A study published in Clinical Immunology finds high percentages of NK CD57+ cells and CD56dim NK cells and low percentages of CD56bright and NKT cells among patients with coronavirus disease 2019 (COVID-19) compared to healthy donors. Moreover, the study shows that severe COVID-19 pneumonia and NKT cell reduction were independently associated.
“NK cells seem to be mainly involved in COVID-19 pneumonia. Little is known about NKT cells which represent a bridge between innate and adaptive immunity,” wrote Maria Antonella Zingaropoli, Sapienza University of Rome, Rome, Italy and colleagues. “To the best of our knowledge, this is the first study that characterized NK populations according to CD56 expression and that investigated NKT cells in patients with COVID-19 pneumonia correlating these subsets to clinical parameters and severity of the disease.”
Between March 2020 and April 2020, 45 patients with laboratory confirmed COVID-19 pneumonia (median age, 62 years) hospitalized at Policlinico Umberto I, Sapienza University of Rome, Italy, were included in the study. In addition, 19 healthy donors with similar age and sex were enrolled as the control group. COVID-19 patients were stratified into severe group (n = 14), defined as breathing rate ≥ 30 times/min, pulse oximeter oxygen saturation (SpO2) ≤93% at rest and ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≤300 mmHg, and non-severe group (n = 31), defined as cases with fever, respiratory symptoms and radiographic evidence of pneumonia.
The researchers found that polymorphonuclear (PMN) cell percentage/T cell percentage (PMN/T) ratio was significantly higher in COVID-19 patients compared to healthy donors (P < 0.05). Additionally, COVID-19 patients had significantly lower percentages of total T cells (0.01 < P < 0.001) and CD3 + CD8- cells (P < 0.0001) than healthy donors. Meanwhile, a significantly higher percentage of CD3 + CD8-CD28-CD57+ cells was observed in COVID-19 patients compared to controls (P < 0.0001).
On the other hand, a higher percentage of NK CD57+ cells was observed in COVID-19 patients compared to healthy donors (0.01 < P < 0.001). COVID-19 patients also showed a significantly lower percentage of CD56bright NK cells (0.01 < P < 0.001) and a significantly higher percentage of CD56dim NK cells (P < 0.05) compared to healthy donors.
In addition, COVID-19 patients, compared to healthy donors, were found to have a significantly lower percentage of NKT cells (0.01 < P < 0.001).
Among COVID-19 patients, a significantly higher PMN/T ratio (P < 0.0001) and a significantly lower percentage of total T cells (0.01 < P < 0.001), CD3 + CD8- cells (P < 0.05) and CD3 + CD8+ cells (P < 0.05) were observed in the severe group compared to the non-severe group. Further, the severe group showed a statistically lower percentage of NKT cells compared to the non-severe group (0.01 < P < 0.001).
Multiple linear regression analysis adjusted for gender and ages showed that higher PMN/T ratio and percentage of CD56dim NK cells as well as lower percentages of T cells, CD56bright NK cells and NKT cells were independently associated with COVID-19 pneumonia. In addition, the increase of PMN/T ratio and the reduction in the percentages of T cells, CD3 + CD8+ cells and NKT cells were independently associated with the severity of the disease in patients with COVID-19 pneumonia. Meanwhile, a negative correlation between PaO2/FiO2 (P/F) ratio and PMN/T ratio as well as a positive correlation between P/F ratio and T cell percentages, and between P/F ratio and the percentage of NKT cells were found.
“The present study showed a reduction of regulatory cell subsets in peripheral blood of patients with COVID-19 pneumonia suggesting that these subsets may play a crucial role in the COVID-19 pneumonia,” the authors concluded. “Specifically, the reduction of CD56bright NK and NKT cells observed in COVID-19 subjects may be explained by their potential recruitment into infected tissues (ie lung) leading to exaggerated or not controlled immune responses. Finally, the independent association between the severe COVID-19 pneumonia and low percentage of NKT cells as well as the positive correlation between NKT cells and P/F ratio that we found suggest a potential role of this subset as biomarker of the severity of the disease. Large-scale multicenter researches are needed to confirm our hypothesis.”
The limitations noted by the authors included the small sample size and the fact that most patients enrolled in the study had non-severe COVID-19 pneumonia. “However, we believe that these preliminary data could stimulate additional [research] on larger cohorts of patients with COVID-19 pneumonia to elucidate lymphocyte subsets in the immunological mechanisms of COVID-19,” the authors noted.