Early remdesivir data will be released

Excerpt

This week, the NIH offered the first peek at results from the closely watched study. In a statement released Wednesday, the National Institute of Allergy and Infectious Diseases—the NIH branch that is conducting the trial—said preliminary data shows remdesivir speeds up the recovery of some COVID-19 patients. “Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received placebo,” according to the statement.

The finding, though modest, would represent the first treatment shown to improve outcomes in patients infected with the coronavirus. However, it’s difficult to evaluate the results without full, detailed data about the patients, how sick they were, and any potential side effects, which the NIAID did not provide. That information is expected to be released within days, according to NIAID director Anthony Fauci, who revealed the study’s results during a meeting with reporters Wednesday afternoon at the White House.

SOURCE: Wired

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Remdesivir clinical trials

Excerpt

The following clinical studies are in progress for the use of remdesivir as a potential treatment for COVID-19:

SOURCE: DRUGS.COM

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Results from phase 3 trial of investigational antiviral remdesivir in severe COVID-19

Excerpt

Gilead Sciences, Inc.  today announced topline results from the open-label, Phase 3 SIMPLE trial evaluating 5-day and 10-day dosing durations of the investigational antiviral remdesivir in hospitalized patients with severe manifestations of COVID-19 disease. <span class=”highlighter”>The study demonstrated that patients receiving a 10-day treatment course of remdesivir achieved similar improvement in clinical status compared with those taking a 5-day treatment course</span> (Odds Ratio: 0.75 [95% CI 0.51 – 1.12] on Day 14). No new safety signals were identified with remdesivir across either treatment group. Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks.

“Unlike traditional drug development, we are attempting to evaluate an investigational agent alongside an evolving global pandemic. <span class=”highlighter”>Multiple concurrent studies are helping inform whether remdesivir is a safe and effective treatment for COVID-19 and how to best utilize the drug</span>,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “These study results complement data from the placebo-controlled study of remdesivir conducted by the National Institute for Allergy and Infectious Diseases and help to determine the optimal duration of treatment with remdesivir. The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir. This is particularly important in the setting of a pandemic, to help hospitals and healthcare workers treat more patients in urgent need of care.”

Remdesivir is not yet licensed or approved anywhere globally and has not yet been demonstrated to be safe or effective for the treatment of COVID-19. This study sought to determine whether a shorter, 5-day course of remdesivir would achieve similar efficacy results as the 10-day treatment regimen used in multiple ongoing studies of remdesivir.

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ACE inhibitors + angiotensin receptor blockers: meta-analysis of effect on severity and survival in COVID-19 (preprint)

Abstract

Methods

We did a meta-analysis to assess the effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (odds ratio).

Findings

Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB.

Interpretation

It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death.

SOURCE: medRxiv

Editor’s note: ‘preprints’ are released prior to publication, and in many cases, prior to peer review.

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Ivermectin inhibits SARS-CoV-2 in vitro

Abstract

Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.

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Heparin-induced thrombocytopenia is associated with mortality in critical COVID-19 (preprint)

Abstract

Methods

Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors.

Findings

Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50×109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors.

Discussion

Continuous renal replacement therapy (CRRT) [induced] a significant decrease in platelet count in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome.

Editor’s note: if this preprint is accepted for publication, the publisher will likely suggest that the conclusion above should be softened to ‘associated with’ rather than ‘resulting in’.

In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as in CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19.

Interpretation

Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

SOURCE: bioRxiv

Editor’s note: Sodium citrate is a circuit anticoagulant often used in CRRT; its use might reduce the incidence of HIT. ‘Preprints’ are released prior to publication, and in many cases, prior to peer review.

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Early detection of superspreaders by mass group pool testing can mitigate pandemic (preprint)

Abstract

Background

Most epidemiological models applied to COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used [due] to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic.

Methods

I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City.

Findings

Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests.

Interpretation

The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow. Though applied to COVID-19 pandemic the results are universal and can be used for other infectious heterogenous epidemics. 

SOURCE: medRxiv

Editor’s note: ‘preprints’ are released prior to publication, and in many cases, prior to peer review.

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Aerodynamic analysis of SARS-CoV-2

Abstract

This study investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the COVID-19 outbreak in February and March 2020.

The concentration of SARS-CoV-2 RNA in aerosols detected in isolation wards and ventilated patient rooms was very low, but it was elevated in the patients’ toilet areas. Levels of airborne SARS-CoV-2 RNA in the majority of public areas was undetectable except in two areas prone to crowding, possibly due to infected carriers in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions showing peaks in submicrometre and/or supermicrometre regions, but these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures.

Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted via aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.

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