Yile Dai

Abstract: Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

TL;DR: In this article, a high-throughput autoantibody discovery technique known as rapid extracellular antigen profiling was used to screen a cohort of 194 individuals infected with SARS-CoV-2, comprising 172 patients with COVID-19 and 22 health care workers with mild disease or asymptomatic infection, for auto-antibodies against 2,770 proteins (members of the exoproteome).

TL;DR: The findings suggest that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses, and age-dependent factors may modulate the antiviral immune response.

TL;DR: Evidence is provided for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS -CoV-2 is demonstrated.

TL;DR: It is established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantsibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection.