SARS-CoV-2; CoVID-19; Coronavirus; Updates and Information

here is small study which points very worryingly to the asymptomatic population of urban eenvironments to be as high as 14 percent
https://youtu.be/6zge9sRI2BA

pingpongpaddy said:

here is small study which points very worryingly to the asymptomatic population of urban eenvironments to be as high as 14 percent
https://youtu.be/6zge9sRI2BA

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14% might be the floor in NYC. At least one hospital is screening every patient admitted through the ER. I heard that in early April 20-30% of patients admitted for something else were testing positive. That's in line with the most reasoned estimate I've seen for NYC (21% implied incidence). Still a lot of guess work, but none of those numbers surprise me. Most people who get it are not being counted.

From what I can tell the results of a complete multi-intitutional trial will come soon. But at Univ Chicago Hospital, part of the trial, out of 113 severely ill patients treated with remdesivir, only 2 died and most have been discharged. We dont yet have data from placebo controls, but based on what seems to be the usual course, this SOUNDS very encouraging.

Hopefully real (i.e complete) data comes soon. Until then, it is best to keep a level head, so to speak.

More on the remdesivir trial that includes the Chicago patients. It will include 2400 patients and will analyze a 7-point ordinal endpoint, which includes the outcomes of death, use of mechanical ventilation or extracorporeal membrane oxygenation, use of high-flow oxygen or noninvasive ventilation, low-flow oxygen, hospitalization without oxygen but other medical care, hospitalization only for protocol remdesivir, and no hospitalization, assessed on day 14.

It is not a blinded study and there is no placebo control in the design (I dont know why they set it up that way). It is far from an ideal design, but maybe they have some sort of biostatistical approaches to deal with that. If the results continue as with the results in Chicago it may not matter in the short run.

There are many Remdesivir trials registered. NIAID led one double-blinded RCT over placebo. Gilead led two open-label RCT over standard of care (one for mild/moderate, one for severe). China led two double-blinded RCT over placebo (one for mild/moderate, one for severe) and enrolled patients were much fewer than the planned. It is said that the results of severe group (planned for 400+, enrolled 200+, remdesivir placebo 2:1) will be out soon.

I am not familiar with trials in multi centers. Chicago's results seem to be part of the Gilead severe trial which has 152 study locations. Are there any SOC group in Chicago or are they comparing with SOC group pooled from all over the locations? Too early to say it works now. BTW, look at Gilead stock YTD and the surge is really nothing big on 4/16. It dropped on previous day because the trials in China were officially terminated/suspended due to lack of patients.

rainneverever said:

Chicago's results seem to be part of the Gilead severe trial which has 152 study locations. Are there any SOC group in Chicago or are they comparing with SOC group pooled from all over the locations? Too early to say it works now. BTW, look at Gilead stock YTD and the surge is really nothing big on 4/16. It dropped on previous day because the trials in China were officially terminated/suspended due to lack of patients.

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Yes, this my understanding too, but I dont know what the standard of care (SOC) group will be either.

Hopefully we'll have more definitive news soon.

[size=+2]Death Cases reported on April 17, 2020[/size]


China encountered the Second Wave of COVID massive attacks. Third wave is also expected till the end of 2020.

/ GOD FORBID, PLEASE /

igorponger said:

[SIZE=+2]Death Cases reported on April 17, 2020[/SIZE]
China encountered the Second Wave of COVID massive attacks. Third wave is also expected till the end of 2020.
/ GOD FORBID, PLEASE /

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I wouldn't trust those numbers. The US had over 2000 deaths yesterday. The east coast is starting a new day and a new count. The Chinese numbers are always suspect.

The US death count is 34,000. I don't think there is a chance that the total will stop at Dr Fauci's 60K.

Washington state is doing relatively well compared to other states even though it was hit first.

I do agree that China will have a second wave because they reduced their restrictions too soon. I know that many states want to get back to business. The pressure is on and any decision will not be a perfect one. It will be a compromise. That means criticism from both sides.

In what I do, a cost function is created for a design or decision. Then the goal is to minimize the cost but there is never a no cost solution. The two main parameters here are lives vs economy.
cost(deaths, economy) = A*deaths^2+B*economy^2. Now you must chose the coefficients A and B.

Will things ever get back to normal before a vaccine comes out?

ILoveTT said:

Will things ever get back to normal before a vaccine comes out?

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Well, every situation gets to be normal after a little while, as inurement sets in.

