Coronavirus (COVID-19) Research

[zen2010]

repeating my previous request for one direct link to the original lancet article discussed, and one more direct link to the original response letter.

Hi JL,
That will be my last post on this topic

original lancet article discussed
https://www.thelancet.com/journals/lanc ... 6/fulltext


direct link to the original response letter
https://zenodo.org/record/3862789#.XtDIRDozaUn


Stay safe

[jimmylegs]

better; thank you zen. i suppose i ought to have specified titles with links. mea culpa.

• Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis (May 22)
  https://www.thelancet.com/journals/lanc ... 6/fulltext

i managed to find the letter after searching the unfamiliar zenodo database for results including the name of the lancet article's lead author.

• An open letter to Mehra et al and The Lancet (May 28)
  https://zenodo.org/record/3864691#.XtKEIjpKhPY

commentary:

• Safety fears over hyped drug hydroxychloroquine spark global confusion (May 29)
  A study that suggested treatment with the malaria drug could be dangerous to people with coronavirus has slowed clinical trials — but the study itself has also been questioned.
  https://www.nature.com/articles/d41586-020-01599-9
  
  In light of the study, this week, the World Health Organization (WHO) has paused enrolment in its trial of the drug as a treatment for COVID-19, as have regulators in the United Kingdom, France and Australia, where similar trials are under way. But the picture isn’t clear-cut: on 28 May, 120 researchers signed a letter to The Lancet, which published the study1, highlighting concerns about the quality of the data and its analysis.
  ...
  observational studies can also be prone to real-world bias: one concern, for example, is that physicians might be more likely to give a drug to patients who are sicker and more likely to die.
  ...
  Nevertheless, the results have led regulators and clinical-trial sponsors to take action...
  ...
  The Lancet study’s lead author, Mandeep Mehra, a cardiologist at Brigham and Women’s Hospital in Boston, Massachusetts, says that he agrees with the WHO’s decision to take a hard look at the safety data from the Solidarity trial. But he does not support ending clinical trials of hydroxychloroquine altogether. “We never called for halting clinical trials,” he says. “In fact, we called for the opposite.”
  ...
  In the midst of it all, the Lancet analysis itself has come under fire. Some researchers have pointed to oddities in the data...
  ...
  Following these criticisms, Mehra’s team tracked down some errors ... The Lancet will soon issue a correction, Mehra says, but the errors did not affect the paper’s conclusions. And the company that gathered the proprietary data, Surgisphere Corporation of Chicago, Illinois, says that it will accept proposals from other researchers to analyse its data...
  ...
  but some remain sceptical ... patients who received hydroxychloroquine in the study were often sicker in the first place than those who did not...
  ...
  [Mehra] says, his study merely highlights an association between the treatment and increased death, but because it is an observational study and not a clinical trial, it cannot exclude the possibility that other factors may have contributed to that difference in mortality'.

update:

• 'Serious' questions raised about hydroxychloroquine study, medical journal says
  Study tied controversial drug to increased risk of death in hospitalized COVID-19 patients (Jun 2)
  https://www.cbc.ca/news/health/hydroxyc ... -1.5595575

end update

personally, recognizing that i am generally distanced from others in ways not available to all, i will continue as previously throughout lockdown and any gradual reopening. more careful with social distancing and hygiene than most of my acquaintance (even within my household, which includes a much less careful 70-something) or wider community in general, with as well nourished an immune system as I can manage - including as much evidence of optimal status as possible given my somewhat limited access to testing.

other than that, i will await the results of forthcoming properly designed and implemented RCTs with interest.

[jimmylegs]

five part COVID webinar series available at:
Multiple Sclerosis Information (MSi) Video Library
On-Demand Videos, Webinars, and Webcasts
https://mymsaa.org/ms-information/videos/
(scroll down to the last five links in the Multiple Sclerosis/Symptoms/Research section)

[jimmylegs]

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 (June 3)
https://www.nejm.org/doi/full/10.1056/N ... tured_home
...
CONCLUSIONS
After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.

