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Viral Positivity, Seroconversion, and Disease Severity in COVID-19
Quick Takes
- Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity with extremely high levels of C-reactive protein, IL-6, and IL-8 present throughout the disease course in critically ill patients.
- These data suggest that appropriate prevention and therapeutic approaches should be based on viral kinetics, clinical manifestations, and laboratory testing.
- Additional studies are indicated to improve our understanding of the potential effects of the virus, host innate and adaptive immune responses, and their interactions during the acute and convalescent phases of COVID-19.
Study Questions:
What are the patterns of viral polymerase chain reaction (PCR) positivity and their correlations with seroconversion and disease severity?
Methods:
The investigators conducted a retrospective cohort study in three designated specialty care centers for coronavirus disease 2019 (COVID-19) in Wuhan, China. They included 3,192 adult patients with COVID-19 and collected demographic, clinical, and laboratory data. Critically ill cases were defined as those that required intubation or involved shock, other organ failure, or admission to the intensive care unit. Mildly, moderately, and severely ill patients were categorized as noncritically ill. The association between disease severity and viral positivity duration was examined using Kaplan–Meier curves with the log-rank test.
Results:
Among 12,780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2,142 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% confidence interval [CI], 18.9-29.1 days) in critically ill patients and 18.0 days (95% CI, 16.8-19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700; 95% CI, 0.595-0.824; 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 9-10 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.
Conclusions:
The authors concluded that dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity.
Perspective:
This cohort study reports that the rate of viral PCR positivity peaked within the initial few days of infection while seroconversion rates peaked within 4-5 weeks. Furthermore, dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity with extremely high levels of C-reactive protein, interleukin (IL)-6, and IL-8 present throughout the disease course in critically ill patients. Low IgM titers (<100 AU/ml) appear to be independent risk factors for persistent viral positivity. These data suggest that appropriate prevention and therapeutic approaches should be based on viral kinetics, clinical manifestations, and laboratory testing. Additional studies are indicated to improve our understanding of the potential effects of the virus, host innate and adaptive immune responses, and their interactions during the acute and convalescent phases of COVID-19.
Clinical Topics: COVID-19 Hub, Prevention
Keywords: Coronavirus Infections, COVID-19, C-Reactive Protein, Critical Illness, Interleukin-6, Interleukin-8, Primary Prevention, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, severe acute respiratory syndrome coronavirus 2, Shock, Virology
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