On 2020-11-17 01:51:32, user Chris Barker wrote:
Maybe I missed in the article. where is the formal definition of MAPE? and did you have access to the actual computer programs to run the projections or was it based on evaluation of the literature?
On 2020-11-17 01:51:32, user Chris Barker wrote:
Maybe I missed in the article. where is the formal definition of MAPE? and did you have access to the actual computer programs to run the projections or was it based on evaluation of the literature?
On 2020-11-18 13:37:42, user Dr Gareth Davies (Gruff) wrote:
Thank you for this important study.
I have some observations and suggestions regarding interpretation and reporting of this data.<br /> 1. A low or high P-value does not prove anything with regard to the effectiveness of an intervention. It only tells us whether we can confidently reject the null hypothesis or not. In this case, any treatment effect was obviously too small for a study of this power to measure. It does not mean there was no effect.<br /> 2. There appears to be a long time between onset of symptoms and randomisation and initiation of treatment (~10 days?). It takes up to a week for cholecalciferol to metabolise to 25(OH)D so it's not very surprising that by the time it did so, it was too late for these patients. The actions of 25(OH)D on renin gene supression and modulation of ACE2 expression need to occur much earlier to be beneficial in preventing an overactive RAS and cytokine storm.<br /> 3. The patient demographics show that the patient populations were overweight and obese, many with comorbidities (hypertension and diabetes) so again, it's unsurprising that this dose of D3 administered this late was not effective. This does not mean that D3 in general is innefective, merely that this protocol was not for patients of this type. I strongly suggest you make your conclusion statements more precise to reflect this, especially since Castillo et al have shown that administration of high dose calcidiol was very effective. Calcifediol is able to raise serum levels in hours compared to cholecalciferol.
It would be a great shame to report this as a failure of vitamin D3 to treat COVID19 in general when it was simply this protocol for patients of this type and late disease progression which failed for enitrely comprehensible reasons.
It was just too little too late.
On 2021-08-11 15:21:36, user circleofmamas wrote:
They need to include vaccination status of the cases, hospitalizations and deaths. Canada is one of the most widely vaccinated countries in the world, and we can see from Israel data and UK data that the vaccinated are particularly vulnerable to the Delta variant.
On 2021-08-12 19:41:47, user Steven Ramirez wrote:
I wonder if the study disentangled time since vaccination. If protection diminishes over time for both vaccines it needs to be controlled for.
On 2021-08-15 12:39:25, user Jérémy LLL wrote:
Thank you for the useful work. In your Figure 1, the green trend line does not seem to fit any data on the right half of the plot. Can you explain this? Did you exclude the negative detections (Ct 50) from the fit?
On 2021-08-19 15:59:30, user Dan Miller wrote:
Where is table 4 ?
On 2021-07-29 13:25:58, user DogDays wrote:
Are there any likewise studies in relation to Nocebo and vaccine efficacy?
On 2021-07-31 22:40:33, user Dlya Truby wrote:
Supplementary appendix page 12: Deaths : vaccinated group - 15 ; placebo(=unvaccinated) - 14. ... ???
On 2021-08-01 17:13:02, user Catriona wrote:
No number needed to vaccinate for any outcome (death, severe COVID, hospital admission, ICU admission)? Of course, NNV to prevent death is infinite as no deaths were prevented. But what about the other outcomes?
No number needed to harm?
What were the severe adverse reactions?
30 people in the placebo group were diagnosed with severe COVID and 1 in treatment group, so that’s a difference of 29.
150 severe reactions in placebo group vs 262 in vaccine group is a difference of 112. I feel we need to know a lot more details on these adverse events to be able to make informed decisions. As it looks like the number needed to harm is greater than the number needed to prevent harm.
I’m assuming that reducing PCR positivity if you have a mild illness isn’t what most people are really interesting. People are most worried about getting sick enough to be admitted to hospital, admitted to intensive care, dying or getting chronic fatigue syndrome and “long COVID” or some other autoimmune complication afterwards. Particularly if it affects their quality of life, employment, financial security, etc.
This study wasn’t designed to detect how the vaccine affects contagiousness or herd immunity. So can’t assume that reduced mild COVID will improve those things as it could as easily cause atypical symptoms which didn’t warrant a PCR test and allowed participants to interact with others while infectious.
On 2021-08-05 20:42:44, user Sven wrote:
Where can I find Fig. S1A and Fig. S1B about adverse events? Can't find it in the supplementary appendix!
As I just realized now, this was already asked by I. Bokonon<br /> It seems that these tables are indeed not provided. Please add the referenced tables about adverse events.
On 2021-10-05 09:40:08, user leecanning123 wrote:
A major issue is that the pcr test is being used in this study, it is well known pcr produces false positives and as such any one of the placebo cases could be illness that is not connected to sarscov2, much like millions of "cases" around the world over the last 20 months. The FDAs own document stated that early pcr was based on "contrived" samples, meaning, not even real sarscov2.
On 2021-08-26 05:20:32, user Fat wrote:
How was irrigation done? Netipot? Squeeze bottle?
On 2021-08-26 05:56:47, user William Brooks wrote:
This is an interesting paper that fails to find an effect of early bar/restaurant closures during Japan's second state of emergency (SoE). However, I think it has several limitations.
1) Were early closures actually justified?
The authors fail to point out that the SoE started one week after the effective reproduction number (Rt) had peaked and 2/3 days after it had gone under 1 throughout Japan [1, slides 17-18], so the SOE was unnecessary for preventing the "collapse of the medical system", which was the government's justification. Also, the early closure of bars/restaurants in Tokyo/Osaka prior to the SoE didn't stop Rt increasing during the second half of December exactly the same as in the rest of Japan without early closures [1, slides 19-20]. This isn't surprising since even the extreme lockdowns in Peru and Argentina couldn't counteract seasonal rises in Covid infections [2].
Furthermore, even if there were statistically significant reductions in self-reported coughs and sore throats, do the authors think these could justify the negative effects on employment, firm exit, and mental health mentioned in Introduction?
2) Why suggest capacity limits but not ventilation improvements?
In addition to early closures, the Japanese government also recommends mask-wearing while dining out (which is unlikely to be effective [3] [4]) and the use of plastic partitioning in restaurants/bars (which may actually increase infection risk [5]). The authors suggest capacity limits, but this doesn't solve the socioeconomic impacts mentioned in Introduction. Fortunately, even modest improvements in ventilation may be as effective as high-quality R95 masks [4], so investments in improved ventilation/air-purification could be a better solution.
[1] https://www.mhlw.go.jp/cont...<br /> [2] https://www.scirp.org/pdf/o...<br /> [3] https://doi.org/10.7326/M20...<br /> [4]https://aip.scitation.org/d...<br /> [5] https://doi.org/10.1101/202...
On 2021-07-03 04:25:21, user Sumedh Bhagwat wrote:
COVAXIN preprint says: (Protocol, Supplementary appendix 2) but there is just a single supplementary file which is not the protocol .<br /> Please attach Supplementary appendix 2.
Actual Vaccine Efficacy against symptomatic Covid when calculated using formula is 77.27% ~77.3%<br /> Paper reports 77.8% which is due to rounding off of fractions
On 2021-07-05 05:35:47, user The Scrutinizer wrote:
Sumedh Bhagwat you are really worried about the difference of 0.5% error? That is not the most imp thing to worry about right now. If you don't know this vaccine might be the best so far in comparison to all the genetic vax
On 2021-07-04 13:13:09, user Sebastian Rosemann wrote:
Dear authors,
you write: "For each country we predicted the ‘baseline’ mortality in 2020 based on the 2015–2019 data (accounting for linear trend and seasonal variation; see Methods). We then obtained excess mortality as the difference between the actual 2020 and 2021 all-cause mortality and our baseline. For each country we computed the total excess mortality from the beginning of the COVID-19 pandemic (from March 2020) (Figure 2, Table 1)"
For Germany Table 1 shows 36.000 excess deaths, which makes up 4% increase, suggesting a baseline of 900.000 for March 2020 - Mai 23th 2021.<br /> According to destatis<br /> https://www.destatis.de/DE/...<br /> the yearly number of deaths for 2015-2019 in Germany was always above 900.000.<br /> How can your baseline for a timespan of ~14 month be lower than the actual number of deaths for 12 months within the last years?
On 2021-07-06 02:38:59, user Nonyo Business wrote:
This is consistent with the 2019 WHO mask guidelines, saying there is little evidence they work but that in an epidemic maybe give them a try.
On 2021-07-06 09:34:12, user David wrote:
Just 188 participants were seropositive. So if long covid would occur in 1% of patients one would statistically expect 1,88 long covid sufferers in this group. Obviously, this sample size is too small to quantify the long covid risk. It could probably be anywhere between 0 and 3% according to this study. Assuming this survey covers long covid symptoms well which it obviously does not as already mentioned in the 2 previous comments.
On 2021-07-15 07:33:35, user Timothe Menard wrote:
It has been published in Drug Safety and is now available online - DOI:10.1007/s40264-021-01094-8
On 2021-07-18 17:48:18, user Olavo Amaral wrote:
In their discussion, the authors attribute the imbalance between study arms within hospital sites in Table S1 to the fact that randomization was not stratified by study site and to batch delivery of drugs to remote sites. However, if the trial was truly randomized as described in the Supplementary Appendix, it is hard to understand how the extreme imbalance in the distribution of arms in each site could have happened by chance alone.<br /> When one considers the distribution of arms in the 3 centers located in Manaus, where patients are described to have been randomized independently, there is a total of 97 patients in the active group vs. 298 in the placebo group. Using the chisq.test function in R, the p value for obtaining this distribution if patients had an equal chance of being randomized to either group is 4.8e-24 (amounting to a chance of roughly 1 in 200 sextillion).<br /> For the remote sites, one cannot estimate this chance exactly, as the authors report that randomization was performed for batches of 5-50 patients. Nevertheless, the distribution is even more unbalanced (220 patients in the active group vs. 30 patients in the placebo group), and also seems unlikely to have occurred by chance (and in the opposite direction as that of Manaus, thus balancing the distribution in the whole trial almost exactly).<br /> Although this imbalance would not explain the difference in the main outcomes between groups by itself, as the stratified analyses in Tables S3 and S4 show effects favoring the active treatment at all sites, it does call into question whether randomization was really carried out as described. Can the authors please clarify on what happened?
On 2021-07-23 21:59:46, user Vuong Trieu wrote:
This paper is now published at
On 2021-07-25 17:46:53, user Ullrich Anton Schuler wrote:
I recommend to reduce percentages to 3 significant digits. E.g. "33.76% of SARS-CoV-2 exposed children" means with 548 children: 1% is 5 children, 0,1% represents 0,5 children, 0,01% means 1/20th of a child. Therefore two digits after the decimal point in my opinion are nonsense (as it is the case in very many situations!). The unnecessary question arises as to whether the authors have a sensible feeling for numbers and sizes.
On 2021-07-26 10:03:20, user Christoph Terasa wrote:
In Table 2 on page 12, the heading on the rightmost column reads
Control group of unvaccinated users testing negative
Shouldn't that be
Control group of unvaccinated users testing positive
This is what I gathered from the text, and it makes more sense.
On 2021-07-27 14:07:32, user VailShredBetty wrote:
Additionally, the only conclusion I can see that this study and subsequent studies illustrate is the vaccine is stopping ore severe infections....but at what cost??
On 2021-07-29 08:14:23, user Alenita Luz Mateo wrote:
Thank you for this very informative research, my mom is currently on dialysis and suffering from comorbidities. As of today 7/29/31, we are on the MECQ status here due to a surge of covid19 cases, with delta variant on the loose. I think our health care system is breaking, from 5:18 nurse to patient ratio it now down to 3:18. Our health care providers are already contracting the virus, are now exhausted. I'm afraid they cannot function well anymore to do their duties for their patients. Yesterday another EKD patient died and contracted the covid19. We are a third world country and access to materials needed are very crucial. I hope we can survive this pandemic.
On 2021-07-29 17:01:13, user Jodi Schneider wrote:
An Israeli study of healthcare workers published in NEJM says "Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks)." http://doi.org/10.1056/NEJM...
