrote:

This systematic review is focusing on measuring effectiveness of mHealth interventions on antenatal and postnatal care utilization in low and middle-income countries. A strong methodology was used along with wide inclusion of relevant studies from low and middle-income countries. The search strategy criteria were used very specific. I appreciate this work and recommend.

On 2020-12-25 16:08:55, user Deepak K. Gupta wrote:

Full paper now published in the Tremor and Other Hyperkinetic Movements journal here: https://tremorjournal.org/a...

On 2020-12-26 04:49:01, user Peter Tomasi wrote:

Correction: If we assume a latency of 28 days, a substantial amount of samples REPRESENTING A POINT IN TIME WHEN THE level of the exposure in the environment was not yet as high as the one the authors draw their conclusions for, could have been collected.

On 2020-12-27 21:03:59, user CO2lover wrote:

I wonder if those samples are ever tested for influenza?

On 2021-01-01 12:19:30, user Ed wrote:

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

..and yet it is being used for exactly that, ref. Department of Health and Social Care Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination, 30 December 2020 6th bullet-point of the introduction.

On 2021-01-05 07:56:40, user Rita Pizzi wrote:

previous researches

Ghate VS, Ng KS, Zhou W, Yang H, Khoo GH, Yoon WB, Yuk HG.

“Antibacterial effect of light emitting diodes of visible wavelengths on

selected foodborne pathogens at different illumination temperatures.”

International Journal of Food Microbiology. 166 (2013) 399.

Ghate VS, Leong AL, Kumar A, Bang WS, Zhou W, Yuk HG. “Enhancing the

antibacterial effect of 461 and 521 nm light emitting diodes on selected

foodborne pathogens in trypticase soy broth by acidic and alkaline pH

conditions” Food Microbiology. 48 (2015) 49.

Ghate, V, A Kumar, W Zhou and HG Yuk. 2015. Effect of organic acids

on the photodynamic inactivation of selected foodborne pathogens using

461 nm LEDs. Food Control 57:333–340.

Vaitonis and Ž. Lukšiene – Institute of Applied Research, Vilnius

University, Saul?etekio 10, LT-10223 Vilnius, Lithuania “Led-based light

sources for decontamination of food: modelling photosensitization-based

inactivation of pathogenic bacteria” Lithuanian Journal of Physics,

Vol. 50, No. 1, pp. 141–145 (2010)

http://www.lmaleidykla.lt/p...

Nicolai Ondrusch, Jürgen Kreft “Blue and Red Light Modulates

SigB-Dependent Gene Transcription, Swimming Motility and Invasiveness in

Listeria monocytogenes” Published: January 11, 2011DOI:

10.1371/journal.pone.0016151

http://journals.plos.org/pl...

On 2021-01-06 22:52:53, user Ana Laura Teodoro De Paula wrote:

Where's the funnel plot? The result can't be considered if you cite a funnel plot and don't show it.

On 2021-01-07 03:20:52, user Robin Whittle wrote:

The Mark Alipio article (43) is fake and was withdrawn in August. Please see https://researchveracity.in... for information on this article and two more by "Raharusun" et al. and "Glicio" et al.

On 2021-01-07 08:06:09, user Giuseppe novelli wrote:

Congratulations, the work confirms and extends the considerations reported by us in two published papers, which happy if the authors could quote in an updated version of the manuscript Thanks

Giuseppe Novelli

1. Novelli A, et al., Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients. Hum Genomics. 2020 Sep 11; 14 (1): 29. doi: 10.1186 / s40246-020-00279-z. PMID: 32917283

2. Latini A, et al., COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells. Genes (Basel). 2020 Aug 27; 11 (9): E1010. doi: 10.3390 / genes11091010. PMID: 32867305

On 2021-01-07 14:34:51, user Meerwind7 wrote:

Households with single parents are also considered as socially deprived in other contexts. For infection rates, it might be of benefit if there is no second adult that could bring infections to the family. It was a pity if the effect was not taken into account. I also do not know if the social deprivation was evaluated for each individual child and its infection risks, or just for the schools and the aggregat of their pupils overall.

On 2021-01-08 21:53:07, user Marek J wrote:

Your study says that methylglyoxal contained in honey cause immunostimulatory or pro-inflammatory action via stimulating the production of immunological mediators, also IL-1?. This study https://www.nature.com/arti...<br /> Shows that low levels of IL-1 are linked to lower mortality.<br /> Is it then safe to recommend using honey rich for MGO, e.g. Manuka honey?

On 2021-01-09 18:28:12, user Alex Backer wrote:

This study appears to have been used to Curative to justify their methodology, yet the false positive and false negative rates in the FDA report are incredibly high. Look at the numbers: https://www.linkedin.com/pu...

On 2021-01-10 12:16:07, user Hans Binder wrote:

The paper is published under<br /> https://www.mdpi.com/1999-4...

On 2021-01-10 19:47:40, user Wayne Griff wrote:

21 days after the 1st dose of the Pfizer Vaccine, patients have 1/5th the viral neutralizing power of Convalescent Plasma. In contrast, 7 days after the 2nd dose, patients have 2-4 times the neutralizing power of Convalescent Plasma. NEJM Also, the 47% effectiveness rate is only up to 3 weeks. It's definitely going to be less at 6, 9, or 12 weeks.<br /> Giving only 1 vaccination is a waste of a vaccination. It provides little, if any immunity.

