On 2020-04-20 15:36:38, user Philip Davies wrote:

Interesting study, thank you.

This is another study that attempts to ascertain if oral HCQ tablets can be of clinical use in patients more than one week into symptomatic disease, hospitalized with bilateral pneumonia and with evidence of established inflammatory reaction (cytokine storm). That's a big ask for any oral medication.

The study is again small (both arms have less than 100 patients). The most significant outcome measured (death) is realized in very small numbers (3 and 4). The confidence levels are extremely wide.

The are several problems with this study. There are marked differences in the two populations. The study honestly attempts to accommodate these confounding factors using a propensity score method (IPTW). Normally this method is valuable but here I can’t see that it has been well applied.

It pays to look at the raw data. There is a significant difference (between the two arms) in the initial intensity of disease.

At baseline (admission), HCQ arm comprises 78.3% men (>20% more of these higher risk patients than control arm with 64.9%); HCQ arm has 21.9% patients with more severe disease in the form of CT showing >50% lung affected). This is >80% more than in control arm (12.1%). HCQ arm has 90.5% patients with CRP > 40mg/l (CRP is a good indicator of impending/current severity). This is 10% higher than control arm (81.9%). HCQ arm had median O2 flow on admission = 3 litres/minute (50% higher than control arm at 2 litres / minute).

So, at baseline, the HCQ arm had significantly more patients with severe disease than control arm. The O2 flow is actually more significant than first sight would suggest. 2 l/m is always the first step in O2 therapy. The data shows us that most patients in the control arm could hold their sats on this first step therapy. This also means they may have been OK on just 1 l/m. We don't know. But we do know that most patients in the HQN could not hold their sats at that first step and needed an increase (3 l/m ... so that's 50-300% more O2 than control arm).

Admittedly there were other confounding factors which compromised the control arm more than HCQ arm (some chronic disease elements). But it's clear to me that disease severity was markedly more established in the HCQ arm.

Another factor to note: the HCQ treatment was not initiated at the moment those baseline values were obtained (on admission). The HCQ was initiated within 48 hours. So let’s look again at the timelines. The median duration of symptoms at admission shows that the HCQ arm comprised patients who were further into worsening illness: they were admitted on D8 compared to control, D7. They may not have had HCQ initiated until D10.

Then we look at outcomes: the raw data shows that the disadvantaged HCQ arm actually does better in the two most important outcomes, death and ICU admission. The HCQ delivers 12% less death and ICU admissions than the control arm. Admittedly the numbers are small so the confidence levels are very wide.

So what does that tell us? The answer is not much. But even accepting the poorly aligned baseline for disease severity, the outcomes with their wide 95% confidence levels do deliver a mildly promising indication on the 'swingometer'. They point more towards benefit than harm when using HCQ in this advanced disease state.

As a final comment on significant side effects (increased QT interval) from the use of HCQ. Once again, this trial used a particularly high dose of HCQ (600mg/day...right at ceiling dose for rheumatological use and much higher than the total antimalarial treatment dose). They also added azithromycin (another QT lengthening drug) to 20% of the HCQ patients. It’s not surprising at all to find such QT lengthening in a sick, more elderly population taking these medications in particularly high doses).

Further trials should utilize conservative doses of CQ/HCQ which have been proven safe in many millions of patients.

We don't yet know how this will pan out. We urgently need proper evidence. Statistically robust studies into prophylaxis and early intervention are likely to deliver the most interesting results.

Dr Philip Davies<br /> Aldershot Centre For Health<br /> http://thevirus.uk

On 2020-11-25 15:43:07, user Jayebird58 wrote:

The Danish masks study proves masks don’t work!

On 2020-04-06 18:50:52, user Sinai Immunol Review Project wrote:

Main Findings: Currently, the diagnosis of SARS-CoV-2 infection entirely depends on the detection of viral RNA using polymerase chain reaction (PCR) assays. False negative results are common, particularly when the samples are collected from upper respiratory. Serological detection may be useful as an additional testing strategy. In this study the authors reported that a typical acute antibody response was induced during the SARS-CoV-2 infection, which was discuss earlier1. The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker was total antibody followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days-post exposure (d.p.e) or 9, 10- and 12-days post-onset (d.p.o). Seroconversion was first detected at day 7d.p.e in 98.9% of the patients. Interestingly they found that viral load declined as antibody levels increased. This was in contrast to a previous study1, showing that increased antibody titers did not always correlate with RNA clearance (low number of patient sample).

Limitations: Current knowledge of the antibody response to SAR-CoV-2 infection and its mechanism is not yet well elucidated. Similar to the RNA test, the absence of antibody titers in the early stage of illness could not exclude the possibility of infection. A diagnostic test, which is the aim of the authors, would not be useful at the early time points of infection but it could be used to screen asymptomatic patients or patients with mild disease at later times after exposure.

Relevance: Understanding the antibody responses against SARS-CoV2 is useful in the development of a serological test for the diagnosis of COVID-19. This manuscript discussed acute antibody responses which can be deducted in plasma for diagnostic as well as prognostic purposes. Thus, patient-derived plasma with known antibody titers may be used therapeutically for treating COVID-19 patients with severe illness.

Reference:

1. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

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

On 2020-04-23 17:27:44, user Sinai Immunol Review Project wrote:

Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors

Braun J et al.; medRxiv 2020.04.17.20061440; https://doi.org/10.1101/202...

Keywords

• SARS-CoV-2 specific CD4 T cells

• Human endemic coronaviruses

• COVID-19

Main findings

In this preprint, Braun et al. report quantification of virus-specific CD4 T cells in 18 patients with mild, severe and critical COVID-19, including 10 patients admitted to ICU. Performing in vitro stimulation of PBMCs with two sets of overlapping SARS-CoV-2 peptide pools – the S I pool spanning the N-terminal region (aa 1-643) of the S protein, including 21 predicted SARS-CoV-1 MHC-II epitopes, and the C-terminal S II pool (aa 633-1273) containing 13 predicted SARS-CoV-1 MHC-II epitopes – the authors detected S-protein-specific CD4 T cells in up to 83% of COVID-19 patients based on intracellular 4-1BB (CD137) and CD40L (CD154) induction. Notably, peptide pool S II shares higher homology with human endemic coronaviruses (hCoVs) 229E, NL63, OC43, and HKU1 that may cause the common cold, but it does not include the SARS-CoV-2 receptor-binding domain (RBD), which has been identified as a critical target of neutralizing antibodies in both SARS-CoV-1 and SARS-CoV-2. S I-reactive CD4 T cells were found in 12 out of 18 (67%) patients, whereas CD4 T cells against S II were detected in 15 patients (83%). Intriguingly, S-specific CD4 T cells could also be found in 34% (n=23) of 68 SARS-CoV-2 seronegative donors, referred to as reactive healthy donors (RHD), with a preference for S II over S I epitopes. Only 6 of 23 RHDs also had detectable frequencies of S I-specific CD4 T cells, overall suggesting S II-reactive CD4 T cells had likely developed in response to prior infections with hCoVs. Of 18 out of 68 total healthy donors tested, all were found to have anti-hCoV antibodies, although this was independent of concomitant anti-S II CD4 T cell frequencies detected. This finding mirrors observations of declining numbers of specific CD4 T cells, but persistent humoral memory after certain vaccinations such as against yellow fever. The authors further speculate that these pre-existing virus-specific T cells against hCoVs might be one of the reasons why children and younger patients, usually considered to have a higher incidence of hCoV infections per year, are seemingly better protected against SARS-CoV-2. Unlike specific CD4 T cells found in RHDs, most S-specific CD4 T cells in COVID-19 patients displayed a phenotype of recent in vivo activation with co-expression of HLA-DR and CD38, as well as variable expression of Ki-67. In addition, a substantial fraction of peripherally found HLA-DR+/CD38+ bulk CD4 T cells was found to be refractory to peptide stimulation, potentially indicating cellular exhaustion.

Limitations

This is one of the first preprints reporting the detection of virus-specific CD4 T cells in COVID-19 (also cf. Dong et al., https://www.medrxiv.org/con... Weiskopf et al., https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.04.11.20062349v1.article-info)"). While it generally adds to our current knowledge about the potential role of T cells in response to SARS-CoV-2, a few limitations, some of which are discussed by the authors themselves, should be addressed. Findings in this study pertain to a relatively small cohort of patients of variable clinical disease. To corroborate the observations made here, larger studies including both more healthy donors and more patients of all clinical stages are needed to better assess the function of virus-specific CD4 T cells in COVID-19. Specifically, the presence of pre-existing, potentially hCoV-cross-reactive CD4 T cells in healthy donors needs to be explored in the context of COVID-19 immunopathogenesis. While the authors suggest a potentially protective role based on higher incidence of hCoV infection in children and younger patients, and therefore a presumably larger pool of pre-existing virus-specific memory T cells, the opposite could also be the case given cumulatively increased number of hCoV infections in older patients. In this context, it would therefore have been interesting to also measure anti-hCoV antibodies in COVID-19 patients. Furthermore, this study did not quantify virus-specific CD8 T cells. Based on observations in SARS-CoV-1, virus-specific memory CD8 T cells are more likely to persist long-term and confer protection than CD4 T cells, which were detected only at lower frequencies six years post recovery from SARS-CoV-1 (cf. Li CK et al., Journal of immunology 181, 5490-5500.) Morover, no other specifities such as against the N or M epitopes were evaluated. Robust generation of virus-specific T cells against the N protein was shown to be induced by SARS-CoV-2 in another pre-print by Dong et al. (Dong et al., https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.03.17.20036640v1)"), while Weiskopf et al. recently reported preference of both CD8 and CD4 T cells for S epitopes https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.04.11.20062349v1.article-info)"). Moreover, the authors seem to suggest that some of the virus-specific CD4 T cells detected could be potentially cross-reactive to predicted SARS-CoV-1 epitopes present in the peptide pools used. Indeed, this has been recently established for several SARS-CoV-2 binding antibodies, while it was found not to be the case for RBD-targeting neutralizing antibodies (cf. Wu et al., https://www.medrxiv.org/con... Ju et al., https://www.biorxiv.org/con... "https://www.biorxiv.org/content/10.1101/2020.03.21.990770v2)"). A similar observation has not been made for T cells so far and should be evaluated. Finally, since reactive healthy donors were only tested for anti-S1 IgG, however not for other more ubiquitous binding antibodies, e.g. against M, and only a fraction of these donors was additionally confirmed to be negative by PCR, there is, though unlikely, the possibility that some of the seronegative reactive donors had been previously exposed to SARS-CoV-2.

Significance

Quantification of virus-specific T cells in peripheral blood is a useful tool to determine the cellular immune response to SARS-CoV-2 both in acute disease and even more so post recovery. Ideally, once immunogenic T cell epitopes are better characterized, tetramer assays will allow for faster and more efficient detection of their frequencies. Moreover, assessing the potential role of pre-existing virus-specific CD4 T cells in healthy donors in the context of COVID-19 pathogenesis will be of particular importance. The observations made here are also highly relevant for the design and development of potential vaccines and should therefore be further explored in ongoing research on potential coronavirus therapies and prevention strategies.

This review was undertaken by V. van der Heide as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

On 2020-06-23 10:31:41, user OxImmuno Literature Initiative wrote:

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

On 2023-07-24 23:20:31, user Dangard wrote:

This paper was published in Nature

https://www.nature.com/arti...

On 2020-06-24 11:34:40, user Renzo Huber wrote:

This is a nice review that might also be valuable to the field of layer-fMRI. <br /> I think the manuscript might benefit from an additional brief discussion of the related laminar connectivity findings from non-invasive human fMRI studies:

-> layer-dependent connectivity in Fig. 6 and 7 of the following study: <br /> Huber L, Handwerker DA, Jangraw DC, et al. High-Resolution CBV-fMRI Allows Mapping of Laminar Activity and Connectivity of Cortical Input and Output in Human M1. Neuron. 2017;96(6):1253-1263.e7. doi:10.1016/j.neuron.2017.11.005

-> layer-dependent connectivity with gppi in this study: <br /> Sharoh D, Mourik T van, Bains LJ, et al. Laminar Specific fMRI Reveals Directed Interactions in Distributed Networks During Language Processing. PNAS. 2019:1907858116. doi:10.1101/585844

-> layer-dependent hierarchical connectivity discussed in this study: <br /> 1. Huber L, Finn ES, Chai Y, et al. Layer-dependent functional connectivity methods. Prog Neurobiol. 2020:in print. doi:j.pneurobio.2020.101835

On 2020-06-05 17:35:30, user wbgrant wrote:

Dark-skinned people living in Spain are at an increased risk of COVID-19 due to lower vitamin D production from solar UVB. This effect probalby explains the finding for Sub-Saharan Africa and the Caribbean. Not sure about Latin America, where rates are very high in several countries. See:<br /> Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JA, Bhattoa HP. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020, 12, 988. https://www.mdpi.com/2072-6...<br /> and references thereto at scholar.google.com<br /> as well as this response<br /> Grant WB, Baggerly CA, Lahore H. Response to Comments Regarding “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths”. Nutrients 2020, 12(6), 1620; https://doi.org/10.3390/nu1...

