Asymptomatic COVID-19 Rare, Especially for Unvaccinated People

Since the beginning of the COVID-19 pandemic, the narrative has been circulating that anywhere from 4-80% of cases are asymptomatic. However, new research finds that asymptomatic infection is very unlikely, especially in unvaccinated people.

The study, published this week in Open Forum Infectious Diseases, determined the frequency of asymptomatic COVID-19 infections in a cohort of vaccinated and unvaccinated healthcare workers.

From the Walter Reed National Military Medical Center (WRNMMC), the investigators enrolled PCR-negative healthcare workers 18 years and older. The study ran from August 25, 2020-February 28, 2021, before the more infectious Delta and Omicron variants caused the majority of COVID-19 infections.

Every month, the investigators collected serum samples from the cohort to test for COVID-19 antibodies. The participants also completed a viral respiratory infection symptom questionnaire each day they experienced COVID-19 symptoms, as well as twice a month to establish a health baseline.

The 34 symptoms included in the screenings were organized within the domains of nasal, throat, eye, chest, gastrointestinal, body/systemic, and taste/smell. Symptom severity was measured 0-4, and the participants were also asked if they felt at their usual state of health each time they completed the questionnaire.

The investigators used a Mann-Whitney test for unpaired comparisons, applying the Bonferroni correction to analyses with multiple comparisons. They examined rates of asymptomatic infection in contrast to a hypothesized value from a 1-sample binomial test.

The study included a total of 263 participants, of which 69.2% were female and 30.8% were male. The average age was 41 years, and the racial composition was 71.1% White, 12.9% Black, 10.3% Asian, 0.4% Native Hawaiian/Pacific Islander, and 3.4% multiple racial identities.

Of the cohort, 12 healthcare workers (4.6%) contracted COVID-19. 10 were diagnosed with a positive PCR test, and 2 were diagnosed via seroconversion with negative PCR testing. None of the infected participants were from the same household or hospital department.

All 12 infected participants experienced COVID-19 symptoms. The 1-sample binomial tests found that the 100% symptom rate would be extremely unlikely if the true rate of asymptomatic infection was 50% or even 30%.

The participants who were never diagnosed with COVID-19 reported an average score of 3.0 when feeling not in their usual state of health, compared to a mean score of 4.7 among COVID-19-infected individuals.

The most notable findings of the study were that completely asymptomatic COVID-19 infection is rare in unvaccinated individuals, and the symptoms of mild COVID-19 are not sufficiently distinctive from other viral upper respiratory infections.