Interferon Beta-1α ring prophylaxis to reduce household transmission of SARS-CoV-2 (preprint)

Background Evidence suggests that early, robust type 1 interferon responses to SARS-CoV-2 are critical determinants for COVID-19 disease outcomes, accelerating viral clearance and limiting viral shedding. Accordingly, we undertook a ring prophylaxis study to determine whether pegylated IFN{beta}-1 could reduce SARS-CoV-2 household transmission. Methods A household cluster randomized controlled study of IFN{beta}-1 administered to non-hospitalized, symptomatic COVID-19 index cases and treatment-eligible household contacts aged 18-70 years compared to standard care, was conducted. Following randomization participants received IFN{beta}-1 on days 1, 6, and 11 or standard care. Viral shedding was determined by sequential salivary polymerase chain reaction measurements until day 29 in both study arms. A post-hoc at risk population was defined as households where the index case was positive at the start of the study and there was at least one treatment eligible contact in a household who tested negative for SARS-CoV-2. Frequentist and Bayesian analyses were undertaken to determine the effects of treatment on (i) reducing viral shedding in index cases and (ii) reducing viral transmission to post-exposure household contacts. Results In total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFN{beta}-1 and 565 to standard care. Based on intention to treat and per protocol analyses, IFN{beta}-1 treatment was ineffective. However, in the at risk population, the relative risk of infection was reduced by 23% in treated individuals and that there was a 95% probability that IFN{beta}-1 reduced household transmission. Conclusion Ring prophylaxis with IFN{beta}-1 reduces the probability of SARS-CoV-2 transmission within a household.

ACE2 Expression is elevated in Airway Epithelial Cells from aged and male donors but reduced in asthma (preprint)

Rationale: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter airway epithelial cells (AECs). Objective: To determine what factors are associated with ACE2 expression particularly in patients with asthma and chronic obstructive pulmonary disease (COPD). Methods: We obtained upper and lower AECs from 145 people from two independent cohorts, aged 2-89, Newcastle (n=115), and from Perth (n= 30) Australia. The Newcastle cohort was enriched with people with asthma (n=37) and COPD (n=38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry were assessed by quantitative PCR, protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AECs. Results: Increased gene expression of ACE2 was associated with older age (p=0.02) and male sex (p=0.03), but not pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma (p=0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in asthma (p=0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface was increased (p=0.02). ACE2 protein levels were lower in endobronchial biopsies from asthma patients. Conclusions: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.