Peripheral innate and adaptive immune cells during COVID‐19: Functional neutrophils, pro‐inflammatory monocytes, and half‐dead lymphocytes

Abstract

Background A better understanding of innate and adaptive cells in COVID‐19 is necessary for the development of effective treatment methods and vaccines. Methods We studied phenotypic features of innate and adaptive immune cells, oxidative burst, phagocytosis, and apoptosis. One hundred and three patients with COVID‐19 were grouped according to their clinical features into the categories of mild (35%), moderate (40.8%), and severe (24.3%). Results Monocytes were CD16+ pro‐inflammatory monocytes and tended to shed their HLA‐DR, especially in severe cases (p < 0.01). Neutrophils were mature and functional, although a decline of their CD10 and CD16 was observed (p < 0.01). No defect was found in the reactive oxygen species production and their apoptosis. The percentage of natural killer cells was in the normal range, whereas the percentages of CD8+NK and CD56+T lymphocytes were found to be high (p < 0.01). Although the absolute numbers of all lymphocyte subsets were low and showed a tendency for a gradual decrease in accordance with the disease progression, the most decreased absolute number was that of B lymphocytes, followed by CD4+ T cells in the severe cases. The percentages of double‐negative T cells; HLA‐DR+CD3+ and CD28−CD8+ subsets were found to be significantly increased. Importantly, we demonstrated the increased baseline activation of caspase‐3 and increased lymphocyte apoptosis. Conclusion We suggest that SARS‐CoV‐2 primarily affects the lymphocytes and not the innate cells. The increased baseline activation of Caspase‐3 could make the COVID‐19 lymphocytes more vulnerable to cell death. Therefore, this may interrupt the crosstalk between the adaptive and innate immune systems.

Expansion of CD56dimCD16neg NK Cell Subset and Increased Inhibitory KIRs in Hospitalized COVID-19 Patients

“…On the other hand, the CD56 neg CD16 bright NK cell subset was found to be depleted in COVID-19 patients in our study; this subset is reported to be an unconventional cytotoxic mediator for chronic diseases [15]. NK cells participate in a complex network, interacting with dendritic cells as well as T and B cells through chemokines and a variety of cytokines involved in the differentiation and function of NK cells [23,30,31,38,39].…”

“…The CD56 dim CD16 pos NK cell subset is characterized by a strong cytotoxicity and high expression of KIR receptors. CD16 binds to the Fc part of the IgG molecules mediating antibody-dependent cellular cytotoxicity (ADCC), allowing the killing of target cells through cytotoxic function (CD56 dim ) or leading to a late inflammatory process (CD56 bright ) [30,31]. In this way, the COVID-19 patients in our study showed a deep depletion of both CD56 dim CD16 dim and CD56 dim CD16 bright NK cell subsets.…”

Efficacy and Safety of Lithium Treatment in SARS-CoV-2 Infected Patients

“…In our clinical trial, lithium increases lymphocyte levels much more rapidly, and lithium patients remain lymphogenic for fewer days than controls. A recent study shows that SARS-CoV-2 mainly affects lymphocytes and not innate cells ( Ekşioğlu-Demiralp et al, 2021 ), resulting in a dysregulation of the system between the adaptive and innate immune systems. Our data show that lithium is a good treatment to rapidly increase lymphocyte levels and prevent the severity of infection.…”

Evaluation of Covid-19-Associated Hypercoagulability with Functional Coagulation Assays and Extracellular Vesicles

“…Several studies have reported increased levels of pro-inflammatory cytokines (e.g. IL-6, TNF-α, Type 1 IFN), as well as reduced IFN-γ that result in the apoptosis of CD4+ lymphocytes 18 . COVID-19 patients with ARDS often show elevated levels of D-dimer, IL-6 and fibrinogen, and have poor prognosis 19 .…”