Two distinct immunopathological profiles in autopsy lungs of COVID-19

Abstract

Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.

Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses

“…Second, given that IL1-β and other pro-inflammatory cytokines are primary targets of monoclonal antibody therapeutics under investigation 36 , these results raise the question of whether further suppression early during the course of the disease may be detrimental in the setting of an already suppressed inflammatory response to SARS-CoV-2. That said, it is important to consider that the attenuation of inflammatory pathways we observed may not hold over the course of the disease, especially in severe cases of COVID-19 where the lower and not upper respiratory tract is the primary site of pathology [37][38][39] . Additional work examining the temporal dynamics of the host response to SARS-CoV-2 in both the upper and lower airways is needed to address these outstanding questions.…”

SARS-CoV-2 leads to a small vessel endotheliitis in the heart

“…Discrepant viral evidence results between qRT-PCR, ISH and IF/IHC technologies have been the subject of several recent studies 60 , 61 , 62 , 63 . The presence of current viral load, the phase of disease course as well as the severity of COVID-19 all have impact on the detection rate of viral RNA or viral protein in a given sample 60 , 61 , 62 , 63 .…”

Akt-Fas to Quell Aberrant T Cell Differentiation and Apoptosis in Covid-19

“…In an autopsy series, Nienhold et al describe two “immunopathological reaction patterns” ( 18 ). The first is characterized by lung infiltration of CD8+ PD1+ T cells that they speculate are causing diffuse alveolar damage (DAD) but better viral control, and they question whether the PD-1 positivity denotes exhaustion, but no conclusions are drawn.…”

“…The first is characterized by lung infiltration of CD8+ PD1+ T cells that they speculate are causing diffuse alveolar damage (DAD) but better viral control, and they question whether the PD-1 positivity denotes exhaustion, but no conclusions are drawn. The other immunopathological pattern is characterized by significantly higher CD4+ T cell lung infiltrates and a higher viral load ( 18 ). They conclude this suggests CD8+ T cells indeed contribute to viral clearance but may exert a degree of end organ damage ( 18 ).…”

“…The other immunopathological pattern is characterized by significantly higher CD4+ T cell lung infiltrates and a higher viral load ( 18 ). They conclude this suggests CD8+ T cells indeed contribute to viral clearance but may exert a degree of end organ damage ( 18 ). Schurink et al found either one of two types of T cell infiltration in all autopsies: a CD8+ infiltrate causing DAD, or a CD4+ interstitial infiltrate with exudative diffuse alveolar damage and bronchopneumonia ( 19 ).…”