In this study, we performed a retrospective analysis of 777 patients with SARS-Cov-2 infection. According to the severity of the disease, we divided the patients into two types: severe patients (417/777, 53.7%), and non-severe patients (360/777, 46.3%). Table 1 illustrates the baseline characteristics of 777 patients with COVID-19. The mean age of the cohort was 58.1 years. The proportions of males and females did not differ significantly between the two groups. Patients in the severe group (62.2 ± 13.8 years) were significantly older than the non-severe group (53.5 ± 16.7 years). The most common comorbidity was hypertension (31.2%). Besides, it was also the only comorbidity that existed a significant difference in prevalence between the two groups. Also, diabetes and coronary heart disease were common comorbidities of patients. In terms of symptoms, the most common symptoms in more than half of patients were fever (67.8%) and cough (54.8%). Furthermore, expectoration (40.5%) was also one of the common symptoms of patients. The results indicated that among the symptoms with statistically different distributions (P<0.05), such as fever, cough, dyspnea, which were happened in severe patients more frequently than in non-severe patients. All the patients have reached the endpoints of the observation by April 26, and the clinical outcomes are summarized in Table 1. 5.3% (41/777) patients were deceased. 94.7% (41/777) of patients were discharged, and all the dead patients were severe cases.
In Figure 1, we observed the dynamic changes of the positive rates of IgG and IgM in severe/non-severe patients. In the first 14 days from the onset of the symptoms, the positive rate of IgG was significantly higher in severe patients (91.8%) compared with non-severe patients (74.2%, Figure 1a), and the same trend was also observed in IgM (77.6% to 61.7%, Figure 1b). In addition, the phenomenon of higher a positive rate of IgM remained in severe patients within 15-21 days. After 21 days, the positive rates of IgG and IgM were similar in two groups. In addition, in severe patients, the positive rate of IgG maintained at a relatively high level (>90%) during the whole duration. However, the positive rate of IgG of the non-severe patients had an obvious ascent process, and it reached a peak of 93.2% after 21 days.
To further explore the characteristics of the patients’ immune response to the SARS-Cov-2 infection, we analyzed correlations between levels of specific antibodies and clinical progression. The average levels of IgG and IgM of COVID-19 patients are shown in Figure 2a-2b. The level of IgG was significantly higher in severe patients compared to non-severe patients. However, there was no difference in the average level of IgM among the two groups. Due to the antibody positive rates changed over time, we suspected the antibody levels would also be time-dependent. The average levels of IgG and IgM from the beginning of the symptom until the first detection of corresponding antibodies are shown in Figure 2c-2d. During the first two weeks after disease onset, there were increases in the level of IgG of severe patients, and then it began a slow decline. We observed that in the first 14 days, the IgG level of severe patients was significantly higher than that of non-severe patients. Whereas the change law of IgM with time is not obvious, there was no such time point among severe-non-severe patients. We statistically tested the antibodies levels of the two groups ≤ 14 days and ≥ 15 days. A significant difference was only observed in the level of IgG ≤ 14 days post-disease onset (Figure 2e, P<0.0001).
To determine the potential impact of laboratory indicators with IgG/IgM differences, we divided patients into different groups according to whether their corresponding laboratory parameters were within the normal range or not. Then, we compared the levels of specific antibodies among distinct groups. Among the 19 laboratory parameters, in the normal range groups and the abnormal range groups of most laboratory indicators, most of parameters had no significant difference in IgG, except IL-10 (P=0.035), procalcitonin (P<0.0001), albumin (P=0.049), total bilirubin (P=0.0092) which have shown significant difference among the groups. However, these statistical differences of normal/abnormal range groups of laboratory parameters became more pronounced in specific IgM. There were lymphocyte count (P=0.0010), D-dimer (P=0.019), ferritin (P=0.021), alanine aminotransferase (P=0.036), aspartate aminotransferase (P=0.012), albumin (P=0.0020), high sensitivity C-reactive protein (P=0.0091), tumor necrosis factor α (P=0.0069) have reached statistical difference among the different groups.
To investigate the profile of dynamic changes of IgG and IgM among the same person during the course of COVID-19, we screened 74 cases in patients who took serological specific antibodies detection at least 3 times. T1 represents the first detection after hospital admission, T2 represents the detection closest to the midpoint of the whole hospital stay, and T3 detection the last test before discharge. We observed that both the levels of IgG and IgM were in a downward trend. The severe patients had a higher average level of IgG and IgM compared with non-severe patients among the whole three time points. In addition, we further found that the difference in IgG was more evident than IgM, especially in T1 and T2 time points. The levels of IgM in severe/non-severe groups were relatively close at different time points.
Logistic regression was conducted to identify the correlation between the log-transformed level of IgG and the progression of COVID-19. In the multivariate logistic regression, we included comorbidities, age, sex as the potential co-factors, which have reported may influence the progress of COVID-19 or differential distribution among the patients of different severity. After adjustment for co-factors, we observed a higher level of IgG before 14 days from disease onset independently associated with severe illness (odds ration [OR]=1.310, 95% confidence interval [CI]: 1.137-1.509). However, this significant correlation did not hold after 15 days from disease onset (OR=0.930, 95%CI: 0.799-1.083).