Effector memory T cell subset CD45RA−CCR7−CD27−CD28− EM3 increases in direct proportion to the disease severity of COVID‐19

COVID‐19, which emerged in December 2019 and continues to wreak havoc, has led to the death of many people around the world. In this study, we aimed to uncover the variables underlying the exacerbation of the disease by considering the changes in T cell subsets in adults and juveniles with different disease severity of COVID‐19. Peripheral blood samples of 193 patients (128 adults and 65 juveniles) diagnosed with COVID‐19 were evaluated in a flow cytometer, and a broad T cell profile was revealed by examining T cell subsets in terms of exhaustion and senescence. We found remarkable differences in the effector memory (EM;CD45RA−CCR7−) cell subsets of severe pneumonia cases. The frequencies of EM2 CD4+ T, EM3 CD4+ T, EM3 CD8+ T, EM2 DN T and EM3 DN T cells were found to increase in severe pneumonia cases. Consistently, these cells were found in juveniles and uncomplicated adults in similar or lower proportions to healthy controls. The findings of our study provide a view of the T cell profile that may underlie differences in the course of COVID‐19 cases in juveniles and adults and may provide new insights into the development of effective treatment strategies.

Effector memory T cell subset

COVID-19, which emerged in December 2019 and continues to wreak havoc, has led to the death of many people around the world. In this study, we aimed to uncover the variables underlying the exacerbation of the disease by considering the changes in T cell subsets in adults and juveniles with different disease severity of COVID-19. Peripheral blood samples of 193 patients (128 adults and 65 juveniles) diagnosed with COVID-19 were evaluated in a flow cytometer, and a broad T cell profile was revealed by examining T cell subsets in terms of exhaustion and senescence. We found remarkable differences in the effector memory (EM;CD45RA(-)CCR7(-)) cell subsets of severe pneumonia cases. The frequencies of EM2 CD4(+) T, EM3 CD4(+) T, EM3 CD8(+) T, EM2 DN T and EM3 DN T cells were found to increase in severe pneumonia cases. Consistently, these cells were found in juveniles and uncomplicated adults in similar or lower proportions to healthy controls. The findings of our study provide a view of the T cell profile that may underlie differences in the course of COVID-19 cases in juveniles and adults and may provide new insights into the development of effective treatment strategies.

Effector memory T cell subset CD45RA‐CCR7‐CD27‐CD28‐EM3 increases in direct proportion to the disease severity of COVID‐19

COVID‐19, which emerged in December 2019 and continues to wreak havoc, has led to the death of many people around the world. In this study, we aimed to uncover the variables underlying the exacerbation of the disease by considering the changes in T cell subsets in adults and juveniles with different disease severity of COVID‐19. Peripheral blood samples of 193 patients (128 adults and 65 juveniles) diagnosed with COVID‐19 were evaluated in a flow cytometer, and a broad T cell profile was revealed by examining T cell subsets in terms of exhaustion and senescence. We found remarkable differences in the effector memory (EM;CD45RA‐CCR7‐) cell subsets of severe pneumonia cases. The frequencies of EM2 CD4+ T, EM3 CD4+ T, EM3 CD8+ T, EM2 DN T and EM3 DN T cells were found to increase in severe pneumonia cases. Consistently, these cells were found in juveniles and uncomplicated adults in similar or lower proportions to healthy controls. The findings of our study provide a view of the T cell profile that may underlie differences in the course of COVID‐19 cases in juveniles and adults, and may provide new insights into the development of effective treatment strategies.

The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.

The Relationship between COVID-19 Severity and Bacillus Calmette-Guérin (BCG)/ Mycobacterium tuberculosis exposure history in healthcare workers: a multi-center study.

The COVID-19 pandemic has brought countries' health services into sharp focus. It was drawn to our group's attention that healthcare workers (HCWs) had a lower mortality rate against higher COVID-19 incidence compared to the general population in Turkey. Since risk of exposure to tuberculosis bacillus among healthcare workers are higher than the population, we aimed to investigate if there is a relationship between BCG and Mycobacterium tuberculosis exposure history with COVID-19 severity in infected HCWs. This study was conducted with 465 infected HCWs from thirty-three hospitals to assess the relationship between COVID-19 severity (according to their hospitalization status and the presence of radiological pneumonia) and BCG and Mycobacterium tuberculosis exposure history. HCWs who required hospital admission had significantly higher rates of chronic diseases, radiological pneumonia, and longer working hours in the clinics. Higher rates of history of contact and care to tuberculosis patients, history of tuberculosis, and BCG vaccine were observed in hospitalized HCWs. HCWs who had radiological pneumonia had a significantly increased ratio of history of care to tuberculosis patients and a higher family history of tuberculosis. The findings from our study suggest that the lower mortality rate despite the more severe disease course seen in infected HCWs might be due to frequent exposure to tuberculosis bacillus and the mortality-reducing effects of the BCG vaccine.

Do initial hematologic indices predict the severity of COVID-19 patients?

Background/aim: In this study, we aimed to evaluate the initial hematological findings analyzed on admission in confirmed COVID-19 patients who were transferred to the intensive care unit (ICU), to predict possible hematological indices. Materials and methods: Initial neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), red cell distribution width to platelet ratio (RPR), mean platelet volume to platelet ratio, and lymphocyte multiplied by platelet count (LYM × PLT), of 695 patients with laboratory-confirmed COVID-19 were investigated and comparisons were made between the mild/moderate and severe groups. Results: The proportion of COVID-19 cases admitted to the ICU was 3.9%. The median age of patients admitted to the ICU was significantly higher than those who were not; [68.5 (interquartile range (IQR); 21.5] years vs. 41.0 (IQR; 15.7) years; P < 0.001. Severe cases had higher NLR (6.6 vs. 2.4; P < 0.001), and MLR (0.40 vs. 0.28; P = 0.004) and lower PLR (180.0 vs. 129.0; P < 0.001) compared to that of mild or moderate patients. Among all of the parameters, the ROC curve of NLR gave us the best ability to distinguish serious patients at an early stage (AUC = 0. 819, 95% confidence interval 0.729­0.910; P < 0.001). Conclusion: These data showed that age, initial NLR, PLR, and LYM × PLT were associated with the severity of COVID-19 disease and patients' need for the ICU. Therefore, initial hemogram parameters may be essential to predict the prognosis of COVID-19 patients.