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Reverse Transcriptase Polymerase Chain Reaction

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19

Author/s: 
Fu, Yu, Li, Yongsheng, Guo, Ensong, He, Liang, Liu, Jia, Yang, Bin, Li, Fuxia, Wang, Zizhuo, Li, Yuan, Xiao, Rourou, Liu, Chen, Huang, Yuhan, Wu, Xue, Lu, Funian, You, Lixin, Qin, Tianyu, Wang, Chaolong, Li, Kezhen, Wu, Peng, Ma, Ding, Sun, Chaoyang, Chen, Gang

Background: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited.

Objective: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity.

Design: Retrospective cohort study.

Setting: 3 designated specialty care centers for COVID-19 in Wuhan, China.

Participants: 3192 adult patients with COVID-19.

Measurements: Demographic, clinical, and laboratory data.

Results: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity.

Limitation: Retrospective study and irregular viral and serology testing.

Conclusion: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity.

Keywords 
COVID-19 coronavirus SARS coronavirus Polymerase chain reaction PCR

Kinetics of viral clearance and antibody production across age groups in SARS-CoV-2 infected children

Author/s: 
Bahar, Burak, Jacquot, Cyril, Mo, Yunchuan D., DeBiasi, Roberta L., Campos, Joseph, Delaney, Meghan

Abstract

Objectives: To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with SARS-CoV-2 infection.

Study design: This retrospective analysis of children tested for SARS-CoV-2 by RT-PCR and IgG antibody at a quaternary-care, free-standing pediatric hospital between March 13, 2020 to June 21, 2020 included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity.

Results: The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and time from RT-PCR positivity to negativity was 25 days. Of note, patients aged 6 through 15 years demonstrated a longer time of RT-PCR positivity to negativity, compared with patients aged 16 through 22 years (median=32 versus 18 days, P = .015). Median time to seropositivity, by chemiluminescent testing, from RT-PCR positivity was 18 days while median time to reach adequate levels of neutralizing antibodies (defined as comparable to 160 titer by plaque reduction neutralization testing) was 36 days.

Conclusions: The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. It is unknown whether this correlates with persistent infectivity. Only 17 of 33 patients demonstrated adequate neutralizing antibodies during the timeframe of specimen collection. It remains unknown if IgG antibody against spike structured proteins correlates with immunity, and how long antibodies and potential protection persist.

Copyright © 2020. Published by Elsevier Inc.

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