Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19

Abstract

To investigate the immune status of people who previously had COVID-19 infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19+ B cells (69.70%), and CD56+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 (100%), IL-4 (80.88%), IL-6 (79.41%), IL-10 (98.53%), TNF-α (89.71%), IFN-γ (100%) and IL-17 (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells, along with significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 levels, and IL-6 positively correlated with TNF-α and IFN-γ. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

Recovery of functional fitness, lung function, and immune function in healthcare workers with nonsevere and severe COVID-19 at 13 months after discharge from the hospital: a prospective cohort study

“…Patients infected with the SARS-COV-2 (Qin et al, 2020;Wan et al, 2020), SARS-COV (Huang et al, 2005), H7N9 (Zhou et al, 2013) and H5N1 (Henter et al, 2006) were found to have increased levels of cytokines (especially IL-6) which indicated an uncontrolled systemic inflammatory reaction process, and might lead to severe immune pathological damage. Similar to the present study, a study in China demonstrated that two weeks post recovery, patients with COVID-19 had elevated levels of IL-6 (20.59%), IL-4 (19.12%), TNF-α (10.29%), IL-17 (2.94%) and IL-10 (1.47%) while levels of cytokine in healthy controls were all in normal ranges (Hasichaolu et al, 2020). Another study in China compared the levels of cytokines in hospitalized and discharged patients with non-critical COVID-19, it reported that the levels of IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 were all upregulated in the hospitalized patients (Lin et al, 2020).…”

“…In addition to our previous study, there were also other researches indicating that the immune system gradually recovered after COVID-19 infection. A study in China found decreased levels of CD8 + T cells, CD19 + B cells, total lymphocytes, CD3 + T cells, CD4 + T cells and CD56 + NK cells in COVID-19 patients two weeks post recovery (Hasichaolu et al, 2020). Another study in China suggested that the levels of neutrophils, monocytes, NK cells, and CD4 + T cells increased, and levels of total lymphocytes and CD8 + T cells significantly decreased in discharged non-critical patients with COVID-19 than those hospitalized (Lin et al, 2020).…”

Systemic cytokines in elderly patients with coronary heart disease at early recovery from COVID-19

“…В связи с этим авторы считают, что повышенные уровни указанных цитокинов являются независимыми предикторами эффективности реабилитации. Эти результаты также показывают постепенное восстановление иммунной системы после перенесенного COVID-19, а устойчивый гипервоспалительный ответ, обусловленный цитокинами, более 14 дней предполагает необходимость продолжения медицинского наблюдения после выписки из стационара, но для полного понимания последствий COVID-19 в аспекте цитокиновых нарушений, по мнению авторов, необходимы лонгитюдинальные исследования выздоровевших пациентов [14].…”

Association Of Hepcidin (HAMP) Gene Polymorphism And Cytokines, Iron, And Hb Levels In Covid-19 Patients

“…There was a study founded that the value of IL-6 remains high after infection with Covid-19 disease, and the explanation for this might be that postrecovery declines in lymphocyte subsets and elevations in cytokines have been found as independent predictors of rehabilitation success (40).…”