On 2021-07-30 16:26:33, user Kirsten Elliott wrote:
The search strategy for this review has not been adequately reported as there is not enough information in the appendix to replicate the search in any database, as it hasn't been made clear which fields were searched. It is therefore not compliant with PRISMA 2009 or PRISMA 2020 reporting standards. Furthermore, from what has been reported it appears that relevant search terms and subject headings have not been included, meaning that it is likely relevant papers have been missed. The other paper based on this search will also have the same problem (https://www.medrxiv.org/con... )
On 2021-07-30 16:44:39, user Kirsten Elliott wrote:
There seem to be at least three reviews based on the same literature search, so I'm posting similar comments on each of them.
The search strategy for this review has not been adequately reported as there is not enough information in the appendix to replicate the search in any database, as it hasn't been made clear which fields were searched. It is therefore not compliant with PRISMA 2009 or PRISMA 2020 reporting standards. Furthermore, from what has been reported it appears that relevant search terms and subject headings have not been included, meaning that it is likely relevant papers have been missed.
For this paper, there's also a mistake in the flow diagram in figure 1 - it appears as if papers have been excluded on the grounds of "non Spain" when that should be "non Africa".
On 2021-08-02 18:38:34, user WMnax wrote:
Hello, thank you for this study. Will there be any continuation results as we move through this high season of Delta variant?
On 2021-08-04 20:52:35, user johns1956 wrote:
I don't see Supplemental Table 4, can you please provide it if you have it?
On 2021-08-05 06:56:54, user Piet Streicher wrote:
How do you account for "survivorship bias" in the case of the vaccine. If prevalence was high during the vaccination phase, then infection prior to the 14d after 1st dose or prior to 7d after 2nd dose would remove people from the pool, creating a bias towards those that made it past this point. They then appear to have a higher level of protection (say 86%) when in fact this group has been through a selection process already.
On 2021-08-08 03:47:33, user theasdgamer wrote:
This is a very, very interesting paper. I'm not a molecular biologist nor medical, so please excuse any questions I have which may seem silly.
First, are there any conditions which might lead to viral escape from lysozomes but not zinc escape? It seems to me likely that if zinc isn't escaping, then maybe the viruses aren't escaping the lysozomes either. And should there be conditions where the viruses escape, then I would expect zinc to also escape into the cytosol. Could you perhaps give a little background here? Am I totally mistaken, and if so, how?
Second, are there bio-regulatory systems in human cells in vivo that might be triggered by high pH in lysozomes that might cause acidification of lysozomes to increase?
Third, how much variability is there in CQ protonization over time from continual lysozome acidification, or am I mistaken in thinking that cells continually acidify lysozomes?
If CQ is given twice daily, how much variation in CQ levels would there be in the lysozomes of cells in vivo?
What differences in results might we expect if we were to use hypothetical human vascular endothelial cells as the cell medium for in vitro studies?
Hydroxychloroquine is the more active form of chloroquine and I wonder if it might make some difference in results versus chloroquine.
Thank you for a most interesting paper.
On 2021-08-09 19:22:35, user Pedro Nomad wrote:
As a 65 year-old participant in phase 2 of these Medicago clinical trials, I can say that after receiving my 2 doses of their candidate-vaccine in February 2021, I am still Covid free (tested twice, negative each time) and have been very active doing outdoor activities: skiing, skating, hiking, rollerblading, cycling. Couldn't feel better! Just hoping to get a 3rd (booster) shot in time to resume my teaching job this Fall. Hurry up and give Medicago the GO!
On 2021-09-16 10:25:45, user kdrl nakle wrote:
Yup, Alberto is right, the sample is really not much to speak of. I actually tend to believe conclusions but not based on this paper. Folks, you need to do a lot more work.
On 2021-09-17 08:58:04, user Johannes Schultz wrote:
Note from the authors: This article has now been published Open Access in Schizophrenia Research: Cognition online on September 9, 2021. Here is the link: https://doi.org/10.1016/j.s...
On 2021-09-17 16:27:49, user Daniel Keyes wrote:
I commented previously that the apparently long delay in peer review is understandable, and typical for many journals. However, given the extremely high profile of this article, it should have been considered for expedited review. Now even "regular" review seems to be taking rather long. This could be due to reviewer delay, reviewers or editors requiring a large number of changes, or it may even reflect a general reluctance to publish an article with this conclusion.
On 2021-09-17 17:39:54, user Gabriel Lee wrote:
I do not understand the numbers for vaccine doses administered during the June 1 to July 31 period. These seem far too low for a city with a population of almost 1 million and the two-month period during which some of the fastest vaccination rates in Ontario and Canada were recorded. I downloaded the CSV file from open.ottawa.ca and tallied the Moderna and Pfizer-BioNTech doses in this period, and found 352,687 and 481,264 doses, respectively. Could you please explain?
On 2021-09-22 17:13:20, user dansari wrote:
The authors do not describe their methodology for comparing incidence of myocarditis/pericarditis to background rates, and thus whether they have been disproportionately reported following vaccination, nor whether this comparison has indeed been performed. Reference (8) does include this detection.
As mentioned in other comments, the "Vaccinated in Ottawa" data (is this the dataset that was used?) indicate that 838,442 vaccinations were given during the time frame of this study. This would yield approximately 4 cases per 100,000, a figure more in line with currently understood vaccine statistics.
On 2021-09-25 19:07:25, user Peter Dimitrov wrote:
Time frame : 60 days following vaccination; Location: who presented at a single academic institution/Ottawa Heart Centre. Patients were identified by admission and discharge records of the Ottawa Heart Centre. Sample size: 32 patients, 29 of which were male! Median time between vaccination dose and pain symptoms was 1.5 days. Startling findings by themselves, ought to raise curious questions not outright dismissal/withdrawal.
However, obviously the incidence rate based on total MRna vaccines in Ottawa area is waay off. Am curious to know disaggregated sex/age etc data of Myo/peri cases recorded in the exact same time period in all the other hospital treatment centres in Ottawa area?
On 2021-09-21 14:02:09, user Isatou Sarr wrote:
If it works, why not!!!!! What is the genome similarity index between MEASLES-MUMPS-RUBELLA (MMR) and COVID-19? Is there any common clinical manifestation identifiers between the ailments?
On 2021-09-25 09:47:21, user Jan Podhajsky wrote:
Hi there. There is a question about personal and sensitive data protection during obtaining answers via questionnaire distributed through social web.
I raised these concerns to data protection authority of Faculty of Scince, CUNI.
The questionnaire research did not met personal and senstive data protection standards. It is unethical research by my opinion.
On 2021-09-25 12:55:23, user Raja Mugasimangalam wrote:
Excellent.<br /> The title of the article can be compressed a bit.
On 2021-09-27 18:07:42, user DiogenesNJ wrote:
"early attention directed towards identifying SARS-CoV-2 in returning <br /> international travelers may have led to a failure to recognize locally<br /> circulating infections..."
And why were we limited to that? A shortage of testing capability attributable to CDC's insistence on their own test, which turned out to be flawed, and FDA's refusal to allow any of several other tests developed by the private sector or universities to be used during the crucial first months of the pandemic. A classic NIH problem (Not Invented Here, not to be confused with the National Institutes of Health).
Compare and contrast with South Korea, which called in every big pharma company in the country during their New Year holiday, approved a private-sector test in early February, and had massive testing up and running in less than a month (15k tests/day capacity by the end of February).
On 2021-09-30 02:46:32, user Fiona Weir wrote:
70% of people in Dane County are vaccinated [6-your source]. If representative, you would expect a similar profile in your study; however only 38% of your cohort is vaccinated. This raises crucial questions about selection/inclusion... Was self-reporting reliable? Were cases excluded when vaccination status was not self-reported? Were unvaccinated people much more likely to test? Were vaccinated people likely to test only if they were actually ill, and therefore likely to have a higher virus load in any case? These issues plus the low cohort size may make your findings unreliable.
On 2021-09-30 12:14:12, user Joren Buekers wrote:
Exciting research! I hugely support focussing on continuous SpO2 measurements instead of discrete/spot check measurements only! I'm happy that this finally found its way to COVID research. <br /> A small remark/request: you indicated that "preprocessing of the raw SpO2 signal was performed using a block filter as in Levy et al.", but this block filter was actually developed in another study (https://doi.org/10.2196/12866) "https://doi.org/10.2196/12866)"). Would it be possible to acknowledge the original paper as well? (Sorry for the self-promotion, but I do think it's more correct to refer to the original paper).
On 2021-09-30 20:18:12, user Navneet Dhillon wrote:
This article is now published in Journal of Extracellular Vesicles 2021;10:e12117, <br /> “Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity” PMID: 34262673
On 2021-10-01 13:49:12, user Jasper wrote:
I'm wondering if there's any research on the long term effect of the single-shots. Most studies have antibodies, B and T cell checks at one week after the second dose. Doesn't that result interfere with a possible prolonged effect of the first dose? This study shows that there's a sound immune response, that apparently (according to the BNT162b2 clinical studies) provides ample protection 12 days after the first dose (especially if you don't take into account the positive cases during the first 12 days without protection). VE also seems really good in real-life - albeit the time period and groups are smaller - but still massive, considering the magnitude of this operation. Maybe we don't need to boost with 0,3ml, and so on.
On 2021-10-01 15:08:14, user Vince Dhimos wrote:
The developers should now do a comparative study with other competing vaccines.
On 2021-10-03 18:28:32, user Joseph Psotka wrote:
It would be much more useful to look ar discrepancies in the immune system of the twins. Even dizygotic twins can have the same immune system.
On 2021-10-04 07:26:13, user Wolfgang Wagner wrote:
Int J Mol Sci. 2021 Aug 27;22(17):9306.<br /> Epigenetic Clocks Are Not Accelerated in COVID-19 Patients
PMID: 34502212 <br /> PMCID: PMC8431654 <br /> DOI: 10.3390/ijms22179306
On 2021-10-06 06:00:28, user Stuart wrote:
Could the incorporation of altered nucleosides into the viral RNA affect the ability of the reverse transcriptase in the RT-PCR reaction from actually detecting the viral RNA, even if it is there? Can they verify the results using antigen tests instead?
On 2021-10-10 05:14:46, user kdrl nakle wrote:
Needs to point out that this is all prior to Delta and that changes everything.
On 2021-10-11 16:09:28, user sentner wrote:
I'm surprised this article is still in a pre-print state. It's a hot topic and it's now been available for 6 weeks, which is plenty of time for peer review. Usually by now it's either rejected or accepted for wide publication in peer reviewed journals. It makes me wonder if, due to the politicization of this topic, some scientists are deciding not to review this document at all in a fair way.
On 2021-10-14 14:17:58, user Julian von Mendel wrote:
This paper has now been peer-reviewed and published, with no substantial revisions: https://www.mdpi.com/1311862
Citation:<br /> Borsche, L.; Glauner, B.; Mendel, J.v. COVID-19 Mortality Risk <br /> Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close <br /> to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients 2021, 13, 3596. https://doi.org/10.3390/nu1...
On 2021-10-14 19:09:32, user Dave Green wrote:
This trial was listed as one of the clinical trials being done on Ivermectin on the FDA website. The media has portrayed the use of this drug as completely ridiculous and idiotic. Yet, there are several clinical trials underway to prove or disprove its effectiveness. If its use is so "idiotic" then why would highly educated people bother to study it???
This is an example of one (of several) that shows it is effective and has promise. From what I have read this "effectiveness" increases if it is given early on. Where I live in Canada, if you have symptoms you are just told to self isolate until they become so bad you have to be hospitalized. You are not provided Vitamin D, Zinc, Ivermectin or any other form of treatment that could help prevent you from being hospitalized. Everyone criticizes any study that comes out and nothing can be proven or believed. It is so frustrating.
Thank-you to the people who performed this study. Your efforts to help the world are appreciated, if not by everyone, at least by me.
On 2021-10-18 20:32:04, user Immede wrote:
Nice, the city of Wuhan is actually out of the zone indicated on their probabilistic maps.
On 2021-10-25 19:36:50, user Henry wrote:
Could these studies possibly be construed as gain of function?