On 2021-01-12 20:36:18, user Michael Meyer wrote:

Can someone tell me if this study has completed the peer-review process prior to publication in the Journal of Infectious Diseases? If not, is it currently in that process?

On 2021-01-13 13:34:01, user Tavpritesh Sethi wrote:

Great work. Please do have a look at our work from June, 2020 on similar lines using explainable models https://www.medrxiv.org/con...

On 2021-01-14 00:01:25, user Emmanuel Aluko wrote:

Will such a study be done on older cohorts to show the age-dependent efficacy of Ivermectin on reducing mortality, for mortality is seen mainly in older patients with associated co-morbidities? Days to negative tests on such cohorts would also provide a better basis for accepting Ivermectin as a worthy COVID-19 therapeutic.

On 2021-01-14 14:10:21, user Jeroen van Kampen wrote:

Finally peer-reviewed and online.<br /> See: https://www.nature.com/arti...

On 2021-01-15 12:19:29, user Kit Byatt wrote:

Given that:<br /> 1. Excess mortality for a year can't be known for several weeks into the following year <br /> 2. Especially in a year with Christmas & New Year's Day on Fridays, and a pandemic impeding the bureaucracy of collecting & collating mortality data - particularly in cases where the Coroner [or equivalent] is involved)<br /> 3. Different countries have exhibited different patterns (or none) of winter excess mortality peaks (as shown in Figure 1c)

a) Is it not premature to undertake a comparison before all the data are in (or alternatively, at least title as 'Preliminary observations on...'?

b) Might not the association end up significantly higher, the same, or lower, then?

On 2021-01-27 10:12:04, user Elias Hasle wrote:

some countries being hardly hit while others to date are almost unaffected

Readers will tend to read this as "barely hit", the opposite of the intended meaning. "hit hardly" would be less ambiguous.

On 2021-01-17 06:42:44, user Seri Ratu Putri Binti Baharom wrote:

Hi, where can I see the survey form?

On 2021-01-18 11:40:13, user Kit Byatt wrote:

Re Length of stay [LOS]

1. Was there a sex difference in LOS?

2. We know there are age differences in LOS (median & variance increasing with age). What were the LOSs for age brackets (e.g. each decade)?

3. Given the very skew LOS distributions in hospital in-patients usually, and especially here, mightn't it be helpful to put the inter-quartile range for the median LOS in 'Outcomes' para 2?

4. Could you calculate the 'decay' in in-patient numbers (i.e. the equation for the 'current number of inpatients' curve from time zero, for 1000 pts with the LOS distribution you know)? This could be invaluable for modelling bed occupancy.

Minor presentational points:

1. Figure 15 Middle (symptoms combination in ICU patients matrix) p 23

It is difficult to know the percentage figure for each bar in the symptom combinations and ICU admission matrix. Either putting the number over/in each column (as in Figure 15 Top), or at least showing minor tick marks at 0.01 intervals would greatly improve the clarity of this chart.

1. Is there a reason for presenting LOS data as a density plot and time from symptoms to admission as a Gamma distribution curve? They are essentially the same phenomena: time to an occurrence; why the different graphical representation?

On 2021-01-21 13:24:54, user Miroslava Stancíková wrote:

Testing was not voluntary, it was in conflict with the Constitution of the Slovak Republic and the Charter of Fundamental Human Rights

On 2021-01-23 01:56:50, user Super Science wrote:

Interestingly similar Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis ‘Chronic Fatigue Syndrome’ (ME/CFS) patients were also found<br /> – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts - ScienceDirect<br /> August 2020<br /> https://www.science direct.com/science/article/...

On 2021-01-25 15:10:24, user Chip Hughes wrote:

Thank you all for this great research. It will really help OSHA target enforcement to the highest risk sectors and job classifications so that we can hope to reduce deaths among frontline workers with the highest level of COVID19 exposures on the job. Chip Hughes, USDOL-OSHA DAS

On 2021-02-02 18:17:42, user Robert Enger wrote:

The #1 candidate is "cook". Frequently that person stands in proximity to the grill, which is a high air flow location, due to the high power exhaust fan system in the range-hood over the grill. This acts as a funnel, sucking air from the kitchen (and surrounding areas back to the various points of makeup-air ingress). The cook is thus "downstream" from numerous co-workers in the kitchen, and from persons in other locations between the makeup-air ingress points and the range hood (potentially all the restaurant patrons, if interior dining resumes).

This should sound familiar. Recall the studies of remote distance Covid transmission studied in Korea and China. In those studies, high air flow from air conditioner output ports carried virus from infected individuals to victims many feet removed from the infected party. In this case, the cook near the range-hood is "downstream" from potentially significant numbers of individuals (depending on the location of makeup-air ingress points, etc).

If this line of reasoning is found to be sound, then providing a direct ingress path for outside fresh air to enter into the kitchen "may" reduce the exposure of the cook (and nearby kitchen staff).

On 2021-01-26 01:45:47, user jsihje wrote:

Why is Ivermectin and Embelin not considered at all?

On 2021-01-26 01:57:03, user Steven David Stoffers wrote:

what about a model run where there wasn't any air travel at all, including private air travel, that needed to still be made let alone any actual air travel at all, as of January 30, 2020 thru to today? what does that model show?

On 2021-01-30 20:33:49, user Michael Höhle wrote:

Dear authors,

thanks for posting this very relevant manuscript! Please consider having a look at the statistical methodology of the two following papers, which are very closely related to your work, as they also use an imputation + nowcast + backprojection approach:

• Nowcasting the COVID-19 pandemic in Bavaria:<br /> https://onlinelibrary.wiley...

