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Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China

Our take —

In this cohort study of 175 patients hospitalized with mild COVID-19 in Shanghai, China, there was wide variation in the level of SARS-CoV-2 specific neutralizing antibodies at discharge, with levels generally reaching their peak 10 to 15 days post symptom onset, and then decreasing following discharge. Interestingly, the same factors that are frequently reported as associated with worse COVID-19 outcomes, including age, male sex, lower lymphocyte counts, and higher CRP levels, were also associated with increased higher neutralizing antibody titers.

Study design

Retrospective Cohort

Study population and setting

This cohort study includes 175 patients with PCR-confirmed SARS-CoV-2 infection who were admitted to Shanghai Public Health clinical Center from January 24 to February 26, 2020, and were classified as having mild symptoms, including fever, respiratory symptoms, and radiologic evidence of pneumonia. Patients were followed up to 2 weeks post discharge or March 16, whichever came earlier. Plasma samples collected at the time of discharge were analyzed to measure SARS-CoV-2 specific neutralizing antibodies (NAb) and levels were compared to 13 healthy controls. Eleven participants additionally had sequential plasma samples collected between hospital admission and discharge in 2 to 4 day intervals.

Summary of Main Findings

Among the 175 patients (median age 50 years, 53% female) with mild COVID-19, none required ICU admission, median length of stay in the hospital was 16 days, and 165 (94%) had developed SARS-CoV-2 specific NAb by the time of discharge; the patients who did not develop NAbs were generally younger (median age 35 years) and 80% were women. Of the 165 who developed SARS-CoV-2 specific NAbs, 30% had low levels of NAb titers (ID50 <500), 17% medium (500-999), 39% medium-high (1000-2500), and 14% high (>2500). NAb levels were higher on average among men (1417 vs. 905), and appeared to increase with age, length of hospital stay, and disease duration. Two of the main factors associated with worse COVID-19 outcomes, low lymphocyte counts and higher CRP counts, were also moderately associated with higher NAb titers at discharge. Among 117 patients with NAb titer from 2 week post discharge, levels had significantly decreased from discharge values (886 vs. 1110), and patients who hadn’t had detected detectable NAb levels at discharge did not go on to develop them. Among 11 patients with serial NAb titers during hospitalization, levels began to increase within 4-6 days of disease onset and peaked 10-15 days post-disease onset.

Study Strengths

This study explores a number of clinical factors associated with SARS-CoV-2 specific NAbs upon discharge from the hospital. Presence of NAb titers was compared to healthy controls, and validated.

Limitations

Despite having NAb titers at discharge for 175 patients, kinetics of NAb during hospitalization were only available for 11 patients, and 2 week follow-up was only available for 117 patients; each of these analyses warrant additional study in larger samples with longer follow-up. Though all patients were classified as mild, they were all hospitalized exhibiting symptoms of fever, respiratory illness, and radiological evidence of pneumonia, and therefore the results may not be generalizable to patients who present with fewer or no symptoms. No adjusted analyses were conducted, and confounding is highly likely. This was a single site study and the degree to which results are generalizable to other populations is unknown.

Value added

This is one of the first studies to characterize clinical characteristics associated with NAb levels among patients with mild COVID-19.

This review was posted on: 8 September 2020