On 2021-11-01 14:33:28, user happydog wrote:
This article has now been accepted for publication in Epidemiology & Infection (https://www.cambridge.org/c... "https://www.cambridge.org/core/journals/epidemiology-and-infection)").
On 2021-11-05 19:55:40, user Mazen Baroudi wrote:
Now published by BMJ Open
On 2021-11-09 23:59:36, user Jessica Grevis wrote:
Very interesting article. I'm curious if there is information on more specific professions, like an extended Table 2. I'm particularly interested in the construction trades.
On 2022-10-26 10:01:47, user Christian Jauernik wrote:
This study seems to now have been published in the Danish Medical Journal
On 2022-11-04 00:15:41, user Brian Mowrey wrote:
Study design inadvertently results in the 3rd-dosed experiencing their "primary Omicron" infections mere weeks after injection. Bias for lower viral loads, antibody masking, and higher false positivity rates (because lower overall infection rates), which the 1-to-1 matching cannot fix. Adjusting for the 90-day delay between positive test and "follow up" start:
"Median duration between the third dose and [primary Omicron test] was [34] days (IQR, [13-53] days), and between the second dose and [primary Omicron test] was [244] days (IQR, [196-281] days)"
Oops.
On 2022-11-07 07:35:58, user Renier Mendoza wrote:
Now published in AIMS Mathematics:
On 2022-11-08 00:00:25, user japhetk wrote:
This preprint makes the wrong comparison.<br /> It is possible for there to be more than one cause of death in the Ministry of Health, Labour and Welfare's report of suspected post-vaccination deaths. Myocarditis and myocardial infarction can be the cause of death even if myocarditis is listed.<br /> Demographic causes of death, on the other hand, list only one underlying cause of death: there can only be one cause of death per death. Therefore, it is not possible to compare the frequency of occurrence of the two.<br /> Also in terms of demographics, in 2021 there are 155 deaths from acute myocarditis I40; in 2020 there are 168; in 2019, 162; in 2018, 177; and in 2017, 167. Why are there the fewest deaths from acute myocarditis I40 in 2021 in the last five years if deaths from myocarditis caused by vaccines are identical to deaths from demographic I40 as the underlying cause?<br /> So from this you can see that the authors have clearly made the wrong comparisons and drawn the wrong conclusions.
Translated with www.DeepL.com/Translator (free version)
On 2022-12-09 22:42:39, user Josipa Domjanovic wrote:
This is an interesting and well-written randomized controlled trial that examined the effect of intradialytic exercise on the survival of patients undergoing treatment with intermittent hemodialysis. The main findings suggest that intradialytic exercise improves survival in this population. The methodology of this study is robust and the results are well-presented, but there are several important constraints that should be acknowledged.
Major remarks:
Minor remarks:<br /> - The authors are encouraged to correct the typos and improve the textual flow throughout the manuscript. Paragraphs should be justified.
Nevertheless, this well-organized study warrants publication so it could act as an incentive to start similar ones on a larger sample and with a longer follow-up, which could lead to change in the treatment practice of these patients.
On 2022-12-22 13:04:03, user Howard Waitzkin wrote:
Here is another peer-reviewed article from the same project. Constructive comments welcome. Thanks.
Howard Waitzkin
Fassler E, Larkin A, Rajasekharan Nayar K, Waitzkin H. Using absolute risk reduction to guide the equitable distribution of COVID-19 vaccines. BMJ Evid Based Med 2022. doi:10.1136/bmjebm-2021-111789. [Epub ahead of print: 07 Mar 2022
On 2022-12-27 18:27:33, user Bahrad Sokhansanj wrote:
A peer-reviewed version of this manuscript has now been published: Sokhansanj BA, Zhao Z, Rosen GL. Interpretable and Predictive Deep Neural Network Modeling of the SARS-CoV-2 Spike Protein Sequence to Predict COVID-19 Disease Severity. Biology (Basel). 2022 Dec 8;11(12):1786. PMID: 36552295; PMCID: PMC9774807. https://doi.org/10.3390/bio....
On 2023-01-06 03:26:21, user Danuta Skowronski wrote:
The peer-reviewed publication of this paper with the Canadian Medical Association Journal (CMAJ) is freely available as of December 5, 2022, at the following link : https://www.cmaj.ca/content...
On 2023-01-06 18:49:46, user Ahmet Tas wrote:
Important Notice<br /> In this preliminary version, signal analysis is suboptimal due to inadequately designed filter for raw signal smoothing. Moving average method with inappropriately wide window length has caused blunted waveform peaks. For the actual study, authors have re-analyzed the PPG signals with an accordingly designed Savitzky - Golay filter.
Importantly, comparisons between subgroups remained the same since all data had undergone the same processing (filtering).
On 2023-01-26 06:31:51, user Yasir E A Elsanousi wrote:
Splendid well structured article addressing an interesting and contemporary health issue. My comments towards improving this study:<br /> 1) The authors may wish to begin the methodology & data section with a paragraph that explicitly names the method type and clearly describes what was going to be done with data. The research problem should be stated here.<br /> 2) Although use of 'first-person' style of writing is not inappropriate, but there is overuse of first person pronoun ('we' .., and also 'our'). It is advisable to replace most of these instances with third person items (e. g 'the study focuses on..etc) or use of passive voice (dengue incidence was calculated..etc)<br /> 3) The ‘Conclusion’: authors may wish to present the most important outcomes of the study first. The sentence “The short period ... relationships." may be deferred to a later position in the section, or better still be duly recognized as one of the ‘Limitations’ of the study.<br /> Thank you: Yasir Elsanousi
On 2023-02-07 08:39:11, user Frauke Mattner wrote:
Hi, congratulation to your very informative preprint. I am just looking for a figure comparing vaccinated with non-vaccinated persons. Could you still add it? You defined vaccination as at least one shot obtained. Could you also provide data for thoses being at least two-fold or triple-fold vaccinated ?
On 2023-03-06 09:52:44, user baba aurhum wrote:
Now published in Communications Medicine: https://www.nature.com/arti...
On 2023-03-08 22:43:36, user Daniel Davis wrote:
This paper has been published in the journal Delirium: doi:10.56392/001c.36822
On 2023-03-09 12:14:10, user Guido van Wingen wrote:
Great study showing that high quality multimodal MRI data does not improve classification performance beyond multicenter resting-state fMRI as reported for two other large cohorts (REST-meta-MDD with N=2338 and PsyMRI with N=1039): https://www.nature.com/arti...
On 2023-03-21 09:47:06, user Aamir Fahira wrote:
Hello Cato Romero<br /> How you computed MAF for summary statistics using UK BioBank, can you please share reference method or your code
On 2023-04-11 00:51:25, user Xianyong Yin wrote:
We did a similar analysis between vitamin D and psoriasis. We achieved similar results at https://pubmed.ncbi.nlm.nih...
On 2023-04-20 05:53:06, user José F. Català-Senent wrote:
Hello everyone,
I am glad to inform you that the preprint has been published in the journal Neurobiology of Disease: https://doi.org/10.1016/j.n....
On 2023-05-11 08:01:12, user Siri Fløgstad Svensson wrote:
This paper has now been publised in Neuro-Oncology Advances:<br /> https://academic.oup.com/no...
On 2023-07-06 06:27:06, user Dimitrios Karagiannakis wrote:
I declare that our article entitled "Prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria. Alterations in ultrasonographic parameters of both left and right ventricles before and after stress" has been published in Annals of Gastroenterology <br /> Dimitrios S Karagiannakis <br /> Corresponding author<br /> Email: dkarag@med.uoa.gr
On 2023-07-21 21:15:45, user zmil wrote:
Worth noting that the deletion reported in this pre-print appears likely to be the pre-integration site of a transposable element insertion. That is, the minor allele is not a true deletion, but rather the major allele is an *insertion,* specifically of an Alu element. See twitter thread here: https://twitter.com/genomer...
On 2023-08-14 20:23:31, user Peter Lange wrote:
This paper reports the prevalence of common symptoms in the population after covid-19. There is no control group. The paper is therefore of no utility and no conclusions can be drawn. The authors should make some effort to derive useful comparisons before attempting to publish.
On 2023-08-21 16:51:06, user Maria Vanderléia Araujo Maximi wrote:
This review resulted from the graduate-level course "How to Read and Evaluate Scientific Papers and Preprints" from the University of São Paulo, which aimed to provide students with the opportunity to review scientific articles, develop critical and constructive discussions on the endless frontiers of knowledge, and understand the peer review process.<br /> The preprint titled “Differential modulation of attentional ERPs in smoked and insufflated cocaine-dependent associated with neuropsychological performance” associated the cocaine consumption with reduced attentional event-related potentials (ERPs, namely P3a and P3b, indicating bottom-up and top-down deficits respectively. In this study was evaluated these ERPs considering the route of cocaine administration. <br /> This study had the hypothesis that smoked cocaine dependent (SCD) would exhibit reduced modulation of the P3a, while both SCD and insufflated cocaine dependent (ICD) would show reduced modulation of the P3b.<br /> The authors examined the differences in the P3a and P3b potential between SCD and ICD, and their relationship with neuropsychological performance.<br /> Below are some suggestions for revisions pertaining to the various sections of the manuscript.<br /> Abstract: The abstract provides a nice summary of the study.<br /> Introduction: The introduction section would be strengthened by further discussion, such as including a description of differences between schooling and SCD and/or ICD use, and their relationship with neuropsychological performance.<br /> Methods: If possible, it would be important to have information about how long the participant has been a cocaine user.<br /> Results: Descriptive statistics are good, including mean age, biological sex and education for the study group and comparison group. Additionally, if available, the authors are encouraged to include participants’ handedness. Missing data, if any, should be indicated in this results section. <br /> The preprint could be improved by expanding the comparisons and analyzes obtained from data on schooling and use of SCD or ICD. It could also be improved by emphasizing the need for these findings to be known and shared with the scientific community. This way, the authors would be able to analyze schooling and use of SCD and/or ICD, granting a deeper assessment of this information.<br /> Discussion: Limitations of the study have been pertinently included in the discussion section.<br /> The content of this research is very interesting, innovative and may have implications for the relationship between differential modulation of attentional ERPs in smoked and insufflated cocaine-dependent and neuropsychological performance.
On 2023-09-04 21:32:53, user Joilson Xavier wrote:
This study is now published in Nature Communications doi:10.1038/s41467-023-40099-y
On 2023-09-11 12:43:46, user youni wrote:
Can chronotype be discerned from activity tracking data or self-report?
Might chronotype account for a portion of variance in the association with mortality?
Would interpretation vary if the sleep-wake schedule (reported as circadian rhythmicity) were dictated by 'lifestyle" choices versus genetic chronotype?
On 2023-09-21 10:06:53, user Glenn Tisman, M.D. wrote:
Beautiful work. Great team cooperation. Possibly gives credence to some of those swearing that high-dose B12 helps their symptoms of various neurologic disorders in spite of normal serum B12 levels. I wonder if our paper "https://www.academia.edu/68..." in 1993 revealing that XRT and or chemotherapy drugs (e.g. Hydrea) cause a decrease in HOLOTCII may add to the discussion. Neuropathy in patients on various chemo and XRT (e.g. Hydrea) and non chemotherapy drugs (statins said to induce subtle EMG signs of peripheral neuropathy in 40% of patients) may add to the discussion. Glenn Tisman, M.D.
On 2023-11-03 11:35:08, user Alex wrote:
Some elements seem to be misquoted or false in the introduction, and collected pubmed data only in french language does not actually reflect published data with selected keywords, discussion in this thread :
On 2023-11-15 15:22:22, user Ryon wrote:
The analysis evaluating off-label use of hormonal therapy in OC is fascinating. The methods of adjustment for known, quantifiable variables via IPTW is valid. However, this work could be improved by a discussion of unknown confounders that might have affected the observed associations. For instance, in breast cancer and prostate cancer, the decision to give hormonal therapy or chemotherapy is very influenced by patient frailty, for which ECOG scores are a crude measure. Things like total disease burden, sites of metastases, etc, which are difficult to quantify and sometimes not included in the FH database would be things that should be absolutely considered. More granular commentary of what variables are balanced / imbalanced, and variables that could affect treatment assignment other than the ones quantified, and likely direction of residual bias, are needed for more thorough evaluation of whether the reported analysis supports the hypothesis of off-label effectiveness of these drugs.