• Analysis of the early Covid-19 epidemic curve in Germany by<br /> regression models with change points:<br /> https://www.medrxiv.org/con...

Best regards,<br /> Michael Höhle

On 2021-02-04 19:21:10, user Eli Rosenberg wrote:

We note that the final form of this article was published in JAMA Network Open on February 3, 2021:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775827

We thank the medRxiv community for your interest in our work.

Eli Rosenberg<br /> Associate Professor<br /> Department of Epidemiology and Biostatistics<br /> University at Albany School of Public Health, State University of New York

On 2021-02-22 19:53:12, user Alexander Porter wrote:

What does: '8,041 individuals received two doses of a COVID-19 vaccine and were at risk for infection at least 36 days after their first dose.' mean? Were these individuals exposed to SARS-CoV-2 directly every day?

Were all PCR methods run with the same cycle threshold before and after administration?

On 2021-02-23 12:35:42, user Marek J wrote:

Great. We need more trials like this. There is huge potential: https://www.medrxiv.org/con...

On 2021-04-15 21:01:27, user CY Liu wrote:

Did you control batch effect, position effect, covariates in the data analysis? I could not see it in the paper.

On 2020-11-06 05:07:01, user Schneide Fu wrote:

Not sure they got the dosage correctly, as Nitazoxanide has a half life of 2.9 hrs. Should have been on divided doses, several times a day.

On 2020-11-06 14:33:43, user Dr. Thiagarajan wrote:

Timely need article and very interesting. We need to understand the challenges faced by dialysis professionals during this COVID 19. I congratulate Dr. Ravi Kumar for this timely article. Looking for this complete manuscript.

On 2020-11-12 12:47:34, user leesohyun19 wrote:

is it possible without masking image?

On 2020-11-13 04:37:18, user Ryo Honda wrote:

Now it's revised and published in Sci. Total Environ.<br /> https://doi.org/10.1016/j.s...

On 2021-08-10 22:41:16, user Ashley Derrick wrote:

I had covid in May of 2020. I had many long covid issues for months after - but the biggest issue was chest (heart and lung) pain. The symptoms included shortness of breath, burning sensation in the chest, difficulty getting a deep breath and feeling as if I was having a heart attack when more active (exercising). I went to both a heart specialist and a pulmonary specialist and nothing ever was found to be "wrong". The heart doctor was convinced it was inflammation in and around my lungs and heart that caused this. After 9 months, it went away (shortly before my first vaccine). I felt "normal" for about 4.5 months, but two weeks ago, the chest and heart issues came back. Same feelings. I am a fit 49 year old woman. Wondering if there are any studies that see symptoms going away and then months later coming back. Thanks -

On 2021-08-12 06:11:36, user Gabriele Pizzino wrote:

The study brings up relevant insights.<br /> I agree with Richard, uniformity of testing frequency is a potential confounding factor that should be taken into account.

Also, you may have a selection bias generated by vaccination policies, and timeline.<br /> I’m gonna use Italy to give you the idea: Pfizer was rolled out earlier, and in a much more massive way, than Moderna. The same was true for the AstraZeneca one.<br /> The Italian government gave priority to high-risk workers (especially health workers, and whoever was working into medical facilities or nursing homes), and to high-risk individuals (so elderly people, and/or people with severe underlying conditions).<br /> At the time, the choice was between Pfizer and AstraZeneca; considering Pfizer showed a better efficacy, and it was better perceived in terms of safety profile by the public, the very very large majority of those high-risk categories received the Pfizer shots.

That is a textbook-level selection bias, which could potentially affect the results in a significant way.<br /> I live in Italy, so I followed the vaccination process here much more closely; I don’t know if the same dynamics I described stand true also for the US, but I think it is worth to take a look and check it.

On 2021-08-12 19:49:26, user Steven Ramirez wrote:

From the preprint:

"Date of vaccination (bucketed). For a given individual in the mRNA-1273 cohort who<br /> received their first vaccine dose on a given date, only individuals in the BNT162b2<br /> cohort who were vaccinated on the same date or within two weeks after that date were<br /> considered for matching. This match helps to ensure that matched individuals reach their<br /> date of full vaccination (14 days after the second dose) on approximately the same date."

This seemingly addresses my point and effectively controls for diminution over time.

Perhaps an explicit sentence in the preprint would help clarify this point.

On 2021-08-12 17:18:46, user Iñigo Ximeno wrote:

Although the observation is very interesting, it does not lead to the conclusion that it is the most prudent thing to continue with indiscriminate vaccination in the middle of a pandemic when the vaccine does not prevent the transmission of the pathogen.

It is not relevant how many mutations are detected but the importance of them. It is obvious that among people with some immunity the mutations for which the antibodies can neutralize the virus will not be spreaded and therefore those will not be detected. However the mutations that can evade the immunity, even if they are few, will be more virulent and letal.

On 2021-08-12 20:58:05, user Raul Sanchez-Lopez wrote:

This article is now "in press" in Frontiers in Neuroscience:<br /> https://www.frontiersin.org...

On 2021-08-13 11:07:32, user BO Dong wrote:

This paper has been published elsewhere!!!<br /> https://celljournal.org/jou...

