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Wednesday, June 3, 2020

Claims of a Weaker COVID-19 Virus Disputed

After Italy saw its first case of COVID-19 in late February 2020, the country quickly became a global hub for the virus. With over 233,000 cases and more than 33,000 deaths to date, the virus was more fatal in Italy than in China. To slow the spread, the government ordered everyone to stay home. Now, infection rates are finally falling.
And as the country begins to reopen, a handful of Italian doctors say the deadly virus is losing steam.
“In March and April, patients reached the emergency room very sick. They had acute respiratory distress syndrome, multi-organ failure. They needed immediate oxygen, ventilation, and in two to three days, we had patients that died,” says Matteo Bassetti, MD, director of the Infectious Diseases Clinic at the San Martino Hospital in Genoa. “But now, in the past four to five weeks, it’s been totally different. Patients of a similar age as the ones before, even very elderly patients, are not as sick as patients were just four to six weeks before.”
In stark opposition to Bassetti’s and other doctors’ statements, Italian public health officials and the World Health Organization (WHO) warn there’s no evidence to support these claims. They urge health care providers and the public to continue to take the virus extremely seriously. Meanwhile, Bassetti says proof is on the way.

Can a Virus Weaken?

“One of the golden rules of virology,” says Mark Cameron, PhD, an associate professor of population and quantitative health sciences at Case Western Reserve University School of Medicine, “is that viruses that circulate in the community do change and mutate.”
They do this, he says, to survive. A virus that’s deadly enough to kill all of its hosts will die out as soon as the last infected person dies. A weaker form of the virus — one that doesn’t make people quite as sick — can continue to travel from person to person.
“A virus is interested in its own survival,” says Cameron. “It needs to maintain high viral fitness and not kill its host — us. COVID-19 has already struck that perfect balance.”
It could take generations for enough genetic change to take place to substantially weaken a coronavirus — both the one that causes COVID-19 and other forms that were around before it. Human coronaviruses are known to be extremely stable in their genetic makeup. They change very little over time. Early tracking of SARS-CoV-2, the coronavirus that causes COVID-19, suggests that it is behaving like its relatives, changing slowly and subtly over time.
That’s not to say that the virus isn’t changing at all. When researchers at Arizona State University analyzed coronavirus samples collected from nasal swabs, they found one individual sample that had a major genetic difference from other samples.
But it’s unknown whether this particular variation of the virus results in more or less severe illness or any difference in symptoms at all. To confirm a theory like that will require much more research. Scientists will need to align the various genetic sequences of numerous nasal swabs with patient symptoms.
Still, Cameron says, this single mutated sample won’t prevent other strains from continuing to spread and cause illness. Viral strains survive independently of each other. That’s why, for example, several flu strains circulate every season.
With so many people infected with SARS-CoV-2, a mutation in a single sample is unlikely to change the course of the outbreak, Cameron says.
Though researchers say it’s unlikely that the virus has mutated enough to make major differences in how severe an illness will be, that’s not all bad news. That makes the virus a stable target for researchers working on a vaccine. The flu, for example, changes so quickly that vaccine developers have to come up with a new shot every year.

Proof Is on the Way?