On 2020-06-06 01:33:13, user David Hood wrote:

I think the "39.5% of cases seeking medical consultation in primary care settings" may be overly conservative in the model for a parameter representing getting medical advice, as it is based of influenza in the 2018 'flu season (a fairly typical year). We know from the ESR influenza surveillance site that healthline historically (I don't know the period for what they determine historical) get around 40000 Influenza like illness calls a year, and for the period from the week of 14/2 to 29/5 there are historically around 10000 ILI calls. In 2020, for the period from the week of 14/2 to 29/5, there were around 26000 ILI calls. Even allowing for false positive worries from anxious people boosting call numbers, it suggests that people seeking official advice about ILI is dramatically higher in 2020 (which I also acknowledge is not the same as visiting a primary care location about an ILI, which is the 39.5% figure, but the official advice was to ring Healthline, who were presumably advising testing/ isolation/ primary health as appropriate)

On 2021-06-06 09:28:02, user Ulltand wrote:

4 days after one dose. What does it say? We know from other studies that 21 days after one dose protection is about 90 %. 14 days is a to short period.

On 2020-06-06 13:05:56, user OxImmuno Literature Initiative wrote:

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

On 2020-06-08 14:35:52, user Francesco Rossi wrote:

Dear Dr.Streeck, <br /> is it possible, with your experimental approach, giving an estimate of the percentage of people hospitalized and treated in ICU?<br /> The theoretical model supporting lockdown was published by Ferguson and collaborators in The Imperial College report 9 (https://www.imperial.ac.uk/..., hereafter ICR9). In this reports, authors extimated that in Covid-19 epidemic “optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half. However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over.” (ICR9). Therefore they concluded that “epidemic suppression is the only viable strategy at the current time.” (ICR9). They focused their prediction on UK and US, but they claimed that their prediction could be applied to other high-income countries (ICR9).<br /> However the model they proposed is controversial for several reasons (https://retractionwatch.com... ; https://pubpeer.com/publica... "https://pubpeer.com/publications/227C0B09C78E146F96F7D679348BF7#)").<br /> May be possible to extimate the percentage of people of Gangelt that would be hospitalized and treated in ICU over the total citizen of Gangelt extimated to be infected with SARS-COV2, according to the parameters used in table 1 of ICR9 reports (which are taken from Verity et al., 2020, https://www.thelancet.com/p...? "https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30243-7.pdf)?")<br /> The parameters are “Under the China case definition, a severe case is defined as tachypnoea (>=30 breaths per min) or oxygen saturation 93% or higher at rest, or PaO2/FiO2 ratio less than 300 mm Hg.7 Assuming severe cases to require hospitalisation (as opposed to all of the patients who were hospitalised in China, some of whom will have been hospitalised to reduce onward transmission), we used the proportion of severe cases by age in these patients to estimate the proportion of cases and infections requiring hospitalisation.” (Verity et al., 2020)

On 2020-05-17 10:23:42, user yvesdeveyrac wrote:

I quote an extract of the Discussion section p.12 :"Given the high contagiousness of SARS-CoV-2, one would expect high rates of transmission. However, in our study we found a relatively moderate increase of the secondary infection risk which depended on the household cluster size". This observation confirms that children are not contagious at all : bigger household cluster size means more childrens in the household and as they do not transmit the infection, secondary infection rate decreases.

On 2020-06-29 19:23:20, user Thomas Ichim wrote:

What do you guys think of using QuadraMune? AT least it is natural

On 2020-06-30 08:08:24, user OxImmuno Literature Initiative wrote:

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

On 2020-06-30 15:59:24, user Dr. Hans-Joachim Kremer wrote:

Very good trial.<br /> It is interesting that the analysis by days since symptoms onset (<=7 vs. >7) appeared to be as discriminative as the main analysis or the subgroup analysis by respiratory support. Then, the onset of symptoms was strongly correlated with type of respiratory support. Hence, it would be interesting which of both (days since symptoms onset or respiratory support) was more discriminative, i.e. the independent predictor of efficacy of dexamethasone.

On 2021-01-10 08:48:26, user JS wrote:

This preprint was published in Nature in July,<br /> doi.org/10.1038/s41564-020-0761-6

On 2020-07-02 13:57:50, user Dr. Amy wrote:

It would be useful to see how obesity and A+ blood type change the HLH genetic expression. This paper has extremely useful clues toward targets to reduce severity.

On 2020-06-11 13:53:48, user peter tofts wrote:

please include: 1.) what type of corticosteroid was used (meythyleprednisolone) 2.) the dose (?1mg/kg or other v pulsed) duration etc... 3.) timing: the authors mention timing around 7 days from onset of symptoms- also Delay respect to Sx 13+/- 4.2 so I suppose maybe 6 days +/- 4 into their hospitalization? interesting paper thankyou

On 2020-07-03 19:26:50, user Jun Wan wrote:

Dr. Anthony Fauci warned this Tuesday (https://www.youtube.com/wat... "https://www.youtube.com/watch?v=m5l5UGS9ngc)") that a new strain of the coronavirus was found to be dominant around the world which was published the past Sunday by the Cell (https://www.cell.com/action... "https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2930820-5)"). The new strain G614 they referred is the exactly same as what this paper identified associated with the mutation A23403G (group A). In addition to the mutation on Spike (614), another mutation C14408T on ORF1ab (P4715 changed to L4715) was also reported by this paper which co-occurred with the mutation on Spike (614). Both can become the features of these strains. Indeed, the paper combined both together to name them as strain GL (G614+L4715) or DP (D614+P4715). Their results suggest "that the GL strain of SARS-CoV-2 might become much more stable and prevailing than DP identified from Wuhan-Hu-1 after 6-month evolution and transmission." Actually, when you read the paper carefully, you may find more novel interesting findings discussed in their work.

On 2020-07-07 20:00:16, user Ron Conte wrote:

The article above assumes that ivermectin works as an inhibitor, and therefore compares approved dose to IC50. But the results of clinical studies (Chowdhury et al. ResearchGate; Rajter et al. medRxiv) suggest that ivermectin works in some other way, i.e. not as an inhibitor that would depend upon concentration.

On 2020-07-10 14:48:32, user jeromee5000 wrote:

And possible effect on fresh fish production<br /> And transmission by foodborn.

On 2020-07-11 14:17:56, user DMelanogaster wrote:

I understand that this study was done just to explore safety, not efficacy, but doesn't the finding that mortality rates were not decreased in those infused with the antibodies in such a large sample indicate that the antibody treatment was not at all useful for severely ill patients?

On 2021-01-26 10:38:27, user ??u?????? ????????? wrote:

Hi,<br /> the UK, South African and the Brazilian virus mutations can alter the results/conclusions of the study?

On 2020-06-21 13:22:30, user Joe Rubi wrote:

Will 70%-80% alcohol solutions kill the SARS-CoV-2 mutant of Covid-19?

On 2020-07-14 16:13:09, user CruiseLaw wrote:

Why isn't there a reference to a prior unpunlished study (not peer reviewed either) in the same server three months ago which reached an opposite conclusion? https://www.medrxiv.org/con...

On 2020-05-01 23:43:12, user Sinai Immunol Review Project wrote:

Title A single-cell atlas of the peripheral immune response to severe COVID-19<br /> Wilk, A.J. et al. MedRxiv ; doi:10.1101/2020.04.17.20069930

Keywords<br /> scRNAseq; Interferon-Stimulating Genes (ISGs); Activated granulocytes

Main Findings<br /> The authors performed single-cell RNA-sequencing (scRNAseq) on peripheral blood from 6 healthy donors and 7 patients, including 4 ventilated and 3 non-ventilated patients. 5 of the patients received Remdesivir.

scRNAseq data reveal 30 gene clusters, distributed among granulocytes, lymphocytes (NK, B, T cells), myeloid cells (dendritic cells DCs, monocytes), platelets and red blood cells. Ventilated patients specifically display cells containing neutrophil granule proteins that appear closer to B cells than to neutrophils in dimensionality reduction analyses. The authors named these cells “Activated Granulocytes” and suggest them to be class-switched B cells that have lost the expression of CD27, CD38 and BCMA and acquired neutrophil-associated genes, based on RNA velocity studies.

SARS-CoV2 infection leads to decreased frequencies of myeloid cells, including plasmacytoid DCs and CD16+ monocytes. CD14+ monocyte frequencies are unchanged in the patients, though their transcriptome reveals an increased activated profile and a downregulation of HLAE, HLAF and class II HLA genes. NK cell transcriptomic signature suggests lower CD56bright and CD56dim NK cell frequencies in COVID-19 patients. NK cells from patients have increased immune checkpoint (Lag-3, Tim-3) and activation marker transcripts and decreased maturation and cytotoxicity transcripts (CD16, Ksp-37, granulysin). Granulysin transcripts are also decreased in CD8 T cells, yet immune checkpoint transcripts remain unchanged in both CD8 and CD4 T cells upon SARS-CoV2 infection. The frequencies of memory and naïve CD4 and CD8 T cell subsets seem unchanged upon disease, though gdT cell proportions are decreased. SARS-CoV2 infection also induces expansion of IgA and IgG plasmablasts that do not share Ig V genes.

Interferon-signaling genes (ISGs) are upregulated in the monocyte, the NK and the T cell compartment in a donor-dependent manner. ISG transcripts in the monocytes tend to increase with the age, while decreasing with the time to onset disease. No significant cytokine transcripts are expressed by the circulating monocytes and IFNG, TNF, CCL3, CCL4 transcript levels remain unchanged in NK and T cells upon infection.

Limitations<br /> The sample size of the patients is limited (n=7) and gender-biased, as all of them are men.<br /> The activating and resting signatures in monocytes should be further detailed. The authors did not detect IL1B transcripts in monocytes from the patients, though preliminary studies suggest increased frequencies of CD14+ IL1B+ monocytes in the blood of convalescent COVID-19 patients[1].<br /> Decreased NK cells, B cells, DCs, CD16+ monocytes and gdT cells observed in peripheral blood might not only reflect a direct SARS-CoV2-induced impairment, but also the migration of these cells to the infected lung, in line with preliminary data suggesting unchanged NK cell frequencies in the patient lungs[2].<br /> The authors identified platelets in their cluster analyses. Recent reports of pulmonary complications secondary to COVID-19 describe thrombus formation that is probably due, in part, to platelet activation[3, 4]. A targeted characterization of the platelet transcriptome may thus benefit an increased understanding of this phenomenon.<br /> The transcriptome of the Activated Granulocytes should be further detailed. As discussed by the authors, IL24 and EGF might be involved in the generation of the Activated Granulocytes, though these cytokines are poorly represented in the blood of the patients. The generation of these cells should therefore be further investigated in future studies.

Significance<br /> The authors show a SARS-CoV2-induced NK cell dysregulation, in accordance with previous studies[5]. Alongside the upregulation of ISGs in NK cells, these findings suggest an impaired capacity of the NK cells to respond to activating signals in COVID-19 patients. The unchanged expression of immune checkpoints on CD4 and CD8 T cells suggest distinct SARS-CoV2 dysregulation pathways in the NK and the T cell compartments. In particular, the downregulation of transcripts encoding for class II HLA but not for the HLA-A, -B, -C molecules in monocytes suggest an impaired antigen presentation capacity to CD4 T cells, which should be further investigated.<br /> The authors provide preliminary results suggesting an age-related activation of the monocytes in the COVID-19 patients. Future studies will be needed to evaluate if the age impacts the involvement of the monocytes in the cytokine storm observed in COVID-19 patients.

References<br /> 1. Wen, W., et al., Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing. MedRxiv, 2020.<br /> 2. Liao, M., et al., The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing. MedRxiv, 2020.<br /> 3. Giannis, D., I.A. Ziogas, and P. Gianni, Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol, 2020. 127: p. 104362.<br /> 4. Dolhnikoff, M., et al., Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost, 2020.<br /> 5. Zheng, M., et al., Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol, 2020.

