A SARS-CoV-2 infection can result in a wide spectrum of symptoms, from asymptomatic to gravely ill. The majority of people infected with SARS-CoV-2 experience a mild to severe respiratory illness with symptoms that include fever, cough, and shortness of breath—appearing 2–14 days after exposure. However, other infections remain asymptomatic. Neither the clinical features nor the immune responses of asymptomatic cases have been well described.

The difference in the severity of the disease is a matter of intense research. Some hypotheses (none of which have been proven) concern the amount of virus one initially comes into contact with, potential immunity from previous infections with similar coronaviruses, age and previous health history, or the immune response of the person infected. Now, a small study performed by a group from Chongqing Medical University in Chongqing, China, found that people who fail to develop COVID-19 symptoms may have a weaker immune response to the virus. They also found that people’s antibody response to SARS-CoV-2 may diminish rapidly after infection which may have implications for the interpretation of negative serological results.

The study, which presents a detailed clinical and immunological analysis of 37 asymptomatic patients is presented in a paper in Nature Medicine titled, “Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.”

Ai-Long Huang and colleagues studied 37 asymptomatic individuals from the Wanzhou District who were diagnosed with RT–PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 days and during hospitalization. The authors wrote that “the asymptomatic individuals were admitted to the government-designated Wanzhou People’s Hospital for centralized isolation in accordance with policy.”

Of the 37 asymptomatic patients—identified in a group of 178 people with SARS-CoV-2 infection—22 were female and 15 male, with ages ranging from 8 to 75 years (median age, 41 years).

The authors found that these patients had a significantly longer duration of viral shedding, with median duration of viral shedding of 19 days, compared with 14 days in a group of 37 symptomatic patients.

Levels of virus-specific IgG antibodies were significantly lower in the asymptomatic group than in the symptomatic group during the acute phase of infection, when the virus could be detected in the respiratory tract.

Eight weeks after the patients were discharged from the hospital, antibody levels were measured. Of asymptomatic individuals, 93.3% and 81.1% had a reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% and 62.2% of symptomatic patients.

In addition, asymptomatic patients had lower levels of 18 pro- and anti-inflammatory cytokines. The authors suggest that this indicates that the asymptomatic patients may have had a weaker immune response to SARS-CoV-2 infection.

The authors also observed that IgG levels began to diminish within 2–3 months of infection in a large proportion of the asymptomatic patients, which was determined using a magnetic chemiluminescence enzyme immunoassay test. Indeed, 40% of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. The authors noted that reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

They argue that this finding, along with previous analyses of neutralizing antibodies in patients recovering from COVID-19, highlights the potential risks of using “immunity passports” and supports the continuation of public-health interventions and widespread testing. Additional studies of larger groups of symptomatic and asymptomatic patients are urgently needed to determine the duration of antibody-based immunity.

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