Public health officials stress there’s no scientific proof that the virus is now weaker. Until that proof is found, health authorities warn that the public cannot lower its defenses against the spread of the virus. But Bassetti promises the evidence is coming. He cites studies in progress in the northern Italian cities of Milan and Brescia that will show that people are carrying lower viral loads than before — a sign of less severe disease — and that genetic mutations in the virus have made it less deadly.
One of the golden rules of virology is that viruses that circulate in the community do change and mutate. Dr Mark Cameron
“We are not here to say that the virus is gone,” Bassetti says. “We are here to say that it is different.” He attributes these differences to a potential combination of things, including biological changes in the virus, and the success of the lockdown, social distancing, mask use, and hand-washing. Flattening the curve, Cameron adds, allows testing to catch up and makes medical care available to those who need it without delay.
In response to the WHO’s rebuttal of his claims, Bassetti says, “The WHO does not take care of patients. They are seated at a table in Geneva. These are the impressions of the majority of doctors on the ground. We have admitted more than 500 [COVID-19] patients at San Martino hospital since the beginning of the epidemic, and I have seen a dramatic reduction in the severity of the disease.”
It could be that the work of on-the-ground health care providers is responsible for this dramatic change, Cameron says.
“I would lay the credit for the consistently improving patient outcomes in Italy right at the doctors’ and health care workers’ feet,” he says. “It’s a testament to their heroics that they’ve broken this virus’s back without much, if any, help from the virus itself. We will have to wait for virus sequencing studies and clinical studies to resolve the issue.”
https://www.medscape.com/viewarticle/931670#vp_1

Humana medical group to open 20 primary care clinics in coming year

Humana-owned Partners in Primary Care is opening 20 primary care centers in the next year as it begins phase one of its three-year expansion plan, the medical group said June 2.
Half of the senior-focused primary care centers will be opened in two new markets: Las Vegas (eight) and the Shreveport-Bossier City, La., area (two). The remaining 10 centers will be in Houston, tripling Partners in Primary Care’s footprint there.
The additions come after Humana and private equity firm Welsh, Carson, Anderson & Stowe entered into a joint venture agreement in February to expand Humana’s primary care centers.
Partners in Primary Care serves 35,000 patients from a variety of Medicare Advantage health plans, not just Humana. The company has 48 centers across Kansas, Missouri, North Carolina, South Carolina, Texas and Florida.
https://www.beckershospitalreview.com/payer-issues/humana-medical-group-to-open-20-clinics-in-coming-year.html

Coronavirus Vaccine Race: Updates On The 10 Candidates In Clinics

The global economy is slowly emerging from lockdowns enacted to beat back the coronavirus.
The pandemic isn’t going anywhere, however, and hopes of a return to a semblance of normal rest heavily on the speedy development of vaccines against SARS-CoV-2, the virus that causes COVID-19.

Fast-Tracking Vaccine Programs

Vaccine development typically takes about 10-15 years, as it has to go through the same general pathway as that of drugs and biologics. With the advent of new classes of vaccines such as DNA and mRNA vaccines, development timelines could be tightened relative to traditional vaccines.
Pandemics in recent history such as the MERS and SARS, also caused by coronaviruses, set in motion several R&D programs that have come in handy in today’s scenario, as the new coronavirus shares 80% of its traits with its predecessors.
Public-private partnerships have been forged to expedite vaccine programs. In mid-April, the National Institutes of Health announced a co-operative framework involving several biopharma companies, the Health and Human Services Office of the Assistant Secretary for Preparedness and Response, the CDC, the FDA and the European Medicines Agency for expediting drug and vaccine research. Federal agencies have extended funding for companies with promising vaccine candidates in their pipeline, and this has given them the freedom to focus on research without having to worry about finances.
The U.S. government recently launched the “Operation Warp Speed” project, which has among its objectives ensuring the availability of substantial quantities of a safe and effective vaccine for Americans by January 2021.

US Government Backs 5 Vaccine Candidates

In order to narrow the focus on the most deserving vaccine candidates, the Trump administration has shortlisted five from a crowded field and will likely make an announcement in this regard in the next few weeks, the New York Times reported.
The shortlisted companies are, according to the Times:
Incidentally, Merck was a late entrant in the vaccine race, with the pharma giant announcing partnerships and deals to develop COVID-19 treatments and vaccines only recently.