Credit<br /> Reviewed by Bérengère Salomé 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 2020-05-04 18:15:10, user Dr SK Gupta wrote:

High Dose Chloroquine with Poor patient selection are the culprits- not the drug <br /> Investigators were over enthusiastic in using a higher dose of chloroquine in elderly patients. In China National Health and Care Commission officially included the Chloroquine as medical agent on 19 Feb 2020 to be used in corona virus treatment plan. The dose of 500mg of chloroquine twice a day was decided following in vitro studies EC50 values, PBPK modeling and mice RLTEC data projected on Human beings (1). <br /> The initial recommended dose of 500 mg of chloroquine phosphate salt twice per day can quickly approach danger thresholds with sustained use at the maximum course of 10 days (Total chloroquine base 6gm). The lethal dose of chloroquine base in adults is about 5g. In China, On Feb 26, 2020, the treatment guidelines were revised, shortening the maximum course to 7 days to keep the total dose of chloroquine base 4.2 gm much lower than toxic dose (2). <br /> Elderly population is particularly prone to chloroquine toxicity especially at high doses. It is unfortunate in present study, that a base line ECG was not done to measure the QTc interval because the drug should be avoided if the QTc was more than 500ms especially in patients with severe disease prone to develop myocarditis due to primary disease Covid-19 per se(3). On the contrary we find that the higher dose regimen included Older age population with mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years with more heart disease (5 of 28 [17.9%] vs 0) as compared to lower dose regimen. We in India having hige experience of using the drug would refrain from using such high doses.<br /> Gao et al reported results from more than 100 patients demonstrated that chloroquine phosphate is superior to the control treatment: in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus-negative conversion, shortening the disease course. Severe adverse reactions to chloroquine phosphate were not noted in the aforementioned patients (4). <br /> Poor patient selection and use of toxic doses of chloroquine seems to have brought disrepute to a promising drug. More studies are required before condemning the drug in present indication of Covid 19<br /> References:<br /> 1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30:269–71<br /> 2. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression Dan Zhou, Sheng-Ming Dai and Qiang Tong J Antimicrob Chemother doi:10.1093/jac/dkaa114

1. Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society<br /> Aditya Kapoor, Ulhas Pandurangi,Vanita Arora, Anoop Gupta, Aparna Jaswal et al. Indian Pacing and Electrophysiology Journal, https://doi.org/10.1016/j.i...

2. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Bioscience Trends 2020; 14:72–3

On 2020-04-17 23:52:12, user Daniel H Vlad, PhD wrote:

Dear Author, <br /> I appreciate your efforts to shed light on this very important topic but I believe the article has a major bias, which is indeed mentioned in the article.<br /> "Other biases, such as ... bias favoring those with prior COVID-like illnesses seeking antibody confirmation are also possible. The overall effect of such biases is hard to ascertain. "

I think this is a very serious bias and let me explain why. It's very likely that your Facebook ads attracted a fair number of participants that were concerned they may have been infected with Covid-19. People who had experienced Covid-like symptoms in the recent past were more likely to pay attention to your Facebook ad and were also more likely to enroll in your study. Therefore your sample is not random.<br /> Let's make some reasonable assumptions. Let's assume that 10% of your sample, or 333 participants had Covid-19 like symptoms in the past and were seeking antibody confirmation. I believe this percentage is very reasonable. <br /> According to California statistics, approximately 25% of people tested for Covid-19 test positive. It could be very reasonable to assume that 15% of these 333 participants seeking antibody confirmation had been indeed infected. So that will equal to 50 positive participants, or the entire number of antibody test positive participants in your sample.<br /> The example above proves that this bias is a valid concern. Your entire list of 50 antibody positive participants could have been participants seeking antibody confirmation.

There are several ways to remove the bias:<br /> a. You mention in the article that you asked survey participants if they had prior clinical symptoms. You should try to exclude all participants that had symptoms (fever, chest pressure) similar to Covid-19 this year. This will indeed exclude all people that were ill, not only those who replied to the add to seek antibody confirmation. However, it will give you insight into the percentage of silent Covid-19 carriers, which is a question as important as the question you are trying to answer, and in a way equivalent. And the results will be unbiased. <br /> b. Attempt to adjust for this bias. Calculate the percentage of participants in your sample who experienced Covid-19 symptoms and compare this with reasonable epidemiological data. Calculate a weight and apply it to your sample in addition to your zip-sex-race weights.

Regards, Daniel H. Vlad, PhD.

On 2020-04-18 17:13:58, user Animesh Ray wrote:

I do not believe these conclusions. A crucial control for the estimate of false positive detection by their method is grossly inadequate. This manuscript should not have seen the light of the day in this form, let alone be published even in a pre-print format because of the sensitivity of the topic.

Here is the reason: The common cold coronaviruses that could potentially cross-react to existing pre-COVID19 IgM/IgG are quite prevalent in the population. To address this, the authors tested 30 pre-COVID19 sera.

Given an unadjusted detection rate of 2.8% seropositives in post-COVID-19 samples, if all were false positives, they needed to test, for 99% confidence, a MINIMUM of log(0.01)/log(0.972) = 162 pre-COVID19 sera of similar demographics (age/sex/location).

Instead, they tested only 30!

[They do cite the kit validation data by the supplier/vendor as having tested 371 negative samples--this is as spurious an argument as stating that a q.RT-PCR kit produced x frequency of true negatives by the supplier and therefore we don't need to do the appropriate control in our experiment!! This statement has no place in a scientific publication other than trying to obfuscate the real weight of the lack of sufficient control to determine the false positive rates.]

On this basis I cannot attach any value to this report.

These false conclusions, given the current pre-print version, are dangerous because they could be naively interpreted to imply a lesser morbidity of COVID19 than the current numbers otherwise suggest.

I fear that this pre-print will now be used by the public media and sections of political interest groups to advocate for lesser stringency in COVID-19 pandemic control than desirable, and might lead to unfortunate loss of lives.

On 2020-04-21 15:33:02, user ?????Ozymandias????? wrote:

I'm just an undergrad with no expertise, but based on Bayesian logic, when the sensitivity of a test isn't perfect, and given the low prevalence of a trait in a population, won't the test tend to elicit enough false-positives to cloud the results?

On 2020-05-22 00:41:34, user Spaceman3 wrote:

Something critical that hasn't been asked to my knowledge is what percentage of counted Covid-19 deaths could be attributed to flu or other illnesses? Why is no one asking this question? It's as if the very sketchy data on fatalities is taken as gospel and there are no error bars.

On 2020-04-21 20:54:48, user Dr. Héctor Musacchio wrote:

I am confused about the interpretation of this study. Asymptomatic people who are tested, most likely are false positives. I would like to know the opinion of the authors

On 2020-05-05 18:21:51, user Valerie Natale wrote:

I looked at supplementary figure 1 and I'm not convinced that anyone should be jumping to use the N protein in a diagnostic assay.

It looks like the ELISA for the N protein had MORE false negatives than the ELISA for the S protein (10 vs. 8).

Also, the negatives in the N assay in both systems were all over the place, with at least 1 or 2 giving false positives. The legend doesn't explain what all those lines in the figures are, but the N protein ELISA is in no way as tidy as the N protein LIPS assay.

Why is there no ELISA for ORF8?

Finally, the sample size (15 patients and was very small. They should have done this work on 50+ patients and the same number of controls. Results using small sample sizes can look sooo good, until you pile more data in, and suddenly...it gets messy.

On 2019-10-10 12:11:25, user GuyguyKabundi Tshima wrote:

EPIDEMIOLOGICAL SITUATION

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT OCTOBER 06, 2019<br /> Monday, October 07, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,205, of which 3,091 are confirmed and 114 are probable. In total, there were 2,142 deaths (2028 confirmed and 114 probable) and 1006 people healed.<br /> 363 suspected cases under investigation;<br /> 1 new confirmed case at CTE in North Kivu at Oicha;<br /> No new confirmed deaths<br /> 2 people healed from Butembo CTE;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

7 people healed from Ebola Virus Disease released Monday at Komanda CTE<br /> - A total of 7 people cured of Ebola Virus Disease were released on Monday October 7th at the Ebola Treatment Center (ETC) in Komanda. ;<br /> - This is 4 people from Mambasa and 3 cases from Komanda Health Zone to whom discharge certificates were given by the director of this Ebola Treatment Center<br /> - This certificate of discharge bears as inscription: "On the date of issue of this document the bearer of this certificate does not present any risk of contaminating other people, because his test was negative for the Ebola virus disease. He / she is thus DECLARE GUERI (E) . His current state of health is not a danger to the community. That is why he / she can return to his household and his professional environment to continue the daily activities. The family, the community and the authorities are asked to welcome him to promote his social integration ".

VACCINATION

• Continuation of vaccination around the confirmed case of 04 October 2019 in the Tenambo Health Area in Oicha, North Kivu;
• Continuation of the vaccination of newly recruited front-line staff at the General Reference Hospitals of Katwa and Kyondo in North Kivu;
• Since vaccination began on 8 August 2018, 234,693 people have been vaccinated;
• The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature increase) at the sanitary control points is 103,167,809 ;
• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-10-17 18:36:39, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS OF OCTOBER 15, 2019

Wednesday, October 16, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,227, of which 3,113 are confirmed and 114 are probable. In total, there were 2,154 deaths (2040 confirmed and 114 probable) and 1038 people healed.<br /> 530 suspected cases under investigation;<br /> 3 new confirmed cases, including:<br /> No cases in North Kivu;<br /> 3 in Ituri in Mandima;<br /> 1 new confirmed death, of which:<br /> 1 community death in Ituri in Mandima;<br /> No confirmed deaths;<br /> 2 people healed from the CTE in Ituri in Mambasa;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

The state of play of the response at the center of an interview in Goma between the Technical Secretary of the CMRE and the United Nations Emergency Coordinator for Ebola<br /> - The Technical Secretary of the Multisectoral Committee on Epidemic Response to Ebola Virus Disease (ST / CMRE), Prof. Jean Jacques Muyembe Tamfum, granted a hearing on Wednesday, October 16, 2019 in Goma to the United Nations Emergency Coordinator for Ebola;<br /> - During their meeting, the two personalities discussed the state of play of the response to the 10th Ebola Virus Disease outbreak and the security situation in the areas affected by this epidemic;<br /> - It should be noted that the 10th Ebola epidemic has been taking place in the Democratic Republic of the Congo in areas of armed conflict, particularly in the provinces of North Kivu and Ituri, for more than a year;<br /> - Some time before this meeting, the technical secretary of the Multisectoral Committee for the Response to the Ebola Virus Disease Epidemic (ST / CMRE), Prof. Muyembe Tamfum, who is currently staying in Goma, North Kivu to inquire about the evolution of the response, chaired the morning meeting of the general coordination of the Ebola response to the epidemic.

Pygmies at Mahombo camp in Mambasa territory in Ituri pledge to fight Ebola Virus Disease

• The pygmies residing in Mahombo camp located more than 30 minutes walk from the main road from the village Nyangwe in the territory of Mambasa in ITURI, pledged Tuesday, October 15, 2019 to fight against Ebola by raising alerts with teams of the response;<br /> This commitment is the result of awareness raising by the Community Risk and Commitment (CREC) teams for 79 pygmies about the generalities of the Ebola virus disease, its methods of prevention and contamination;<br /> Pygmies have, for this purpose, asked for hand washing kits to break the chain of transmission of the Ebola virus in their respective communities.

VACCINATION

• Since vaccination began on 8 August 2018, 238,700 people have been vaccinated;
• The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

MONITORING AT ENTRY POINTS

• The Governor of North Kivu, Carly Nzanzu Kasivita accompanied by a strong delegation, visited Maboya Control Points (PoCs) in Kalunguta and Kangote in Butembo in North Kivu Province;
• The providers of the Mususa Point of Control (PoC) in Butembo, North Kivu, in collaboration with the Ndondo Primary School and the Kyambogho School Complex, participated in a mass sensitization session (travelers and riverside population) under the theme " All Eliminate Ebola Virus Disease "on International Handwashing Day;
• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 106.625.956 ;
• To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-11-17 04:20:48, user GuyguyKabundi Tshima wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT NOVEMBER 15, 2019<br /> Saturday, November 16, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,292, of which 3,174 are confirmed and 118 are probable. In total, there were 2,195 deaths (2077 confirmed and 118 probable) and 1070 people healed.<br /> • 517 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • No new deaths of confirmed cases have been recorded;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

Goma opens leadership capacity building workshop for Ebola epidemic response to Ebola Virus Disease.

