By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Repeat infection with endemic seasonal coronavirus occurs commonly and raises concerns about immunity to SARS-CoV-2 as well as about the efficacy of vaccines in the protection against infection due to this virus.
SOURCE: Galanti M, Shaman J. Direct observation of repeated infections with endemic coronaviruses. J Infect Dis 2020; July 7. doi:10.1093/infdis/jiaa392
Galanti and colleagues examined data from the Virome project carried out in Manhattan from October 2016 to April 2018 to determine the frequency of recurrent infection with endemic coronaviruses. In this study, 214 healthy individuals had regular sampling for respiratory virus infection, with self-reporting of symptoms and episodes of clinical care. The cohort included children attending two daycare centers, as well as their parents and siblings; students and teachers from a high school; adults working in emergency departments at a pediatric and an adult hospital; and adults working at a university medical center.
Nasopharyngeal samples were collected weekly and, using a respiratory virus panel, were tested for the presence of nucleic acid from 18 respiratory viruses, including the α-coronaviruses 229E and NL63 and the β-coronaviruses HKU1 and OC43. Participants also self-reported symptoms each day.
Of the 191 participants who contributed samples at least six times in the same season, 86 had evidence of at least one episode of infection by a coronavirus, with OC43 the most frequently identified. The probability of a test-positive episode of OC43 infection during the 80 weeks of the study was 0.47. Twelve of the 86 tested positive for the same virus during at least two episodes, with OC43 accounting for nine of these 12. Of the nine people with repeated OC43 episodes, six people had two episodes and three people had three such episodes. The median interval between episodes was 37 weeks (range, 4 to 48 weeks).
Repeat episodes did not appear to be associated with either worse or milder symptoms, but there was a significant association between symptom severity and inclusion within the same family cluster. In individuals whose initial coronavirus infection was asymptomatic, all subsequent infections with the same virus also were asymptomatic.
Seroconversion to one or more of the endemic seasonal coronaviruses first occurs at an early age and, overall, more than nine in 10 people in the general population are seropositive. Although limited evidence indicates that pre-existing antibodies may correlate with some degree of protection, the occurrence of repeat infection with the same serotype suggests that any protection is limited.
To the extent that these data are relevant to COVID-19, they raise concern regarding the long-term protective nature of antibody to SARS-CoV-2 — with obvious implications for dealing with this infection and for the efficacy of vaccines. Although almost all patients who recover from COVID-19 develop antibodies to the virus, and these antibodies often are neutralizing, evidence indicates that their serum levels rapidly decay, at least in those people with mild or asymptomatic infection.
Ibarrondo et al found that the serum half-life of IgG antibody in patients with clinically mild COVID-19 was only 36 days, while Long and colleagues found that 40% of patients with asymptomatic infection and 12% of those whose infection was symptomatic lost detectable serum antibody during the early convalescent period.1,2
The finding by Galanti and colleagues of clustering within families of symptomatic infection due to seasonal endemic coronaviruses suggests the possibility of human genetic influences on the inflammatory response elicited via the innate immune system. Some evidence suggests that genetic factors affecting that system may play a role in COVID-19. Van der Made and colleagues evaluated two sets of brothers in the Netherlands who, despite being young and previously healthy, required mechanical ventilation for their management.3 They were found to have putative loss-of-function mutations in the gene encoding TLR7, and this was associated with an impaired interferon response to agonists of this toll-like receptor.
Thus, just as with endemic coronaviruses, the necessary elements of immune protection against SARS-CoV-2 remain undefined.
- Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med 2020; July 21. doi: 10.1056/NEJMc2025179. [Online ahead of print].
- Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020. doi:10.1038/s41591-020-0965-6
- van der Made CI, Simons A, Schuurs-Hoeijmakers J, et al. Presence of genetic variants among young men with severe COVID-19. JAMA 2020; Jul 24. doi: 10.1001/jama.2020.13719. [Online ahead of print].