Lymphopenia with relative sparing of Treg and CD8+ effector memory subsets define hypoxemic COVID-19 progression.
The absolute counts of total lymphocytes and T cells (both CD4+ and CD8+) in MD and SV groups were significantly decreased compared to AM, SM and SN (Supplementary figures S1 and S2A). Additionally, SV group also showed significant depletion of total lymphocytes compared to MDs. Similar depletion profiles (in MD and SV groups) were observed for both T (CD4+ and CD8+) and non T (B and NK) cell compartments. However, no significant difference was observed among mild patients (AM & SM) and compared to SN (Supplementary figure S2B-G). No apparent difference in the frequency of these lymphocyte subsets was observed except for a significant decrease for total T lymphocytes and a significant increase for total non-T lymphocytes in both MD and SV compared to other groups (Supplementary figure S2H-M). This suggested a pan lymphopenic phenotype that was observed in hypoxemic (MD and SV) individuals. Additionally, to evaluate the impact of lymphopenia on T cell compartment, distribution of CD4+ and CD8+ T cell subsets was also evaluated(11). Based on the surface expression of CD45RA and CCR7, CD4+ and CD8+ T cells were differentiated into Naïve (T­N; CD45RA+CCR7+), Central memory (TCM; CD45RA-CCR7+), Effector memory (TEM; CD45RA-CCR7-) and Terminally differentiated (TTD; CD45RA+CCR7-) T cells (Supplementary figure S3). While both MD and SV groups had significant depletion of absolute count for all CD4+ T cell subsets (Figure 1A), our findings do not support preferential depletion of any particular subsets in the CD4+ T cell compartment (Figure 1B). In CD8+ T cell compartment, comparison of absolute counts revealed profound depletion of all subsets in hypoxemic (MD and SV) individuals (Figure 1C). In contrast to the CD4+ T cell compartment however, we observed relatively lower frequency of naïve (CD8+ T­N) and concomitant elevation of effector memory (CD8+ TEM) frequency (Figure 1D). This reflected a distinct depletion profile for CD8+ T cells with relative sparing of effector memory cells.
Interestingly, while memory subsets of CD4+ T cell compartment seemed to be equally depleted in hypoxemic individuals, we report here depletion in Treg count that was exacerbated in the SV group (Figure 1E). Also, elevated frequency of CD4+ T regulatory cells in hypoxemic individuals indicated selective preservation of this subset (Figure 1F). When the non-lymphocyte monocyte compartment was evaluated, we observed an elevated frequency of the intermediate (CD14+CD16++) subset that defined both mild (AM, SM) and hypoxemic patients (Figure 1G).