• The coordinator of the epidemic response to Ebola Virus Disease in North and South Kivu Province and Ituri, Prof. Steve Ahuka Mundeke, opened this Saturday, November 16, 2019 in Goma North Kivu a workshop on building the capacity of actors involved in the response against Ebola;<br /> • For four days, participants, coordinating and sub-coordinating officers from the response, the Ministry of Health, the World Health Organization (WHO), national security, CDC and DFID will be equipped with management skills epidemics before, during and after the tenth epidemic of Ebola Virus Disease, especially in the event of any outbreak;<br /> • According to Prof. Ahuka, this workshop will not only benefit this epidemic, but will help, through acquired skills, to cope with other epidemics or other crises in a collective and individual way. " Each participant will be able to use these skills in his daily life ," he concluded;<br /> • This training for the response officers, from 16 to 20 November 2019, is organized by the Ministry of Health in collaboration with WHO with funding from UKaid from the British people.

VACCINATION

• 93 people were vaccinated with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two Health Zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 252,835 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine complements the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this outbreak, manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. It has recently been approved.

MONITORING AT ENTRY POINTS

• Since the beginning of the epidemic, the total number of travelers checked (temperature rise) at the sanitary control points is 117,333,420 ;<br /> • To date, a total of 112 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2019-11-30 16:39:58, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AT NOVEMBER 26, 2019<br /> Wednesday, November 27, 2019<br /> • Since the beginning of the epidemic, the cumulative number of cases is 3,304, of which 3,186 are confirmed and 118 are probable. In total, there were 2,199 deaths (2081 confirmed and 118 probable) and 1077 people cured.<br /> • 366 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • No new deaths among confirmed cases;<br /> • No cured person has emerged from CTEs;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths.

NEWS

Closure of training of Ebola Rapid Response Teams in Goma

• The Ebola response coordinator for the Ebola response to operations, Dr. Luigino Mikulu, closed on Wednesday 27 November 2019 the training of Rapid Response Teams (RRTs), composed of units of the Armed Forces. (FARDC) and the Congolese National Police (PNC), on the Ebola virus disease that took place in Goma, capital of North Kivu Province from 22 to 26 November 2019;<br /> • For Dr. Luigino, this team is the first in the Rapid Response Teams to be composed of elements from other sectors, such as those of the Ministries of Defense and Security and the Ministry of the Interior;<br /> • This training aligns with the vision of the Technical Secretariat of the Multisectoral Ebola Virus Disease Response Committee (ST / CMRE), through the overall coordination of the response, to expand its mixed and multidisciplinary teams available and able to intervene 24 hours a day, 7 days a week and everywhere, where they will be deployed, not only for the response to this epidemic to Ebola Virus Disease, but also for other epidemics;<br /> • This training was a pride for WHO to accompany the Ministry of Health in order to capitalize the capacity building of FARDC and PNC units in public health;<br /> • The participants, in turn, reassured the overall coordination of the response, the Ministry of Health and all those who contributed to the delivery of this training, particularly to WHO and all facilitators, to be faithful disciples in the field by putting into practice all the notions learned during these sessions;<br /> • At the end of this training, the thirty participants, including the facilitators, received a participation certificate.

VACCINATION

• Despite the tense situation of the city of Beni, a vaccination ring was opened around the confirmed case of 24 October 2019 in the Kanzulinzuli Health Area of the General Reference Hospital;<br /> • 724 people were vaccinated, until Tuesday, November 26, 2019, with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two health zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 255,247 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine is in addition to the first, the rVSV-ZEBOV, vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018. has recently been pre-qualified for registration.

MONITORING AT ENTRY POINTS

• Sanitary control activities are disrupted in the towns of Beni and Butembo in North Kivu province following demonstrations by the population which decries killings of civilians;<br /> • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 121,159,810 ;<br /> • To date, a total of 109 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2020-01-07 12:53:20, user Guyguy wrote:

EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI ON 05 JANUARY 2020

Monday, January 06, 2020

• Since the start of the epidemic, the cumulative number of cases has been 3,390, including 3,272 confirmed and 118 probable. In total, there were 2,233 deaths (2,115 confirmed and 118 probable) and 1,114 people healed;<br /> • 373 suspected cases under investigation;<br /> • 2 new confirmed cases in Ituri in Mambasa;<br /> • No new deaths among the confirmed cases, including:<br /> o No community deaths have been recorded;<br /> o No death among the confirmed cases;<br /> • No healed person has left the CTE;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 164 (approximately 5% of all confirmed / probable cases), including 41 deaths;<br /> • Mambasa again reported a confirmed case after 66 days of silence.

NEWS<br /> Organization of an evaluation session of awareness-raising activities in the Malepe health area in Beni<br /> • The sub-coordination of the response to the Ebola virus disease epidemic organized this Monday 06 December 2020 an evaluation session of awareness-raising activities in the Malepe health area in Beni;<br /> • According to the Coordinator of this Sub-coordination, Dr. Pierre-Céleste Adikey, this evaluation aims to intensify surveillance around visitors and raise alerts. These strategies, he said, will strengthen measures to protect the City against any possible reinfection of the City;<br /> • On this occasion, it was announced the resumption of free healthcare within the Malepe health center with the support of the NGO ALIMA which, from now on, provides drugs for the free care of the sick;<br /> • In addition, the Ebola Treatment Center (CTE) in Mangina unloaded the first eight Ebola winners in 2020 on Monday. These survivors, who were reintegrated into their respective communities, notably in Aloya / Canteen, testified to good care within this CTE.

VACCINATION<br /> • 4,802 people were vaccinated, until January 2, 2020, with the 2nd vaccine Ad26.ZEBOV / MVA-BN-Filo (Johnson & Johnson) in the two health areas from Karisimbi to Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 261,596 people have been vaccinated;<br /> • Approved on October 22, 2019 by the Ethics Committee of the School of Public Health at the University of Kinshasa and on October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson;<br /> • This new vaccine complements the first, rVSV-ZEBOV, a vaccine used until then (since August 08, 2018) in this epidemic manufactured by the pharmaceutical group Merck, after approval by the Ethics Committee on May 20, 2018. It was recently pre-qualified for certification.

ENTRY POINT SURVEILLANCE<br /> • Since the start of the epidemic, the total number of travelers checked (temperature measurement ) at health checkpoints has been 135,503,900 ;<br /> • To date, a total of 109 entry points (PoE) and health control points (PoC) have been established in the provinces of North Kivu and Ituri in order to protect the country's major cities and avoid the spread of the epidemic in neighboring countries.

As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE EBOLA VIRUS DISEASE RESPONSE are as follows:

1. Respect basic hygiene measures, in particular regular hand washing with water and soap or ash;
2. If an acquaintance from an epidemic area comes to visit you and that he is sick, do not touch him and call the toll-free number for civil protection in North Kivu;
3. If you are identified as a contact with an Ebola patient, agree to be vaccinated and followed for 21 days;
4. If someone dies due to Ebola, follow the guidelines for dignified and secure burials. It is simply a mode of burial that respects funeral customs and traditions while protecting the family and the community from Ebola contamination.
5. For all health professionals, observe hygiene measures in health centers and report any sick person showing symptoms of Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

On 2021-02-22 15:49:56, user Lenisse M. Reyes wrote:

This paper has been provisionally accepted in the journal PLOS ONE.

On 2020-04-18 21:04:02, user Katri Jalava wrote:

Manuscript does not include references for the methodology used. Furthermore, the mathematics behind the model is not being presented. More rigorous, referenced comments why you choose to use a model that is not widely used in infectious disease outbreak modelling would be useful, and preferable present the results in parallel with a standard SEIR model. You could also discuss IHME model.

For the parameters:<br /> • I am not sure how you calculated the deaths. If you used Wuhan data, all case fatality numbers need to be revised as China updated its numbers. This is also obvious from your figure 6. There are 61 deaths as per 18 April in HUS (and it does not include all 48 deaths outside hospitals), and ~ this number should be reached only around 1 May. There is something else wrong than just the Chinese number, I think. If I understand correctly from the text that you may have calculated the deaths from HUS data, it goes badly wrong, I am afraid. There is literature how to correct the ongoing outbreak death numbers to get accurate estimates, or use Chinese numbers. Calculating the mortality rates is one of the most challenging things. Even though new cases would stop today, number of deaths would increase for the next 3-4 weeks from the current case load. Simply dividing the number of deaths by total number of cases may only be used post-outbreak. <br /> • Individual characteristics should include underlying illness if possible, not only age. This is probably available from TTR, and there is surely some sort of enhanced surveillance done.<br /> • Would it be possible to estimate the success of movement restrictions based on overall mobile phone data?<br /> • Excretion is by disease severity/age, https://doi.org/10.1016/S14.... This is likely (one of) the reason(s) why the outbreaks are so explosive in the elderly people’s homes. But as the illness is often mild(er) during the first week (when cases infect onward), and it was also noted in the mentioned publication that there was not a difference between severe and mild cases in the initial/peak excretion (but # observations small), this may not need to be taken into account, but would need to be mentioned. Excretion (or lack of it) may need to be taken into account with children.<br /> • Cases should be ideally categorized to travel, community acquired and mass gathering participants as well as household contacts. These all have different time spent in the community before testing and isolation. Help line has probably an algorithm for the cases which could be used.<br /> • Massong 2008 is pretty outdated reference for a contact matrix, there are more recent ones. Note that especially school aged children from abroad may not be valid as there are no boarding schools in Finland.<br /> • Relative infectiousness period is quite short, it is up to a week, please refer to<br /> https://doi.org/10.1038/s41...<br /> • P(infection|virus contact), test more values, this is out of a hat(?) Needs a distribution (gamma) around it.<br /> • P(symptomatic|infection) 50 %, Ferguson’s figure includes mild cases, ie. it is not really asymptomatic, but “non-GP-seeking”.<br /> • P(death|severe, not hospitalized) 20 % seems too low. Please have a look on the elderly home data.<br /> • The assumption that test positive would lead to 0 % transmission is likely quite false. Most of the mild cases remain at their homes (they should ideally be isolated to a hcf, but this is unlikely happening). There are publications describing household cases where this may be estimated. This could and should be assessed ideally from HUS case data.

A positive thing is that your study clearly shows (what was also known from international data) that suppression works well, mitigation is of less use. This is also logically evident when there is not major community transmission ongoing.

On 2020-02-28 08:19:07, user iraq2010 wrote:

hi sir,<br /> Please share data for the purpose of developing the algorithm.I am a researcher in the field of deep learning especially in classification and CNN algorithms..<br /> Thanks for help the world

falahgs07@gmail.com

On 2021-10-17 14:04:46, user BouncingKitten wrote:

The article mentions "All data is available in the supplementary file" but doesn't provide a link to the file.

Could you update the paper with a link to the supplementary file please?

On 2020-03-08 10:12:04, user Mikko Salervo wrote:

Hi,

I might have missed it, but I could not find any details of the sensitivity analysis considering the february 1st outlier. It looks like the outlier has a considerable effect on the estimated trend between jan. 23- feb. 01, which might lead to an overestimation of the effectiveness of the centralized quarantine measured in comparison to the less rigorous measures during jan. 23-feb. 01.

On 2020-03-13 16:56:55, user Brian Reed wrote:

This is an important contribution to the literature. I have a few questions, the answer to which might make it even more valuable and better able to evaluate the rates of transmission as an effect of age. I take these mostly from carefully table 3 and table 1, but also from the 'transmission characteristics' subsection of the results section.

Of the 1298 close contacts, it appears only 1155 actually had tests come back.

There is evidently substantial overlap between the household (HH) contacts and the meal contacts, which makes sense. Certainly the travel contacts in general are coming back much lower. The question is, where do the age groups stratify within these. I would imagine by far the close contacts with 0-9 and 10-19 are much more likely in the HH, as well as the "often" category" of contact frequency, as there is a much less likelihood of having co-travel and co-non household meals with kids for the substantial majority of your initial cases (except for maybe the 4 who were kids). I suspect this may skew the conclusion that the rates of transmission for these two younger age groups are similar to older groups. I suspect likewise that the substantial portion of the travel negatives are with older age groups. I think performing the age analysis, or at least presenting the data, for each age group for the HH, travel, meal, and contact frequency subgroups would be helpful. I am aware that the n for some of these subgroups might be too low to allow for a real analysis, but then that is part of my point...<br /> Also, there is a substantial gender difference in those infect among close contacts, with females having a far greater % infection rate (almost double!). Similarly to the age effects, stratifying this gender ratio by age as well as close contact type would be of benefit.

I hope you find my comments constructive and can address them. I still think children may be somewhat more resistant, although less so than before i read this preprint, and would like to know if I should adjust my view further still.

Thanks!

On 2021-07-22 18:07:27, user Ken Jacobie wrote:

What was the average age and INNATE IMMUNE SYSTEM STATUS of these 167 person in this study? How many were CHEMOTHERAPY recipients etc...

