Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation.

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

A critical COVID-19 patient managed with timely evaluation, early prone positioning ventilation, and a multi-pronged pharmacotherapy

There is not yet a standard drug regimen for the treatment of coronavirus disease 2019 (COVID-19) patients. Here, we summarize our experience and successful treatment plan with a critical COVID-19 patient who required mechanical ventilation (MV). A 56-year-old man presented with a fever, cough, and dyspnea. He had not been to a medium/high risk epidemic area in the past year and had no family history of a disease cluster. COVID-19 was suspected based on clinical symptoms and radiologically detected ground-glass lung changes in the context of a normal white blood cell count (WBCC) and lymphocyte fraction (L%). A diagnosis of COVID-19 was confirmed by nucleic acid testing. Initially, he was started on noninvasive ventilation (NIV). Because his respiratory distress worsened over the following 2 h, he was transitioned to mechanical ventilation (MV), placed in prone positioning 12 h/day, and given a multi-pronged pharmacotherapy regimen that included an antiviral cocktail (lopinavir/ritonavir plus α-interferon), an immunity enhancer (thymosin α1), an anti-coagulant to prevent thrombosis (heparin). He was given an antibiotic to treat an opportunistic nosocomial infection. The patient has recovered well. The regimen applied in this case of timely evaluation, early prone positioning with MV, and a multi-pronged pharmacotherapy may be an effective strategy for patients with critical COVID-19, particularly with respect to preventing life-threatening worsening of the illness. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)