Abstract Background This study examined the early response of individuals with mild and asymptomatic SARS-CoV-2 infection by analysing cytokine, chemokine, and growth factor responses to CD4 and CD8 cell stimulation, aiming to understand early immune expressions that might inform potential targets for immunotherapy and interventions. Methods Between July and November 2020, we assessed 15 individuals, predominantly males with a median age of 25. Of these, eight displayed mild symptoms, while seven were asymptomatic. We evaluated their response to CD4 and CD8 T-cell stimulation by measuring 48 unique cytokines, chemokines, and growth factors. Random forest and principal component analysis (PCA) methods were utilized to identify pivotal cytokines and classify them according to their functional roles. Results Consistently low levels of specific cytokines suggested their minimal impact on immune activation processes, moderate concentrations of others after CD4 or CD8 T-cell stimulation, implied vital roles in immune modulation, cell recruitment and activation, cytokine regulation, and tissue healing. Optimal immune response was achieved through a balanced interplay between pro-inflammatory and anti-inflammatory processes, striking a delicate equilibrium that averted undue inflammation. A persistent immune response was marked by consistent and moderate levels of specific cytokines and growth factors sustained over the observation period. TGF-alpha, GRO-alpha, IL-6, and IL-10 emerged as promising biomarkers for symptom manifestation and immune activation. Predictive analyses highlighted IL-8, G-CSF, MCP-1, EGF, and MIP-1-alpha as pivotal cytokines in stimulating CD4 or CD8 cells, with MCP-1 and IL-8 particularly displaying persistence. Conclusion This research elucidates the immune expressions during the initial phases of mild or asymptomatic COVID-19 infection. The research outcomes enhance comprehension of initial immune reactions and offer valuable insights for designing immunotherapies. Refining targeted immune responses can improve patient outcomes, manage viral infections, and advance global health. 

Silent Symptoms, Active Immunity: Insights into Early-Stage Cytokine Expressions in Ugandan Mild and Asymptomatic COVID-19 subjects

ABSTRACT There are limited data on inflammatory cytokines and chemokines; the humoral immune response; and main clinical laboratory parameters as indicators for disease severity and mortality in patients with critical and mild COVID-19 without comorbidities or immune-mediated diseases in Saudi Arabia. We determined the expression levels of major proinflammatory cytokines and chemokines; C-reactive protein (CRP); procalcitonin; SARS-CoV-2 IgM antibody and twenty-two clinical laboratory parameters and assessed their usefulness as indicators of disease severity and in-hospital death. Our results showed a significant increase in the expression levels of SARS-CoV-2 IgM antibody; IL1-β; IL-6; IL-8; TNF-α and CRP in critical COVID-19 patients; neutrophil count; urea; creatinine and troponin were also increased. The elevation of these biomarkers was significantly associated and positively correlated with in-hospital death in critical COVID-19 patients. Our results suggest that the levels of IL1-β; IL-6; IL-8; TNF-α; and CRP; neutrophil count; urea; creatinine; and troponin could be used to predict disease severity in COVID-19 patients without comorbidities or immune-mediated diseases. These inflammatory mediators could be used as predictive early biomarkers of COVID-19 disease deterioration; shock and death among COVID-19 patients without comorbidities or immune-mediated diseases. Graphical abstract

Association between inflammatory cytokines/chemokines, clinical laboratory parameters, disease severity and in-hospital mortality in critical and mild COVID-19 patients without comorbidities or immune-mediated diseases

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Association between inflammatory cytokines/chemokines, clinical laboratory parameters, disease severity and in-hospital mortality in critical and mild COVID-19 patients without comorbidities or immune-mediated diseases