On 2020-05-14 15:31:20, user Emanuel Papadakis wrote:

At the statistical level there are two major flaws: What are you using the chi-sq test for? You test a hypothesis. State the hypothesis. Your data for families B and C show rather random infections. Given the 14 day window of symptoms and the date of the start of the lock down the members of the B and C families may have been infected randomly outside of the restaurant. Also, why are the stories of all of these people accurate? You do have something to say but since you do not state the two hypothesis for which you test. Also your table at the end violates the assumptions for the test. The main assumption is independence and these people belong to families so the number of patients in total, namely 5 does not constitute 5 independent cases. Honestly, you try to establish causality and this is difficult because you have families. But your work despite these setbacks is interesting at the exploratory level. But you have no statistical significance as you treat your data because tests can be applied under certain conditions.

On 2020-05-18 18:01:55, user 18wheel wrote:

I believe you're onto something here: nothing to do with infection but the response. The targeting (elderly, populations with low vitamin D uptake for various reasons) will be borne out over the seasonal change (a comparison between north of 35 and south of 35 cities in August/September cross-referenced with local fortification and diet would be most interesting)

On 2020-05-09 21:37:30, user Brandy Wootten McManus wrote:

Is the math right?

On 2021-11-04 03:14:20, user Hiromichi Suzuki wrote:

We thank you for your comments, The reagent was currently approved in October, 2020. We changed the year of approval from 2021 to 2020, which is the mistake of description.

On 2020-03-28 00:45:53, user Adam Sobel wrote:

Would also like to see expanded cohort to include a range of disease severities. Most reproductive-aged men would currently be expected to experience mild symptoms; if there is a correlation, is it linear wrt severity?

On 2020-03-28 22:38:39, user Sinai Immunol Review Project wrote:

Summary of Findings: <br /> - Prospective cohort of 67 patients, clinical specimens taken and follow-up conducted. <br /> - Viral shedding, serum IgM, IgG antibody against NP evaluated and correlated to disease severity and clinical outcome <br /> - Viral RNA levels peaked at 1 week from febrile/cough symptom onset in sputum, nasal swabs, and stool samples. Shedding ranged from 12-19 days (median ranges) and was longer in severe patients. <br /> - IgM and IgG titers stratified patients into three archetypes as ‘strong vs weak vs non-responders’. Strong responders (with higher IgM/IgG titers) were significantly higher in severe patients.

Limitations (specific for immune monitoring <br /> - Patient cohort is small for such a study and no individuals who were asymptotic were included; thus we cannot clearly interpret antibody titer associations with disease severity without "immunity" response.<br /> - Not clear if stool RNA captured from live infection in intestine/liver or from swallowed sputum. Transmission electron microscopy (TEM) carried out on sputum samples as proof of concept, but not stools. TEM unreasonable for actual clinical diagnosis. <br /> - Several patients had co-morbidities (such as pulmonary and liver disease) that were not accounted for when tracking antibody responses. Viral kinetics and IgM/IgG titers in subsets of patients with underlying conditions/undergoing certain medication would be informative.

Relevance (specific for immune monitoring) <br /> - Three archetypes of antibody response to SARS-CoV-2 with different disease progression and kinetics is useful to stratify patients, and for future serological tests.

• Strong spike-IgG levels often correlate with lymphopenia and CoVID-19 disease severity (https://doi.org/10.1101/202... ), similar to macaque studies in SARS (1). It would be critical to see if anti-NP or anti-Spike IgG antibodies for SARS-CoV-2 also elicit similar detrimental effects before clinical use.

References: <br /> 1. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H, et al. JCI Insight 2019; 4(4): pii: 123158. <br /> Doi: 10.1172/jci.insight.123158

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

On 2020-05-20 14:45:40, user OxImmuno Literature Initiative wrote:

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

On 2020-05-26 06:06:22, user Stanley wrote:

Modeling is far from accurate. Modeling predicted 2.2 million deaths in this country.

On 2020-05-21 18:45:30, user Political Hack wrote:

One article referencing this paper states: "The U.S. could have prevented roughly 36,000 deaths from COVID-19 if broad social distancing measures had been put in place just one week earlier in March." So what assumptions did the authors use as far as distancing? Did it use our "current" approach or the "early" approach. Basically, did it include use of masks? That is only a recent change to protocol when we go out in public as the early "science" said wearing masks provided no protection. People were still frequenting essential businesses (grocery stores/Home Depot) at the start of the lockdowns and masks we<br /> re a very rare sight. Based upon what we know now regarding transmission mechanisms, there is little doubt that there was rampant spread during lockdowns thanks to the lack of masks. The number of cases kept going up rapidly for MANY WEEKS during the lockdown, surely for this reason. I certainly hope the peer reviewers have the insight to consider that.

On 2020-05-27 02:04:13, user Chintu Shah wrote:

Interesting. I can see the oral and nasal forms becoming part of the sterile procedure process for many surgical procedures.

On 2020-05-27 21:22:55, user Sinai Immunol Review Project wrote:

title<br /> SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors. <br /> Grzelak et al. medRxiv [@doi.org/10.1101/2020.04.21.20068858]<br /> Main Findings<br /> The prevalence of the SARS-CoV2-specific antibody responses in large symptomatic and asymptomatic populations has been of great interest to understand the incidence of and immunity against SARS-CoV-2 infection. To analyze the virus-specific antibody response, Grzelak et al. designed several assays: anti-nucleocapsid (N) and anti-trimerized spike (S) ELISAs, S-Flow cellular assay, LIPS (luciferase immunoprecipitation assay) and pseudovirus neutralization. They profiled several different populations that included 491 pre-endemic individuals, 51 hospitalized CIVID-19 patients, 209 pauci-symptomatic individuals reporting mild signs compatible with COVID-19, and 200 sera from blood donors.<br /> The full-length N protein or the extracellular domain of S in a trimerized form, which existed naturally on the viral surface, were used as ELISA antigens. In addition, to allow the detection of antibodies binding to various conformations and domains of viral glycoprotein by flowcytometry, S protein was expressed on the surface of 293T cells (S-Flow). Luciferase immunoprecipitation assay (LIPS) was also established with a panel of 10 different S and N-derived antigens, and N and S1 proteins were selected as the antigens for the further analysis based on their sensitivity. <br /> With the four assays, signals were consistently negative or low in the pre-epidemic samples, suggesting that a pre-exposure to human seasonal coronaviruses did not induce obvious cross-reactive antibodies to S and N protein from SARS-CoV-2. The analysis of 161 samples that combined different time point samples from 51 hospitalized patients, detected positives that ranged between 65 to 72 %. On the other hand, positivity rates in pauci-symptomatic individuals varied from 27 to 36 % between assays, suggesting that pauci-symptomatic individuals either had lower viral loads or the reported symptoms were not caused by SARS-Co-V2. Correlation analysis revealed that sera with high antibody levels were well detected by all the assays, and that the highest correlation were observed between ELISA tri-S and S-Flow.<br /> Lastly, the presence of neutralizing antibodies (Nabs) was evaluated by microneutralization (MNT) and pseudovirus neutralization assay using the sera from 9 hospitalized patients and 12 pauci-symptomatic individuals. A neutralization activity >80% was associated with ELISA N (>2.37; OD405 values), ELISA tri-S (>2.9; AUC values determined by plotting the log10 of dilution factor required to obtain OD405), S-Flow (>60%; anti-Spike IgG+ cells) and LIPS-N (>0.049; Signal-to-Noise ratio).<br /> Limitations<br /> As described in the text, the pauci-symptomatic population appears to be a mix of the individuals with SARS-CoV-2 infection and individuals with other conditions that had COVID-19-like symptoms (fever, cough or dyspnea). <br /> It will be informative to investigate the relationship between the presence of anti-viral antibodies and neutralization activity, and severity of COVID-19.<br /> Significance<br /> While some of the assays described here cannot be routinely performed in clinical settings, their higher specificity and sensitivity to detect antibodies and their neutralizing activity is important to understand the protection mechanism against SARS-CoV-2. <br /> Credit<br /> Reviewed by Miyo Ota as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.

On 2020-05-30 11:44:57, user Dude Dujmovic wrote:

29,500 reported yesterday May 29, out of your 95% CI. LOL

On 2020-06-04 17:10:24, user Mandy Lyons wrote:

"only 37.4% of suspected SARS-CoV-2 patients seroconverted"<br /> 1) What are the criteria for suspected SARS-CoV-2 patients?

2) Do these suspected cases have SARS-CoV-2, or do they have an infection which mimics SARS-CoV-2?<br /> 3) Is the test testing for the test? I.e. is there something functionally different in the infection causing presumed cases which, if it actually is SARS-CoV-2, would cause the antibody test to be inaccurate?<br /> 4) Is there another illness circulating which mimics SARS-CoV-2 which has heretofore not been identified?<br /> 5) Is there any follow-up or investigation on these negative antibody cases in both the confirmed and suspected cases?

On 2020-05-11 08:25:11, user M.E.Valentijn wrote:

The assumption that a neutralizing antibody IgG titer of 160 is sufficient to produce immunity may be overly optimistic, as it's based on a case study of one recovered patient who had mild symptoms - and her titer was much higher on Day 20 after symptom onset, reaching 1,280.

On 2020-06-07 05:04:06, user Marm Kilpatrick wrote:

This is a very interesting study. There are several important details that aren't clear from the methods and data presented that would help in understanding the patterns:<br /> 1) When were household individuals tested for viral RNA? After the first person in the household became asymptomatic? If children are less likely to be symptomatic, they could be the primary case but not tested until after they infect their household member and that person develops symptoms which could be quite a long time after the child was infected (at the least, an average of 5.5 days after being infected). Given that sensitivity by swab decreases quickly with days since symptom onset, this by itself could lead to an underestimate of infection in children.<br /> 2) Are there data on viral loads? This would help greatly in supporting or refuting the potential infectiousness of children.<br /> Thank you,<br /> marm

On 2020-06-07 17:05:34, user Dr Shyamapada Mandal wrote:

Dear authors,<br /> Nice presentation; but before lockdown I, India adopted some containment measures that are required to be reflected in your work. Plus the current situation is different. <br /> Thanks,<br /> Dr. Shyamapada Mandal, University of Gour Banga, Malda-732103, West Bengal.

On 2020-06-08 18:27:55, user Alpesh Pansheriya wrote:

Herd Immunity is meaningless in India.

http://alpeshbol.blogspot.c...

On 2020-05-07 03:37:58, user sekkai wrote:

The authors fail to declare potential COI.

As shown in the website of the facilities conducting this research, the authors recruited patients for commercial purpose, and each of the patients paid approx. 50 US dollars for antibody testing.

Also, Mr Eiji Kusumi, one of the authors and directors of the facilities responsible for this study, often advocates for the usefulness of antibody testing on television, and could benefit financially from the disclosure of this study.

These two points above were not mentioned in this study, which casts ethical doubts.

On 2020-05-07 04:29:09, user Paul Bollyky wrote:

Interesting paper but it's not clear to me what link there is to hyaluronan in these data. Hyaline membranes are made up of dead cells, surfactant, and proteins - not HA. HA staining and other specific tests would be need to be done to support the argument that HA is present and responsible for the disease manifestations of COVID-19.

On 2020-05-07 21:12:07, user helgarhein wrote:

Would you please link the outcomes of covid illness (mild, severe, death) to 25(OH)D? I imagine lowest vitamin D levels linked to worst outcomes, like in other studies. Thanks

On 2020-05-08 13:26:30, user Jamie Rosenblum Lichtenstein wrote:

Thanks for the contribution. In your abstract, you state " 5875-9738 more deaths in New York State (168-213% more) (95% CI (14502, 18365) vs. 8627 COVID-19 deaths)." "(168%-213% more) should either be "(168%-213% of expected)" or "(68-113% more)". I would argue that the former is clearer.

On 2020-05-08 19:29:54, user vinu arumugham wrote:

Here's why famotidine works.

Immunological mechanisms explaining the role of IgE, mast cells, histamine, elevating ferritin, IL-6, D-dimer, VEGF levels in COVID-19 and dengue, potential treatments such as mast cell stabilizers, antihistamines, Vitamin C, hydroxychloroquine, ivermectin and azithromycin

https://doi.org/10.5281/zen...

My comment posted in the Annals of Internal Medicine:<br /> Please see comments section:<br /> https://annals.org/aim/full...

On 2020-05-08 22:29:12, user Jessica wrote:

This reports a high proportion of isolated BA families with putatively causal large effect alleles. This proportion is higher than expected for families with isolated BA but not necessarily higher than expected for families with syndromic BA. It would be helpful for the authors to provide further detail about the specific ascertainment criteria and phenotyping performed on each proband and their parents, as well as whether any families were multiplex, especially for those with biallelic candidate variants, and if that family history is consistent with the mode of inheritance reported for each family's candidate gene.

