Dynamics of Cytokine, SARS-CoV-2-Specific IgG, and Neutralizing Antibody Levels in COVID-19 Patients Treated with Convalescent Plasma

Abstract

Coronavirus disease 2019 (COVID-19) is a contagious illness worldwide. While guidelines for the treatment of COVID-19 have been established, the understanding of the relationship among neutralizing antibodies, cytokines, and the combined use of antiviral medications, steroid drugs, and convalescent plasma therapy remains limited. Here, we investigated the connection between the immunological response and the efficacy of convalescent plasma therapy in COVID-19 patients with moderate-to-severe pneumonia. The study included a retrospective analysis of 49 patients aged 35 to 57. We conducted clinical assessments to determine antibody levels, biochemical markers, and cytokine levels. Among the patients, 48 (98%) were discharged, while one died. We observed significantly higher levels of anti-nucleocapsid, anti-spike, and neutralizing antibodies on days 3, 7, and 14 after the transfusion compared to before treatment. Serum CRP and D-dimer levels varied significantly across these four time points. Moreover, convalescent plasma therapy demonstrated an immunoregulatory effect on cytokine parameters, with significant differences in IFN-β, IL-6, IL-10, and IFN-α levels observed at different sampling times. Evaluating the cytokine signature, along with standard clinical and laboratory parameters, may help to identify the onset of a cytokine storm in COVID-19 patients and determine the appropriate indication for anti-cytokine treatment.

Keywords: COVID-19; antibodies; convalescent plasma treatment; cytokine; retrospective study.

Figure 1

The anti-nucleocapsid protein immunoglobulin G (IgG) response in patients with COVID-19 on the day before COVID-19 convalescent plasma (CCP) transfusion (day 0) and on days 3, 7, and 14 post-transfusion. (A) The changes in anti-nucleocapsid protein IgG antibody on days 0, 3, 7, and 14. (B) The levels of IgG antibodies against the anti-nucleocapsid protein were compared across four time periods after the onset of illness. The anti-nucleocapsid IgG S/C index distribution is depicted by a scattered dot plot with a median and interquartile range (IQR). A red circle symbolizes death.

Figure 2

The anti−spike receptor−binding domain (RBD) IgG response in patients with COVID-19 on the day before COVID-19 convalescent plasma (CCP) transfusion (day 0) and on days 3, 7, and 14 post-transfusion. (A) The changes in anti−spike RBD IgG levels on days 0, 3, 7, and 14. (B) The levels of IgG antibodies against the anti−spike RBD protein were compared across four time periods after the onset of illness. The distribution of anti-spike IgG (U/mL) is depicted by a scattered dot plot with a median and interquartile range (IQR). A red circle symbolizes death.

Figure 3

The neutralizing antibody titer in patients with COVID-19 on the day before COVID-19 convalescent plasma (CCP) transfusion (day 0) and on days 3, 7, and 14 post-transfusion. (A) Neutralizing antibody titer trends on days 0, 3, 7, and 14. (B) The levels of neutralizing antibodies were compared across four time periods after the onset of illness. The distribution of log₁₀ neutralizing antibody titer is depicted by a scattered dot plot with a median and interquartile range (IQR). A red circle symbolizes death.

Figure 4

The measurement range of cytokines was evaluated in all samples collected from severe COVID-19 patients (n = 49) who had undergone convalescent plasma transfusion (CCP) on the day before the treatment in contrast to serum samples obtained on days 3, 7, and 14 after the treatment. The summary statistics illustrated in the box plot encompass the subsequent features: Each data point is represented by a dot, the centerline indicates the median, and the lower and upper hinges correspond to the first and third quartiles, respectively, while the upper and lower whiskers extend from these hinges to encompass the highest and lowest values, respectively. The distinctions between these groups were assessed through the utilization of the Friedman test. The comparisons derived from the Friedman test revealed significantly disparate levels of IFN−β (p = 0.0168), IL−6 (p < 0.0001), IL−10 (p < 0.0001), and IFNα2 (p < 0.0005) in samples taken on day 0 when compared to samples obtained on days 3, 7, and 14.

Figure 4

The measurement range of cytokines was evaluated in all samples collected from severe COVID-19 patients (n = 49) who had undergone convalescent plasma transfusion (CCP) on the day before the treatment in contrast to serum samples obtained on days 3, 7, and 14 after the treatment. The summary statistics illustrated in the box plot encompass the subsequent features: Each data point is represented by a dot, the centerline indicates the median, and the lower and upper hinges correspond to the first and third quartiles, respectively, while the upper and lower whiskers extend from these hinges to encompass the highest and lowest values, respectively. The distinctions between these groups were assessed through the utilization of the Friedman test. The comparisons derived from the Friedman test revealed significantly disparate levels of IFN−β (p = 0.0168), IL−6 (p < 0.0001), IL−10 (p < 0.0001), and IFNα2 (p < 0.0005) in samples taken on day 0 when compared to samples obtained on days 3, 7, and 14.