On 2021-08-14 05:50:28, user Brad Mellen wrote:

I assume the 167 infected people tracked in the study were previously vaccinated. Is it possible that antibody mitigated viral enhancement played a role in the increased viral loads? A study done by Wen Shi Lee et al in the Nature Microbiology volume 5, pages 1185–1191 (2020) noted the potential dangers of Covid 19 vaccinations could increase viral loads and ultimately increase the spread of Covid 19.

On 2021-08-15 14:53:19, user Johannes Hambura wrote:

The study authors found that the prevalence of mutations is higher in B cell epitopes than in T cell epitopes. They infer that vaccines that rely primarily on T cell immunity should confer protection more durable against the worrisome variants of SARS-CoV-2.<br /> It would be logical and consistent to assess this T cell immunity in unvaccinated and recovered Covid-19 patients, in order to better coordinate the strategy towards collective immunity.

The authors report, based only on 47 cases studied, that unvaccinated patients share significantly more genomic mutational similarities with the variants of concern than patients with a breakthrough infection.<br /> This finding is interesting, but it requires statistically significant evaluation and verification.<br /> Especially since<br /> - in vitro, the selection pressure imposed by the antibodies, induced by the vaccines, has led to the emergence of new variants of SARS-CovV-2 (1);<br /> - in vivo, the case of a severe and prolonged form of infection by SARS-CoV-2, treated with antibodies taken from convalescents, favored the appearance of a variant. The variants decreased when the treatment with the injected antibodies was stopped and reappeared with new doses of the injected antibodies. In the absence of the antibodies, the wild strains again became the majority (2).

In addition, the following findings by the authors tend to favor selective pressure exerted by vaccinations:<br /> - the diversity of SARS-CoV-2 lines decreases at country level with an increased rate of mass vaccination (negatively correlated with the increase in the rate of mass vaccination in the countries analyzed);<br /> - The decline in lineage diversity is coupled with the increased dominance of variants of concern;<br /> - vaccine breakthrough patients harbor viruses with significantly lower diversity compared to unvaccinated COVID-19 patients.

The question still remains open, whether vaccination should not be limited to only vulnerable people in the world population, in analogy with a risk calculator for the population proposed by American scientists (3).

1. Wang, Z., Schmidt, F., Weisblum, Y. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 592, 616–622 (2021). https://doi.org/10.1038/s41...
2. Kemp, S.A., Collier, D.A., Datir, R.P. et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature 592, 277–282 (2021). https://doi.org/10.1038/s41...<br /> (3) Jin, J., Agarwala, N., Kundu, P. et al. Individual and community-level risk for COVID-19 mortality in the United States. Nat Med 27, 264–269 (2021). https://doi.org/10.1038/s41...

On 2021-08-18 16:51:05, user Diane Krall wrote:

We need data for severe COVID patients and reactogenicity. These patients had high dose steroids during their illness, which may be a confounding factor.

On 2021-08-18 17:39:03, user John Baron wrote:

The first sentence states that this is a study of individuals who underwent SARS-CoV-2 testing, presumably (though not stated) during the study period. Unless there was population testing surveillance in place, there must have been selection factors (e.g. COVID exposure or symptoms) prompting testing. This would bias estimates of infection rates upward, though the bias is unlikely to differ between vaccine groups and may not differ much between vaccinated and unvaccinated groups. Tthe relative infection measures might be OK.

In the "final" paper, it would be important to account for the usual cohort issues: censoring, movement out of the health care system, etc. Also, the first paragraph of the Methods section should include unvaccinated individuals.

On 2021-08-19 02:48:38, user Sheila Halpenny wrote:

I assume everyone responding here will use the same “logic” to apply to every other poll taken.

On 2021-08-09 21:26:26, user CdSS wrote:

Where can I get the reasons why PhDs answered "probaly not/definitely not"?

On 2021-08-21 17:14:03, user Alan wrote:

How will increased vaccination make a difference if the efficacy is as is being reported less than 50%? Once one is infected it does not appear to reduce one's odds of being hospitalized. So if the efficacy approaches zero, there would be zero benefit to being vaccinated, with the currently available vaccines.

On 2021-08-23 13:04:39, user Eyal Oren wrote:

I don't see any mention of vaccination status. Were these patients vaccinated or unvaccinated? Also the study would be stronger if comparison done to other patients in your catchment area vs CDC data (I believe that dataset is across US and not limited to Georgia?).

On 2021-08-25 16:22:39, user Sajjad Nasiri wrote:

I am wondering if you considered manually sniffing nasal saline irrigation?

On 2021-08-24 09:17:07, user Martin Steppan wrote:

A fundamental methodological caveat of this article is the date / season of sample collection. Breakthrough infection samples were collected in the sprjng-summer period of 2021 only (apr-jul), whereas unvaccinated samples seem to be predominantly from fall / winter 2020 (apr-dec). It has been shown in many studies that sars-cov-2 virions are temperature-sensitive and less active / infectious in warm environments. Hence, the results of this manuscript may reflect a seasonal pattern in infectivity. The authors may want to control for this statistically by either (1) using a matched design of samples from similar dates; (2) include historical temperature data for the Netherlands as a covariate / proxy for this likely bias. Due to this reason, the analyses in their current form do not rule out this bias, which casts doubt on the authors' implicit hypothesis that vaccination status moderates the link between viral load and infectiousness.

On 2021-08-26 11:54:58, user Gubbedefekt wrote:

Can someone confirm: what difference did it make if the natural immunity was acquired from a delta variant infection compared with one from another variant? Did the study look at this?