On 2020-05-10 20:24:21, user Petard Stamo wrote:

The article is still not peer reviewed. Ironically it has been used to guide clinical practice.

On 2020-05-11 14:50:43, user Quant wrote:

I published an article Apr 26th with a similar theme that may interest readers. I described this as a Jensen's Inequality effect. It can apply to any source of heterogeneity including population density. Its good to see progress like this paper towards a more nuanced understanding of the turning point of an epidemic. <br /> https://www.linkedin.com/pu...

On 2020-05-11 18:13:35, user Dianelos Georgoudis wrote:

The IFR is very sensitive to the age distribution of a country, so the same model can produce an IFR varying from 0.3% for Pakistan to 1.4% for Italy (and 0.6% for the world). So I don't understand what the 0.75% value in this paper even means.

On 2020-05-12 15:25:42, user Francois Alexandre wrote:

I believe that there is another major limitation for this work, that should be at least acknowledge by the authors in the study limitation section: the R0 of 3.1 they used in the study is the R0 calculated at the beginning of the lockdown in France. Yet, the R0 during the middle of March, in the ascending phase of the outbreak, could be very different at that time. The authors state that this R0 is consistent with those observe in China during the ascending phase of the outbreak during January. However, R0 of a given virus is usually not stable across region and time (depending on several factors not restricted to temperature, such as humidity, weather, natural immunity due to vitamin D...). For example, the other human coronavirus have a R0 below 1 during summer in France, but the R0 increases during winter. And they also have different dynamics with some peaking in november, while some peaking in February. Furthermore, in early March, some observations in other countries (Brazil, West Africa) have underlined lower transmission rates compared with that observed in the countries located in the latitude 25-55° (Europe, USA). Therefore, serious doubts exist that the R0 of March will still be the same at May in France after the lockdown, without taking into account the potential unknown natural dynamic of the outbreak that has been masked by the lockdown and other procedures to slow the outbreak.

On 2020-05-12 17:11:33, user Sui Huang wrote:

Hi Anne (et al) - nice, heroic work! 2 quick questions as this work inspires similar approaches for scaling up community testing...:<br /> (1) Have you examined longer transports, more than the 5hrs @RT, and on ice, or even frozen for a longer time?<br /> (2) Have you tried to skip the RNA isolation step and do qPCR directly in the saliva as others have done?<br /> Thank you

On 2020-04-19 08:34:23, user V Ferreira wrote:

Good morning are there any studies concerning interaction with water?

On 2020-05-13 14:39:31, user Sinai Immunol Review Project wrote:

Main Findings <br /> - Study evaluated PBMCs of 63 italian patients with COVID-19 early after diagnosis (~5 days post-symptom start) using flow cytometry, and determined any association of inflammatory biomarkers with 28-days mortality.<br /> - Observed reduction in circulating lymphocytes (CTL, NK and NKT) and phenotypic changes in CD4+ T cells towards Th2 polarization, compared to reference intervals. Serum IL-6 levels not associated with monocyte counts, but correlated with Th2-polarized CD4+ T cell prevalence. <br /> - Detected enrichment of high-scatter atypical monocytes (in 11/14 subgrouped patients) with low CD14 and low HLA-DR MFI, but classical/non-classical monocytes abundance within normal reference range. <br /> - Lymphopenia, but also activation of T lymphocytes (defined as CD38+HLA-DR+ CTLs) reported to correlate with death within 28 days (more severe progression).

Limitations <br /> - All the analysis is using peripheral blood, which provides superficial global immune context but might not necessarily inform local inflammation in the alveoli or other organs. Concordant studies in BAL or rapid-autopsy tissue would be helpful <br /> - Activation of lymphocytes defined by CD38 and HLA-DR would need to be assayed functionally, potentially using IFN-g or Gzm-B ELISpot. <br /> - There is no breakdown of inflammatory markers across 28-day patient survival stratification in Table 3. Additionally, there is no correlation analysis shown for IL-6 levels (or other biomarkers) with the density of atypical monocytes. Such a multi-variate correlation study could tease out inflammatory biomarkers useful for prioritizing care on the hospital frontline.

Significance <br /> - Provides on-the-ground clinical report of early COVID-19 immunological characteristics from Milanese patients (despite being single-center small cohort of patients). <br /> - Results are in line with confirmed lympho-dysfunction observed in COVID-19 patients by multiple groups, and also support observations of atypical HLA-DR-low monocytes in severe disease (Giamarellos-Bourboulis et al. 2020). <br /> - Lymphocytopenia linked strongly to 28-day mortality stratification, in addition to <br /> standard clinical variates such as age, P/F ratio, LDH and CRP/Ferritin <br /> levels. Whether lymphocytopenia and associated innate-immune dysfunction<br /> is causal to adverse outcome is unclear, and will hopefully be revealed by prospective longitudinal clinical studies and potentially animal models.

Reviewed by Samarth Hegde as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn School of Medicine, Mount Sinai.

On 2020-05-15 12:51:43, user Melimelo wrote:

Thanks for this interesting analysis and plausible explanation! Another plausible explanation is that countries with endemic malaria have a better public health system than wealthier countries. I have been impressed with the excellent work done in the region of Maradi, Niger to rapidly investigate and isolate cases, test, and do contact tracing, despite extremely limited means. They’re very strained and could use support but they’re doing an amazing job, better than we are in the U.S.

On 2020-05-15 13:19:16, user thxzetec wrote:

This is an interesting study, but not across the finish line. We need a double-blind, randomized study. Right now remdevir (sp?) has taken the lead, this is partly due to profit. I'm not saying it is a conspiracy, but you have a basically generic drug against a patented $$ drug . . . there is reason to study the latter more if you are the maker.

BTW it does not do anyone any good calling Fauci a "liar". The whole problem with our covid19 response is that it has become too politized.

On 2020-05-18 16:23:32, user Daniel Connelly wrote:

From the beginning, it was known that Zinc is the active portion of the HCQ & Zinc combination. The HCQ was necessary to increase intracellular Zinc to block viral replication. The organizers of this study are both brave and brilliant.....but they also were not fully truthful. They called it a retrospective study when it is really a prospective study. The experimental arm was with Zinc and the control was without Zinc. The cohorts for the 2 arms were well matched and the regimen standardized. HCQ was not officially part of the study as it was dosed the same in both cohorts. <br /> Why would they need to organize the study this way? IMO, because they would have been blocked from doing a prospective study around HCQ. That is to dirty politics that good physicians are fighting against to save lives.<br /> What does this "prospective" study of "Zinc" show????<br /> 1. All other studies which did not use Zinc along with HCQ are at best, irrelevant and at worst, fraudulent.<br /> 2. HCQ with or without Zinc is useless in severely ill ICU patients.....as expected.<br /> 3. Zinc with HCQ was effective early to increase recovery and prevent death....as expected.<br /> 4. The study strongly supports the proposed mechanism of action of HCQ as a zinc ionophore.

What we don't know:<br /> 1. How effective is HCQ + Zinc + Azithromycin when given in the ambulatory setting with the onset of symptoms?<br /> 2. How many hospitalizations would be avoided? Deaths?<br /> 3. How much is the transmission R0 value reduced for patients on this drug combo, especially in closed environments like nursing homes? How much is the environmental viral load decreased?

On 2020-05-15 17:25:31, user Kom Mentar wrote:

I would be curious to learn more about your results of your assay validation. The Methods part describes how you were proceeding, but it would be great to see the resulting numbers for test sensitivity and selectivity. Any distributor-independent evidence for the key performance parameters of the EurImmune test would be highly welcome!

On 2020-05-16 16:43:20, user Itsme Forsure wrote:

A study of 65,000 italians who took HCQ for lupus or RA revealed that 20 people had the antibodies for covid19 and NONE have severe symptoms of covid19. Someone told me the same was found in 1.5million americans, but I can't find the study.

On 2020-05-16 20:44:07, user Javier Mancilla-Galindo wrote:

I would advise reviewing this OR and CI for hospitalization in patients >=74 years: "individuals aged 50-74 and >=74 years were more likely to be hospitalized than people from 25-49 years (OR 2.05, p<0.001, 95% C.I. 1.81-2.32, and OR 23.84, p<0.001, 95% C.I. 2.90-5.15, respectively)". This apparent error is present in both the abstract and the manuscript.

The finding that only 67% of hospitalized patients developed pneumonia is quite remarkable, since this is a similar rate to pneumonia findings on CT scans for ASYMPTOMATIC/PRE-SYMPTOMATIC patients (67.3-70.8 %). The rate for patients with mild COVID-19 was 95.5% in one study. Therefore, the authors could adress how this rate compares to other more recent studies and what the possible causes of these differences could be (i.e. few CT scans performed, commonly used definitions of pneumonia). Otherwise, this could lead to false conclusions such as thinking that patients are being admitted with milder disease or even with few or no symptoms at all.

On 2020-05-17 18:31:03, user vinu arumugham wrote:

Severe COVID-19 (and dengue) are cases of "slow rolling anaphylaxis" as detailed here:

Immunological mechanisms explaining the role of IgE, mast cells, histamine, elevating ferritin, IL-6, D-dimer, VEGF levels in COVID-19 and dengue, potential treatments such as mast cell stabilizers, antihistamines, Vitamin C, hydroxychloroquine, ivermectin and azithromycin<br /> https://doi.org/10.5281/zen...

So you are basically observing elevated troponin due to Kounis syndrome.<br /> Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction?<br /> www.ncbi.nlm.nih.gov/pmc/ar...

Same as in dengue:<br /> Abstract 19104: Troponin Elevation is Strongly Associated With Death in Dengue Patients With Cardiac Involvement<br /> https://www.ahajournals.org...

As expected, histamine H2 blockers (like famotidine) help.<br /> Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Cohort Study<br /> www.medrxiv.org/content/10....

You can also try mast cell stabilizers, histamine H1 blockers such as cetirizine and other anaphylaxis treatments.

On 2020-05-18 04:13:11, user Alex Backer wrote:

A similar result to this was previously reported in https://papers.ssrn.com/sol...

On 2020-05-18 14:12:18, user OxImmuno Literature Initiative wrote:

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

On 2020-05-18 14:28:17, user OxImmuno Literature Initiative wrote:

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

On 2020-05-18 21:44:48, user Paulo J. S. Silva wrote:

We have now a github repository:

https://github.com/pjssilva...

On 2020-05-19 13:34:54, user Tom Johnstone wrote:

The very certain quote "Seven of the 12 inferred IFRs are in the range 0.07 to 0.20 (corrected IFR of 0.06 to 0.16) which are similar to IFR values of seasonal influenza" cites no reference to back up the range for seasonal influenza. Where is the good data on the IFR (note, not CFR) for seasonal influenza that high? For it to be a legitimate comparison it would need to be a comparable measure, namely taken from a random sample of the population unbiased by presence of symptoms.

On 2020-05-23 08:40:57, user Jon Arnold wrote:

Very interesting discussion, but isn't the more important question what is the IFR rate for different age groups, and those with different underlying medical conditions? For a 80 year old male with high blood pressure the IFR is clearly rather high compared to a 20 year old with no underlying conditions where the IFR is absolutely tiny. Surely this is the essential question with this outbreak? It informs who should be protected or should protect themselves and who doesn't need to and who can therefore carry on living a normal life, go to work and help prevent the collapse of the economy which in turn will cause potentially yet more early deaths directly and, due to lower future health budgets, indirectly.

On 2020-05-23 23:07:44, user Hilda Bastian wrote:

I think it's critical that the author's co-authorship of one of its included studies be added to the disclosures, including noting that when some of them being controversial is mentioned. I have written other comments after initial review in this post: http://hildabastian.net/ind...

On 2020-05-19 19:13:19, user Plonit Almonit wrote:

The study assumes that behaviour changes coincided with official pronouncements. Except for school closures, that is not necessarily the case. For example, Sweden shows restrictions of movements and private contacts comparable to countries in lockdown. A direct behavioural measurement should be included in the study before publication. Speaking from my own private experience, the public discussion cumulating in Merkel's speech on the 12th of March, especially the news from Italy and France, caused behavioural changes (like avoidance of public transport, cancelling of parties) before they were officially mandated. Masks began to appear in public around that time and were sold out in the pharmacies, even though they were officially discouraged. Hoarding also began around that time, also a sign of behavioural change.

On 2020-05-20 02:15:46, user ed whitney wrote:

I am unable to read any of the figures at the end of the pdf. Nothing past page 13 is legible. This is a problem for anyone trying to examine the forest plots. Anyone else having better luck?

On 2021-01-22 03:19:14, user Roberto wrote:

Ok but, whats is this? More than 200 scientifics and academic articles saying HDC is effective for COVID-19? https://c19study.com

On 2020-05-21 16:19:59, user Lynn Wilson wrote:

Are virus titers being done for other illness such as rubella or measles?

