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COVID-19 Research in Brief: 6 June to 12 June, 2020

Credit: sorbetto / DigitalVision Vectors / Getty

Clinical trials

The UK’s RECOVERY COVID-19 Trial has announced that it has suspended its hydroxychloroquine arm following the recommendations of its independent Data Monitoring Committee. The randomized trial, in which 1,542 patients with COVID-19 received hydroxychloroquine and 3,132 COVID-19 patients received the standard of care, showed no effects of the drug on death rates (25.7% for hydroxychloroquine versus 23.5% for standard of care) or duration of hospital stays. Data from the study has yet to be published.

Regeneron has launched clinical trials of REGN-COV2, the company’s dual antibody cocktail therapy for COVID-19. The two monoclonal antibodies non-competitively target the SARS-CoV-2 spike protein’s receptor binding domain. REGN-COV2 will be tested independently as a therapeutic agent for COVID-19 patient and as a preventive cocktail in high-exposure-risk groups.

Human studies

Mark Roschewski (National Institutes of Health) et al. describe outcomes for 19 patients with COVID-19 suffering from severe hypoxia who were treated with the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib. The study, published in Science Immunology, included 11 patients receiving supplemental oxygen and 8 on invasive mechanical ventilation; 18 of the 19 patients showed signs of inflammation. Eight of the patients receiving supplemental oxygen no longer required supplementation and were discharged from hospital. Four of the patients on ventilation were extubated, and two died before the completion of the study. Inflammatory markers also improved in the supplemental oxygen group (10 out of 11 patients achieved normal C-reactive protein (CRP) levels), but levels were less affected in the patients receiving mechanical ventilation (only 2 out of 8 patients’ CRP levels returned to normal).

Preclinical studies

Two studies, one led by Mikael Simons of Technical University, Munich, and the other by Peter Cullen and Yohei Yamauchi at the University of Bristol, suggest that neuropilin-1 (NRP1) facilitates SARS-CoV-2 infection of host cells. Both teams identified a C-terminal motif in the spike protein S1 domain generated by processing of its polybasic furin-type cleavage site as a neuropilin-binding motif, and found that anti-NRP1 monoclonal antibodies reduced SARS-CoV-2 infection of NRP1-expressing cells in vitro. Simons and collaborators further show evidence of SARS-CoV-2 infection of NRP1-expressing cells in the olfactory epithelium and olfactory bulb in 5 out of 6 deceased patients who suffered from COVID-19.

Work led by Catherine Blish (Stanford University) compared single-cell RNA sequencing data of peripheral blood mononuclear cells from seven hospitalized patients with COVID-19 and six healthy controls. As reported in Nature Medicine, the authors find several innate immune subsets depleted in patients with COVID-19. γδ T cells and plasmacytoid dendritic cells (DCs) were depleted in all patients with COVID-19, while conventional DCs (CD16+ monocytes) and natural killer (NK) cells were significantly reduced in only four patients with acute respiratory distress syndrome (ARDS). Patients with ARDS also harbored an atypical population of neutrophils lacking canonical markers such as FCGR3B and CXCR2, but expressed genes usually associated with neutrophil progenitors.

Hui Wang (Beijing Institute of Biological Products Company) et al. cultured a patient-derived SARS-CoV-2 strain (HB02) in Vero cells to produce a β-propionolactone-inactivated vaccine formulation termed BBIBP-CorV. Rhesus macaques were immunized at days 0 and 14 with either 2 µg or 8 µg of BBIBP-CorV and then challenged at day 24 with intratracheal SARS-CoV-2. As reported in Cell, macaques immunized with the 8 µg dose showed reduced viral loads in throat and anal swabs throughout the infection (macaques immunized with the 2 µg dose had a similar viral load in the throat to the placebo group at day 5, which significantly declined by day 7, and evidenced no reduction of viral loads in anal swabs); macaques receiving either dose exhibited complete absence of SARS-CoV-2 in the lungs at day 7 post-infection. Average neutralizing antibody titers at day 7 post-infection were 1/16 for the placebo, 1/860 in the high-dose group and 1/512 in the low-dose group. The authors reported no signs of antibody-dependent infection enhancement.

Epidemiology and public health

Seth Flaxman (Imperial College London) et al. analysed the impact of lockdown measures and other non-pharmaceutical interventions (NPIs) in 11 European countries. The authors use a Bayesian model to estimate the changes in the SARS-CoV-2 effective reproduction number (Rt) based on reported deaths and conclude that, in all countries examined, the measures successfully drove Rt below 1 (the authors estimate that the average initial reproduction number for these countries was 3.8). The study, published in Nature, posits that Belgium had the highest attack rate, with 8% of its population putatively infected by SARS-CoV-2, and estimates that 3.1 million deaths were averted by the interventions. Solomon Hsiang (University of California, Berkeley) and collaborators examine the impact of NPIs in six countries (China, South Korea, Italy, Iran, France and the USA) using econometric approaches, applying them to local and regional data within countries for a total of 1,717 interventions analysed. The authors conclude that without the NPIs, China would have suffered 465 times more confirmed COVID-19 cases, Italy 17 times more and the USA 14 times more. This study was also published in Nature.

doi: https://doi.org/10.1038/d41591-020-00024-y

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