On 2023-11-20 10:05:27, user Koen Wortelboer wrote:
This preprint was published in September 2023 in Nature Communications and can be found via this DOI: https://doi.org/10.1038/s41...
Citation:<br /> Wortelboer, K., de Jonge, P.A., Scheithauer, T.P.M. et al. Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety. Nat Commun 14, 5600 (2023).
On 2023-12-10 17:31:49, user Scott Lear wrote:
I have several serious concerns with the study and manuscript:
This is an observational study and despite what is written in the manuscript, an observational study cannot lead to the clear conclusions the authors suggest the results indicate. The authors should temper their interpretation of the results and take into account the below.
The authors do not address their findings in the context of the 1000s of other observational studies indicating activity (and at high levels) has consistently been associated with reduce risk for premature mortality.
The authors state previous studies have not robustly adjusted for other lifestyle measures. This is untrue. Many of the existing observational studies have robustly adjusted for the measures the authors of this study say weren't done (and have done so for decades). Here are a few:
https://pubmed.ncbi.nlm.nih...<br /> https://pubmed.ncbi.nlm.nih...<br /> https://pubmed.ncbi.nlm.nih...
All of these studies (there are many more) had more robust adjustment than the present one and found that high levels of activity either provided further risk reduction or a plateau but no reduced risk reduction. The last study had 30 years of follow-up and 15 points of LTPA assessment- a point that the authors of the current study infer that their study is the only study to have a long follow-up.
Self-reported questionnaires to assess LTPA are not as accurate as the authors indicate. While questionnaires are used in many studies, they tend to overestimate activity levels compared to objective measures such as accelerometers (plenty of studies to support this). They also are not accurate in distinguishing different levels of intensity of activity which is also pertinent to consider. Lastly, the study only assessed leisure time activity ignoring occupational, household and transport activities. Given the surveys were done in 1975, 1981 and 1990, this is likely to be a substantial amount of activity missed (as all jobs were more active back then, than now). There is no indication in the Methods how the participants were put into the four activity groups (sedentary to highly active).
The biological ageing was based only on a sub-sample of 5% of the study population. There is no description in the methods how this sub-sample<br /> was selected. Was it random, and thus possibly representative of the larger cohort, or was a convenience or selective sample that could introduce bias?
BMI was self-reported, and again, there is ample literature to indicate self-reported BMI underestimates true BMI and this is greatest in those with higher BMI. In addition, if one is looking to assess the true affect of LTPA, BMI should not be adjusted for as it is in the causal path between LTPA and mortality.
We have good quality randomized trials from the 1980s in cardiac rehab that indicate the benefit of structured exercise on <br /> reducing early death (and leading to greater lifespan) in people with heart disease. While the authors quote a single study (#5) stating RCTs <br /> have not shown activity to result in longer life, the study quoted is not a real study but rather a commentary. The advantage of the RCTs from the 1980s is the lack of pharmacological management of participants in usual care because statins and anti-hypertensives where either not around or readily prescribed at the time. More recent RCTs have control groups that are optimally medically managed.
On 2023-12-26 14:48:44, user Donald R. Forsdyke wrote:
LATE ONSET POST-VACCINATION MYOCARDITIS
The acceleration of SARS-CoV-2 vaccine research post-2020 was so rapid that preprint postings became the norm for many of us working in the field. This preprint of Watson et al. (1) describing 3 case histories is in line with previous preprints describing single case histories (2, 3). It now appears that late-onset post-vaccination myocarditis in elderly subjects can be either overt (symptomatic; 1, 2) or cryptic (not symptomatic; 3).
The cases described here (1) developed symptoms of myocarditis several weeks after vaccination and a few weeks after initiating anti-PD-1 treatment (Immune checkpoint blockade; ICB). The latter would have decreased constraints on autoimmune phenomena. The reported period following vaccination prior to symptom onset, coincides with that reported early in the pandemic by Guatam et al. (2) for a subject with a previous cardiac condition (prior morbidity). It also concides with the post-vaccination periods that preceded protracted, yet asymptomatic, transient dips in blood pressure (BP) in a normal subject, which has been attributed to myocarditis (3).
In the latter case, an episode of cardiac fibrillation during a run, prompted a retrospective analysis of blood pressure (BP) readings for the period when five sequential anti-SARS-CoV-3 vaccinations has been given (3). This resulted in the unexpected discovery of the extreme BP dips that progressively increased in extent with successive vaccinations. A cause-and-effect relationship was evident. The myocarditis was cryptic and was deemed likely to remain so, unless the subject had made excessive demands on cardiac function (e.g., vigorous exercise). Alternatively, the delicate balance between normal immunity and autoimmunity might have been shifted as in (1), or a comorbidity might have emerged as in (2).
The present preprint begins by stating that association between vaccination and myocarditis is rare and affects younger subjects (1). The other preprints suggest the existence of a vulnerable population-subset that may include many elderly subjects and may be less rare than is generally understood. A “crowd sourcing” follow up has been suggested (3,4).
1.Watson RA, Ye W, Taylor CA, Jungkurth E, Cooper R, Tong O, et al. Severe acute myositis and myocarditis upon initiation of six-weekly Pembrolizumab post-COVID-19 mRNA vaccination. medRxiv 2023; doi.org/10.1101/2023.11.24....<br /> 2.Gautam N, Saluja P, Fudim M, Jambhekar K, Pandey T, Al'Aref S. A late presentation of COVID-19 vaccine-induced myocarditis. Cureus 2021; 13: e17890.<br /> 3.Forsdyke DR. Cryptic evidence on underreporting of mRNA vaccine-induced cardiomyositis in the elderly: a need to modify antihypertensive therapy. Qeios Here<br /> 4.Forsdyke DR. Physician-scientist-patients who barketh not. The quantified self movement and crowd-sourcing research. J Eval Clin Pract 2015; 21: 1024–1027.
On 2024-01-08 18:05:42, user jhick059 wrote:
This article was published in the peer-reviewed journal Cureus Journal of Medical Science on Dec. 14, 2023: https://doi.org/10.7759/cur...
On 2024-01-16 13:30:11, user Jan Egger wrote:
The paper has been published in CMPB from Elsevier:<br /> https://www.sciencedirect.c...
On 2024-02-26 15:44:36, user Anthony Dallosso wrote:
Hi - supp figure S3 is mentioned in the text but I can't see it in the Supplementary info link. Is this available somewhere please?
On 2024-02-26 17:17:40, user Ciarán McInerney wrote:
Please, explain the<br /> situation that warranted the Bonferroni correction, and explain precisely how<br /> you came to the threshold of 0.01. The Bonferroni correction scales the level<br /> of significance by the number of comparisons being made. With 19,314 candidate<br /> features, this would make for a staggeringly small Bonferroni correction of<br /> 0.00005.
On 2024-04-27 23:54:27, user Dee McDonald wrote:
Currently suffering from TSW for 17 months and agree this study is extremely valuable insight into the condition. It is difficult to communicate how life changing this condition is to experience, and any progress we can make in recognizing it, can be an aid in preventing its occurrence for others in the future. It is hideous to experience! Furthermore, TSW communities find dermatologists denying the condition exists, make it additionally challenging. So few resources are available to help patients (or victims of practitioners over prescribing) one must be self educated and advocate for their case continually to get any medical assistance. <br /> I am fascinated by the science of these skin abnormalities, and how I can potentially induce more affective healing. It is studies like this that will make a huge impact in treatment of the TSW condition.
On 2024-05-03 17:29:02, user Jackie Kilpatrick wrote:
I have been through this hellish condition, experiencing all of the classic symptoms which differentiate it from eczema, including inability to control body temperature, bone deep incessant itch ( I slept in boxing gloves, ffs!), hair loss, insomnia, full red sleeve, oozing and flaking. I was told by doctors that the condition doesn’t exist. My consultant dermatologist said “if you don’t want my drugs, why are you here?” and when I said that I was hoping we could discuss other ways to maintain skin health like PH or microbiome issues she said scathingly that I and ‘my internet’ would know far more about that than she. <br /> For too long there has been a total disconnect between patients suffering a condition which not even medieval torture professionals could have dreamt up and a medical profession refusing to see the growing mountain of irrefutable even while anecdotal evidence emerging globally from social media. With the new video technology now available to all the number of brave selfless souls documenting in almost scientific detail what they are going through means that this, maybe one of the biggest medical scandals of all time, will soon be properly exposed for all to see. Proper research will support what all of us sufferers already know, the medical community will be forced to become as informed as their patients… imagine! … and maybe these horrendous drugs will be used as an absolute desperate measure of last resort rather than being doled out like sweeties for the most minor of complaints. More research and quickly please. Be the people who break this story properly and stand up for all the benighted souls burning in agony in their own skin.
On 2024-05-10 18:06:25, user Adam Jones wrote:
Now published in Computers in Biology and Medicine doi: 10.1016/j.compbiomed.2024.108545
On 2024-07-01 17:32:52, user Cristian Riccio wrote:
Hello, there is a typo in the title. "half-a-million" -> "half a million"
On 2024-07-26 14:15:20, user Gauthier wrote:
This preprint has now been published in the Journal of Dentistry: https://doi.org/10.1016/j.jdent.2024.105130
On 2024-09-13 06:49:57, user Shicheng Guo wrote:
Really impressive work! Congratulations!! I am wondering will the pLoF based burden test result will be included in this study?
On 2024-10-04 15:29:55, user Santiago Vasco wrote:
This preprint has been published as a peer-reviewed article in Revista de Gestão Social e Ambiental. The link to the published article is: https://doi.org/10.24857/rgsa.v18n10-074
On 2024-10-07 13:30:05, user Dimy Fluyau wrote:
Preprint is published.<br /> Fluyau, D.; Kailasam, V.K.; Revadigar, N. Rapid and Prolonged Antidepressant and Antianxiety Effects of Psychedelics and 3,4-Methylenedioxy-methamphetamine—A Systematic Review and Meta-Analysis. Psychoactives 2024, 3, 476-490. https://doi.org/10.3390/psychoactives3040029
On 2024-10-09 14:55:31, user Emma Chambers wrote:
This is now published in the peer-review journal npj Vaccines and the link to the paper can be found here https://www.nature.com/articles/s41541-024-00878-0
On 2024-10-22 02:44:40, user CDSL_JHSPH wrote:
Thank you for sharing your preprint paper, which I found to be a substantial contribution to the field of clinical trial design, especially in optimizing treatment duration for TB. Your adaptation of model-based methods, such as MCP-Mod and FP, to duration-ranging trials demonstrates their superiority over traditional qualitative methods in detecting duration-response relationships and estimating the MED, particularly in small sample Phase II trials. I appreciate your acknowledgment of the risk of underestimating the MED in some model-based approaches, especially at smaller sample sizes, and your suggestion to use a more conservative threshold like the lower confidence bound is a crucial safeguard. Expanding on how trial design parameters, such as spacing between durations and sample size imbalances, might influence the accuracy of these methods could provide even greater insights. Overall, this paper provides a great framework for enhancing trial efficiency, and I look forward to seeing how your research evolves in the future.
On 2024-12-03 15:27:15, user Guerard Byrne wrote:
The authors use Goat IgG to block Fc-receptors prior to the flow cross match. If goat IgG contains Gal antigen (likely) then this effectively adds Gal antigen to the GTKO cell surface. Staining the cells after FC-blocking with anti-Gal antibody, or GSIB-4 lectin could determine if this is a problem.
On 2024-12-05 16:47:19, user Anna Carolina Viduani wrote:
This is an excellent and highly relevant paper for Brazilian researchers and practitioners—congratulations on such an impactful contribution!
I have just one very minor observation: while there is indeed a Dourados in Minas Gerais (MG), I believe the city referenced on page 10, particularly in relation to the suicide rate in Indigenous communities, is actually Dourados in Mato Grosso do Sul (MS).