On 2020-05-22 15:28:22, user K N wrote:

Can anyone comment on this sentence: <br /> "The age dependent IFR range from below 0.04% for ages below<br /> 50 years to 2.53%, 7.12%, and17.5% for ages 70-79, 80-89, and above 90 years,<br /> respectively, (Table2)." Is there a reason why ages 50-69 seem to be excluded?

On 2020-04-04 11:58:15, user Mick James wrote:

Doesn't this mean that everyone has to provide 6x as much sample material? Is collecting that amount an issue?

On 2020-04-04 14:12:44, user Ming Ming wrote:

This paper accepted by Lancet EClinicalMedicine

https://www.thelancet.com/j...

On 2020-04-04 23:54:42, user Sinai Immunol Review Project wrote:

Keywords: chronic obstructive pulmonary disease, COPD, smokingE-2, risk factors

Summary: In bronchial epithelial samples from 3 different cohorts of individuals, ACE-2 gene expression was found to be significantly increased in both COPD patients and smokers relative to healthy controls. Across all test subjects, ACE-2 gene expression was also highly correlated with decreased forced expiratory volume in 1 second (FEV1), which may explain the increased COVID-19 disease severity in COPD patients. Former smokers were also found to show decreased ACE2 expression relative to current smokers and had no significant difference when compared to non-smokers.

Limitations: While the upregulation of ACE-2 is an interesting hypothesis for COVID-19 disease severity in COPD patients, this study leaves many more unanswered questions than it addresses. Further studies are required to show whether the specific cell type isolated in these studies is relevant to the pathophysiology of COVID-19. Furthermore, there is no attempt to show whether that increased ACE-2 expression contributes to greater disease severity. Does the increased ACE-2 expression lead to greater infectivity with SARS-CoV-2? There is no mechanistic explanation for why ACE-2 levels are increased in COPD patients. The authors could also have considered the impact of co-morbidities and interventions such as corticosteroids or bronchodilators on ACE-2 expression. Finally, given the extensive sequencing performed, the authors could have conducted significantly more in-depth analyses into gene signature differences.

Importance and implications: This study attempts to address an important clinical finding that both smokers and COPD patients show increased mortality from COVID-19. The novel finding that ACE-2 expression is induced in smokers and COPD patients suggests not only a mechanism for the clinical observation, but also highlights the potential benefit of smoking cessation in reducing the risk of severe COVID-19 disease.

On 2020-04-05 13:34:51, user Jon Watters wrote:

Impressive graphing. But the projections compared by date to what has actually happened in my state, the projections are laughably high.

On 2020-04-06 04:06:46, user Art Mills wrote:

The projections were updated and the numbers appear to be significantly better. But, why are we still projecting 17K in ICU beds as we speak when we know we only have around 3.5K in ICU beds from this nationwide at present? Shouldn't we match what we KNOW?

On 2020-04-08 23:59:15, user Christi Raunig wrote:

Why is this model projecting a much less dramatic climb in daily deaths than has happened in other countries that are ahead of us such as Spain and Italy? I don't see any justification for believing that we will be so much better off. In fact, Italy's lock down has been much more restrictive than ours. Both Italy and Spain have had much longer lasting climbs in daily deaths than what is projected in this model for the US. I can't think of any reason we should expect to be able to blunt our peaks in the graphs compared to theirs. If you look at the graphs of the daily death count in both of those countries and were to project our country to have a similar experience, then we won't see a peak for another 10 days, and it will be closer to 5,000 deaths per day based upon our population.

On 2020-04-01 16:28:50, user Erik Likness wrote:

Also, looking for the modeling methodology... Thank you.

On 2020-04-10 22:18:29, user stephenkirby wrote:

We're seeing a lot of curves on Coronavirus right now, but I'm just wondering, are there similar stats of influenza this year that would be helpful for people's perspectives?

On 2020-04-05 22:00:09, user Kirsten McEwen wrote:

As the authors state, IL-6 could be a biomarker or a central pathogenetic element - in other words, cause vs correlation hasn't yet been determined.

On 2020-04-06 12:54:12, user xdoomx wrote:

Here in South Africa we probably have the highest possible rate of infection in the world due to the high density most of our low income population live in. However, we currently have only 11 deaths out of 1685 cases. We also have an EXTREMELY low testing rate, so bear that in mind. There could be thousands of people infected we don't know about.<br /> The BCG vaccination has been rigorously in place for all newborns since 1973. It is estimated that at least 70% of the population have had it, at most 90%.

On 2020-04-06 19:30:01, user Xavier de Roquemaurel wrote:

Could you please run the same analysis splitting countries which use the Tokyo-172 strain (Japan, Taiwan, Malaysia) from the other countries? This strain dates 1924 and has been less modified than the strains used in other countries like France for example. Thanks. Xavier

On 2020-03-30 20:09:01, user Victor Ng'ani wrote:

Quite excited to read this: I posted this very theory (not specific to BCG though) on my blog on the 22nd of March 2020. Here's the link, leave a comment. Dr. Victor Ng'ani, Kenya.<br /> http://victorngani.com/?p=141

On 2020-04-01 21:11:32, user V. Cheianov, Esq. wrote:

Below I post a link to a recent publication by the Russian Institute for Economic Analysis <br /> (a typical Russian think tank, not an academic institution), which arrives at similar conclusions.

There are some methodological differences.

At the moment the publication is only available in Russian.<br /> The results are published in the form of a blog post

https://aillarionov.livejou...

On 2020-04-02 09:47:58, user Muikari Giturua Wa Tiri wrote:

Its actually very easy to improve on this study because statistics out there exist on the number of people who are vaccinated. The study should possibly compare the mortality rate (possibly at some fixed point after the first case was reported) against vaccination rate. Analysing policies against numbers (mortality and morbidity) is a bit tricky in my opinion. The other thing is that I would either leave out morbidity (different countries are reporting number of infections differently....and I agree the same applies to number of deaths. <br /> Otherwise, I would say, well done to the authors. At least this is a start

On 2020-04-02 18:30:40, user Kannapiran P wrote:

Sure, not all studies are comprehensive or definitive as a single cause or effect to be responsible for a disease resistance or susceptibility.

Also, i do not see (testing feasibility) to be different or infavour of the economic status of <br /> country. All countries have kept out the option of checking everyone, <br /> symptomatic patients are tested or interactions with confirmed patients <br /> are tested - all these have been cited to non-availability of voluminous<br /> testing and treatment facility, be it third world nation or developing <br /> or developed nation.<br /> i do not see the correlation between economic or infrastructure facility only (as we call in genetics to be environmental factors) but the genetic moderation a population shows <br /> towards a disease spread. This is truly spelled by targets vulnerable in various steps in pathogenesis. I see this paper to have effected the impact of any changes owing to generated resistance in such populations(BCG vaccinated). I think if the use of retroviral drug cocktails is working the impact of resistance developed cited in this paper is also <br /> feasible.

On 2020-04-06 19:59:00, user Brothers in arm wrote:

This is my view. I am not sure if both groups have equal severity. The HCQ reported as TTCR were shortened. They did not seem to report the initial temperature or the severity of cough for both groups. If the HCQ group started with low temperatures and low # coughs, it would be reasonable to assume that group is less severe and recover quicker. The same applies to the 4 in control group that developed severe illness. Was it because the HCQ worked, or was it caused by the control being more severe resulting in more illness, the HCQ not having an effect then. Lastly, what does improved pneumonia means? I conclude the X-rays looks better in one group. Again, what was the baseline of both groups? I think the less severe group will improve quicker whether there was a therapeutic intervention.

On 2020-04-02 15:17:14, user Mc Uwamwezi wrote:

I have to say I am confused by the numbers, they say they enrolled 62 patients out of which 31 where given the HCQ treatment but then the results show outcomes for n=32 and n=32 respectively in the test and the control arms, so a total of 64??

On 2020-04-06 22:21:01, user Spencer Harris wrote:

If the virus can remain as an aerosol for 3 hours how could they possibly recommend people to go outside without a mask???

On 2020-03-24 02:50:36, user Fred lee wrote:

The study was done in a closed container called Golberg Drum. I have hard time to think that this closed low volumed container is equivalent to the open large volumed air space where gravity works against. Is the virus found on the surface proven to be replicable??? The study 'estimated' vaibility of the virus suing regression modeling, not actually testing its true viability.

On 2020-04-07 16:19:25, user pigah wrote:

This is a really neat paper and a neat use of aggregate data. I wonder if you might be confounding two things in this analysis, though. Obviously, the increase in cases in a country is a result of both import and endogenous growth (and to a lesser extent export). Import will tend to lead to higher apparent initial growth while socioeconomic status and climate would tend to effect the endogenous growth. One potential way to get around this would be to model time to X number of infections and include countries that don't have infections in the database. This would isolate, to a certain extent, the effects of import versus endogenous growth.

On 2020-04-07 22:42:22, user Christos Ouzounis wrote:

Spain 65,082 USA 267,324, estimated peaks.<br /> Today: 141,942 and 394,182 reported.<br /> Just a week later. Stats speak for themselves.

On 2020-04-08 14:43:32, user Snap wrote:

Chinese version:<br /> http://www.eastern-himalaya...

On 2020-04-11 17:14:42, user Sissy Lona Moxley Skaggs wrote:

I was concerned with the volcano activity having some hand in its derivation --Question: Is the virus containing some form of volcanic ash inits formation? Or Is the ash in the air form the recent activity a part of the illness? I am just a MS in psychology with credits in Human Services for a Phd. I am just a grandma right now.

On 2020-04-12 19:00:55, user Loren Schmidt wrote:

These wavelengths need to be scaled to population, and or number of tests per capita being performed. Without that information you're relying on a large assumption that the case identification rate is the same (when it obviously is not).

Even the death wavelength will suffer from differences in identifying deaths caused by SARS-COV-2.

If you want to expand this, you might include plots of the wavelengths per capita of each country for each day from the first identified case. This should show the effects of mitigation efforts (social distancing) and the decrease in the wavelength as the mitigation took hold.

On 2020-04-12 22:12:26, user Klaus K wrote:

Thanks for an interesting paper! However I do agree with Clive Bates that it would be very helpful to have the multivariate analysis rerun to reflect current & former tobacco use as two separate variables, both for hospitalisation and for critical illness. <br /> If the hypothesis that nicotine modulates the ACE2-receptor is valid, this will be reflected as a higher OR in former tobacco users and a lower in current users.

On 2020-03-18 17:18:28, user Teri Frevert wrote:

Publishing this article prior to peer-review is irresponsible. It has the potential to overwhelm our laboratories with blood type testing for paranoid individuals. Additionally, you cannot change your blood type so what would the benefit be? People with type A thinking it would be ok to ignore the rules put in place to slow the spread of CVOID-19? That would be a problem because they could still be a carrier. People with other blood types being more fearful? This is absolutely reckless.

On 2020-03-27 20:21:49, user Jessa Elizabeth wrote:

Yes but out of all those test how many tested positive with a RH -. I ask bc my bf has it, A+, I have A- and did not get it, living in the same house. My daughter is O- and did not get it either. My dad has it, A+, and my friends husband has it A+ both infected but the wife is A- like me and didn't catch it. Just curious on if that plays a part?

On 2020-03-27 22:25:16, user Leon van Engelen wrote:

Is there connectien between rhesus + vs -

On 2020-03-20 09:22:51, user BertieInExile wrote:

Just wondering how this fits with the different picture we have from the Diamond Princess?

More than 80% uninfected. 50% of those asymptomatic.

tests of most of the 3,711 people aboard the Diamond Princess confirmed that 634, or 17 percent, had the virus; 328 of them did not have symptoms at the time of diagnosis. Of those with symptoms, the fatality ratio was 1.9 percent,

.<br /> https://www.sciencenews.org/article/coronavirus-outbreak-diamond-princess-cruise-ship-death-rate

On 2020-03-20 16:01:44, user Mejie Jwano wrote:

For this to be helpful in forecasting outside China, more detail on lockdown measures should be described, as well as test availability. Overall, this seems unhelpful in forecasting US scenarios, where the virus has previously spread undetected due to test rationing, there is no strict enforcement of lockdown measures, there are no state food deliveries to residences, there are no masks available for the general population, and there is an acute shortage of respirator masks even for doctors. The public is freely circulating in supermarkets staffed by unmasked clerks. In state sanctioned video I have viewed of Wuhan, everyone has a mask, and access to food stores and even public streets is restricted. Also, residents of Wuhan are required to log symptoms with an app, which correlates individual movement to automate exposure tracing. With such information detailed in this article, it would reduce the probability of the data being misused in forecasting US scenarios.

