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COVID-19 Research in Brief: 4 April to 10 April, 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.

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Therapy and clinical trials

To date, more than 380 trials for COVID-19 have been posted on ClinicalTrials.gov, ranging from repurposed antiviral drugs to novel diagnostic imaging techniques.

Antibody- and convalescent plasma-based therapeutic approaches have dominated the news. Several hospitals have recruited people who had recovered from COVID-19 to do plasma transfers for COVID-19 patients. Last Friday, the FDA announced the approval of a plasma therapy trial at Johns Hopkins University. Takeda has announced a polyclonal hyperimmune antigen-purified antibody concentrate. The process used to recover antibodies from patients had already been approved for treatment of other infectious diseases, which the company hopes could lead to fast-track approval. Regeneron has announced it is pursuing a monoclonal antibody strategy using their humanized mouse antibody screening platform to produce an antibody cocktail for both therapeutic and prophylactic use.

Although hopes for antibody-based immunity are high, there is currently little available data on whether human populations develop immunity to SARS-CoV-2. The World Health Organization (WHO) has announced a large-scale effort (named SOLIDARITY II) to aggregate serological data collected in different countries and expects to post results from the initiative within the next few months.

Several studies have found a correlation between serum levels of interleukin-6 (IL-6) and severity of COVID-19 symptoms. Additionally, a report, published as a preprint, suggests that treatment of 20 people diagnosed with severe or critical COVID-19 with the anti-IL-6 receptor drug tocilizumab could have been effective. Of note, the peer-reviewed version of these results has not yet been published. Roche announced the launch of a trial of tocilizumab, with a recruiting target of 330 participants diagnosed with severe COVID-19. Initial results are expected in the summer. Regeneron and Sanofi have expanded the testing in an existing clinical trial of their own anti-IL-6 receptor monoclonal antibody in rheumatoid arthritis to include severe or critically ill COVID-19 patients.

The WHO is curating a list of vaccine candidates, of which two are currently undergoing clinical evaluation: an adenoviral vector-based approach by CanSino Biological Inc. and the Beijing Institute of Biotechnology, and an RNA product by Moderna Inc. and the National Institute of Allergy and Infectious Diseases.

Serology

A study surveying levels of neutralizing antibodies (NAbs) to the SARS-CoV-2 spike protein in the plasma of 175 patients who had recovered from COVID-19 in one health center in Shanghai, China, published on medRxiv, shed some light on the development of natural immunity to the virus. These results have not yet been peer-reviewed. Though patients in this study were classified as mild cases, antibody levels correlated positively with C-reactive protein and inversely with lymphocyte counts (NAb levels also tended to be higher in older subjects). A troublesome finding of the study was that approximately 30% of recovered patients showed low NAb titers, including 10 patients with NAbs below the detection limit of the assay.

Preclinical research

A study in Cell shows that human angiotensin-converting enzyme 2 (ACE2) can block SARS-CoV-2 infection of both Vero cells and human blood vessel and kidney organoids. Importantly, the drug has been shown to be safe in humans, though it failed to show efficacy in a 2017 trial of acute respiratory distress patients. Apeiron Biologics has received approval to test recombinant ACE2 in COVID-19 patients in Europe.

Epidemiology

An analysis of 1,591 patients in 72 regional hospitals in Lombardy, Italy, published in JAMA, reports that mortality in the intensive care unit was 26%. Among the patients studied, the majority were male (82%) and had extensive comorbidities, confirming previous reports that these factors may play a part in the severity of the disease. The most frequent comorbidity was hypertension (49% overall and 62% of deaths).

Among those patients whose files had respiratory support data, 88% were put on mechanical ventilation.

A Brief Communication, published in Nature Microbiology, reports evidence of community spread of SARS-CoV-2 within the city of Wuhan, China. The researchers re-analysed 640 throat swabs collected for influenza-like illness in Wuhan between October 2019 and January 2020. Nine of the swabs tested positive for SARS-CoV-2; the first positive sample was collected in the first week of 2020.

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