Immunogenicity and safety of the CoronaVac inactivated SARS-CoV-2 vaccine in people with underlying medical conditions in China: a retrospective study (preprint)

People living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national COVID-19 vaccination campaign in China due to the uncertainty of vaccine safety and effectiveness. However, this special population made up of most severe symptom and death cases among SARS-CoV-2 infected patients and should be prioritized in vaccination program. Thus, safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitancy in this special population. Here, we report a retrospective cohort study evaluating the immunogenicity and safety of the inactivated COVID-19 vaccine, CoronaVac, in people with at least one of the six common diseases, focusing on seniors (N = 969). We found that CoronaVac is as safe in people with chronic diseases as that in healthy control, without serious adverse event reported in this study. By day 14-28 post vaccination, we observed no significant difference for the antibody responses between disease groups and healthy control, except for the coronary artery disease (p=0.03) and chronic respiratory disease group (p=0.04) showing moderate reduction. Such difference diminished by day 90 and 180, as neutralizing antibodies significantly reduced in all participants. Most people showed detectable SARS-CoV-2-specific T cell response at day 90 and day 180 without significant difference between disease groups and healthy control. Overall, our results highlight the comparable safety, immunogenicity and cellular immunity memory of CoronaVac in seniors and people living with chronic diseases, addressing vaccine hesitancy for this special population.

SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury (preprint)

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.