On 2020-03-20 22:29:51, user Brian Coyle wrote:

This effort estimated the CV19 RO as 25. Peeking into their parameters, they assume one is asymptomatic and transmitting the disease for 20 days. The largest study to date, Li et al., which Aguilar and Gutierrez use for other data, found this was 2 or 3 days. Aguilar and Gutierrez claim the symptomatic infectious period is almost 40 days. Li et al. found 5 or 6. Although camouflaged with a lot of statistics, with assumptions like these, results like RO 25 are inevitable.

On 2020-03-22 22:28:02, user The Mad Viking wrote:

I do not understand the use of the words "asymptomatic infection" in this article.? Your 24 patients all had Hubei contacts, where it seems likely they were in contact with a symptomatic individual. I see no evidence that they were infected by an individual that was asymptomatic. But that is what the media is reporting, referencing work like this.

On 2020-03-25 05:18:54, user Sinai Immunol Review Project wrote:

Summary: Based on a retrospective study of 522 COVID patients and 40 healthy controls from two hospitals in Wuhan, China, authors show both age-dependent and clinical severity-dependent decrease in T cell numbers with elderly patients and patients who are in ICU-care showing the most dramatic decrease in T cell counts. Cytokine profiling of COVID patients reveal that TNF-a, IL-6 and IL-10 are increased in infected patients with patients in the ICU showing the highest levels. Interestingly, these three cytokine levels were inversely correlated with T cell counts and such inverse relationship was preserved throughout the disease progression. Surface staining of exhaustion markers (PD-1 and Tim-3) and flow cytometry of stained peripheral blood of 14 patients and 3 healthy volunteers demonstrate that T cells of COVID patients have increased expression of PD-1 with patients in ICU having the highest number of CD8+PD-1+ cells than their counterparts in non-ICU groups.

Limitations: Compared to the number of patients, number of control (n= 40) is small and is not controlled for age. Additional data linking inflammatory cytokines and the quality of the adaptive response including humoral and antigen specific T cell response is much needed. T cell exhaustion study relies on marker-dependent labeling of T cell functionality of a very limited sample size (n=17)—a functional/mechanistic study of these T cells from PBMCs would have bolstered their claims.

Significance of the finding: Limited but contains interesting implications. It is already known in literature that in the context of acute respiratory viral infections CD8 T cells exhibit exhaustion-like phenotypes which further underscores the importance of mechanistic studies that can elucidate how COVID infection leads to lymphopenia and T cell exhaustion-like phenotype. However, as authors have noted, the data does point to an interesting question: How these inflammatory cytokines (TNF-a, IL-6 and IL-10) correlate with or affect effective viral immunity and what types of cells produce these cytokines? Answering that question will help us refine our targets for immune-modulatory therapies especially in patients suffering from cytokine storms.

On 2020-03-27 13:17:39, user Sinai Immunol Review Project wrote:

Title: <br /> Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing<br /> The main finding of the article: <br /> This study analyzed the presence of anti-2019-nCov antibodies in serum samples utilizing a commercial automated chemiluminescent immunoassay. Samples included 228 patients admitted to a fever clinic in Shengjing Hospital, 3 of which tested positive for COVID-19 by nucleic acid detection, and 225 that tested negative (non-COVID-19). Other serum samples from outpatients with other diseases, from medical staff in the fever clinic, and from healthy subjects were included. Both SARS-CoV-2-specific IgM and IgG were detected in the COVID-19 patients, while single positivity of IgM or IgG were detected in very few samples from the other populations. In addition to the increase of anti-2019-nCov IgM 7-12 days after morbidity, the increase of IgG was detected in three patients with COVID-19 within a very short of time of IgM detection (0-1 day). <br /> Critical analysis of the study: <br /> The main limitation of this study is that only 3 confirmed COVID-19 cases were included, so that the relationship between anti-2019-nCov antibodies and disease progression could not be clearly defined. Another limitation is that the authors did not show the course of 2019-nCov specific antibodies in the cases with either IgM or IgG positivity for COVID-19 but without clinical symptoms.<br /> The importance and implications for the current epidemics:<br /> The detection of anti-2019-nCov antibodies can be an additional and complementary method to viral detection to identify patients infected by 2019-nCov virus, and can also be used to identify 2019-nCov exposed individuals regardless of symptoms. It may be also helpful to understand the course of individual cases with COVID-19 to predict the prognosis if more cases will be evaluated.

On 2020-03-28 11:05:53, user Aaron Richterman wrote:

In addition to potential age-varying susceptibility related to immunity, there are also important anatomic differences in the airways of children vs adults - this is why children tend to be higher risk for infections of the medium-size airways (bronchiolitis) relative to adults. SARS-CoV2 appears to involve the terminal airways in the lung. Relatedly, there may also be a differential distribution of ACE2, the target receptor for SARS-CoV2, by age.

On 2020-03-31 08:01:00, user elsässerlab wrote:

Impressive study, put together almost in real time!! Would you be able to follow up on the population volunteers in a longitudinal study? Did the covid positive individuals that did not report symptoms develop symptoms later? Why did they chose to test? Did they believe they were exposed to someone with covid symptoms (e.g. within a family several volunteers may test positive but only one shows symptoms)? Will you test them again over time? I think there's huge potential for you to uncover the main routes of spreading, role of asymptomatic cases etc. Please keep it up!

On 2020-04-03 02:55:33, user Gideon Mordecai wrote:

Thank you for this work, I think it is an important contribution. Can you please add more information in the methods for the network/ cluster analysis. Also, is it possible to use the genomic/ network data to quantify which group contributes more to transmission; asymptomatic (/mild symptoms) vs more severe symptoms?

On 2020-03-31 15:54:29, user Nicholas DeVito wrote:

Please note, the provided registration number for this trial is inaccurate. Both in the abstract, and the pre-print paper, the trial registration number is provided as ChiCTR2000030048.

Searching this trial ID on the Chinese Clinical Trial Registry (ChiCTR) brings up the following trial:<br /> http://www.chictr.org.cn/sh...

This is a trial entitled "Evaluation of the effect of 3D double-echo steady-state with water excitation sequence on the localization of parotid gland tumors and intraparotid facial nerves." This is clearly not a trial of convalescent plasma therapy in COVID-19 patients.

On review of the trial record, and registered COVID-19 trials on the ChiCTR, brings up the following study (ChiCTR2000030046) which includes contact information for some of the listed authors and matched the characteristics of this trial.

http://www.chictr.org.cn/sh...

Can the authors please correct the provided trial id for this clinical trial of convalescent plasma therapy in convalescent plasma therapy in COVID-19 patients. Ensuring correct record linkage between registries and results is an important aspect of trials transparency.

On 2020-03-31 23:07:45, user skwique wrote:

Hi. I'm a non-scientist who has arrived here via a link in a tweet. This yet was in a Twitter thread involving an excited discussion about the extent to which the UK government was lying in its announcement, and repeated assertion today, that there is a delay in the supply and distribution of covid19 tests due to the lack of reaction agents available in the supply chain for the test. Whether or not this is the case, or is part of a deliberate govt policy to allow the virus to spread and to reach 'herd immunity' is a matter of heated debate, but not necessarily of concern to you. However, should your simple pre-heating method be proven effective and reliable, it would clearly be a game-changer. So, my question to you, as a layperson, is this: how much peer review is required to establish this process as proven safe and reliable, in scientific and legal protocol terms, and how quickly do you expect this to be achievable? Thank you.

On 2020-04-01 13:42:32, user Sinai Immunol Review Project wrote:

The authors analyzed lymphocyte subsets and cytokines of 102 patients with mild disease and 21 with severe disease. CD8+T cells and CD4+T cells were significantly reduced in both cohort. particularly in severe patients. The cytokines IL6 and IL10 were significantly elevated in severe patients as compared to mild. No significant differences were observed in frequency of B cells and NK cells.<br /> The authors argue that the measurement of T cell frequencies and cytokine levels of IL6 and IL10 can be used to predict progression of disease from Mild to severe Cov-2 infection.

Limitations of the study: The study demonstrates in a limited cohort similar associations to several other reported studies. The authors didn’t compare the changes in lymphocyte and cytokine with healthy individual (Covid-19 Negative) rather used an internal standard value. The recently preprint in LANCET shows The degree of lymphopenia and a pro-inflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity .

Relevance: This translational data identifies key cytokines and lymphopenia associated with disease severity although mechanism and key cellular players are still unknown. Higher level IL-6 production in severe patient suggests potential role of Tocilizumab (anti-IL6R) biologic although clinical trial will be necessary.

Reference: 1. Longitudinal Characteristics of Lymphocyte Responses and Cytokine Profiles in the Peripheral Blood of SARS-CoV-2 Infected Patients. Lui et al. LANCET infectious Diseases preprint<br /> https://dx.doi.org/10.2139/...

Reviewed By Zafar-RS

On 2020-04-02 06:24:25, user Tibi Kiss wrote:

According to network medicine practicioners at #barabasilab, in their data it was predictable the brain tissue damage. https://covid.barabasilab.c...

On 2020-04-03 05:53:48, user Abhijit Dasgupta wrote:

Is the data you are using based on confirmed cases (RT-PCR tests) and mortality in India till March 28? You do realize that due to low testing rate the incidence of COVID infection is probably grossly underestimated, and that, given the early stage of the epidemic in India, you do not have very robust numbers for deaths and cases anyway. These issues propagate into your predictions. You would also have to account for the probable increase in testing rate over time which will accelerate the reporting of confirmed cases faster than the actual increase in spread of the infection. The fundamental data that is available for training your model is flawed, and so the predictions are suspect.

On 2022-10-13 01:36:58, user Renier Mendoza wrote:

Now published in PeerJ <br /> https://doi.org/10.7717/pee...

On 2021-08-11 01:45:23, user Sli wrote:

Would be useful if you add a table listing the time from full vaccination for all those green dots beyond 10 days.

On 2020-11-23 20:10:20, user TheMeerkat wrote:

To me the graphs in the pdf look like random distribution. I have no clue how anyone could decide that there is any correlation between values on two axes unless they decided it would be there before starting this research.

On 2020-11-30 01:00:57, user lbaustin wrote:

Does your hospital not routinely check vitamin D status - 25(OH)D levels? Recent studies have shown that if vitamin D is given early, it can decrease Covid-19 severity, but it is far less effective in severely ill patients.

On 2023-01-14 13:18:53, user Basheer Marzoog wrote:

the paper is published https://www.eurekaselect.co...

On 2021-08-12 13:33:46, user brikz wrote:

Yep, the PHD factor stood out to me as well. Love to hear why that is.

On 2021-08-13 05:55:13, user Joseph Akins wrote:

The PhD finding is not surprising. Given how most PhDs live their lives the difference in getting the vaccine vs not getting it may be viewed as negligible. That pro vaccine "arguments" broadly fall into one of three logical fallacies there is reasonable skepticism as to the motivation behind them. The three basic fallacies used are: appeals to authority, appeals to sentiment and ad hominem attacks.

Additionally, those with PhDs are hopefully trained to not be fooled by logical fallacies and those that have no university "education" have not been brain washed to mindlessly find them compelling (at least that's what 10 years enlisted in the military showed me).

Those with PhDs in the sciences are more likely to understand that science is a process and cannot "say" anything and is only "followed" by fools. This is similar to David Hume's idea that "you cannot derive an ought from an is". How the world operates tells us nothing about what we ought to do in any situation including whether any particular individual "ought" to get vaccinated, or wear a mask.

Those with PhDs in non STEM related fields are in my opinion, as one with a PhD in the physical sciences, much more likely to see science as a social instrument and probably support vaccine promotion and even coercion. Unfortunately, too many people, in general, ignorantly see science as an instrument with which they can bludgeon their political adversaries. This is willful ignorance that results in people being treated as means towards an end and not as thinking people with their own ends in mind.

I not only have a PhD, but I left Academia and have worked as a Registered Nurse for over 15 years. As to whether I personally believe in vaccines is of no importance because the disagreement is actually not over vaccines, or masks, but over the millenia old tension between individual autonomy and the collective "good". I fall squarely on the side of individual autonomy and against arguing by logical fallacies regardless of any view on whether I ought to get a vaccine. That I, on occasion, actually take care of COVID positive ICU patients is not a factor most people need to consider.

On 2023-01-30 12:28:48, user Aniko Lovik wrote:

This preprint has been now published in Stress and Health after peer-review: https://doi.org/10.1002/smi...

On 2020-07-18 05:45:16, user Peter Lange wrote:

Those last 2 #covid symptom clusters associate strongly with frailty... seems frailty and covid are associated with delirium and poor outcome. Not sure structuring as "symptom clusters" helps