COVID-19 Research in Brief: 9 May to 15 May, 2020

Nature Medicine summarizes all the research you need to know this week to keep on top of how science is responding to the COVID-19 pandemic.
Thiago Carvalho is an immunologist writing from Lisbon, Portugal.

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The Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for Quidel’s Sofia 2 SARS Antigen Fluorescent Immunoassay. According to the manufacturer, the test, which must be read on a dedicated analyser, detects SARS-CoV-2 nucleocapsid protein from nasal swabs or nasopharyngeal swabs in 15 min. The agency has also granted an EUA for a clustered regularly interspaced short palindromic repeats (CRISPR)-based SARS-CoV-2 fluorescent assay marketed by Sherlock Biosciences. The test is based on technology developed by Feng Zhang, at Massachusetts Institute of Technology (MIT) and Harvard’s Broad Institute, and James Collins, at MIT, and should give results in an hour.

Clinical trials

The combination of HIV protease inhibitors lopinavir and ritonavir was an early drug repurposing bet in the search for COVID-19 treatments. The pair was one of the four therapies in WHO’s SOLIDARITY trial, which has as another arm lopinavir–ritonavir combined with interferon (IFN)-β. However, a randomized, controlled, open-label trial of lopinavir–ritonavir failed to detect any reduction in SARS-CoV-2 viral load or significant clinical benefit. The study of 199 severe COVID-19 patients in Jin Yin-Tan Hospital, Wuhan, was published in the New England Journal of Medicine.

A second trial compared a combination of lopinavir–ritonavir, IFN-β and the guanosine analog ribavirin to a control group receiving lopinavir–ritonavir. The trial recruited 127 patients with mild COVID-19 in six Hong Kong hospitals and had as a primary endpoint time to negative nasopharyngeal swab for SARS-CoV-2. The results, published in Lancet, show reduced time of viral shedding (7 days for the treatment group versus 12 for the lopinavir–ritonavir treated controls), faster alleviation of symptoms and reduced hospital stay.

Clinical studies

Hillary Hosier (Yale School of Medicine) et al. describe a case of COVID-19 in a second trimester pregnancy with preeclampsia. The study, published as a non-peer-reviewed preprint, found SARS-CoV-2 infection of placental syncytiotrophoblasts. The authors speculate that inflammation caused by SARS-CoV-2 may have contributed to the early-onset preeclampsia.

A retrospective analysis of 423 cancer patients who tested positive for SARS-CoV-2 at New York’s Memorial Sloan Kettering Cancer Center found an overall case-fatality rate of 9%. The study pointed to therapy with immune checkpoint inhibitors, but not chemotherapy or surgery, as a risk factor for severe COVID-19 illness. The work was posted as a preprint and has not yet been peer-reviewed.

Preclinical studies

Bats are natural reservoirs of multiple coronaviruses, including RaTG13, the closest known relative of SARS-CoV-2. In an important step for comparative studies, Kwok Yung Yuen (University of Hong Kong) and collaborators have developed human and horseshoe bat intestinal organoid models of SARS-CoV-2 infection. The study, published in Nature Medicine, found that both human and bat enteroids express angiotensin-converting enzyme II (ACE2) and the protease TMPRSS2, and are permissive to SARS-CoV-2 infection. The researchers were also able to recover infectious viral particles from the stool of a 68-year-old patient with diarrheal COVID-19.

Epidemiology and public health

A retrospective study of patients admitted to the pediatric unit of Hospital Papa Giovanni XXIII in Bergamo during the COVID-19 outbreak found 10 pediatric cases in which SARS-CoV-2 infection was associated with a syndrome resembling the pediatric vasculitis Kawasaki disease. Although the authors estimate the frequency of this Kawasaki-like syndrome at less than one in a thousand SARS-CoV-2-infected children, this nonetheless represents a 30-fold increase in incidence of this rare disease. The study, published in Lancet, also reports an increase in severe cases: 5 of the 10 COVID-19 patients developed Kawasaki disease shock syndrome (KDSS), while none of the 19 Kawasaki disease cases presenting in the hospital over the previous 5 years had developed KDSS.

A non-peer reviewed preprint reports that in an 11-day period from 27 April to 11 May, Necker-Enfants-Malades University Hospital in Paris admitted 17 children diagnosed with Kawasaki Disease (the hospital averaged a case every two weeks in 2018-2019). Eleven of these children presented with KDSS, and all had gastrointestinal symptoms.

Science has published a modeling analysis of the French COVID-19 outbreak, a work led by Simon Cauchemez at the Institut Pasteur. The study estimates that 3.6% of infected individuals are hospitalized, with an overall infection fatality rate of 0.7%. As the French government began easing lockdown measures earlier this week, a key question is what fraction of the population has already been exposed to SARS-CoV-2. The report projects that 2.8 million people, or 4.4% of the French population, will have been infected by 11 May. Similarly, although the data has not yet been peer-reviewed, the Spanish Ministry of Health calculates that, based on a serological survey, about 5% of the country’s residents have been exposed to SARS-CoV-2.

doi: 10.1038/d41591-020-00018-w

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