On 2024-12-11 21:15:30, user Basheer Abdullah Marzoog wrote:
the paper is published https://www.mdpi.com/2227-9059/12/12/2814
On 2024-12-13 13:28:40, user Mahalul Azam wrote:
This article now published at http://dx.doi.org/10.2174/0118749445361291241129094132
On 2024-12-14 16:10:34, user Yann Kull wrote:
First of all, thank you to the researchers for advancing biomedical research on Long COVID.
Here are some notes I had:
individuals meeting long COVID criteria were defined as those who (1) reported presence of COVID-19 symptoms that could not be explained by alternative diagnoses; (2) reported ongoing significant impact on day-to-day activities; or (3) had any diagnosis codes of long COVID in their electronic health records. Primary analyses used population controls (i.e., all non-cases)
What irks me about this selection is it is completely unclear what happens to people that develop post COVID cases of ME/CFS, POTS, or other common labels often included in long COVID subtypes.
Does that count as an “alternative diagnosis” which means they aren’t in the study cohort. If so it might end up being a weird exclusion of more severe ME and POTS cases resulting from COVID because they are more likely to be separately diagnosed, while including mild ones under the long COVID label? This makes the data quite messy, and it worries me the long COVID label is doing more harm than good at this point. Studying a heterogeneous set of conditions resulting from a viral infection, perhaps through different mechanisms, as a single entity, will likely dilute useful subtype level findings.
The data seems to be coming from the 2023 long COVID GWAS using the COVID Host biobank. Who’s major finding was an association with FOXP4 Locus
FOXP4 has been previously associated with COVID-19 severity6, lung function8, and cancers9, suggesting a broader role for lung function in the pathophysiology of Long COVID.
This suggests the signals they are picking up are likely related to susceptibility to lung damage from COVID, Post-ICU syndrome and the such. In this context, this study’s association with clotting genes makes more sense, and perhaps points to the fact even if there is a buildup of evidence behind the microclot data, it likely isn’t going to be relevant for post-COVID ME/CFS.
On 2025-01-20 17:02:49, user Lucy Mackrell wrote:
An updated version of this article has been published in BMJ Open: https://bmjopen.bmj.com/content/14/12/e089021
On 2025-02-17 11:02:33, user Sebastian Röner wrote:
The paper has been published by GigaScience in December 2024.<br /> DOI: https://doi.org/10.1093/gigascience/giae102 <br /> PMCID: https://pmc.ncbi.nlm.nih.gov/articles/PMC11659977/
On 2025-03-15 20:32:14, user Hani Molaie wrote:
The failure to critically address alternative factors such as economic sanctions and healthcare capacity further weakens the argument, as these variables likely play a significant role in shaping public health outcomes in addition to political populism.
On 2025-04-05 17:39:07, user Ellie Murray wrote:
My 2023 public peer-review comments of this article can be found at: https://epiellie.substack.com/p/from-the-archive-shingles-vaccine
The tl;dr: although I would love this hypothesis to be true, there are a number of methodological concerns I have with this analysis which leave me unconvinced.
On 2025-04-16 08:57:01, user Idan Menashe wrote:
This manuscript has now been published here: DOI: 10.1186/s11689-024-09573-6
On 2025-04-17 08:53:34, user Nitzan Paldi wrote:
For this research project to be considered valid, a few items are missing and should be provided by the authors. The most pertinent outstanding issues are:<br /> 1) The analysis of wMel was done in the months July-October, but the 2023 and 2024 summer wMel prevalence data is missing. This is important because almost all previous studies, including those done in Niteroi, have shown a very large dip in Wolbachia detection in the summer. <br /> 2) The analysis done to demonstrate the impact on dengue compares an arbitrary 10 year-period and takes into account the extremely high 2013 outbreak in Niteroi to demonstrate how Niteroi moved from one of the highest dengue cities in the state of Rio to the lower part of the spectrum. However, the period from 2013 onwards marks a massive reduction of dengue regardless of intervention or non-intervention status, and is identical in almost all >100k population cities in a 100 km radius around Niteroi. Moreover, the adjacent city of San Goncalo, that had half the level of dengue in the 2024 outbreak, had an almost identical reduction since the 2013 epidemic and all of this without any connection to Wolbachia releases. <br /> 3) The authors compare the dengue cases of Niteroi in 2024 with other cities in the state, but do not make a comparison with the city of Rio, across the bay, where another massive Wolbachia project had no impact on the prevalence of dengue in 2024, and resulted in a massive dengue epidemic of 1300 cases per 100k population. Omitting, or more likely “conveniently forgetting” this project underscores the unacceptable “cherry picking” of this manuscript. <br /> When these comparisons with the adjacent cities of San Goncalo (no Wolbachia – low dengue, half from Niteroi in 2024), and Rio de Janeiro (massive Wolbachia project- identical high epidemic dengue to non-intervention areas) are both taken into consideration, the conclusion is that the Wolbachia project had no demonstrable impact on dengue prevalence.
On 2025-05-09 19:16:34, user Tom Hähnel wrote:
Accepted publication: 10.1002/mdc3.70094
On 2025-06-13 08:49:30, user TU wrote:
From an author of Ref.60: Thank you for your citation of our work on DOCK8 (Life Sci Alliance, 2021). The structure reported is DOCK8 DHR-1 domain, which binds PI(4,5)P2. I believe that the relevant structure in your context is rather DOCK8-DHR2/Cdc42 reported in another work: DOI: 10.1182/blood-2012-01-407098. Please check it.
On 2025-07-30 10:53:20, user Esther van Kleef wrote:
This preprint has been accepted for publication in Eurosurveillance and is awaiting final editing.
On 2022-06-07 20:44:20, user Iver Juster wrote:
Suggestion: Table 4 shows state of subjective recovery at various time points according to various forms of treatment. Suggest making it clear that the top 3 rows together sum up the 23 subjects, and the 4th row (IVIG) is a subset of the 23, who had not recovered by months 5-9, and were given IVIG. PS: Really good to see post-vaccination sequelae investigated; much to learn about how immune responses go awry here.
On 2022-06-11 16:21:38, user Miles Markus wrote:
RHETORICAL QUESTION: Is there a possibility that drug-treatment-based estimates of "relapse" percentages (such as are given in the article) might not be entirely accurate? Just asking. SEE: Markus MB. 2022. Theoretical origin of genetically homologous Plasmodium vivax malarial recurrences. Southern African Journal of Infectious Diseases 37 (1): a369. https://doi.org/10.4102/saj....
On 2022-07-25 08:51:05, user Abdullah A. Al-Shammari wrote:
This study has been published. The published version of this manuscript can be found here
On 2022-07-26 03:01:00, user Phil Pellett wrote:
This is an interesting and potentially important paper. It is worth noting that Yang et al. published a possibly related article in Journal of Infectious Diseases in 2019, “Evaluating for Human Herpesvirus 6 in the Liver Explants of Children With Liver Failure of Unknown Etiology” (PMID 30418598). I wrote an accompanying commentary (PMID 30496434). Searching Pubmed with "liver failure, hhv-6" turns up several other papers that connect to the subject. It seems prudent to expand the background of the paper to include mention of this literature.<br /> Best wishes,<br /> Phil
On 2022-07-26 17:55:22, user Matthew Whitaker wrote:
This paper has now been published in Nature Communications: https://www.nature.com/arti...
On 2022-08-01 17:42:19, user Nils Yang wrote:
Published at Lancet Child & Adolescent Health https://doi.org/10.1016/S23...
On 2022-08-03 13:35:17, user V Morris wrote:
Abstract needs editing for clarity, i.e., this "In all, 243 subjects were infected with COVID-19, of whom 97 had been wearing masks and 146 had not. " where no data on total number of people in studies is provided so it could be interpreted as masks not being very effective in preventing infection.
On 2022-08-13 14:11:20, user Vijay Iyer PhD wrote:
Thank you to all the authors for this contribution towards understanding Long Covid.
A first-pass set of comments on the manuscript:<br /> * Fig 3 has 10 subpanels (A-J) but the caption references 11 subpanels (A-K)<br /> * Acronym CVC in Fig 4 does not appear to be defined <br /> * The phrase "double positive CD4+ and CD8+" T-cells may cause confusion in the field. Manuscript appears to be referencing their IL-4/IL-6 positivity. Some ME/CFS researchers (Selin & Gil) have meanwhile found hybrid CD4+CD8+ T-cells, which they also refer to as "double positive".<br /> * No commentary is given wrt why Galectin is chosen for the suggested "minimal set" of biomarkers over the various CCL & LCN markers with higher spearman rho wrt LCPS<br /> * Some commentary may be warranted of any lower significance distinction between the HC & CC cohorts with your models. There appears to be weak separability based on cortisol in Fig 6F. This may be a small hint towards the possibility of subclinical LC.
On 2022-09-14 16:39:34, user Dr. Amy wrote:
In press https://pubmed.ncbi.nlm.nih...
On 2022-09-22 05:17:40, user Mehrdad Pedram wrote:
A peer-reviewed version of the above article has been E-published online ahead of print by the Journal of Autism and Developmental Disorders back on February 27, 2022:
https://link.springer.com/a...
Panahi Y, Salasar Moghaddam F, Babaei K, Eftekhar M, Shervin Badv R, Eskandari MR, Vafaee-Shahi M, Pezeshk H, Pedram M. Sexual Dimorphism in Telomere Length in Childhood Autism. J Autism Dev Disord. 2022 Feb 27. doi: 10.1007/s10803-022-05486-2. Epub ahead of print. PMID: 35220523.
On 2022-09-29 15:48:37, user Gabriel Costa wrote:
Update: The work can now me cited in BMJ EBM. https://ebm.bmj.com/content...
The abstract is published but not the full paper, we're still working on ramifications of the main analysis.
On 2022-10-10 15:27:53, user Brian Mowrey wrote:
"We do not interpret the associations between vaccination and long COVID here as causal, as we fail to fully account for two important conditions: unconfoundedness and latent variables."
Too bad this is not what will be reported.
This is a nicely-designed paper, but even with the adjustment it seems hazardous to compare a Delta-infection-heavy unvaccinated cohort with an Omicron-infection-heavy vaccinated cohort. It would be nice to see unadjusted, but time-segregated results here.
And while the adjustment *may* reduce the risk that this skew is reflected in the results, it diminishes the relevance for the vaccinated. Most so-called breakthrough infections are Omicron infections. So the specific Long Covid Efficacy for Omicron should be shown.
Likewise for age group - is the protective association consistent for young and old, or is only the latter powering it? Again, it would be nice to just see the unadjusted, age-segregated results. But there's no apparent raw data to allow the reader to parse this (eTable 7 doesn't distinguish "With Long Covid" by vax status.
On 2020-05-25 16:42:05, user Kirsi Liimatainen wrote:
Great work!<br /> This article was answer to my question why not to use saliva as Covid-19 virus sample material. If looking for smaller sample vial and method to collect saliva, I just tested using Samco 691-1S Large Aperature Plastic Transfer Pipet for collection of saliva: thought about some delicious food and pushed saliva between my lip and gum to be drawn up from there with soft transfer pipet. Collecting about 300 ul of saliva was easy task. Smaller orifice pipettes do not collect as well. As collection vial I used Thermo Scientific 3422 0.5 ml Screw CapTube, non-sterile. Caps to these tubes are separate and available with multiple colours, I think I used 3471GS. Pipet tip does fit to 2D barcoded "biobank" tube (like Matrix 3744-BR) , but there foaming makes filling the tube difficult.
On 2020-05-05 22:31:22, user John Waldeisen wrote:
Nice work Anne & team!!
Do you know which swab the BD Universal Viral Transport system used in the trial? (i.e. cotton, polyester, or nylon flocked swabs?) From my past work, the flocked swabs are much better than cotton swabs and woven swabs at releasing pathogens off the swab. The better sensitivity from saliva might have been due to using a woven fiber or cotton swab, which retain more material (>80%), instead of a flocked swab.
Also, it's been shown that asymptomatic infections are largely upper respiratory infections whereas severe infections (hospitalized) have moved to the lower respiratory tract. Hence, saliva may be more sensitive in more severe patients, yet nasopharyngeal swabs may be more appropriate for asymptomatic testing (i.e. drive-through clinics). It seems Fig. 3a may support this conclusion.