[NHE]

The Lancet retracts large study on hydroxychloroquine

https://www.nbcnews.com/health/health-n ... e-n1225091

The medical journal The Lancet on Thursday retracted a large study on the use of hydroxychloroquine to treat COVID-19 because of potential flaws in the research data. The study, published two weeks ago, found no benefit to the drug — and suggested its use may even increase the risk of death.

Thursday's retraction doesn't mean that the drug is helpful — or harmful — with respect to the coronavirus. Rather, the study authors were unable to confirm that the data set was accurate.

Researchers from Brigham and Women's Hospital in Boston had worked with a health care analytics company, Surgisphere Corp., on the study.

"After publication of our Lancet article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation," the study authors wrote in their retraction.

The study authors said they launched an independent review to confirm the findings, but said the company would not provide access to all of the data.

"Based on this development, we can no longer vouch for the veracity of the primary data sources," the authors wrote.

[jimmylegs]

Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis (Jun 4)
https://www.thelancet.com/journals/lanc ... 6/fulltext

"...Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process..."

Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 (Jun 4)
https://www.nejm.org/doi/full/10.1056/NEJMc2021225

"Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.”1 We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused."

Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients (Jun 4)
https://www.the-scientist.com/news-opin ... uine-67613

'... Today, three authors—all the coauthors on the study except Surgisphere founder and CEO Sapan Desai—contacted The Lancet to retract their report. “They were unable to complete an independent audit of the data underpinning their analysis,” the retraction notice in The Lancet reads. “As a result, they have concluded that they ‘can no longer vouch for the veracity of the primary data sources.’” ...'

Lancet, New England Journal retract Covid-19 studies ... (Jun 4)
https://www.statnews.com/2020/06/04/lan ... ria-drugs/

"... Meanwhile, on Wednesday, researchers reported the results of the first gold-standard clinical trial of hydroxycholoroquine in Covid-19, concluding that it did not prevent infections any better than placebo. Other clinical trials, including some looking at the drugs as treatments, are ongoing..."

[NHE]

FDA Withdraws Emergency Use Authorization For Hydroxychloroquine
June 15, 2020 2:30 PM ET

https://www.npr.org/sections/coronaviru ... hloroquine

The U.S. Food and Drug Administration today withdrew a special status known as emergency use authorization for the drugs chloroquine and hydroxychloroquine.

Emergency use authorization is designed to facilitate the availability of drugs needed during public health emergencies. It allows unapproved medical products or unapproved uses of approved medical products to be used in such emergencies.

President Trump was an early and vocal champion of the drugs, and even declared in May that he was taking the drugs to prevent COVID-19.

Hydroxychloroquine and chloroquine were initially designed as anti-malarial drugs and later shown to be useful in treating certain autoimmune disorders. Early on in the pandemic, some researchers thought the drugs might be useful in treating COVID-19. Laboratory tests showed hydroxychloroquine interfered with the ability of the coronavirus that causes COVID-19 to enter cells. There were also hints from the use of the drugs in patients that they might be helpful. The FDA granted the emergency use authorization in March.

But those early positive results came from small studies that did not stand up well to scientific scrutiny. Larger, more carefully designed studies failed to show a benefit.

"It is no longer reasonable to believe that oral formulations of [hydroxychloroquine] and [chloroquine] may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks," said FDA chief scientist Denise M. Hinton put it in the letter explaining the agency's decision.

The FDA decision does not affect the use of the drugs in approved clinical trials.

[NHE]

Flushing the Toilet May Fling Coronavirus Aerosols All Over
A new study shows how turbulence from a toilet bowl can create a large plume that is potentially infectious to a bathroom’s next visitor.

https://www.nytimes.com/2020/06/16/heal ... shing.html

Here’s one more behavior to be hyper-aware of in order to prevent coronavirus transmission: what you do after you use the toilet.

Scientists have found that in addition to clearing out whatever business you’ve left behind, flushing a toilet can generate a cloud of aerosol droplets that rises nearly three feet. Those droplets may linger in the air long enough to be inhaled by a shared toilet’s next user, or land on surfaces in the bathroom.

