Unconventional T Cells in COVID-19
Bronchial alveolar lavage fluid analysis of 3 COVID-19 patients reveals a high number of NKT cells during the acute phase of infection (Kim et al., 2020). This increase in NKT cells was similarly reflected in the peripheral blood. Conversely, a decline in the number of these cells was found during the recovery phase. These results thus suggest a close correlation of the NKT cell activity in COVID-19 and the presence of these cells may be required for the clearance of virus during the initial phase of infection. Concomitantly, increased infiltration and activity of these cells may lead to a more severe outcome associated with eosinophilic pneumonia, as shown in one study. However, no direct correlation of these cells types with disease severity was found, probably due to meagre sample size (n = 3). Further, the samples used in this study were collected at different time points after the onset of symptoms, which may have complicated the interpretation of the results.
In another study on 30 COVID-19 patients with a varied range of disease severity from mild, moderate to severe, a reduction in the total peripheral blood NKT cells was seen across groups, with no difference in the overall number between ICU (n = 10) and non-ICU patients (n = 11) (Mazzoni et al., 2020). Similarly, a study by Jouan et al. (2020) found a decrease in NKT and MAIT cells in the peripheral blood of COVID-19 patients (n = 30, with varied disease severity) as compared to healthy controls (n = 20). This decline in circulating MAIT cells was concomitantly associated with an increase in these cells in the endotracheal aspirates (ETA) obtained from critically ill patients who needed mechanical ventilation (n = 12), while no changes in NKT cell number in ETA were detected. The presence of circulating IL-18 reflected the activation of these cells, and the expression of PD-1 suggested subsequent exhaustion throughout the infection. This study thus indicates that the presence of the activated status of these unconventional T cells may serve as a predictive assessment of disease severity. More research about the activation, proliferation and differentiation status of these cells to the disease severity and local vs systemic effect is needed to fully understand their contribution in COVID-19 (Chen and John Wherry, 2020).