On 2020-08-12 06:45:37, user Mohammad Khaja Mafij Uddin wrote:
This is really a great job!!!<br /> I have just started a project in which we will find the use of saliva sample as alternative to nasal swab from the suspected COVID-19. we are collecting saliva directly in to sterile container by stimulating with flocked swab. We are keeping the swab under the tongue for approx 2 min and then collect the saliva. So far we found 90% similary among the positive cases with nasal swab. Could you please let me know how long time is better for saliva collection (2 or 3 or 5 min?)<br /> Thanks <br /> Dr. Md K M Uddin
On 2020-05-26 10:38:48, user OxImmuno Literature Initiative wrote:
On 2020-05-26 21:39:01, user Sam Wheeler wrote:
Interesting. But please note: in many countries that have given a lot of BCG vaccines, they have given also a lot of MMR vaccines. What if it is the MMR vaccine that helps? Or should an adult take boosters of both? With which schedule?
On 2020-05-27 16:52:06, user Gordon Freeman wrote:
Can you please share the source code....
On 2020-05-28 17:30:13, user RJones1 wrote:
Without a weekly count of the number of new cases each week, by age, this is meaningless data. Keep in mind 8 weeks ago was early April -- a long, long time ago in most of our experience.
Is there a link to that specific data? Thanks.
On 2020-05-29 18:17:32, user Peter Juhasz wrote:
Another study, that does not make too much sense, most likely because problems with the underlying assays. The flawed conclusions are so obvious that the authors should seriously consider retracting their paper (which now CNN has picked up and presented as "Breaking News".
So let's just do a back on the envelope math: if we assume that succumbing to or surviving COVID-19 takes about the same time until infected individuals develop antibodies of the IgG type (3-4 weeks), we had ~2,000 dead by the end of March in NY and ~2,000,000 infected claimed in the manuscript is suggesting a 0.1% mortality. However the fact is that by today we have almost 30,000 dead in NY suggesting 30,000,000 infected that is way over the entire population of the state.
Even if the numbers would be off by a factor of two or three, the early results extrapolate to a very high prevalence today. The authors should have run a small validation cohort at a high infection prevalence to prove such projected high prevalence on a recently collected sample set.<br /> This is poor science on display that does not help anyone.
On 2020-06-12 07:36:28, user Meki Shehabu wrote:
From my experiences in plant genetics, some QTLs are specific to some populations. can this be true for Africans? might lead to the answer why the covid19 incidence is relatively low in Africa?. I know similar result was reported from China.
On 2020-06-14 13:13:11, user OxImmuno Literature Initiative wrote:
On 2020-05-02 07:01:51, user Javier Mancilla-Galindo wrote:
I believe this manuscript is lacking work in the introduction, discussion and conclusions. Authors could try adressing: Why is it useful to have done such a study besides having available local epidemiological data? What are the lessons to be learned form the experience at your center which could be of use to the medical community? What other conditions (structure of the health system, burden of disease, demographics, etc.) make Mexico unique and should be taken into account when using this study to compare to others?
Two of the main highlights of this study are the high extubation rate and low mortality rate. However, the authors have not compared enough these two outcomes to other studies and barely commented on them. It would be important to dicuss further on these topics since it could serve as an example to improve COVID-19 care and patient outcomes in other centers.
Also, further work regarding adequate references is needed. For instance: How does reference number 2 relate at all to the statement the authors are making? "The flow of information from China, Europe and the United States could be used as a basis for our population; however, we must recognise that the Mexican population has very different social and health characteristics.(2)" 2. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:343-346.
On 2020-05-05 22:40:25, user Woolsey wrote:
Most of the charts tracking deaths per day for 5-5-2020 indicate an immediate drop in cases. This seems very unlikely since most or many of these show a current uptick in deaths. Why would all these curves suddenly reverse direction? It seems an underlying assumption is that the future direction must be down, which is just wishful thinking.
On 2020-05-08 16:24:34, user Rich Dzikowski wrote:
If this virus can survive in the air for so long and still remain infectious, you don't need to be an expert to imagine that it will stick to clothing, skin, hair and other objects we carry with us. So what good is wearing masks, washing our hands and using a tracking app if we inevitably end up reaching for the virus-contaminated areas and infecting ourselves at home?
On 2020-05-09 15:11:13, user fvtomasch wrote:
Worldwide deficiency started in my opinion back in the late 70's and 80's with the onset of the ozone hole in the southern hemisphere due to the release of CFC'S into the air. Many in Australia were getting skin cancer and if you recall SPF's on sunblocks were 10-15 but were steadily increased to 50-100 and above thus blocking UV rays which are needed to synthesize Vit D. Now 15-20 years later statins were introduced to reduce cholesterol levels and cholesterol is also needed to synthesize Vit D. So even in summer we are not getting the proper amount of D. Perfect storm of disease and death that can be minimized by a 10 cent daily pill.
On 2020-05-10 04:11:31, user JM V wrote:
Not taking shot noise of the 7 deaths into account. If the expected deaths would have been 14.6, the two sigma plausibilty range would have been 7 to 22. The error bounds in this paper do not reflect this.
On 2020-05-10 20:55:36, user knbizz wrote:
Would be nice to see the data itself.
It is not the same, for example, DM2 with 6.8 and with 10 or DM1. Given the lactate it is not the same if the DM is treated with metformin or insulin.
It is not the same high blood pressuse130/80 and 160/100. Will be good if data are provided as is.
On 2020-05-11 10:58:14, user Paul Revere wrote:
https://www.cdc.gov/nchs/nv...
Here is the CDC data. Approximately 20,00 excess deaths in April in NY area mainly but overall US deaths YTD below three year average.
On 2020-05-11 14:36:45, user Willyboy wrote:
What about the age? and other factors which can impact the result?<br /> most of the countries with low death rate are also countries with young population.<br /> for example, Morocco has only 7% of 65+<br /> while a country like Germany has 22% of 65+ people !!!
so the analysis must be executed by group of age, and also has to insure the way the people are counted (as this differs from 1 country to another)<br /> and the analysis must also exclude other factors which can impact the results.
Russia has authorized all the drugs, and based on my finding they are not using the HCQ , they claim using other drugs with effective impact on the patients. (I dont have the name of these drugs, but its not HCQ)
On 2020-05-12 07:59:56, user Erik Hansson wrote:
Thank you for your work, it is a valuable addition to consider that that people have different social activity levels, but I am concerned that your approach miss two important aspects which will underestimate the herd immunity threshold and make it less valid as an indicator of the risk of new severe epidemic flares:
Social distancing recommendations from Swedish authorities likely have different effects on levels of social activity between social strata. R is probably more flexible downwards in more affluent social classes leading to different seroprevalence in different strata when the global disease-induced herd immunity threshold is reached.
Post-social distancing (i.e. after achieving disease-induced herd immunity threshold) social interaction will happen primarily within social strata (i.e. within seroprevalence strata).
Lower social classes will be less able to achieve a low level of social activity due to household crowding, dependence on public transportation and inability to work from home due to having manual work (https://gupea.ub.gu.se/hand... "https://gupea.ub.gu.se/handle/2077/64124)"). This may lead to higher disease transmission in lower than higher social classes. Add to this the situation in elderly care in which the absence of PPEs has probably led to quite intense transmission both to and from workers, who are strongly concentrated to lower social classes in Stockholm. Disaggregated outcome data is scarce but there seems to be empirical evidence for such a social gradient in covid-19 infections both in hospitalized cases and very limited seroprevalence studies (contact Björn Olsen in Uppsala for more details or read Expressen article from last week - their study found 0% seroprevalence at Östermalm (~Kensington and Chelsea) in the end of April, n=?). Information from other major cities tell a similar story of a social gradient.
Under normal circumstances persons from lower social classes may not necessarily have higher levels of social activity than persons from the more affluent classes. I am concerned it may rather be the opposite as people from higher social classes may more likely engage in several activities less accessible to persons from lower classes, activities that are greatly reduced in a semi-quarantine setting such as cultural and sports events, parties, eating and drinking out, office work and meetings, conferences, university education, etc, but that are expected to be possible to do in a society having reached herd immunity.
Furthermore, due to segregation by class and ethnicity such post-social-distancing activities will likely primarily be done together with other persons likewise having been able to limit their activities during the first phase of the epidemic. There are thus conditions that allow rapid disease transmission in more affluent social strata if these go back to business as usual. It may even be argued that estimating a herd immunity threshold as an average percentage within a strongly segregated population (and segregation is probably aggravated during social distancing) is not especially meaningful. If there are large enough pools of connected susceptible individuals there is still a possibility of epidemics that overwhelm the healthcare system.
Another concern, which is not directly related to the present manuscript but to a media appearance in relation to it is the use of uncertain modeled estimates to make predictions of when Stockholm will reach the disease-induced herd immunity threshold, in June 2020 - less than weeks from now. This model estimated 26% had been infected by May 1. A critique of this model estimated 5-10% (https://twitter.com/AdamJKu... "https://twitter.com/AdamJKucharski/status/1254084771535376391)"), and the only (to my knowledge) somewhat representative seroprevalence study found 7.5% (Björn Olsen) at that time. Two separate methods that concur so well seems more credible than one modeled estimate, and the difference is large.
The combination of estimating an artificially low herd immunity threshold and using potentially exaggerated cumulative infected proportion risk declaring “all-clear” in Stockholm much prematurely.
Erik Hansson<br /> MD, MSc Epidemiology
On 2020-05-13 10:14:16, user Shohei Hidaka wrote:
We are posting the predicted evolution of COVID-19 almost everyday.<br /> You can see the visualized result online: <br /> http://www.jaist.ac.jp/proj...<br /> Project Prepidemics
On 2020-05-13 15:14:17, user Fred Douthwaite wrote:
Nearly all of the comorbidities in those who contract Covid-19 are associated with zinc deficiency. Furthermore, the SARS-CoV-2 virus robs the body of some of its zinc, further reducing immune response. If zinc plus a zinc ionophore (hydroxychloroquine) works as a rescue therapy, a federally directed program of targeted zinc supplementation for vulnerable groups seems sensible.
Is a single nutrient capable of resolving this pandemic? The single nutrient iodine resolved past goiter epidemics. The single nutrient vitamin D resolved past rickets epidemics. The single nutrient thiamine resolved past beriberi epidemics. Zinc conceivably could resolve this present pandemic and prevent future pandemics.
On 2020-05-18 03:32:28, user D J wrote:
University of Washingoton to conduct a study, but no mention of zinc.
On 2020-05-14 03:50:20, user Hey Dr Drew wrote:
https://www.medrxiv.org/con...<br /> Also this !
On 2020-05-14 15:34:13, user Neil Blumberg wrote:
Some suggested additional analyses. Compare results in recipients of ABO identical versus ABO compatible plasma. ABO compatible is associated in observational studies with increases in ARDS, sepsis, bleeding and mortality, as compared with ABO identical. Report incidence of thrombosis post-infusions (perhaps at 7 days). Allogeneic plasma is pro-inflammatory for innate immunity and immunosuppressive for T cell immunity, and these may well predispose to thrombosis and sepsis. If progressive SOFA or other scores are available, these would also be helpful. Big ask, I know :).
On 2020-05-15 08:15:51, user Ron Sills wrote:
Maybe they should look into the anti-h factor in the blood type or bombay and para-bombay influence on the infection rate and mortality rate. That might better explain the minor differences in percentage rates for the O blood group.
On 2020-05-15 09:34:45, user Dude Dujmovic wrote:
The newer NY survey had the data "weighted" down, with lower rates.
On 2020-05-15 15:43:49, user Michael Shmoish wrote:
Dear authors, thanks for your important contribution! <br /> Could you please inform how many ICU admissions and deaths were recorded out of 173 "complicated COVID-19" cases?