In any case the comparison looks devastating for Pfizer and other vaccine producers.

On 2021-08-26 18:20:25, user thestreetlawyer1 wrote:

Love to see this peer reviewed. Been really trying to determine what is the best move for me. Hard to put all the dogma and peer pressure aside (from both sides). I'm curious how this data reckons with u.s data on hospitalizations, seems most of our hosp cases are unvaccinated.

On 2021-08-28 19:52:31, user Catriona wrote:

“ individuals who were previously infected with SARS-CoV-2 and given a single dose of the BNT162b2 vaccine gained additional protection against the Delta variant.”

I’m confused. Didn’t your study show no significant difference for symptomatic infections in previously infected individuals with or without a single vaccination dose? Or did I get that wrong? The table says the previously infected and vaccinated odds ratio for symptomatic infection is 0.65 but confidence intervals were 0.34-1.25 and P value was 0.194.

In which case, exactly what were they protected against? Is there some sort of clinical significance regarding a positive PCR in the absence of any symptoms? Or are you implying that individuals can have atypical symptoms that can cause them health problems but aren’t recorded as symptoms? The study didn’t look at infectivity.

Are you claiming the vaccinated individuals were healthier in some way because they had fewer positive PCRs? Or are you claiming they did not pass on the Delta variant as often? Or was there something else that you meant by “additional protection against the Delta variant?”

Would love some clarification on these issues.

On 2021-12-24 18:05:32, user Michael Ruimerman wrote:

Natural Immunity > Vaccinated Immunity!!! Governments should be considering EVERY unvaccinated person that has survived a COVID infection as "immunized", since they have a stronger, more robust resistance to another COVID infection.

On 2021-08-27 11:08:39, user Lakesha Scout wrote:

Most people do not understand how their immune system works, and fall back upon the inept press as their inept narratives. Antibodies do not continue long term, as such a condition would in fact prove disastrous.

Long term immunity relies upon the creation of memory .. specifically memory B and T cells. These are the cells which identify later reemergence of a pathogen (such as SARS-CoV-2) in the body and mount a successful and rapid response to its demise.

There are two pathways to "Active" immunity (infection, and inoculation) <br /> Also there is "Passive" immunity which occurs through such things as a blood plasma infusion from a prior infected person who has existing antibodies. <br /> Any of these three paths, can provide immunity to a pathogen.

The false narrative being pumped by the media is that the only way to overcome a pathogen is through inoculation (vaccination).... that quite simply is not true, neither in medical sense nor in scientific sense. As a mater of medical fact, some inoculations (specifically mRNA) have been proven to enhance a pathogens capability to infect. This condition is known as Antibody Dependent Enhancement or (ADE).

On 2021-08-27 17:26:33, user Mohammad Ali wrote:

Please find the published article at BMJ Open here: https://bmjopen.bmj.com/con...

On 2021-08-03 22:35:32, user Gemma Hollie wrote:

Can you advise how many pregnant women / live births / still births there was during this period. Also, for moderate to severe disease, you report 45% for the delta variant. Can you advise, is this of the total 3371 women or the 1137 admitted due to symptoms of covid? <br /> Vaccine safety for pregnant women has not been well filtered down to health care professionals, therefore the uptake of women getting the vaccine has not high. Now more women are having the vaccine, i wonder if future results of women getting moderate to severe disease will continue to support recommending the vaccine. Will you be doing another study in the near futute to update the findings? Thank you

On 2021-08-04 16:08:46, user Sam Chico wrote:

They compare raw Ct values which are meaningless in qPCR testing and must be correlated with something, e.g. a dilutions series of positive control COVID RNA at the very least. Should really be related back to viral counts using plates and plaques.

This is very lazy research that only shows that vaccinated people can harbor detectable amounts of viral RNA, its quite a reach to say that implications of this data is to say that vaccinated people are infectious. The only way to do that without clearly and reproducibly demonstrating it is looking at the population level data.

Its irresponsible and borderline unethical to publish data like this, the MIQE guidelines made clear what publishable qPCR data should look like. These sorts of publications undermine the impact of properly performed studies with truly actionable data. The authors should know better.

On 2021-08-05 17:53:16, user Ultrafiltered wrote:

Not even peered reviewed and yet the authors and local news stations in Dane County are promoting and reporting on this paper. That sends a dangerous message to the public that anyone can write anything and its believable/credible. Seeing the other comments here on the fallibility of the PCR test, as CDC has called out and published authoritatively along with other FDA withdrawals of rapid assay test procedures, indicates mine and their comments are just as good as this paper. The authors should remember that information is like a match, it can burn a whole lot of people if left unchecked/ unqualified / uncontrolled.

On 2021-08-05 16:37:19, user circleofmamas wrote:

So by not being vaccinated, I am reducing my relative risk of a 'severe adverse event' by 74%. And my absolute risk to become a "case" is less than 4%, and severe COVID is 0.1%.

On 2022-03-09 21:24:14, user Les Funk wrote:

Figure 1 caption contains the false statement, "Disposition is presented for all enrolled participants..." There are 1841 participants not included in the figure after dose 2: 1258 from the BNT162b2 group and 583 from the placebo group. What happened to them?

On 2021-08-09 18:06:43, user MJ wrote:

".....assuming that baseline mitigation measures of simple ventilation and handwashing reduce the second+ary attack rate by 40%".

