Abstract
The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
Highlights
Respiratory failure/acute respiratory distress syndrome (ARDS) has been identified as the leading cause of death in COVID-19 by numerous studies [1,2,3,4]
The role of dendritic cells (DCs) in COVID-19 has only recently begun to attract the attention of researchers
In COVID-19, there seems to be a decline in the count of plasmacytoid dendritic cells (pDCs) [20] and a shift toward myeloid dendritic cells (mDCs) [21, 22] in the peripheral blood
Summary
Respiratory failure/acute respiratory distress syndrome (ARDS) has been identified as the leading cause of death in COVID-19 by numerous studies [1,2,3,4]. Complications contributing to organ failure and death in severe cases of COVID-19 include a dysregulated immune system accompanied by a cytokine storm [11, 12]. [17] Dendritic cells can be thought of as a link between the innate and the adaptive immune system [18]. While they usually only make up for a small part of immune cells in lungs [19], their number rapidly increases shortly after the onset of an inflammatory process. In COVID-19, there seems to be a decline in the count of pDCs [20] and a shift toward mDCs [21, 22] in the peripheral blood
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