On 2020-05-15 18:42:04, user Will Wiegman wrote:
Undiagnosed Borreliosis + Covid-19 + severe Thiocyanate and Iodine Deficiencies = respiratory failure
link.springer.com<br /> Expression of ICAM-1, ICAM-2, NCAM-1 and VCAM-1 by human synovial cells exposed to Borrelia burgdorferi in vitro<br /> Sunit K Singh, Verena Baar, Henner Morbach, Hermann J Girschick<br /> Rheumatology international 26 (9), 818-827, 2006<br /> The interaction of resident tissue cells with migratory inflammatory cells is essential for the recruitment of immune effector cells to inflammatory sites. The sustained expression of adhesion molecules in the synovium of patients with chronic Lyme arthritis seems to contribute to this chronic inflammation. Whether cell adhesion molecules influence the early steps of Borreliosis is unclear. Therefore, we examined the expression of ICAM-1, ICAM-2, VCAM-1 and NCAM-1 in synovial cells exposed to two different Borrelia burgdorferi sensu stricto strains Geho and B31. The mRNA expression of ICAM-1, ICAM-2, VCAM-1 and NCAM-1 was not changed in synovial cells exposed to B31. Whereas ICAM-2 and VCAM-1 was upregulated, NCAM-1 mRNA was downregulated and ICAM-1 mRNA was unchanged by strain Geho. The ICAM-1 protein expression on the synovial cell surface was downregulated by both strains. Differential regulation of adhesion molecule mRNA, and subsequent high turnover or elevated shedding from the cell membrane may contribute to early pathogenesis in Lyme arthritis.<br /> View at link.springer.com<br /> [PDF] researchgate.net<br /> Cited by 9<br /> Related articles<br /> All 12 versions
Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts.<br /> Klaus Ebnet, Keith D Brown, Ulrich K Siebenlist, Markus M Simon, Stephen Shaw<br /> The Journal of Immunology 158 (7), 3285-3292, 1997
On 2020-05-16 00:36:41, user Mehdi wrote:
A Stanford whistleblower complaint alleges that the controversial John Ioannidis study failed to disclose important financial ties and ignored scientists’ concerns that their antibody test was inaccurate https://www.buzzfeednews.co...
On 2020-05-16 13:23:57, user Sinai Immunol Review Project wrote:
The RBD of the spike protein of SARS-group coronaviruses is a highly specific target of SARS-CoV-2 antibodies but not other pathogenic human and animal coronavirus antibodies
Premkumar L et al., medRxiv 2020.05.06.20093377; doi: https://doi.org/10.1101/202...
Keywords<br /> • SARS-CoV-2 receptor binding domain (RBD) binding antibodies<br /> • Endemic human coronaviruses<br /> • Cross-reactive abs/ELISA
Main findings<br /> There is an urgent need for both sensitive and specific SARS-CoV-2 serological testing to not only reliably identify all infected individuals regardless of clinical symptoms, but to determine the percentage of convalescent individuals on population level.<br /> In this preprint, Premkumar et al. study the performance of the SARS-CoV-2 receptor binding domain (RBD), which has been found to be largely unique across individual coronaviruses, as a target to specifically detect antibodies against SARS-CoV-2. By generation of recombinant RBDs of SARS-CoV-1, SARS-CoV-2 and human endemic coronaviruses (hCoV HKU-1, OC-43, NL63 and 229E), antigen cross-reactivity of these targets was evaluated by ELISA, using sera obtained from both infected and convalescent COVID-19 patients, healthy control individuals as well as pooled sera collected from various animals immunized with either SARS-CoV-1, SARS-CoV-2 or animal coronaviruses. While sera from mice and rabbits previously exposed to SARS-CoV-1 spike protein were found to be cross-reactive, recognizing both the SARS-CoV-1 and SARS-CoV-2 RBDs (yet none of the hCoVs), serum from SARS-CoV-2-immune mice predominantly reacted with SARS-CoV-2. Importantly, control sera obtained from healthy donors without a prior history of either SARS-CoV-1 or SARS-CoV-2 were found to only detect hCoV-RBDs. Additionally, assessment of highly concentrated sera collected from 20 healthy donors in the US prior to emergence of the SARS-CoV-2 pandemic confirmed high levels of antibodies against hCoVs in the majority of subjects, whereas cross-reactive antibodies against the SARS-CoV1 and SARS-CoV-2 RBDs could not be detected. Furthermore, serological testing of sera obtained from convalescent Dengue and Zika virus patients (n=40) as well as from recently recovered patients with influenza A (n=2) and respiratory syncytial virus (n=1) confirmed frequent antibodies against hCoV RBDs, but a lack of cross-reactive antibodies against both the SARS-CoV-1 and SARS-CoV-2 RBD as opposed to positive controls of pooled sera from SARS-CoV-1 immunized guinea pigs. Notably, sera from recently recovered, PCR-diagnosed hCoV patients (NL-63, OC-43, HKU-1; n=2 each) were found equally not cross-reactive against either the SARS-CoV-1 or SARS-CoV-2 RBDs (again using guinea pigs immunized with SARS-CoV-1, SARS-CoV-2 or various animal coronaviruses as positive and negative controls), suggesting that the SARS-CoV-2 RBD is a highly specific target for serological SARS-CoV-2 testing. Furthermore, assessment of total Ig as well as IgM binding to recombinant SARS-CoV and hCoV RBDs in 77 samples obtained from 70 PCR-confirmed COVID-19 patients of variable clinical disease revealed high sensitivity (Ig: 98%, IgM: 81%) for specimens collected at least 9 days post symptom onset. Of note, 67% (Ig) and 30% (IgM) of these samples were also found to be cross-reactive against the SARS-CoV-1 RBD. Repeated sampling of 14 of these 77 patients suggested that seroconversion had occurred between day 7 and day 9 post symptom onset. In addition, 19/77 patients were tested for development and kinetics of neutralizing antibodies (nAbs). Notably, 14% of these 19 patients had detectable levels of nAbs by day 7, whereas 95% of them were positive for nAbs by day 9. One patient failed to elicit both anti-RBD binding and nAbs. Finally, a robust correlation between levels of RBD binding Ig and IgM as well as nAbs was detected, suggesting that levels of RBD binding Abs in COVID-19 patients might be used as a correlate for the development of potentially protective nAbs.
Limitations<br /> While this is generally a well-conducted study, interrogating a relatively large number of COVID-19 patient and healthy control samples as well as sera from immunized animals, one limitation pertains to the patient cohort enrolled. Given that clinical disease might directly relate to Ab titers, as has been observed in SARS-CoV-1 (https://www.ncbi.nlm.nih.go... "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683413/pdf/nihms109289.pdf)") and has also been suggested in SARS-CoV-2, a more stringent characterization of these patients would add further impact to the observations made here. Moreover, inclusion of COVID-19 patients across all clinical stages and after convalescence as well as longitudinal sampling over several months and longer are needed to further assess serological testing sensitivity and specificity of RBD-binding Abs and whether the latter may be used as a correlate for potentially protective nAb titers. Additionally, detection of other binding Abs against N, M, S1, S2 may add valuable information, in particular with respect to individuals who seemingly fail to develop humoral anti-SARS-CoV-2 RBD responses. Likewise, evaluation of and comparison to other highly specific epitopes such as ORF3b and ORF8, as recently suggested by another preprint (https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.04.30.20085670v1)"), might be helpful to rule out seroconversion failure. Notably, the authors report SARS-CoV-2 RBD binding Ab cross-reactivity against SARS-CoV-1 in some COVID-19 patients, an observation that mirrors previous findings about S-binding Abs in several preprints/publications. Given the rather low number of SARS-CoV-1 convalescent patients in the general population, this is likely not a major issue. However, for future clinical application, additional use of potentially even more specific Abs, e.g. against ORFs, might be favorable.
Significance<br /> In general, this study corroborates previous reports and observations about enhanced specificity of the SARS-CoV-2 RBD over other binding ab epitopes (cf. https://www.nature.com/arti... https://www.ncbi.nlm.nih.go... https://wwwnc.cdc.gov/eid/a... "https://wwwnc.cdc.gov/eid/article/26/7/20-0841_article)"). Most importantly, these data suggest that pre-existing binding Abs against endemic human coronaviruses seem to be not cross-reactive against the SARS-CoV-2 RBD and that titers of anti-RBD binding Abs robustly correlate with nAb levels. These observations are of great relevance but need further assessment in larger studies of hCoV seropositive and SARS-CoV-2 negative healthy donors.
References<br /> 1. Chris Ka-fai Li et al. T Cell Responses to Whole SARS Coronavirus in Humans. The Journal of Immunology. 2008, 181 (8) 5490-5500; DOI: 10.4049/jimmunol.181.8.5490<br /> 2. Yap et al. Patient-derived mutations impact pathogenicity of SARS-CoV-2. PrePrint DOI:<br /> https://doi.org/10.1101/202... <br /> 3. Perera et al . Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020. Euro Surveill. 2020;25(16):pii=2000421. https://doi.org/10.2807/156.... ES.2020.25.16.2000421<br /> 4. Amanat et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med (2020). https://doi.org/10.1038/s41...<br /> 5. Okba et al. Severe acute respiratory syndrome coronavirus 2–specific antibody responses in coronavirus disease 2019 patients. Emerg Infect Dis. 2020 Jul [date cited]. https://doi.org/10.3201/eid...
This review was undertaken by Verena van der Heide and Zafar Mahmood as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.
On 2020-05-18 14:25:25, user OxImmuno Literature Initiative wrote:
On 2020-05-18 19:42:49, user Buck Kopietz wrote:
I would like to see vitamin D levels tested as well. 3 recent published associative studies showed a direct connection between the blood level of vitamin D and seriousness of the COVID-19 infection. The active form of vitamin D, the hormone calcitriol, is important for activation of the immune cells. Black Americans are generally more vitamin D deficient as are seniors unless they are supplementing. This could solve a number of issues in our country. The Endocrinology Society recommends 30 ng/mL. the National average is 28 ng/mL and many of the bottom half , especially Black Americans, are under 20 ng/mL.
On 2020-05-20 04:11:09, user Elek Pafka wrote:
Would be good to understand the spatial characteristics of the 'social venues' linked to the 75-person cluster. Were these closed spaces with less than 4sqm per person? Were these related to ingestion of food and drinks? etc
On 2020-05-20 08:57:29, user rob martens wrote:
This very interesting study could perhaps be supplemented by the relationship between COVID19 and air pollution. This relationship is now getting attention and is relatively well founded. https://www.sciencedirect.c... <br /> But what is usually not seen is that exposure to UV light (thus vitamin D) could also here be the underlying cause. Air pollutants strongly block the amount of UV light reaching the earth's surface. https://www.researchgate.ne... <br /> For example, it could explain the big difference in COVID19 lethality between northern Italy (where smog is common) and the rest of the country. Or the Wuhan district and other regions. By taking air pollution into account, the picture outlined could become even more precise.
On 2020-05-20 14:48:54, user OxImmuno Literature Initiative wrote:
On 2020-05-20 17:05:34, user Steven Sullivan wrote:
detailed critique on Twitter: https://twitter.com/GidMK/s...
On 2020-05-20 17:49:28, user Christopher Leffler wrote:
Bottom line, how many people does Dr. Ioannidis think will die in the US from this epidemic? If one reads the paper, he proposes that " even under congested circumstances, like cruise ships, aircraft carriers or homeless shelter, the proportion of people infected does not get to exceed 20-45%."<br /> Also, he believes that the infection fatality ratio is: " Infection fatality rates ranged from 0.03% to 0.50% and corrected values ranged from 0.02% to 0.40%."<br /> So, these numbers would give estimates for the United States of:<br /> Low end: 331,000,000 people * 0.2 * 0.0002 = 13,240.<br /> High end: 331,000,000 people * 0.45 * 0.004 = 595,800.<br /> The range is so wide as to provide no useful information. And of course, the pandemic is already at 92,387 deaths in the US, as of May 20, 2020. So we know Ioannidis low end is simply wrong.<br /> We have looked at the mortality in different age groups in New York, among residents and transit workers, and on the Diamond Princess:<br /> https://www.medrxiv.org/con...<br /> Quite early in the pandemic (early April), we showed that if the US followed the course that Italy and Spain had already experienced, we would see 100,000 dead in the US:<br /> https://www.researchgate.ne...<br /> More recently, we showed that if the mortality rates seen in New York MTA / New York State / Diamond Princess were observed nationally, the mortality could be over 600,000, which is the high end for Ioannidis work also:<br /> https://www.researchgate.ne...<br /> So, the bottom line is, that the high end projections from all groups could be quite high indeed. So we will need to be vigilant--wearing masks, protecting the vulnerable, etc. The pandemic is real. To say that it is similar to a typical flu is just plain false. Even Ioannidis own projections do not rule out that this is far worse than the flu. When is the last year the flu killed 92,000 Americans and was on track to kill potentially hundreds of thousands more?