10 Vaccine Candidates In Clinics, 123 More In Labs

A June 2 document from the World Health Organization showed that 10 vaccine candidates are in the clinics and 123 more are being evaluated in animal studies. Among the 10 vaccine candidates being tested in human studies, five are developed by Chinese firms or institutions. Here’s an update on the 10 vaccines in the clinics:

University Of Oxford/AstraZeneca

The vaccine developed by the University of Oxford in collaboration with AstraZeneca was codenamed ChAdOx1 nCoV-19, a weakened version of a common cold virus that causes infections in chimpanzees.
It has been genetically modified to make to prevent it from replicating in humans. After the university tied up with AstraZeneca, the vaccine candidate was renamed as AZD1222. AZD1222 is in a Phase 2/3 trial, with the university enrolling participants for the study in late May.
Results from an ongoing Phase 1/2 trial could be available in mid-June; a university official was quoted as saying mid-May. AstraZeneca has received over $1 billion in BARDA funding for the development, production and delivery of the vaccine starting this fall.
In late May, Adrian Hill, one of the lead investigators of the vaccine program, suggested the vaccine has only a 50% chance of succeeding, as the viral incidence receded in the community.

Moderna

Moderna, which is collaborating with NIAID for developing an mRNA vaccine, codenamed mRNA-1273, said recently it has dosed the first participant in a Phase 2 trial. The company also released interim data for its vaccine candidate from a NIAID-sponsored Phase 1 study, which showed dose-dependent increases in immunogenicity between prime and boost within the 25-microgram and 100-microgram dose levels. Moderna has prepped for scaling by forming an alliance with Swiss CDMO Lonza.
See also: Inovio Analyst Watches Coronavirus Play ‘From The Sidelines’

CanSino Biological Inc./Beijing Institute of Biotechnology

CanSino, which was the first to begin vaccine testing, announced last week the publication of Phase 1 data of its vaccine candidate Ad5 that showed most people developed immune responses.
Yet he number of people developing neutralizing antibodies — the ones that count for preventing infection — was 75% among those who received the high dose and 50% among those who received the medium or low dose.
A Phase 2 study of Ad5 was started in April and is underway. Ad5 is a genetically engineered adenovirus that delivers the gene encoding the spike protein of the SARS-CoV-2 into human cells.

Wuhan Institute of Biological Products/Sinopharm

The combo’s vaccine candidate entered Phase 2 trials April 24, according to Xinhua.
The Phase 1 trial is ongoing, the report said at that time. Sinopharm, one of the partners, seemed to suggest it will take one year of evaluation to determine the efficacy and safety of the inactivated vaccine candidate.

Sinovac

Sinovac, which began working on an inactivated vaccine candidate in January, said recently it is 99% confident in its vaccine candidate, codenamed CoronaVac. The candidate is in a Phase 1/2 trial. The company recently received $15 million in funding from private investors in lieu of a stake in the company.

Novavax

Novavax, Inc. NVAX 10.86% identified its vaccine candidate, codenamed NVX-CoV2373, in early April. The vaccine candidate is a stable prefusion protein made using the company’s proprietary nanoparticle technology, with Matrix-M adjuvant incorporated to enhance the immunity response of the vaccine.
The company said May 25 it enrolled the first participant in the Phase 1 portion of a Phase 1/2 study it has initiated, with results from the Phase 1 portion expected in July. In mid-May, the company announced an award of an incremental $384 million in funding by the Coalition for Epidemic Preparedness Innovations. On Wednesday, AGC Biologics said it has been tasked with manufacturing Matrix-M adjuvant by Novavax.

Beijing Institute Of Biological Products/Sinopharm

State-affiliated Beijing Institute of Biological Products, which is developing an inactivated vaccine in a Phase 1/2 trial, has started the Phase 2 trial, a post on the WeChat account of the Chinese state-owned Assets Supervision and Administration Commission said.

Pfizer/BioNTech

Pfizer is collaborating with German biopharma BioNTech SE – ADR BNTX 2.33% for vaccine development. BioNTech is evaluating four vaccine candidates in its BNT162 program. These are mRNA vaccines combined with a lipid nanoparticle formulation. BNT162 is being tested in separate Phase 1/2 trials in Europe and the U.S. Pfizer will be vested with the responsibility of scaling up at risk.

