Lymphocytic infiltration in the lungs of fatal cases of COVID-19 coincides with cessation of viral replication 4444

Abstract Description Background SARS-CoV-2 causes a severe pulmonary infection. Few studies to date have addressed the immune response in the lungs of human cases of COVID-19 or longitudinally sampled at intervals of time from symptom onset. To address this we performed Imaging Mass Cytometry (IMC) on lung tissue from fatal cases of COVID-19. Methods Lung tissue from 45 autopsy cases of COVID-19 was labeled with a 39-marker panel of metal-conjugated antibodies for IMC. Adjacent tissue was used for nucleic acid extraction to quantify SARS-CoV-2 nucleocapsid RNA by digital droplet PCR and SARS-CoV-2 sub-genomic RNA (sgRNA). Results Patients with positive SARS-CoV-2 sgRNA had a higher viral burden (414.9 vs 0.0126 copies/ng RNA, p < 0.0001) and a shorter interval to death (7.5 vs 29 days, p < 0.0001). Patients with positive sgRNA had fewer CD4 T cells (33.5 vs 103, p = 0.0029), CD8 T cells (25 vs 91, p = 0.0098), and B cells (19.5 vs 52, p = 0.0145) per lung region of interest (ROI). There was no significant difference between the number of neutrophils (422 vs 742, p = 0.0623) or macrophages (390 vs 567, p = 0.397) per ROI. Conclusions We found that lymphocytes significantly increase in the lungs of patients who died from COVID-19 after viral replication ceases. This may be due to inhibition of cellular immunity by actively replicating virus or reflect clearance of the virus by lymphocytes. Additional work is required to characterize the phenotype and activation status of immune cells in these tissues. Funding Sources This work was supported by the Intramural Research Program, NIAID, NIH Topic Categories Viral Immunology (VIR)