This toilet plume isn’t just gross. In simulations, it can carry infectious coronavirus particles that are already present in the surrounding air or recently shed in a person’s stool. The research, published Tuesday in the journal Physics of Fluids, adds to growing evidence that the coronavirus can be passed not only through respiratory droplets, but through virus-laden feces, too.

And while it remains unknown whether public or shared toilets are a common point of transmission of the virus, the research highlights the need during a pandemic to rethink some of the common spaces people share.

“The aerosols generated by toilets are something that we’ve kind of known about for a while, but many people have taken for granted,” said Joshua L. Santarpia, a professor of pathology and microbiology at the University of Nebraska Medical Center who was not involved in the research. “This study adds a lot of the evidence that everyone needs in order to take better action.”

[NHE]

Asymptomatic covid19 patients experience lung damage detected via CT scan.

We Still Don't Fully Understand The Label 'Asymptomatic'
June 23, 202010:31 AM ET

https://www.npr.org/sections/goatsandso ... ymptomatic

Even if someone is infected by the novel coronavirus and remains asymptomatic — free of coughing, fever, fatigue and other common signs of infection, that doesn't mean the coronavirus isn't taking a toll. The virus can still be causing mild — although, likely reversible — harm to their lungs.

A new paper in Nature Medicine, published June 18, documents the clinical patterns of asymptomatic infections. It finds that many of the people studied developed signs of minor lung inflammation — akin to walking pneumonia — while exhibiting no other symptoms of coronavirus.

The study shows that being asymptomatic doesn't always mean that no damage has occurred in someone's body; follow-up studies will help researchers assess for potential long-term impacts. It also demonstrates that the intense scrutiny applied to novel coronavirus infections could shed light on how other respiratory diseases operate: asymptomatic carriers of flu or common cold viruses are not studied much, so it's currently unclear whether the documented inflammation is a typical immune response or specific to the novel coronavirus.

The percentage of people with asymptomatic infections is unclear. "Estimates suggest that anywhere between 6% and 41% of the population may be infected but not have symptoms," Maria Van Kerkhove, a top World Health Organization official, said June 9.

Asymptomatic coronavirus carriers are hard to find and study — because people usually get tested for coronavirus only if they think they may have it. And some people who appear asymptomatic at first do later develop classic symptoms such high temperatures, fatigue and difficulty breathing.

The Nature paper analyzes 37 asymptomatic cases, found through the contact tracing and testing efforts of the Wanzhou District Centers for Disease Control and Prevention in central China, which screened 2,088 close contacts of coronavirus patients from February through early April.

The asymptomatic patients were hospitalized for observation. 57% showed lung abnormalities on a CT scan, a sensitive imaging technique that produces a three-dimensional picture of the lungs. Some showed "striped shadows," while others presented with "ground-glass opacities" — clear signs of inflammation in the lungs.

"To find so many asymptomatic patients with such significant changes on CT's is quite surprising," says Dr. Alvin Ing, a professor of respiratory medicine at Macquarie University who was not involved with the study. It shows that even people with no outward signs of infection can be experiencing some temporary damage to their lungs. It feeds into a pattern he's seen in treating COVID-19 patients: "The symptoms underestimate the severity of the disease." In other words, the coronavirus is often taxing a person's body more severely than their symptoms — or lack thereof — suggest.

The findings are consistent with several studies following asymptomatic patients in China, which have found that many can develop lesions in the lungs despite having no outward symptoms, says Dr. Jennifer Taylor-Cousar, a pulmonologist at National Jewish Health in Denver not involved with the paper. "It probably is, at least in this disease, pretty common," she says.

Doctors in New York have seen similar patterns. Dr. Jorge Mercado, a pulmonologist and critical care doctor at NYU Langone Hospital-Brooklyn who is not affiliated with the study, says he's seen many instances where a patient has come to the hospital for a non-COVID-related issue and tested positive for the coronavirus. "Those patients evolved into what this paper illustrates, which is [their coronavirus infections] causing pneumonia, causing inflammatory changes," he says.