The big increase in China's cases and death toll is not due to a second wave. On 4.16, Wuhan announced that after a thorough reexamination of case reports, they revised that by 4.16 Wuhan has had 50333 cases (+325) and 3869 deaths (+1290). Wuhan explained the discrepancies came from (1) At the beginning of the outbreak, hospitals were overwhelmed, some patients did not get hospitalized and died at home. (2) When hospitals were overloaded and healthcare workers occupied, there were case reports that were delayed, missed or mistaken. (3) When the capacity of healthcare systems was expanded with additional designated hospitals, private hospitals, temporary hospitals etc, some hospitals were not connected to the database in time. (4) For some death reports, info was missing and there were repeated or mistaken reports.


There are always questions and doubts about Wuhan's numbers. I hope Wuhan can release the total death number for Q1 but still many people won't believe. Nevertheless, my point is that +1290 is from previous cases in Wuhan not from the second wave in China.


By now, provinces with most active case numbers in mainland China are Heilongjiang 388, Hubei 129, Shanghai 109, Guangdong 93, Inner Mongolia 89, Beijing 76. Shanghai, Inner Mongolia and Beijing reported 0 local case for more than 3 weeks, all active cases are travel-related. In contrast, Heilongjiang, Guangdong, Hubei reported local cases but they were said to have known transmission chain. It is possible that Guangdong will get a second wave and need a local lockdown. There are many illegal immigrants living in very crowded community and a community spreading seems on its way. Therefore, some provinces in China are now even denying entries from certain areas from Guangdong without a negative RNA test. Guangdong has restarted for more than 2 months (from Feb 10); they failed to screen/quarantine/test foreign entries until late March although they were stringent on Hubei entries. That's pretty much the same mistake US made: did nothing on entries from South Korea when outbreak started in South Korea, did nothing on entries from Italy when outbreak started in Italy as they thought they banned entries from China.

A little bit of good news on remdesivir from a group at NIH. Only 6 animals per group. But still the data (assuming they are solid) point in the optimistic direction. For what ts worth, in my field (which is not this) the groups at NIH are really strong.

This is a model of early stage a d not real severe Covid-19 that can progress to pneomonia. In this study there were actual controls.
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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2
Brandi Williamson, Friederike Feldmann, Benjamin Schwarz, Kimberly Meade-White, Danielle Porter, Jonathan Schulz, Neeltje van Doremalen, Ian Leighton, Claude Kwe Yinda, Lizzette Perez-Perez, Atsushi Okumura, Jamie Lovaglio, Patrick Hanley, Greg Saturday, Catharine Bosio, Sarah Anzick, Kent Barbian, Tomas Chilar, Craig Martens, Dana Scott, View ORCID ProfileVincent Munster, Emmie de Wit
doi: https://doi.org/10.1101/2020.04.15.043166
This article is a preprint and has not been certified by peer review [what does this mean?].
AbstractInfo/HistoryMetrics Preview PDF
Abstract
Background: Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods: To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results: In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions: Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.

It's hard to tell from what's out there, but possibly some liver damage reflected in elevated blood levels of liver enzymes. That kind of thing is usually reversible. Ive seen statements that other things might have occurred in critically ill patients (for example acute kidney injury, which is very bad and often presages multiple organ failure) but it's hard to know if it's the drug or the disease. We will know more soon once we get some randomized controlled studies. I'm guessing it won't be too bad but that is based on limited info and very small patient numbers and minimal info. Right now it seems promising more so than chloroquine to me anyway. Emphasis on "seems".

I've read that in phase 1 trials the drug was well tolerated without observed liver or kidney toxicity.

https://www.dailymail.co.uk/news/ar...-death-certificates-coronavirus-patients.html

NHS doctors are being told they DON'T need to list Covid-19 on death certificates of coronavirus patients, leaked documents reveal
...
The leaked hospital guidance, obtained by not-for-profit organisation Good Law Project, tells medics filling in death certificates that 'pneumonia or community-acquired pneumonia are acceptable' to put as the direct cause of death.

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Another thing to keep in mind is that when people die of Covid-19 outside of a hospital it usually doesnt get counted. And that happens a lot.

The data are just do spotty.

ILoveTT said:

Will things ever get back to normal before a vaccine comes out?

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Depends what you mean by normal. The economic damage will probably outlast the pandemic by a lot. For the virus to recede into the background without a vaccine, it would take a reliable treatment safe enough to give to healthy people with mild symptoms outside the hospital. In other words, a pill or IM injection (something that doesn't require IV administration) that's gone through a rigorous clinical trial. That won't happen this year; a vaccine is more likely in the 12-18 month window. On the bright side, things could get considerably closer to normal with an in-hospital treatment that keeps a large majority of patients off a ventilator and out of the ICU. I think there's a reasonable chance that happens this summer or fall. If it does, it'll probably be thanks to passive antibody therapy and possibly Remdesivir.

I have high confidence that vaccines will be available in time for Olympic Games next year.