Congress gave billions of dollars to upgrade schools, to properly fit them with the necessary equipment for proper ventilation/air purification. Schools have had a year to do it, yet it hasn't been done. Schools are going to be reopened in the next few weeks without proper mitigation strategies for airflow.. Schools will be a breeding ground for this virus, even scarier now that the transmission rate is triple what it was a year ago. Speaking as someone who was infected via classroom exposure, and still suffering effects from the virus, more needs to be done to protect and reduce the risk to the children and staff

On 2021-12-08 00:42:55, user Sam Smith wrote:

Summary:<br /> These data demonstrate that both heterologous Ad26.COV2.S and homologous BNT162b2 increased antibody responses in individuals who were vaccinated at least 6 months previously with BNT162b2. <br /> Ad26.COV2.S and BNT162b2 led to Similar antibody titers by week 4 following the boost immunization but exhibited different immune kinetics5. <br /> Ad26.COV2.S led to greater increases in CD8+ T cell responses than BNT162b2!!<br /> However, the durability of these immune responses remain to be determined.<br /> These data suggest different immune phenotypes following heterologous (“mix-and-match”) compared with homologous boost strategies for COVID-19.

On 2021-12-08 18:41:55, user Brian Mowrey wrote:

~18k rapid antigen tests from before Nov 8 were added to the NICD data on November 23, and are included in the results in this update per the text.

How many positives in the Nov 23 dump were missing sample dates? Sample dates are implied not to be "complete within the data set" per the text. Hence why receipt dates were used - but "problems have been identified with accuracy of specimen receipt dates for tests associated with substantially delayed reporting from some laboratories," again per the text.

How many with missing sample dates were scored as "reinfections" in November? 1? 100? 1000? Delayed, non-sample-dated rapid antigen tests for summer Delta infections dumped on Nov 23 could account for the entirety of the "Omicron reinfections" presented in the update, or certainly a significant portion of them.

On 2021-12-13 18:57:26, user joetanic wrote:

breakthrough infections in previously infected

Is this some assumption of the equality of natural immunity to vaccinations? It seems there are more antibodies generated in natural immunity, some that are external to the spike, and furthermore natural immunity seems far longer lasting than does vaccination.

So from whence does this belief come?

On 2021-12-17 16:06:10, user PasserBy wrote:

This article makes several claims of significant differences, yet does not report the statistical tests used. Given the very small sample size, it would be beneficial to know the tests used, the actual data, and the probability levels associated with the statistical test values.

On 2021-12-21 11:23:13, user Shallee Page wrote:

These descriptive data provide really useful data for thinking about LC and the visualizations are good.

It seems like there is a lot of room for more caveats for this self-selected groups.

The speculation about why so many tested negative for COVid seems shoddy. Primer sets are not the main problem here. There is a subset of respondents where there is little evidence that their symptoms are caused by SARS-CoV2. The number of negatives is higher than the false negative rates reported by the molecular biologists. Consulting some would be wise because I think timing of virus load is much more likely to be the problem than some primer pair problems that tests suffered from in early 2020.

On 2021-12-22 18:19:23, user Kurt the Turk wrote:

I hope the post boost samples can be made available to the Emory lab to show neutralization of live viruses. That would really complete the picture.

On 2021-12-29 20:08:54, user Greatwiz wrote:

Did they change anything about the booster shot. Any update sequencing?

On 2021-12-23 08:00:42, user Patrick Bowen wrote:

This study did not control for vaccination status or prior infection. Their findings could be entirely due to these factors.

“Some of this reducton is likely a result of high population immunity.”

On 2021-12-23 12:09:50, user Matthew Nelson wrote:

This is a superb paper, especially the careful approach to CNV calling and the Bayesian methods used throughout. Searching through the supplementary material, there is one important piece of the story that appears to be missing. Where are the counts of de novo missense, PTV, and CNV mutations per gene? These were nicely captured in the Satterstrom and Kaplanis NDD publications. These are really important for understanding potential population sizes for prioritizing therapeutic discovery and development. Have I missed them?

On 2021-12-23 20:05:57, user Julien Reszka wrote:

What does negative effectiveness mean ?

On 2021-12-29 00:23:23, user madmathemagician wrote:

How do they deal with a zero in the data set, there are no zeros in a Benfords' distribution.

On 2021-12-30 08:12:32, user J Sato wrote:

Could you breakdown the risk of hospitalization/death by vaccination status/time?

On 2021-12-30 12:54:21, user madmathemagician wrote:

Lots of double tongue wording to imply evidence of fraud without even claiming evidence of fraud.

On 2021-12-30 16:39:32, user Igor Chudov wrote:

Very interesting article!

Could you please clarify something for me.

You say "Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49).".

This is great, but no Covid vaccine generates or in any way is related to "nucleocapsids" or "membrane proteins". If so, is the mentioned T-Cell reaction to nucleocapsids somehow related to vaccination? Covid-naive vaccinees never come in contact with "nucleocapsids".

Were the nucleocapsid T cell reactions only in the covid-recovered?

A clarification would be greatly appreciated. Thank you very much.

On 2021-12-31 07:47:11, user eriugena wrote:

The current stats in countries like Ireland show 1/3 to 1/2 people testing positive every day. Ok, the PCR test - putting it mildly - is imperfect. However, we can take it using very simple math that 100% of the population is infected within a week. End of "pandemic".

