A study published online ahead of print in The Journal of Infectious Diseases provides intriguing insights into one possible explanation for both the high rates of asymptomatic carriage of SARS-CoV-2 – that is, having no symptoms despite a positive PCR test that indicates the presence of the virus in one’s body – and the extremely low rates of infection, illness and death from SARS-CoV-2 in children: Cross-immunity due to exposure to seasonal coronaviruses, which have been infecting humans for at least several centuries.
The new article’s implications are grave: if the policies that we’re told are required in order for schools to reopen, including obsessively upscaled hand hygiene, physical distancing policies such as those depicted in the chilling photographs below (top photo: school children in China wearing ‘1 meter hats’; bottom photo: children in Surrey, England participating in New Normal ‘play’), and banning contact sports end up succeeding in keeping children away from each other, and thus preventing the spread of common coronaviruses, children may lose their protection against SARS-CoV-2 and become more susceptible to serious outcomes of COVID-19.
The study, titled Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019, analysed the results of diagnostic tests performed on over 70 000 episodes of respiratory illness that occurred in the West of Scotland between 2005 and 2017.
Molecular testing of nasal and/or throat swab samples from each patient was performed in order to check for the presence of multiple respiratory viruses including influenza A and B viruses, respiratory syncytial virus (RSV), human adenoviruses, human rhinoviruses, human metapneumovirus, parainfluenza virus (PIV) types 1–4, and the four seasonal coronaviruses: CoV-229E, CoV-OC43, CoV-NL63 and CoV-HKU1 (which was no longer tested for after 2012 due to low levels of detection).
Seasonal coronaviruses collectively contributed to almost 11% of all respiratory virus detections, and were the fourth most commonly detected viruses during influenza seasons, after human rhinoviruses, influenza viruses, and RSV.
Each of the three coronaviruses that were tested for throughout the entire duration of the study period showed distinct seasonal patterns (being winter pathogens, each peaked on average between January and March) but with notable variations between the different types and also between years:
The study’s authors point out that the “asynchronous seasonality” between the CoV-229E and CoV-NL63 strains, which are both alphacoronaviruses, indicate “a competition dynamic” – that is, only one of these two strains of closely-related human coronavirus can spread widely through the population at any given time, most likely due to cross-immunity.
While CoV-HKU1 occurred with such low frequency in this Scottish population that it was dropped from testing in 2012, other researchers have reported differences in the timing of peak detections with CoV-OC43, suggesting a competition dynamic between these two closely related betacoronaviruses.
Furthermore, coinfections among seasonal coronaviruses were not recorded in this study population (and have rarely been reported elsewhere) – that is, only one strain of coronavirus was detected in each sample – indicating an immune-mediated competition for hosts which provides further support for the cross-immunity proposition.
The fact that serological tests for SARS-CoV (the betacoronavirus that causes Severe Acute Respiratory Syndrome) cross-react with the OC43 betacoronavirus strain (that is, people infected with the OC43 strain can test positive for the SARS strain even though they’re not infected with SARS) lends even more weight to the cross-immunity hypothesis.
Children under the age of 5, and elderly people, were the two population segments most likely to have coronavirus infections detected. Coronaviruses are a rare cause of anything more serious than common cold symptoms in children, but an be highly lethal in elderly, frail adults – for example, a outbreak of human coronavirus OC43 in a Canadian nursing home in 2003 resulted in an 8% fatality rate.
The high rate of seasonal coronavirus (sCoV) infections detected in children prompted the researchers to propose an intriguing hypothesis in relation to SARS-CoV-2 and the illness associated with it, COVID-19:
“In the context of our study population, COVID-19 is closely related to CoV-OC43 (both betacoronaviruses), the most prevalent sCoV detected among patients <5 years old. It is possible that preexisting cross-immunity confers protection and/or attenuates the severity of COVID-19, leading to fewer tested and hospitalized children. The comparatively lower proportion positive and detection odds for school-aged compared with younger children may potentially reflect a sustained level of CoV-OC43 immune-mediated protection, whereas waned immunity is expected to leave adults more vulnerable to CoV infection. Assuming some degree of cross-immunity with sCoVs, our data are consistent with fewer expected cases of COVID-19 in children but more among the adult population. In addition, immunosenescence may exacerbate low levels of protective immunity in elderly persons.”
Or in plain English, because so many children get infected with the OC43 strain of seasonal coronavirus, they are protected against infection with SARS-CoV-2. This immunity wanes during adulthood, and age-related decline in immune function leaves the elderly vulnerable to infection.
While further research is obviously needed in order to confirm or dismiss the cross-immunity hypothesis, the implication of this study is deeply worrying:
If we stop children from sitting next to each other in classrooms, hugging their friends, sharing food, playing contact sports and engaging in other normal behaviours that facilitate the transmission of viruses, we may prevent them from developing infections with seasonal coronaviruses that may confer cross-immunity against SARS-CoV-2. And that means we’re trading an inconsequential common cold for an illness which is potentially much more hazardous, especially if passed to an elderly or chronically ill person.
It wouldn’t be the first time in history that a decision taken in haste and on the basis of inadequate information turned out to have terrible consequences.
Remember, taking good care of your health is even more important than usual due to the high levels of stress generated by the world’s response to COVID-19, and the fact that people with pre-existing chronic disease are at higher risk of serious complications of any type of infection, including SARS-CoV-2.
Update: 12 June 2020
Further support for the cross-immunity hypothesis is provided by a study titled Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals which found that between 40 and 60% of people who had not been exposed to SARS-CoV-2 had activated CD4+ T cells (a type of immune system cell that is heavily involved in defence against viral infections) that were active against SARS-CoV-2.
This finding suggests that past exposure to seasonal coronaviruses grants at least some degree of immunity or protection against SARS-CoV-2.
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