Institute Of Medical Biology, Chinese Academy Of Medical Sciences

In mid-May, the institute received approval for commencing a Phase 1 study.

Inovio

Inovio Pharmaceuticals Inc INO 13.32%, which is developing a DNA vaccine codenamed INO-4800, said in its May 11 earnings release it has completed enrollment in a Phase 1 study.
It anticipates commencing a Phase 2/3 efficacy trial in summer, subject to regulatory approval. Inovio has received funding from the CEPI as well as the Bill & Melinda Gates Foundation.
Among others, J&J, which has identified a lead vaccine candidate, plans a clinical study by September. The company expects the first batches of a vaccine to be available for emergency use authorization by early 2021.
Several other companies are also in the fray, including Sorrento Therapeutics Inc SRNE 13.21%, Regeneron Pharmaceuticals Inc REGN 2.17% and Sanofi SA SNY
https://www.benzinga.com/general/biotech/20/06/16174248/revisiting-the-coronavirus-vaccine-race-updates-on-the-10-candidates-in-clinics

UK doctors to trial ibuprofen in COVID-19 patients with breathing difficulties



British doctors are trialling a formulation of anti-inflammatory ibuprofen to see if it reduces respiratory failure in patients with severe symptoms of COVID-19.
The trial involves a particular formulation of ibuprofen, which researchers said had been shown to be more effective than standard ibuprofen for treating severe acute respiratory distress syndrome (ARDS), a complication of COVID-19.
The formulation is already licensed for use in Britain for other conditions.
“If successful, the global public health value of this trial result would be immense given the low cost and availability of this medicine,” said Matthew Hotopf, director of NIHR Maudsley Biomedical Research Centre.
The trial, known as “LIBERATE”, will be a randomised study, with recruitment of up to 230 patients expected over the coming months.
It is being run by Guy’s & St Thomas’ NHS Foundation Trust in London, King’s College London (KCL) and pharmaceutical organisation the SEEK Group.

In March, France’s health minister said people should not use anti-inflammatory drugs such as ibuprofen if they have symptoms of COVID-19, the disease caused by the new coronavirus.
However, U.S., British and European Union drug regulators as well as Reckitt Benckiser (RB.L), which makes Nurofen, have all said there is no evidence that ibuprofen makes COVID-19 worse.
Mitul Mehta, director of KCL’s Centre for Innovative Therapeutics, said that possible well-known gastric side effects from ibuprofen meant that paracetamol was better to relieve COVID-19 symptoms in its early stages.

But he added there was no evidence to back up the French claims that ibuprofen worsens COVID-19 symptoms, saying the formulation being used in the trial should lessen the possible side effects.
“There’s no way these early reports would’ve been talking about this different formulation,” Mehta told Reuters.
“The trial is the right forum in which to test the side effects and to test the efficacy.”
https://www.reuters.com/article/us-health-coronavirus-britain-ibuprofen/uk-doctors-to-trial-ibuprofen-in-covid-19-patients-with-breathing-difficulties-idUSKBN23A1DV

Sanofi to run consultations over restart of hydroxychloroquine trials

Sanofi said on Wednesday it would review available information and run consultations before deciding whether to enroll patients again for its COVID-19-related hydroxychloroquine trials.
The French drugmaker said on May 29 it had stopped recruiting new COVID-19 subjects for two clinical trials on hydroxychloroquine until concerns about safety are cleared up following a decision by the World Health Organization to pause a large trial.
The WHO said earlier in the day the trial would resume.
“We will review available information and run consultations in the coming days to reassess our position,” a spokesman with Sanofi said.
https://www.reuters.com/article/us-health-coronavirus-sanofi-hydroxychlr/sanofi-to-run-consultations-over-restart-of-hydroxychloroquine-trials-idUSKBN23A2RU

