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Viral Kinetics and Antibody Responses in Patients with COVID-19

Our take —

This study integrated epidemiologic, clinical, and laboratory data to characterize SARS-CoV-2 infection from symptom onset through viral clearance. Though sample sizes were small and did not include non-hospitalized patients, it provides evidence that detection of viral RNA tends to occur coincident with cough but not fever, and is more frequently detected in sputum and stool and for longer durations of time compared to nasopharyngeal swabs. Additionally, they showed that patients with more severe disease had a longer duration of detectable RNA and higher antibody titers than those with milder disease.

Study design

Prospective Cohort

Study population and setting

This study included 67 patients with laboratory confirmed SARS-CoV2 infections who were recruited from Chongqing Public Health Medical Center, the designated COVID-19 treatment hospital in the central area of Chongqing, China between January 26 and February 5, 2020, with follow-up through February 27, 2020. Patients were followed prospectively, and information was collected on demographic and clinical characteristics. Additionally,1602 clinical specimens were collected, including nasopharyngeal swabs, sputum, blood, urine, and stool.

Summary of Main Findings

SARS-CoV2 RNA levels peaked during the first week following symptom onset in nasopharyngeal swabs, 1-20 days following symptom onset in sputum swabs, and 6-13 days following symptom onset in stool samples. RNA was detected at higher concentrations in sputum samples compared to nasopharyngeal swabs or stool, and was not consistently detected in urine or plasma. Median duration of detectable viral shedding was shortest for nasopharyngeal swabs, 12 days, compared to sputum and stool, 19 and 18 days, respectively. More than 20% of patients still had detectable RNA in any sample >30 days after symptom onset. Detectable RNA aligned well with symptoms of cough in all sample types, but not with fever or diarrhea. 57.1% of samples were positive for IgM by 28 days following symptom onset, and declined thereafter, while 74.3% of samples were positive for IgG by day 28, increasing to 86.7% by day 42. Antibody titers were higher, and viral shedding duration was longer in patients with severe disease compared to those without severe disease.

Study Strengths

The major strengths of this study are the prospective follow up, and the serial sampling of multiple sample types from patients with varying degrees of disease severity (mild to moderate and severe). They assessed both the dynamics of viral detection in patient samples, but also the temporal trends of the immune response to infection. Authors were also able to integrate clinical, epidemiological, and laboratory data to provide a comprehensive picture of infection dynamics throughout the time course from exposure to viral clearance.

Limitations

While the study did have a large clinical sample size, the sample size of patients was not large, particularly when performing stratified analysis (e.g. by disease severity).  Further, all of the patients were hospitalized, so these results may not be reflective of mild and asymptomatic cases. Samples were not run in duplicate. The clinical or epidemiological importance of detection of virus in samples like urine, plasma, and stool is unclear– for example is this associated with pathogenesis and is this detectable virus transmissible? Similarly, the epidemiological importance of long-term viral shedding and transmissibility of virus after symptoms have subsided and, the protective nature of antibodies remains to be determined at the time of publication.

Value added

This study provides insight into the temporal dynamics of clinical diagnostic markers of infection with SARS-CoV2 in multiple sample types, as well as the immune response to infection throughout the duration of infection.