From April 19 to May 26, 2020, using the keywords COVID-19, SARS-CoV-2, symptoms and asymptomatically, we regularly searched the published medical literature using the PubMed service of the National Library of Medicine of the U.S. National Institutes of Health. We also searched for unpublished manuscripts using the bioRxiv and medRxiv services operated by the Cold Spring Harbor Laboratory. In addition, we used Google to search for stories and monitor relevant information shared on Twitter. The world is facing a problem that is still very rare today. Since diagnosis in December 2019, 8,860,331 people worldwide have been infected and 465,740 people have died (22 June 2020) (1). Many issues related to this disease are waiting to be clarified. Oran and Topol analysed 16 studies in patients with a positive diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR) and suggested that the disease might be 40-45% asymptomatic (2). Although the level of evidence from the studies is low, we believe that a notable point is mentioned that could affect the day-to-day functioning of healthcare facilities and public health professionals under pandemic conditions. We believe that our review accurately represents the source material we collect.

However, our review is a beginning, not an end. In the coming months and years, we plan to learn much more about asymptomatic SARS-CoV-2 infection. We look forward to seeing which research teams from around the world will contribute to this important field. As discussed here, the exact proportions of presymptomatic and never symptomatic transmission are not known. This also applies to incubation period estimates, which are based on individual exposure and initial windows that are difficult to observe up close and therefore have significant uncertainties, even when using estimates in multiple studies. In addition, they are likely to vary considerably between populations. For example, older people are more likely than younger people to have symptoms,20 so in older populations, asymptomatic transmission may never be less. However, some age groups are rarely isolated exclusively from other age groups, so the asymptomatic risk of transmission remains high in these groups, and even more so in younger age groups, where transmission may be even more dominated by asymptomatic transmission.20 On March 28, a first case of COVID-19 was diagnosed with a positive result at a homeless shelter in downtown Los Angeles. California (10). After identifying a group of symptomatic people earlier this week of April 20, the shelter was closed to new inmates and testing for current inmates began.

On April 22, 43 (24.2%) of the 178 completed tests were positive for SARS-CoV-2 and 27 (63.8%) of those who tested positive were asymptomatic. Like much of SARS-CoV-2, the intricacies of infectivity and asymptomatic transmission are barely regulated at the time of writing. Now, evidence suggests that about one in five infected people will have no symptoms and will transmit the virus to far fewer people than someone with symptoms. However, researchers disagree on whether asymptomatic infections act as a “silent engine” of the pandemic. We have already commented, based on the authors` summary of the Vo` study, that even a low false positive rate could generate enough false positives to account for all people reported as infected and asymptomatic. We have now reviewed the dataset published with the Vo` Preprint (1) and can provide more details. A total of 5,220 tests were performed on 2,900 residents, with 131 positive results on samples from 80 residents. 35 residents were classified as infected and asymptomatic; Of these, 25 have tested positive only once. With the test numbers reported, a false positive rate of only 0.5% would give 25 false positives. Given that the median rate of false positives was 2.3% in 43 external quality assessments of similar viral diagnostic tests (2), 25 of the 35 residents reported as infected and asymptomatic may have been slightly uninfected individuals who received false positive test results.

Transmission by people who are infected but have no symptoms can come from 2 different states of infection: presymptomatic people (who are infectious before developing symptoms) and people who never have symptoms (asymptomatic infections that we will never call symptomatic). Early data modelling studies on COVID-19 cases found that the SARS-CoV-2 generation interval was shorter than the serial interval, suggesting that the average time between 1 infected person and that infected person was shorter than the average time between 1 person developing symptoms and the person who infected them developed the symptoms.2-5 This finding meant that the outbreak spread faster. than expected if it was transmitted at the time of the disease during which the individuals were symptomatic. By the time a second generation of individuals developed symptoms, a third generation was already infected. Epidemiological data from the early stages of the pandemic also suggested the possibility of presymptomatic transmission,6,7 and laboratory studies confirmed that viral RNA levels in airway secretions were already elevated at the time of symptom onset.8-10 Results The basic assumptions of the model were that maximum infectivity occurred at the median onset of symptoms and that 30% of infected individuals did not develop never symptoms and that 75% were also infectious. are like those who develop symptoms. Taken together, these basic assumptions imply that people with an infection who never develop symptoms can account for about 24% of total transmission. In this baseline case, 59% of all transmissions were from asymptomatic transmission, of which 35% came from presymptomatic people and 24% from people who never develop symptoms.

Under a wide range of values for each of these assumptions, it has been estimated that at least 50% of new SARS-CoV-2 infections are due to exposure of people infected but without symptoms.