On 2022-01-10 20:48:26, user Siguna Mueller, PhD, PhD wrote:

Dear authors,

Thank you for providing these important data. I am afraid I cannot see how you actually arrive at your conclusion. Can you please help me understand:

1. How did you actually know people got infected - with the respective variant? You state that cases were identified by “by whole-genome sequencing or a novel variant specific PCR test targeting the 452L mutation.” How many were verified by the former? As for the PCR test, can you please comment how your modifications overcome the limitations as recently announced by the CDC when withdrawing its EUA (https://www.cdc.gov/csels/d...? "https://www.cdc.gov/csels/dls/locs/2021/07-21-2021-lab-alert-Changes_CDC_RT-PCR_SARS-CoV-2_Testing_1.html)?")

2. Can you say more how VE relates to individual people rather than the numbers that your results and conclusions are based on? You seem to draw your conclusion on statistical means alone. Yet, the average person just does not exist. Moreover, your analysis involves huge standard deviation values.

3. You say that in the first month already, for some, VE is only 23.5% or even -69%, for vaccination with the Moderna or Pfizer vaccine respectively. How is this supporting your conclusion, please? Are you suggesting more repeated boosters than every month? What would that do to the already minimal or even negative protection? How could a repeated and ongoing “negative protection” – meaning that the vaccine causes an increased risk of infection - as experienced by some (Moderna), suddenly become positive and even truly protective?

4. You also say that VE is re-established upon revaccination. I am afraid I do not see the results. All I see is numbers – which are less than encouraging: the for the BNT162b2 vaccine: 54.6%, 95% CI: 30.4 to 70.4%. Even if for many the VE may be 54%, this does not mean that VE is re-established. But perhaps the data supporting the VE are still missing? I cannot find details supporting your assertion. The legend to the Table states that there was “[i]insufficient data to estimate mRNA-1273 booster VE against Omicron.” Yet, I am having difficulty finding the data that would support your conclusion that VE is reestablished for revaccination with the Pfizer vaccine. Actually, both the Figure and the Table show the same details for both vaccines under consideration. I am afraid I don’t see anything in your manuscript as to why there are more data for Pfizer, and why these would support your assertion.

5. Your methods section describes that unvaccinated individuals were followed up from November 20th. Unfortunately I do not see any specific outcomes for the unvaccinated. Your data in the Table and Figure list vaccinated persons only.

6. Can you please further explain how VE is calculated? Is zero efficacy relative to those who were unvaccinated? Yet, in the Results section you say that, relative to the booster you used “those with only primary vaccination as comparison.”

7. Further, when assessing the effect of boosters, you state that your “analysis [is] restricted to 60+ year-olds.” Yet, as stated in the beginning of the Results section, the median age of those infected with Omicron by December was 28 years. Why are you suddenly shifting to a different population group when analyzing boosters?

8. You suggest that the “negative estimates in the final period arguably suggest different behaviour and/or exposure patterns in the vaccinated and unvaccinated cohorts causing underestimation of the VE.” While behavioral issues may indeed impact the outcome of your analysis, your data are not merely negative in the final period. Moreover, for Moderna, there were obviously always some individuals for whom the VE was indeed negative. By contrast, for Pfizer, during the first month at least, VE was in the non-negative range (larger than 23.5, that is). So, it cannot be behavior alone. Else, how could there be such a drastic difference between Pfizer and Moderna (23.5 versus -69.9)?

9. Cases of reinfections are exploding for both vaccines, for Omicron but also Delta, in an exponential way (as seen in the Table). Moreover, the negative entries in most of your points of analysis, makes me wonder how VE relates to individual patients? Other than in the 1-30 day group for Pfizer and Omicron, each of the other points contain individuals that obviously are more susceptible to infection once they have been vaccinated. Can you say more about those, please? You say that “VE was calculated as 1-HR with HR (hazard ratio) estimated in a Cox regression model adjusted for age, sex and geographical region.” From your data it is apparent that there are many in your study population who experienced negative VE. They are obviously a large proportion, and according to your VE calculation, apparently not isolated cases only. It instead seems as if those with negative VE comprise entire groups of individuals, stratified according to your analysis. Who are they? Are these the elderly, the immune-compromised, or who else?

On 2022-01-02 11:26:15, user Lu Ko wrote:

the difference between midturbinate and nasophyryngeal swab is around 15-20%. https://pubmed.ncbi.nlm.nih...<br /> https://pubmed.ncbi.nlm.nih...<br /> The saliva swab is more error prone in real world setting I guess . Does it make sense to switch from NP to throat swab with antigen testing?

On 2022-01-03 14:25:00, user sad wrote:

The disrespect of these French researchers for international efforts of genomic surveillance is astounding. GISAID explicitly requests that all providers of sequences analyzed be credited, and a collaboration is encouraged. None of this happened here. <br /> And they dare name a variant based on a hospital acronym despite the Pango designation. Just mediocre and sad… Luckily other countries are more respectful.<br /> A proper analysis would have also estimated the emergence date with confidence intervals (not as done here) and the growth dynamics of the lineage.

On 2022-01-04 18:02:40, user Barbara A. Zambrano wrote:

What do the 21 “uncomplicated pregnancies” mean with respect to the babies, and how does this differ from the 29 who delivered healthy babies? Were the 21 babies born from uncomplicated pregnancies also healthy???

