HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection
2023; Elsevier BV; Volume: 11; Issue: 9 Linguagem: Inglês
10.1016/s2213-2600(23)00295-3
ISSN2213-2619
Autores Tópico(s)COVID-19 and Mental Health
ResumoThe COVID-19 pandemic had a devastating impact worldwide, leading to the loss of millions of lives. However, early in 2020, it became clear that approximately 20% of individuals infected with SARS-CoV-2 showed very mild or no symptoms at all. Reports of couples living together in which one partner had severe symptoms whereas the other remained asymptomatic, despite testing positive for SARS-CoV-2 infection, were not uncommon. This observation has motivated several groups to investigate the issue, as understanding how an individual can remain asymptomatic despite being infected might help to elucidate the host immunological mechanisms leading to rapid viral clearance. More recently, a study led by Jill A Hollenbach (Departments of Neurology and Epidemiology and Biostatistics, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA) adopted a unique approach to find an explanation for this observation. Most studies have looked for genetic associations in patients with severe symptoms; however, Hollenbach's group took the opposite direction by working with individuals who did not develop symptoms. “It is a very welcome study. I really like their approach. During the pandemic, many research groups were wondering how to assess a population of asymptomatic individuals”, said Alexander Mentzer, an infectious disease doctor at the John Radcliffe Hospital (Oxford, UK) and a group leader at the Wellcome Centre for Human Genetics (University of Oxford, Oxford, UK). A total of 29 947 volunteer bone marrow donors from the National Marrow Donor Program in the USA, who previously received high-resolution human leukocyte antigen (HLA) genotyping, were invited to participate in the study in July 2020. Until April 2021, and before the implementation of mass vaccination, the final cohort consisted of 1428 individuals who self-identified as White, provided daily follow-up about SARS-CoV-2 infection, testing, and the development of symptoms using a smartphone app. The study from the University of California found a significant association between the HLA-B*15:01 allele and unvaccinated asymptomatic individuals who tested positive for SARS-CoV-2 infection and showed that individuals carrying one copy of the allele were more than twice as likely to remain asymptomatic after SARS-CoV-2 infection (odds ratio [OR] 2·40 [95% CI 1·54–3·64]; p=5·67 × 10–5). Additionally, people who are homozygous were eight times more likely to stay asymptomatic (OR 8·58 [1·74–34·43]; p=0·001). Overall, 20% of individuals who remained asymptomatic were carriers of HLA-B*15:01 compared with 9% who reported having symptoms. The group also worked with two additional cohorts at the University of California and a smaller cohort of 69 asymptomatic hospital workers in the UK and found similar results. “To explain this association, we had two hypotheses. The first was that the HLA-B*15:01 variant could present the viral peptides better than other HLA variants. Alternatively, and this was our stronger suspicion, individuals carrying this allele have memory cells that could recognise a SARS-CoV-2 immunodominant peptide, despite not having encountered this virus before the pandemic”, explained Danillo G Augusto, an assistant professor in the Department of Biological Sciences at the University of North Carolina (Charlotte, NC, USA) and the first author of this study. By assessing peripheral blood mononuclear cells in volunteers from the National Marrow Donor Program, the group confirmed the initial hypothesis that asymptomatic individuals carrying the HLA-B*15:01 allele have pre-existing T-cell immunity due to cross-reactivity with seasonal coronavirus peptides. “The study uncovers a degree of natural selection in which this allele offers a level of protection. Understanding that for multiple infections might help us respond more effectively to pandemics that could be more lethal worldwide”, Mentzer noted. The allele frequency of HLA genes varies enormously across populations, indicating that natural selection is at play. For instance, although the frequency of HLA-B*15:01 is around 10% among individuals of European ancestry, a substantially higher frequency is found in China, according to the Allele Frequency Net Database. These findings contribute to our understanding of the mechanism of immune protection against SARS-CoV-2 and might play a crucial role in designing effective strategies to mitigate infection. Beyond the scientific implications, these results also hold promise in combating misinformation surrounding COVID-19, as the absence of symptoms reported in some individuals infected with SARS-CoV-2 led to questions around the actual threat that this virus posed to humans. For Natalia Pasternak, an adjunct senior research scholar at the Center for Science and Society (Columbia University, New York, NY, USA), this ground-breaking finding might not affect those who believe in miracle cures and pseudoscientific ideas. However, as Pasternak noted, “having a plausible evidence-based explanation for those stories in which a spouse has developed severe symptoms while the other did not is important to educate people willing to listen to the science”. Licensure laws and other barriers to telemedicine and telehealth: an urgent need for reformA few weeks ago, a man in his mid-60s with worsening pulmonary fibrosis sought the expertise of a specialist physician (GR) via a telemedicine visit. The patient took the visit in his car by the roadside. Although a telemedicine visit in a car is never ideal, it was particularly difficult because he was using supplemental oxygen at 6 L/min and his oxygen saturation was only 90%; every cough during the conversation led his oxygen saturation to drop even further. The patient was not in the car by his choice or because his pulmonologist recommended it—both would have preferred the telemedicine visit from the comfort of the patient's home. Full-Text PDF
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