Clinical trials

It’s been another confusing week for those watching an early frontrunner in drug repurposing for COVID-19: Gilead’s RNA polymerase inhibitor, remdesivir. A randomized, double-blind, placebo-controlled trial published in The Lancet on Wednesday failed to find any significant benefit of the drug in a cohort of 236 patients in ten hospitals in Wuhan, China. The study was underpowered and failed to recruit its target of 453 patients. On the same day, US National Institute of Allergy and Infectious Diseases (NIAID) director Anthony Fauci declared that a larger, highly powered trial sponsored by NIAID showed a clear-cut effect, reducing median recovery time from 15 to 11 days, with no significant differences in survival. The results have not yet been published.

Sanofi and Regeneron have modified the phase 2/3 trial of sarilumab, their monoclonal antibody against the interleukin-6 receptor, to exclude COVID-19 patients classified as ‘severe’. Lackluster results, particularly with the lower 200 mg dose, led the companies to refocus the trial exclusively on patients classified as ‘critical’, who will only receive either the higher 400 mg dose of sarilumab or a placebo.

Testing and diagnostics

Nasopharyngeal swabs have been an Achilles’ heel of SARS-CoV-2 testing due their low sensitivity in early infection, the discomfort of the collection process and the risk to healthcare workers from patients coughing or sneezing. In addition, maintaining an adequate stock of swabs under the demand pressures of a pandemic can be challenging. Albert Ko and co-workers at the Yale School of Public Health compared the sensitivity of PCR with reverse transcription (RT–PCR) detection of SARS-CoV-2 in paired nasopharyngeal swab and saliva samples from patients and healthcare workers. Tests on saliva were more sensitive and more consistent throughout the course of SARS-CoV-2 infection. The work was posted as a preprint in medRxiv and has not yet been peer-reviewed.

Groups led by Naama Geva-Zatorsky at Technion and Constance Cepko at Harvard posted preprints on medRxiv that may help streamline and speed up SARS-CoV-2 detection. Both studies, which have not yet been peer-reviewed, describe loop-mediated isothermal amplification (LAMP) protocols that simplify sample preparation and rely on colorimetric readouts, reducing equipment needs for SARS-CoV-2 diagnostics.

A paper published in Cell may facilitate the identification of COVID-19 patients at high risk of pneumonia and severe acute respiratory failure. The study, led by Guangyu Wang at Beijing’s Tsinghua University, describes an artificial intelligence system for prognosis based on chest computed tomography imaging.

The UK’s Department of Health and Social Care announced plans for at-home COVID-19 testing of 100,000 randomly selected people in England. The initiative will be led by teams at Imperial College, Imperial College Healthcare NHS Trust, and market research firm Ipsos MORI. The programme, termed REal-time Assessment of Community Transmission (REACT), will have two stages. REACT-1 will require participants to collect their own nose and throat swabs, which will be collected by courier for PCR testing for SARS-CoV-2. In the second stage of the programme, REACT-2, a serological tests to detect antibodies to SARS-CoV-2 will be gradually introduced, starting with a small cohort of healthcare workers. Assessing the reliability and accuracy of different COVID-19 serological test kits is one of REACT’s goals.

Preclinical studies

Writing in Cell Host & Microbe, Jianwei Wang of Peking Union Medical College and collaborators describe a molecular signature of the immune response in the lungs of COVID-19 patients based on metatranscriptomic analysis of the broncheoalveolar lavage fluid (BALF) from eight laboratory-confirmed positive cases. The authors report a strong type I interferon signature in the BALF of COVID-19 patients along with increases in activated dendritic cell and neutrophil frequencies. Conversely, analysis of cytokine transcriptional signatures in blood samples from 50 COVID-19 patients in the Paris area found that mild to moderate cases showed signs of a stronger type I interferon response than severe patients. The results were reported in a preprint which has not yet been peer-reviewed.

A multicenter effort led by Alex Shalek at Harvard Medical School and Massachusetts Institute of Technology (MIT) and Jose Ordovas-Montanes at MIT’s Broad Institute and Harvard reports in Cell that treating primary human upper airway basal cells with type I interferon drives the expression of angiotensin-converting enzyme 2 (ACE2), the receptor used by SARS-CoV-2 to infect human cells. Importantly, type I interferon did not strongly induce ACE2 expression in murine basal epithelial cells.

A team led by Steve Boulant at the University Hospital Heildelberg reports that human colon-derived cell lines and non-transformed colon organoids efficiently support SARS-CoV-2 infection and replication. The authors show a key role for type III interferon in controlling viral replication and spread in colonic epithelial cells. The work was posted as a preprint in bioRxiv and has not yet been peer-reviewed.

Epidemiology and public health

A survey of airborne SARS-CoV-2 RNA in two Wuhan hospitals published in Nature found high levels in the patients’ bathrooms. The aerosol samples were collected in February and March during the city’s COVID-19 outbreak.

Retrospective analysis of 391 confirmed SARS-CoV-2 cases and 1,286 of their close contacts compiled by the Shenzhen Center for Disease Control and Prevention, published in The Lancet Infectious Diseases, found that children under 10 years of age were as likely to be infected as adults.

A non-peer-reviewed preprint posted by Christian Drosten at Charite, Berlin, and collaborators examined SARS-CoV-2 viral load using RT–PCR across different age groups. The study found that viral loads did not differ significantly between children under the age of 10 and other age groups.