On 2022-01-05 17:26:08, user Terry Baines wrote:

I greatly appreciate this effort of trying to analyze the unique challenges which Tribes and Tribal members in managing COVID-19 when confounding social, medical, and community issues are involved. With the complex challenges Tribes face, unique and robust solutions need to be devised. Thank you for those efforts; I would love to see more like it.

On 2022-01-06 12:47:12, user Anonymous wrote:

As far as I know that delta variant doesnt have the Deletion at 69 and 70. Yet the Taqpath kit gave sgtf s gene target failure for 8 delta variant samples. This shows that the kit is not a foolproof kit and rather has many issues which is why it was taken out from the market when it started giving false negative results during the alpha variant breakout. Also the authors have conveniently kept mum and skipped over the fact of these questionable 8 delta variant positive cases.

On 2022-01-07 19:58:49, user Clive wrote:

Hi, please correct me if I'm wrong, but reading this study I'm not seeing any comparison to the baseline population that has not contracted COVID. If, as I'm sure you're aware of, a broader worsening of health conditions has increased across the population during the time frame of this study, could the data be misrepresenting a change to the mean in both the vaccinated and unvaccinated groups. For a specific example, I've heard anxiety rates have tripled since the start of the pandemic across the population, and if that pattern was ongoing at the time of this study could the study be overestimating the increase in anxiety among both vaccinated and unvaccinated groups, as everyone, not just those who contracted COVID, experienced an increase in anxiety?

On 2022-01-08 19:16:50, user madza wrote:

Excuse my ignorance but when SAR % is lower in unvaxxed than in vaxxed, how come the Conclusion is that vax reduces the transmissibility?

On 2022-01-09 17:21:03, user Kevin McKernan wrote:

You should test if the primers light up on SARs-CoV-2.<br /> With the high break through rate, People want to differentiate vax from C19. Would also be interested to know if SARs-CoV-2 also ends up in the lipid fraction. I suspect not. The heavy methylation of these RNAs changes their lipophilicity.

Longer testing window would help answer some questions.

Thank you for putting the primers public.

On 2022-01-10 23:36:13, user Fred Ledley wrote:

A peer reviewed version of this work was published in Vaccine in 2021. https://www.sciencedirect.c...

On 2022-01-11 20:23:50, user Sam Smith wrote:

What is the optimal RH = relative humidity for health? Too dry air increases covid risk because it is not healthy for your airways.

On 2022-01-12 17:54:37, user Martha Metevelis wrote:

I am blown away with the similarity to PCS and toxic B6 symptoms I have endured for over three years. I and many others are often dismissed as just suffering anxiety and told thatour symptoms are not real. Many of us rely on a face book site called exploring b6 toxicity for support and share our experiences and what helps. Being ignored and unfairly labeled is the norm. Suicide has occurred with those unable to cope with what becomes a debilitating issue. We experience insomnia, intense pain, sensory and mobility issues, tinnitus that is unbearable, facial pain, anxiety off the chart,vision changes,peripheral neuropathy,swallowing issues, palpitations, internal and extremity tremors, brain fog, memory loss, hair loss to name a few. <br /> I am anxious to know if the subjects involved in your research have vitamin n6 levels checked and if they are taking more than rda of b6 in any form.<br /> I pray that we all get answers soon. The vitamin I took contained 75 mg of b6! And was suggested by my physician. I had been 100% healthy! This upended my life. <br /> I know exactly how long haul suffers feel and hope my input leads to a solution. Thanks for listening.

On 2022-01-13 15:00:50, user Wendi wrote:

This is fascinating because early on a common theme of discussion in some only support groups was that of how covid seemed to have altered one's body odor.

On 2022-01-17 11:18:12, user Free Man in London wrote:

This is another Coke vs. Pepsi paper. There are only 2 conditions in this paper: vaccinated vs. unvaccinated. There are multiple conditions: vaccinated with supplements, unvaccinated with supplements Vitamin D, Quercetin, Melatonin, unvaccinated with supplements quercetin and zinc, etc. The paper prima facie is interesting but devoid of an answer to the real underlying question: are supplements more effective than the vaccines? Moderna and pfizer are more interested in keeping the question framed around simply 2 conditions. Until we force a re-framing to the way this effectiveness question is answered, we are not really solving the problem of stopping the virus. That said, omicron seems to be doing that quite well on its own.

On 2022-01-18 16:19:10, user NoSafeSpaces wrote:

Perfect information on who received a vaccine versus imperfect information on who got COVID. Add in a side of everyone gets the vaccine and not everyone gets COVID with a dash of some of the people getting the vaccine have natural immunity from COVID, and you get a weak justification for putting your children at risk because you don't understand bad assumptions.

On 2022-01-24 16:27:09, user Mary Ellen Mackesy-Amiti wrote:

Published: January 12, 2022 https://doi.org/10.1371/jou...

On 2022-01-31 18:32:19, user Jared Roach wrote:

These are very minor comments about the wording of the Abstract that I would make if I was reviewing the paper:

"strikingly different"<br /> I would delete the vague adjective "strikingly" as it could be interpreted many different ways. Rather insert the exact number of mutations or some similar quantitative metric.

"rapidly replaced"<br /> maybe OK to leave "rapidly", but also add in a sense of how long (e.g., over a period of 3.5 weeks) - or whatever the number of weeks was.<br /> "rapidly" makes sense only in context of other strain replacements such as Alpha-> Delta or Delta-> Omicron. If it isn't much faster than these, I would use an exact time rather than the comparative and vague adjective "rapidly"