Even as the coronavirus disease 2019 (COVID-19) pandemic continues to threaten the world with resurgences in many countries, the risk posed by various degrees of infection, from asymptomatic through presymptomatic to symptomatic infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still undefined.

A new preprint, available on the medRxiv* server, describes how researchers found at least a third of infected individuals to be asymptomatic, but that a fifth of them successfully passed on the virus to others. In comparison, about a quarter of symptomatic cases did so, especially when the symptoms included fever, cough and shortness of breath. In these circumstances, up to 30% of them transmitted the virus.

Background

Asymptomatic carriage has been suspected and reported since the beginning of the pandemic in Wuhan, China. However, the exact proportion has been described to be anywhere between 40% and 77%. Such differences in ascertainment could be due to varying demographic, testing, and interaction patterns.

Most systematic reviews have quoted figures of 30-45% as asymptomatic, while such cases are considered to be associated with significantly less transmission. Secondary attack rates (SAR) have been reported to be as low as 0.7% in these cases, vs. 21% for symptomatic cases. However, follow-up over time was lacking in most of these studies, which meant that asymptomatic and presymptomatic cases may have been combined or falsely classified.

How was the study conducted?

The current study was based on a campus population at a Midwestern university in the USA, during the fall season of 2020. The study included approximately 13,000 and 1,600 students and confirmed cases, respectively.

The scientists found that not only was the SAR different when patients were classified by the presence or absence of symptoms, but the nature of the symptoms also determined the SAR. This could hamper containment efforts, especially as economic activity is burgeoning after a long hiatus.

Moreover, daily checks on employees, visitors or students, in workplaces, public places and schools, respectively, meant to help define the risk of transmission, may not yield the desired results when the wide difference in the type of symptoms and their timing in relation to infection, as well as the SAR, are considered.

Testing patterns

The college campus in this study had a set of measures in place to reduce the risk of viral spread. In particular, this included a daily requirement to assess one’s own health and report on any issues; testing for the virus; contact tracing; case isolation and contact quarantine; and surveillance testing to monitor the spread of the virus.

In August, students began to come back to campus, and this was associated with 151 positive tests for the virus by reverse transcriptase polymerase chain reaction (RT PCR). This led to the suspension of in-person classes, with all teaching being online until August 24.

At this point, graduate and professional students again had in-person classes, while the others continued with online classes until September 2. The number of cases detected by a positive PCR test went down, from just over 600 in August to approximately 150 by September.

A second rise was seen in the middle of October, and by the end of the semester, on November 20, over 1,500 students were positive. Of these, daily health data was present for at least half the days for about 1,200 students.

Testing was administered by a rapid antigen test if a student had symptoms suggestive of SARS-CoV-2 infection or had a history of exposure to someone with COVID-19. If the test proved negative, it was validated by a PCR, with the result coming within 1-2 days. Meanwhile, they were quarantined.

A positive rapid antigen test led to 14 days isolation, along with contact tracing and quarantine. The quarantined students were also advised to do an antigen test, which, if positive, necessitated a PCR test. They were also expected to quarantine until tests on days four and seven also came back negative, at which point they were released.

Surveillance monitoring was also conducted in the hope of catching asymptomatic or presymptomatic cases.

What did the study show?

The scientists found that congestion of the nose, headache and dry cough was higher among those who tested positive within five days, with fever and sensory disturbances (anosmia/dysgeusia/ageusia) were higher among positives only three and two days previous to testing positive. Loss of taste and smell occurred in the greatest proportion of cases by day 4 after testing positive.

The SAR was 19% vs. 25% for asymptomatic vs. symptomatic index cases on day 14 following exposure to the virus. In the four days immediately following exposure, symptomatic cases showed a higher SAR, with presymptomatic cases showing lower SAR and asymptomatic cases the lowest.

Perhaps this was because symptomatic cases have delayed testing, indicating that they had more time to transmit the virus before testing positive.

After this period, presymptomatic COVID-19 had the highest SAR, but symptomatic case SAR began to rise, becoming almost identical thereafter. At seven days from exposure, the SAR in all categories flattened. This is, therefore, the limit of quarantine for contacts.

Symptoms varied in their predictive capacity, but fever, shortness of breath and a dry cough at the onset of infection were found to be associated with an SAR of 30%, provided body aches and/or chills were also reported. The investigators suggest this could be owing to higher viral loads, and therefore greater ability to shed and spread the virus.  

What are the implications?

The findings of this study indicate that the type of daily virus surveillance practiced here does not help in containing transmission. In fact, the only way out may be to use face masks rigorously until enough vaccination coverage has been achieved globally. Asymptomatic and presymptomatic viral transmission are significant contributors to viral spread and challenge efforts to stop the virus, especially when seen in the context of novel emerging SARS-CoV-2 strains.

The researchers conclude:

This study suggests that until the population is sufficiently vaccinated, universal masking, broader testing, and social distancing might be the only reasonable mechanisms that can help overcome the risk of spread through asymptomatic, presymptomatic, or symptomatic transmission.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.