Effects of Coronavirus Disease 2019 (COVID-19) on Peripheral Blood Lymphocytes and Their Subsets in Children: Imbalanced CD4+/CD8+ T Cell Ratio and Disease Severity

Abstract

Introduction: While pathogenesis in COVID-19 is not fully known and the effects between SARS-CoV-2 and the immune system are complicated, it is known that lymphopenia, hyper-inflammatory responses, and cytokines play an important role in the pathology of COVID-19. While some hematological abnormalities have been described among the laboratory features of COVID-19, there have not been studies reported on lymphocyte subset analyses in children. The aim of this study was to describe lymphocyte subsets in pediatric patients with mild/moderate or severe COVID-19.Methods: The subjects in the study were children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia confirmed with the real-time RT-PCR. The subjects were admitted to the Children's Medical Center, affiliated with the Tehran University of Medical Sciences, between March 7th and June 10th of 2020. The complete blood counts and lymphocyte subpopulations were analyzed for each patient.Results: The study included 55 hospitalized patients with confirmed SARS-CoV-2 infection (34 patients (62%) with an observed mild/moderate case of the disease and 21 patients (38%) with severedisease). Lymphocyte counts were found to be lower in patients with a severe case (mean ± SD 1.6 ± 0.9 in the severe group vs. 2.3 ± 2.2 in the mild group). Compared to the group with mild/moderate pneumonia, children with severe pneumonia had an increased count of CD8+ T cell and a lower percentage of CD4+ T cell. However, the differences between the groups were negligible. Interestingly, the severe group had a lower CD4+/CD8+ T cell ratio compared to the mild group (1.1 ± 0.47 vs. 1.4 ± 0.8, p-value: 0.063). CD4+/CD8+ T cell ratio <2, 1.5, and 1 was found in 48 (87%), 40 (73%), and 19 cases (35%). All of the seven cases in which the subject passed (13%) had CD4+/CD8+ T cell ratio of <2, 86% had CD4+/CD8+ T cell ratio of <1.5, and 29% had CD4+/CD8+ T cell ratio of <1.Conclusion: The CD4+/CD8+ T cell ratio was lower in patients with severe COVID-19 compared to those with mild/moderate form of disease. However, although a decline in CD4+/CD8+ ratio may serve as a useful metric in analyzing of the derangement in immune responses in patients with severe COVID-19, further study with larger sample sizes is highly recommended.

The Impact of Past COVID-19 Infection on Selected Lymphocyte Subsets in Pediatric Patients

“…Such pathology is mainly observed in HIV and correlates with an advancement of the disease. Still, in COVID-19 patients a significance of this finding is unclear [ 25 ]. On the contrary, Argun et al did not find any differences neither in total lymphocyte count nor in CD4 + /CD8 + index between mild/asymptomatic COVID-19 pediatric patients and controls.…”

Immune Response to SARS-CoV-2 Infections in Children with Secondary Immunodeficiencies

“…Various researchers have also assessed lymphocyte subsets in immunocompetent children with COVID-19. They proved that children, unlike adults, rarely have lymphopenia in the course of SARS-CoV-2 infections, and if present, its degree correlates with the severity of the disease and usually affects all lymphocyte subsets [ 16 ]. Our study did not reveal a tendency for lymphopenia in children, regardless of the severity of COVID-19.…”

Spontaneous remission of nephrotic syndrome associated with COVID-19 infection in an 8-year-old boy

“…14 Various studies demonstrated T lymphocyte abnormalities in COVID-19 infection and as in other viral infections these alterations may be responsible for the relapses of nephrotic syndrome. 15 Except for multisystem inflammatory syndrome, the most remarkable feature of COVID-19 is the lower risk of severe forms of disease in children when compared with adult counterparts. But even asymptomatic disease course may be responsible for relapses in nephrotic syndrome patients as demonstrated here.…”