On 2020-05-21 13:48:15, user Sander Greenland wrote:
Here are two papers that deal with the general causality theory of collider bias and related phenomena:<br /> Greenland S, Pearl J, Robins JM. Causal diagrams for epidemiologic research. Epidemiology 1999;10:37–48.<br /> Greenland S. Quantifying biases in causal models: classical confounding versus collider-stratification bias. Epidemiology 2003;14: 300-306.<br /> See also Ch. 12 of Rothman Greenland Lash, Modern Epidemiology 3rd ed. 2008.
On 2020-05-22 13:11:46, user Michael Buchwach wrote:
What’s missing from this is equally interesting. What if the measures taken had been taken 1 or 2 weeks later? That is, theoretically how many lives were saved by acting when the US acted?
On 2020-05-22 13:15:29, user fc wrote:
Summation: paper shows model with extreme sensitivity to initial conditions built into mathematical form displays significant changes in long term predictions (now with confidence intervals (TM)!) after changes to said initial conditions.
While earlier intervention would probably have been better in reality, the conflation of the media of 95% confidence intervals on model prediction with 95% confidence intervals on truth is nuts, and its complete disregard of the sensitivity of the predictions to model assumptions is depressing (feedback effects, anyone? Buehler ? Cochrane ...?)
This model is being seen to provide accurate answers to a question which it is least able to model with high precision.
On 2020-05-23 06:41:55, user joe wrote:
Would using the excess deaths of each country to get a more accurate CFR be more accurate?
On 2020-07-27 20:23:39, user Marm Kilpatrick wrote:
Thank you for this large study. Were you able to assess when the patients first lost their sense of smell? I'm convinced by your study (and others) that this symptom is much more specific in identifying COVID-19 patients than other symptoms (e.g. cough or fever). But I'm still not sure if it is a useful symptom for people to use to isolate or get tested. If this is one of the first symptoms then it could be very useful but if it isn't apparent until 3 or more days after cough or fever start then it would be of less importance for isolation (but still could be useful for finding other chains of transmission via contact tracing). Thank you!<br /> marm
On 2020-08-07 07:38:40, user kdrl nakle wrote:
"California, Florida, and Texas are each burdened with nearly<br /> 0.5 million cases, which corresponds to 1% infection in their respective populations"
Really? You just pulled 1% of of your ... hat? And also assumed that CDC reported cases would be precisely the number of all infections? Or active infections? Or what?
On 2020-08-07 12:37:34, user kdrl nakle wrote:
I don't see affiliation of authors in paper.
On 2020-08-12 09:54:15, user kdrl nakle wrote:
The whole paper is only presenting data and makes no estimates. "There is evidence of a considerable excess of deaths". Really?
On 2020-08-12 11:31:19, user Johanna wrote:
I would like to alert the authors and readers that the estimate reported from Aiello 2010 and 2012 is that from the comparison "face mask/hand hygiene vs Control", and not the comparison "face mask only vs Control". Surely, when numbers of face mask vs Control is available, one wouldnt want to include a measure confused with hand hygiene on top of face masks? The corresponding estimate for face masks alone for the 2012 paper was 1.08 (0.86-1.34). For face mask + hand hygiene, it was 0.78 (0.59-1.05), wich tells quite a different story. I am afraid this preprint needs another round of proof-reading of the extraction of raw data from the original articles.
On 2020-08-12 15:00:46, user Peter wrote:
I think there's a small error in the abstract:
"When a CT cut-off of 33 was employed, above which increasingly, evidence suggests there is a very low risk of patients shedding infectious virus, the diagnostic sensitivity was 100%. The DSe and DSp of Direct-RT LAMP was 67% and 97%, respectively. When setting CT cut-offs of <=33 and <=25, the DSe increased to 75% and 100%, respectively."
I think, in the final sentence, you intended to write:
"When setting CT cut-offs of <=33 and <=25, the DSe and DSp increased to 75% and 100%, respectively."
Hang on - perhaps you did mean the sensitivity with different cut-offs, not the specificity...
Hope this helps...
Peter English
On 2020-08-12 20:39:28, user David Curtis wrote:
There may be dozens of groups around the world doing studies like this on 30 or 40 patients. Some of them are naturally going to show "statistically significant" results. There's an argument that it's unethical to perform clinical trials with small sample sizes. This study is impossible to interpret. If you'd done the study with 100 cases and 100 controls we'd have something useful.
On 2020-08-13 02:46:09, user Meaghan Emery wrote:
On Figure 4 where you show individual changes in antibodies, you describe part A as being "only individuals where the peak ID50 occurs before the last time point, and where the last time point is > 30 days POS are included in this analysis." Does that mean you excluded people who had been in the study for, say, 80 days, but were not showing a decline? That's my interpretation, as the only way you could have a peak is if something decreases. This to me suggests there were individuals who potentially had the same antibody levels or increased - and I'm not sure how many you excluded, so I'm not sure if that's potentially a substantial portion of the study or not.
On 2020-08-20 20:15:56, user scvblwxq wrote:
B-Cells should still be available to generate new antibodies if needed.
The antibodies are being used to estimate how many people have been infected in total. That count will be low if people's antibodies become undetectable before they are tested.
On 2020-08-13 21:33:27, user AlvaroFdez wrote:
It would be interesting to clarify if during (or even before) the sampling periods, the patients used the toilet, given the potential particle aerosolization originating via flushing.
On 2020-08-17 06:34:30, user Jesper Markmann wrote:
There are several studies examining whether AC units can transpot virus. There are also studies examining the effect of climate.
If temperature and humidity can have an effect outside, it would have a more pronounced effect in a confined space.
Have you considered the possibility, that the problem isn't that AC is transporting the virus. The problem is that the colder air allows the virus to stay active in the air for longer, increasing the risk that it will infect other people.
This would explain why the virus is much more predominant in meat factories, on cruise ships, and in countries where it is common to cool confined spaces.
On 2020-08-18 14:02:37, user Brad T. wrote:
This may get removed for being a competitor site, but this study found conflicting results.<br /> https://www.ncbi.nlm.nih.go...
On 2020-08-29 09:10:30, user Brenda White wrote:
Can forehead testing affect brain or glands in the head?
On 2020-08-19 14:58:17, user jan homolak wrote:
A comment on the methodological approach used in this study by Trkulja et al. explaining why "A suggested effect of air temperature on severity of COVID-19 in hospitalized patients by Kifer et al. (Effects of environmental factors on severity and mortality of COVID-19; medRxiv 10.1101/2020.07.11.20147157) is most likely an artifact" can be found here: https://bit.ly/3aCVAJk
On 2020-08-20 17:21:13, user m knudson wrote:
This is very interesting data and I am grateful they put this together. To me the dosing data has the potential to be very informative. This data is promising but the analysis does not appear to have been adjusted based on study period. This seems very important to me as it looks likes patient outcomes improved with time. If other centers are like us, our CCP Ab levels also improved over time so I wonder if this could be why the high "titier" CCP appears to perform better, could it be that it was just given later in the study on average when other treatments may have improved.
On 2020-08-21 04:26:05, user N M C wrote:
Very odd FDA put this on hold,
On 2020-08-20 18:06:49, user PB wrote:
For campus opening in the US at present, the analysis in this manuscript is irrelevant. This analysis assumes a single starting infection in a completely susceptible (i.e. uninfected) population. A rough but reasonable order-of-magnitude estimate (but see https://mggg.github.io/esti... ) suggests that in a population of 10K student-age people in California, we would expect O(100) students who would test positive on day 1 if tests were available. That is, the outbreak is already there! It arrives with the students. The idea that it can be controlled with a single round of entrance testing is also wrong. Assuming 85% sensitivity (the value used by these authors, which is very optimistic but not crazy high), the test would catch 85 of those 100 positives, but miss 15. Again, the outbreak is already there. The analysis in this manuscript may be reasonable, but for managing campus infection in the US at the moment, it simply addresses the wrong question.
On 2020-08-21 04:51:59, user Enrique wrote:
Why not brain?
On 2020-08-21 15:33:25, user mikelor wrote:
Interesting. I wonder if the estimation of Q (line 66) can be improved/tailored to a specific Origin/Destination pair by using the LEMMA model. It seeks to provide Local Projections for infection rates.
In addition, Mask Policies for Major Domestic Airlines we're implemented in the latter half of June, so a "refreshed" statistic based on 100% mask compliance would also be interesting.
On 2020-08-21 21:28:15, user Orison Woolcott wrote:
This study has been accepted and published in High Altitude Medicine & Biology: https://www.liebertpub.com/...
On 2020-08-22 20:39:16, user Abhishek Singh wrote:
Reminds me of one of the paper we had written before COVID - https://arxiv.org/abs/1912....<br /> This looked at the physician notes instead of X-ray. A combined multi-task learning model could be more powerful.
On 2020-08-22 21:15:39, user Joserra wrote:
There is something I do not understand completely. It has to do with numbers. The autors state that they exclude deaths in nursign homes but estimated taht outside these institutions there have ben 19,228 laboratory-confirmed COVID-19 deaths and 24,778 excess all-cause<br /> deaths. But in reality the number of deceased in nursing home was 68% of the total laboratory confirmed deaths, that is 19,699, that leave the number confirmed deaths ourside nursing home in less than 9000 thousands and not 19.699. Consecuently IFR is about 0.3% similar to seriours flu outbreaks. The total death excess should no be appointed at the virus but to the lockdown and other measures taken by Spanish Goverment.
On 2020-08-23 15:06:23, user Ibezimako wrote:
This study design is more of a cross-sectional survey and analysis of data from a database. I did not see it as 'prospective/longitudinal cohort.
On 2020-08-25 10:12:56, user Richard Harrison wrote:
Useful paper, with clear message for those suggesting there is no risk of transmission from/between children in schools. It will be interesting to see what happens with higher pupil densities and probably poorer ventilation when schools re-open in September and thereafter, particularly in areas with higher local prevalence.
On 2020-08-25 10:26:04, user Richard Harrison wrote:
Interesting paper. Perhaps unintentionally, illustrates the danger of relying on a T&T system which is worryingly slow, also bearing in mind that incubation periods may be shorter in some cases. Really need to encourage people with symptoms (suspected cases) to self-isolate immediately and notify known contacts directly to suggest they do the same unless/until reliable negative confirmation is received, to contain outbreaks more effectively and help move towards Zero COVID.
On 2020-08-27 21:59:05, user Thomas P. Dooley wrote:
This article has been peer reviewed and is "In Press" in Pulmonary Pharmacology & Therapeutics (an Elsevier journal).<br /> T.P. Dooley (co-author)
On 2020-08-28 17:49:17, user Jean Sanders wrote:
this is excellent information ; it is extremely well written with good data and also it is accessible to the average lay person like myself. I found it fascinating and sent it to school committee members in Massachusetts in the city where I live. Important considerations for September -- some are predicting a peak in Dec. and then another in Feb depending upon what date the kids are back in school and how many are in a classroom etc. a lot of variables and contributing factors -- flatten the curve
On 2020-08-30 11:26:31, user Wolfgang Wodarg wrote:
Does anyone know a study older than one year, giving evidence to let patients, who are infected with respiratory viruses wear masks? Why didn't we pactice this all those flu- corona- rsv-, hMPV, etc- seasons before?
On 2020-09-01 03:16:55, user Dr. Amy wrote:
This discovery that telomere shortening and race increase the likelihood of Nasal ACE2 sars-cov-2 occupation is perhaps THE important piece explaining the disparities in severity while underscoring nasal acquisition and supporting aerosol Transmission.