Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort

Abstract

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the correlations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing (LOWESS) method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL −1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL −1 at the twelfth week. Elevated interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-2R (IL-2R), and tumor necrosis factor-α (TNF-α) levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between low IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

Cytokine Profiles Associated With Worse Prognosis in a Hospitalized Peruvian COVID-19 Cohort

“…A previous study only found a correlation with IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity (39). However, another study hypothesized that IL-8 and overall, the inflammation acts as a mediator between the association of IgG antibodies and the clinical outcome (40).…”

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

“…A growing body of evidence shows that elevated IL-8 is upregulated early and remains elevated during the disease course of COVID-19 [ 10 , 28 ]. These elevated levels of IL-8 have been significantly associated with increased mortality and greater disease severity in patients, indicating that IL-8 plays a role in disease progression [ 10 , 28 – 30 ].…”

“…A growing body of evidence shows that elevated IL-8 is upregulated early and remains elevated during the disease course of COVID-19 [ 10 , 28 ]. These elevated levels of IL-8 have been significantly associated with increased mortality and greater disease severity in patients, indicating that IL-8 plays a role in disease progression [ 10 , 28 – 30 ]. Considering these data, it is possible to speculate that decreased neutrophil recruitment to the lungs due to the CXCR1/2 blockade likely contributed to the improved clinical outcomes seen in this study by mitigating the severe and uncontrolled hyperinflammatory disease manifestations.…”

A comparative study of virus nucleic acid re-positive and non-re-positive patients infected with SARS-CoV-2 Delta variant strain in the Ningxia Hui Autonomous Region

“…Furthermore, stronger antibody responses to SARS-CoV-2 contribute to improved survival, and a protective effect that is independent of the disease severity. Maintaining high IgM and IgG antibody levels may be an indicator of rapid recovery ( 28 ). Our results showed that patients with lower IgG and IgM antibody levels at the time of discharge were more likely to be re-positive, especially patients with lower levels of IgG antibodies.…”