Key PointsQuestionWhat is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)?FindingIn this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant.MeaningAmong patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference.
Background
Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies.
Methods
In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14–15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken.
Findings
Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41–7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October–December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline
vs
1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 ...
Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a worldwide pandemic since it emerged in December, 2019. Previous studies have reported rapid antibody response to SARS‐CoV‐2 with the first 2‐3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum IgM and IgG specifically against SARS‐CoV‐2 in later weeks (mainly 4‐10 weeks) in 97 hospitalized patients with COVID‐19. We observed that serum IgM and IgG, especially in patients with moderate‐to‐high levels, declined significantly between week 4‐10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31/40) rapidly declined by half, from 212.5 (range, 163.7‐420.3) to 96.3 (range, 75.0‐133.4) AU/ml, within 1‐2 weeks in the second month and then sustained around 100 AU/ml until discharge from hospital. Significant reduction of IgM was also observed as SARS‐CoV‐2 nucleic acid converted to negative (p=0.002). In the recovery stage, serum IgG declined significantly (early vs. late recovery stage, n=16, p=0.003) with a median reduction of 50.0% (range, 3.7‐77.0%). Our results suggested the decline of IgM may be an indicator of virus clearance and recovery patients may have robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half arises serious concerns on the robustness and sustainability of humoral immune response in the future period after discharge, which is crucial for immunity strategy and developing vaccine.
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