How Does Asymptomatic COVID-19 Look Beneath Its Surface?


 
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By Molly Walker

Asymptomatic individuals carrying SARS-CoV-2 shed the virus longer than those with COVID-19 symptoms, with other lab findings suggesting the symptomatic patients mounted more robust immune responses, a small study in China found.

Median duration of viral shedding among 37 asymptomatic patients was 19 days (interquartile range 15-26; range 6-45) versus 14 days among 37 matched symptomatic patients (IQR 9-22; log-rank P=0.028), reported Jing-Fu Qiu, PhD, of Chongqing Medical University, and colleagues, though viral shedding does not necessarily mean the patients were infectious.

Virus-specific IgG antibody titers and cytokine levels were also significantly lower among asymptomatic patients in the acute phase of infection, when viral RNA can be found in respiratory specimens, the authors wrote in Nature Medicine -- both of which indicated that immune responses weren't as strong in the asymptomatic group.

Asymptomatic transmission of COVID-19 is one of its biggest mysteries, with the World Health Organization recently reminding the public of the distinction between asymptomatic patients, who never develop symptoms, and presymptomatic patients, who go on to develop symptoms later in the course of disease.

Qiu and colleagues characterized asymptomatic carriers as the "silent spreaders" of COVID-19.

"However, our understanding of the clinical features and immune responses of asymptomatic individuals with SARS-CoV-2 infection is limited," the researchers added.

For the study, they examined data from 178 patients with PCR-confirmed SARS-CoV-2 infection in the Wanzhou District in China, including 37 without symptoms. Median age in the latter was 41, and 22 were women. These individuals were matched by age, sex, and comorbidity with 37 symptomatic patients for antibody detection and cytokine measurement. Qiu and colleagues also included a group of 37 individuals who tested negative via RT-PCR for cytokine comparisons.

Lab values and imaging were not entirely normal for the asymptomatic group. Eleven had increased C-reactive protein levels and six had elevated levels of alanine aminotransferase. Chest CT found "focal ground-glass opacities" in 11 and "stripe shadows and/or diffuse consolidation" in another 10 of the group; in two-thirds of these 21 patients, the abnormalities were in only one lung. The remaining 16 showed entirely normal imaging.

Around 80% of both symptomatic and asymptomatic patients tested positive for IgG antibodies about 3-4 weeks after exposure. The difference was greater when examining IgM antibodies, with positive findings in 78.4% of symptomatic patients and 62.2% of asymptomatic patients.

In the early convalescent phase, defined as 8 weeks after hospital discharge, symptomatic patients had higher IgG levels, though both groups experienced over 90% decreases in IgG levels. A larger proportion of asymptomatic patients had decreases in neutralizing serum antibody levels versus symptomatic patients (81.1% vs 62.2%, respectively).

These findings should serve as a caution against assuming prior infection confers immunity to future infection, Qiu and colleagues said.

"These data might indicate the risks of using COVID-19 'immunity passports' and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups, and widespread testing," the team wrote.

Plasma levels of cytokines were also similar between asymptomatic patients and healthy controls, though significantly higher levels of stem cell factor and leukemia inhibitory factor were found in the asymptomatic group, the researchers noted, calling this a "reduced inflammatory response characterized by low circulating concentrations of cytokines and chemokines."

Qiu and co-authors cited the varying sensitivity and specificity of antibody tests (obtained from a company called Bioscience) as a limitation to their study, adding that the results may be confounded by existing antibodies to other coronaviruses, such as SARS or MERS, as well as common cold viruses.



 
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