Still, Taylor-Cousar cautions that researchers are studying the new coronavirus more intensively than they've studied other respiratory ailments. "Usually if someone is asymptomatic [with a common cold or flu virus], we would never even see them at all," she says, "and we would never think to get a CT scan on them." So there's no comparable data to say whether the lung abnormalities are specific to asymptomatic coronavirus carriers, or common among respiratory viruses.

The patterns of lung disease seen on the CT scan can be caused by several factors. "It can be a little bit of fluid in the lungs, sometimes a little blood in a lung or sometimes just a small area of inflammation in the lung," says Dr. Neil Schluger, chief of pulmonary, allergy and critical care medicine at the Columbia University Medical Center. "When I look at these images, I see what to me looks like small areas of inflammation that we see with many kinds of lung infections."

For asymptomatic cases with mild lung inflammation and no other signs of illness, pulmonologists say they're likely to kick the infection quickly and see no lasting lung damage.

"I suspect that, if you followed up with these asymptomatic people in several months, most of their CT scans would be completely normal unless they were known to later develop symptoms," says Taylor-Cousar.

In the midst of an infection, however, doctors can't predict how an individual's case will progress. "There's no way to know who is going to stop with an asymptomatic infection and likely recover completely and who is likely to go on to more severe infection," says Schluger.

The Nature study also found pieces of the coronavirus in swab samples from asymptomatic patients for an average of 19 days — five days longer than a control group of mildly symptomatic patients. While it doesn't necessarily mean asymptomatic people are infectious the whole time, it does suggest that they're capable of spreading the virus to others at some point in their infections, says Schluger. "As we reopen society, that's why it's so important for people who are going out to wear a mask," he says.

[jimmylegs]

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis (Jun 26)
https://pubmed.ncbi.nlm.nih.gov/32589189/

"...Conclusions and relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic."

[jimmylegs]

The coronavirus and MS – updated global advice (Jul 1)
https://www.msif.org/news/2020/02/10/th ... d-to-know/

[Petr75]

2020 Jun 19
Laboratory of Microbiology and Virology, Università Vita-Salute San Raffaele, Milan, Italy
Interferon-β 1a Inhibits SARS-CoV-2 in Vitro When Administered After Virus Infection
https://pubmed.ncbi.nlm.nih.gov/32559285/

Abstract

The ongoing COVID-19 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against SARS-CoV-2. Under this scenario, the interferon-β 1a (IFN-β 1a) whose antiviral potential is already known, and is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β 1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.

[vesta]

See also:

A Review of SARS-CoV-2 and the Ongoing Clinical Trials.
Tu YF, Chien CS, Yarmishyn AA, Lin YY, Luo YH, Lin YT, Lai WY, Yang DM, Chou SJ, Yang YP, Wang ML, Chiou SH.
Int J Mol Sci. 2020 Apr 10;21(7):2657. doi: 10.3390/ijms21072657.
PMID: 32290293 Free PMC article.

"The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis."

Best, Vesta

[Petr75]

2020 Jul 9
From the NYU Langone Multiple Sclerosis Comprehensive Care Center, New York, NY; and Cohen's Children Medical Center Northwell Health (C.F.-C.), Lake Success, NY
COVID-19 outcomes in MS: Observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center
https://pubmed.ncbi.nlm.nih.gov/32646885/


Abstract

Objective: To report outcomes on patients with multiple sclerosis (MS) and related disorders with coronavirus disease 2019 (COVID-19) illness.

Methods: From March 16 to April 30, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records.

Results: We identified 76 patients (55 with relapsing MS, of which 9 had pediatric onset; 17 with progressive MS; and 4 with related disorders). Thirty-seven underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n = 34, 44.7%) and sphingosine-1-phosphate receptor modulators (n = 10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a nonambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome.

Conclusions: Most patients with MS with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at-risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.

[NHE]

One Man's COVID-19 Death Raises The Worst Fears Of Many People With Disabilities
July 31, 2020 3:29 PM ET

https://www.npr.org/2020/07/31/89688226 ... sabilities

What Melissa Hickson says happened to her husband — and what the hospital says — are in conflict.