Convalescent Plasma Therapy Clinical Effect in Severe COVID-19

Key Points
Question  What is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?
Finding  In this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.
Meaning  Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.
Abstract
Importance  Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.
Objective  To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.
Design, Setting, and Participants  Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.
Intervention  Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity.
Main Outcomes and Measures  Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.
Results  Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, −10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P = .83) (P for interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.65 [95% CI, 0.29-1.46]; P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.93]; P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P < .001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.
Conclusion and Relevance  Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.
JAMA. Published online June 3, 2020. doi:10.1001/jama.2020.10044

LabCorp Launches Website to Connect Patients with COVID-19 Clinical Trials

Laboratory Corporation of America Holdings, or LabCorp, is one of the two largest clinical diagnostic laboratory companies in the U.S. The company announced its Covance drug development business was launching COVID-19 Clinical Trial Connect in the U.S. to help people find information on taking part in clinical trials related to COVID-19.
The site specifically notes five categories of potential participation: if you have been exposed to a confirmed case of COVID-19; if you are experiencing COVID-19 symptoms; if you have been diagnosed with COVID-19; if you have recovered from a confirmed case of COVID-19 infection; and if you are healthy or have interest in vaccine research studies.
“Our goal is to link people interested in these clinical trials with sponsors so that together we may find solutions for this global pandemic,” said Michael Brooks, Covance’s president of Clinical Development and Commercialization Solutions.
The Clinical Trial Connect site can notify potential trial participants of studies run by Covance for the drug industry, as well as studies included in clinicaltrials.gov, the government’s database of privately and publicly funded clinical studies. If patients are interested, they can register on the site.
“With our COVID-19 Clinical Trial Connect, we’re helping bridge the gap,” Brooks added. “Patients who choose to participate in a clinical trial are true medical heroes. We are thrilled to have the capacity to directly engage with patients who would not otherwise be aware of ongoing trials and give them the opportunity to consider participation, particularly at this time.”
LabCorp has more than 65,000 employees and rakes in about $11.5 billion annually. Covance is a global contract research organization (CRO).
LabCorp also announced that it is partnering with digital clinical trial software maker Medable to allow clinical trial participants to engage with trials remotely. This is expected to help with remote data collection, patient engagement and easier app access for trials.
Business Insider noted, “Covance is one of the largest CRO’s globally—and its increased focus on digital trials could be significant in helping LabCorp reduce participant churn amid the pandemic. Social distancing recommendations resulting from the coronavirus pandemic have placed a number of clinical trials on pause—which is leading to participant attrition.”
The adoption of digital access and remote approaches to clinical trials is picking up steam. In early June 2019, the U.S. Food and Drug Administration (FDA) issued a draft guidance on improving the diversity of patient populations in clinical trials. The biggest focus was on getting sponsor companies to include more historically underserved populations in trials, including women, the elderly and minorities. Part of the 18-page guidance included recommendations on remote access.
The guidance stated: “Reduce the frequency of study visits to those needed to appropriately monitor safety and efficacy and consider whether flexibility in visit windows is possible and whether electronic communication (e.g., telephone/mobile telephone, secured electronic mail, social media platforms) or mobile technology tools can be used to replace site visits and provide investigators with real-time data.”
LabCorp, and its biggest competitor, Quest Diagnostics, announced return-to-work services for employers recently. On May 14, LabCorp indicated it would offer staffers check-in health questionnaires, temperature screens and on-site and off-site COVID-19 test collection.
Quest, on May 27, announced on-site temperature checks, respiratory and blood specimen collection, online questionnaires, access to telemedicine services, contract tracing and other services. Quest also said that because “some jobs are higher risk than others,” it will prioritize testing for organizations that employ healthcare workers, first responders and other companies that play a critical role in pandemic response.
https://www.biospace.com/article/labcorp-launches-covid-19-clinical-trial-connect/