ABSTRACT
Background: The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods: A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results: Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterised by a very low risk of mortality. Conclusions: By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
ABSTRACT
Background The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods Longitudinal prospective cohort of hospitalized patients with COVID-19 (N=254) was followed up to 35 d after admission (median, 8 d). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T, B, NK lymphocyte subsets and serum interleukin-6 response. We used machine learning to identify patterns of the immune response, and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results Overall, 45 (18%) patients died within 28 days after hospitalization. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR, 3.36–21.69;95% CI, 1.51–163.61 and HR, 8.39–10.79;95% CI, 1.20–82.67;P≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1- anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterized by a very low risk of mortality. Conclusions By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6 mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
ABSTRACT
Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted.
Because cancer patients are especially endangered by SARS-CoV-2 infection and have worse disease course and outcomes, it is crucial to protect them from this infection. This study was aimed at assessing protective antibodies after patients received mRNA-based SARS-CoV-2 vaccines. Protective antibodies (e.g., anti-SARS-CoV-2 S1 IgG antibodies) were assessed in patients' blood before vaccination, after the first and second doses and 3 months after a complete primary course vaccination. Patients' oncological treatment was unaffected by the vaccination received. The results of protective antibodies were also compared with healthy control subjects who were vaccinated in the same manner. More than 110 cancer patients participated and agreed to have their blood samples analyzed. The rate of antibody production was 96% after a complete primary course of vaccination and was similar with that of healthy control subjects. However, there were some differences noted regarding the oncological treatment that the patients were receiving, with patients who were treated with targeted therapy achieving the highest levels of protective antibodies. Adverse events after vaccination were mostly mild and did not interfere with patients' general performance. The rate of antibody production for cancer patients after SARS-CoV-2 vaccination is high and similar to that in healthy control subjects but varies with regard to the oncological treatment that patients are receiving. However, antibodies decline substantially after 3 months, and thus a third vaccination is desirable. There were no new safety concerns after vaccination, and most adverse events were mild and short-lived.