Signatures of mast cell activation are associated with severe COVID-19 (preprint)

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in severely ill patients and the pathophysiology of disease is thought to be immune-mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens, often promoting inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and non-human primates. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype. MC activation in humans was confirmed, through detection of the MC-specific protease, chymase, levels of which were significantly correlated with disease severity. These results support the association of MC activation with severe COVID-19, suggesting potential strategies for intervention.

Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease (preprint)

PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

Assessing the Impact of the COVID-19 Pandemic on Medical Student Education (preprint)

Background: The full impact of the COVID-19 global pandemic has yet to be seen, yet medical education has already been critically disrupted. As U.S. hospitals were forced to aggressively limit non-essential care to preserve personal protective equipment and minimize COVID-19 exposure, in-person education and hands-on training was nearly eliminated for students. The objective of this study was to immediately and comprehensively investigate the impact of the COVID-19 pandemic on medical student education. Medical students in the U.S. were invited to complete an online survey about the impacts of the COVID-19 pandemic on their medical education experience. Students provided basic demographic information and answered questions about the impact of COVID-19 on their training/education, finances, and mental health. Results: Medical students reported nearly 18 fewer hours of patient care per week, an immediate switch to virtual learning (74%) along with grading changes (62%), and widespread cancellation of national exams. Additionally, 55% of fourth year students graduated early to provide direct clinical care. Students across years felt that changes from the pandemic would negatively affect their residency applications and that upcoming rotations would be impacted (p<0.001). Students reported that the pandemic had negatively affected their finances, increased their anxiety/stress, increased their feelings of burnout, and negatively impacted their work-life balance (p<0.001). Conclusion: Medical education has been critically impacted by COVID-19. Student perceptions and evaluation of experiences to date should be considered as educators prepare to ready students for academic and professional transitions in the context of continued COVID-19 disruptions and distanced learning.