But this much is for sure: Michael Hickson, a 46-year old quadriplegic who'd contracted COVID-19, died at St. David's South Austin Medical Center in Austin, Texas, on June 11 after the hospital ended treatment for him and moved him from the intensive care unit to hospice care.

Melissa Hickson says her husband was denied potentially lifesaving treatment because doctors at the hospital made a decision based on their biases that, because of his disabilities, Michael Hickson had a low quality of life.

The hospital says it acted based on the man's dire medical prognosis and that it would have been pointless and cruel to give him invasive treatment.

Michael Hickson's death has become a cause among many with disabilities, an emblem of a medical system that they believe views their lives as having less value, even before a pandemic put doctors and hospitals under stress.

And now Hickson's death may get the scrutiny of a federal civil rights office.

ADAPT of Texas, a disability rights group in Austin, sent a complaint on July 24 to the federal Office for Civil Rights at the Department of Health and Human Services. And on Friday, the National Council on Independent Living filed a similar complaint to ask the Office for Civil Rights to open an investigation into Hickson's death.

"In Mr. Hickson's case, the issue is not abstract," the complaint says. "The treating professional for Mr. Hickson made a discriminatory determination that, due to his disabilities, Mr. Hickson's life would not be supported."

In addition to those formal complaints, two members of the U.S. House of Representatives from Texas expressed alarm. Rep. Chip Roy, a Republican, called the circumstances around Hickson's death "highly troubling." And Rep. Joaquin Castro, a Democrat, said Hickson's death "should be immediately investigated."

Since the start of the pandemic, the federal civil rights office has kept an eye on health care rationing. Specifically, it has warned states, doctors and hospitals that they can't place elderly and disabled people at the back of the line for care for COVID-19.

"We're concerned that stereotypes about what life is like living with a disability can be improperly used to exclude people from needed care," said Roger Severino, the Office for Civil Rights director, on March 28 as he announced guidelines for states and medical providers.

To do so, he warned, would violate laws — including the Americans with Disabilities Act and the Affordable Care Act — that guarantee the disabled and older people will not face discrimination when they need medical care.

.....

On June 5, Hickson went to see her husband in the ICU at St. David's South Austin Medical Center.

Michael Hickson was a quadriplegic who'd been diagnosed with COVID-19. Now he had pneumonia. A BiPap machine, a kind of ventilator that people often use in their own homes, was pushing air into his lungs to help him breathe.

Through the mask, he answered her questions with short answers. Would you like me to get you a Long Island iced tea, she joked. Yes, he said with a smile. Will you pray with me? Yes.

She asked him "to keep it in your mind: You will live and not die. You will live." She asked him to repeat the words with her and she saw, under the mask of the breathing device, his lips move as he repeated it with her.

She called the kids on the phone — their five teenage children — for a FaceTime conversation. They told their Dad what they were up to. The 16-year-old was excited she was going to get her driver's license.

.....

That day at St. David's hospital, on June 5, the medical staff had something to tell Melissa Hickson. They were going to stop treating her husband. And move him from the ICU to hospice care.

In the hallway, Hickson found the doctor. She asked why. And she recorded their conversation.

The recording is hard to hear, the doctor's voice a bit distant. But he tells Hickson: "The decision is: Do we want to be extremely aggressive with his care or do we feel like this would be futile?"

And then he adds: "As of right now, his quality of life — he doesn't have much of one."

Hickson challenges the doctor. "What do you mean?" she asks. "Because he's paralyzed with a brain injury, he doesn't have quality of life?"

"Correct," the doctor replies.

After a while, the doctor gives a different explanation: If we have to intubate him — put him on a more powerful ventilator — in his weakened condition, he's not going to survive.

That didn't make sense to Melissa Hickson. The hospital wasn't overwhelmed with COVID-19 patients. It didn't need to ration care. Her husband had dealt with pneumonia before, and other hospitals had successfully treated it.

Listen to the recorded conversation between the doctor and Melissa Hickson. https://www.youtube.com/watch?v=jq-_gtjnzZg

[continued]