Researchers from Bangalore, India, have found that 68 percent of pre-symptomatic patients with COVID-19 may be shedding the virus and potentially infecting others. Their study titled, “Quantitative COVID-19 infectiousness estimate correlating with viral shedding and culturability suggests 68% pre-symptomatic transmissions,” was published on the open-access preprint server Medrxiv*.
Novel Coronavirus SARS-CoV-2: This scanning electron microscope image shows SARS-CoV-2 (round gold objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Credit: NIAID-RML
What was this study about?
The researchers wrote that those who have been infected with the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 disease are known to infect others around them both before and after their symptoms appear and resolve. They explain that this is very important from the point of view of epidemiology because this determines the number of people a person can infect before the symptoms appear – the pre-symptomatic stage when he or she has not been identified or isolated.
They explain certain parameters such as the “R-naught (R0),” which “signifies how many new infections are caused on average by an infected person.” They explained that this R0 value is around 2.2 to 2.5 at present and it is regularly being assessed in communities and nations to see the spread of the infection and its containment. This study primarily focused on not only the R0 but also the length of time a person can infect others. They wrote, “A substantial amount of infections of COVID-19 are transmitted through asymptomatic individuals, and their infectiousness profiles are harder to track.”
Another parameter they talked about is the cycle threshold (Ct) obtained from the test - PCR with reverse transcriptase (RT-PCR). The researchers wrote that Ct was the “value from RT-PCR are converted to RNA copy numbers in the sample and interpreted.” It provided clues regarding the viral RNA shedding.
What was done in this study?
For this study, the team looked at serial interval information from 1,251 persons from three different studies (689 patients, 485 patients, and 77 patients from the studies respectively). Infectious estimation was made. Infectiousness was noted at time t and then at serial time periods t1, t2, etc. The team also used a linear regression method to correlate this time and the R0 values and predict the infectiousness. They wrote, “Using the best estimates for the serial interval in each replicate, the distribution of the infectiousness before symptoms were obtained.”
What was found?
The results of this study showed that 68.4 percent of all infections were caused due to the spread of the virus before the symptoms appear. This is stronger than the evidence available, which says that 44 percent of the infections come from pre-symptomatic persons. The earlier 44 percent of data was obtained from a small study of 77 patients only, wrote the researchers.
They explained that this had been done before for other infectious diseases such as influenza H1N1. For this study, they used longitudinal data only they explained. They looked at the correlation between average shedding of viruses and the chances of getting a positive culture. They wrote that both these correlations were very significantly strong. The correlation coefficients were 0.83 and 0.97, respectively, they wrote. They explained that this meant, “if one uses the sputum samples as a criterion for understanding the infectiousness, the Ct threshold will be much higher, comparing both the observed culturability and the infectiousness.”
Conclusions and implications
The team wrote that this is a highly infectious virus, and the propensity to spread from human to human is high. Most protocols suggest that persons with symptoms of the condition who have been diagnosed to be positive for the virus need to be isolated and kept away from those who are healthy. However, previous studies have shown that this viral shedding was higher among elderly patients and persisted long after symptoms were resolved. There are also studies showing that viral shedding may begin much before symptoms appear in a person. In both cases, the risk of transmission to healthy persons around a patient is substantially raised. In fact, the rapid spread of the infection from one person to another usually during pre-symptomatic stages and during convalescence when symptoms are resolved may be the main reason for such massive spread of the infection around the world across all nations, explain experts.
The authors of the study concluded that 68 percent of the infections are most likely to be caused before the onset of symptoms among patients. The parameters studied were surrogate measures of each other, they noted. These included “viral shedding, culturability, and the infectiousness.” This could imply that persons who are at risk of contracting the infection but are still not symptomatic may be spreading the infection, and caution needs to be applied. Norms of social distancing among those apparently healthy thus remain vital.
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.