Vaccines and clinical trials
Pharma giant Pfizer and a German biotech company named BioNTech have announced that a US phase 1/2 trial of their COVID-19 vaccine candidates, a group of four related RNA-based formulations, began this week. The initial US trial aims to recruit up to 360 participants and follows a smaller German study of 12 volunteers, which began late last month.
Roche’s COVID-19 antibody test has been granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA). The company claims its test has 100% sensitivity and over 99.8% specificity at day 14 post-PCR confirmation of SARS-CoV-2 infection. The FDA has made information on the performance of COVID-19 serology tests, based on data submitted for EUA, available on a dedicated webpage.
A retrospective study of 7,336 confirmed COVID-19 cases in Hubei, China, published in Cell Metabolism, confirmed that type 2 diabetes (T2D) significantly increases the risk of all-cause mortality (an in-hospital death rate of 7.8% versus 2.7% for non-diabetic individuals). In the cohort of COVID-19 patients with T2D, those with well-controlled blood glucose were less likely to develop acute respiratory distress syndrome or to die in hospital.
The Annals of Internal Medicine have published findings from the autopsies of 12 COVID-19 patients who died in Hamburg, Germany. Seven of the twelve had deep vein thrombosis, and pulmonary embolism was the direct cause of death in four cases. In addition to high SARS-CoV-2 levels in the lungs of all patients, five had high viral RNA titers in the liver, kidney or heart.
A team led by Tsinghua University’s Chen Dong analysed blood collected from 14 recently recovered COVID-19 patients. As reported in Immunity, all 14 patients had significant titers of IgM and IgG against SARS-CoV-2 antigens. Thirteen of the fourteen patients’ sera exhibited neutralizing activity, as scored in a pseudovirus assay. Peripheral blood mononuclear cell analysis revealed a significant correlation between neutralizing antibody levels and circulating nucleocapsid protein-specific T cells.
A team led by Max Crispin at the University of Southampton analysed glycosylation of the SARS-CoV-2 spike protein by site-specific mass spectrometry. The results, published in Science, suggest that the protein is not densely glycosylated. The potential vulnerability conferred by this reduced ‘glycan shield’ may be good news for immunization strategies targeting the SARS-CoV-2 spike protein.
Frank Grosveld (Erasmus Medical Center), Berend-Jan Bosch (Utrecht University) and collaborators screened 51 hybridomas derived from H2L2 chimeric mice immunized with SARS spike protein for cross-reactivity to the SARS-CoV-2 spike protein S1 subunit. One of the four cross-reactive clones was used to generate a fully humanized monoclonal antibody, termed 47D11, which showed neutralizing activity against both SARS-CoV and SARS-CoV-2. The authors note that “in an interesting twist, rather than directly blocking spike protein’s binding to ACE2, 47D11 appears to block the subsequent membrane fusion step”. The results, published in Nature Communications, support the existence of an unknown alternative mechanism of SARS-CoV-2 neutralization by anti-spike antibodies.
Daniel Wrapp et al. report in Cell that a single-domain antibody cloned from a llama immunized with SARS-CoV-1 spike protein also has neutralizing activity against SARS-CoV-2. These so-called ‘nanobodies’ have several potential therapeutic advantages, including increased stability and ease of production. A previous study on a lamb model of respiratory syncytial virus infection showed that nanobodies can be delivered via nebulization.
While several groups have developed animal models of COVID-19, Yusen Zhou at the Beijing Institute of Microbiology and Epidemiology and collaborators have pursued a complementary strategy of selecting, by multiple in vivo passages in 9-month-old mice, a mouse-adapted SARS-CoV-2 strain. The strain, termed mouse-adapted SARS-CoV-2 at passage 6 (MACSp6), infects both young and aged mice and provokes a moderate pneumonia, as reported in a non-peer-reviewed preprint in bioRxiv.
Epidemiology and public health
Analysis of contact survey data in Wuhan and Shanghai shows that social isolation protocols reduced the number of daily contacts per participant sevenfold (from 14.6 to 2.0) at the outbreak’s epicentre, in Wuhan. Modeling based on this data suggests that social distancing alone would be sufficient to halt the outbreak. The study, published in Science, estimates that one of the more controversial measures, school closures, reduced peak incidence by 40–60%.
A study published in Nature concludes, using anonymized smartphone data and epidemiological modeling, that social distancing measures, early identification and contact tracing were essential to COVID-19 outbreak control in mainland China. The authors recommend that maintaining vigilance to allow early identification and isolation of new cases should be a part of re-opening plans.