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Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and its determinants is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. In addition, understanding the extent of antibody cross-reactivity with other human coronaviruses (HCoV) is important to elucidate the impact of such pre-existing antibodies on COVID-19 immunity. Four low-pathogenic HCoV causing common cold have circulated among humans for at least 100 years: the alphacoronaviruses 229E and NL63, and the betacoronaviruses OC43 and HKU1. They account for about 10% of all acute respiratory tract infections, thus, a substantial proportion of the global population is expected to carry antibodies against them.
We measured IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the four endemic HCoV by suspension array technology (Luminex), and assessed the antibody neutralization capacity by flow cytometry, in a cohort of 578 health care workers from Hospital Clínic followed-up for 6 months. Seroprevalence increased over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, were stable over time, except IgG to nucleocapsid antigen and IgM levels that waned. Interestingly, after the peak response, anti-spike IgG levels increased from ~150 days post-symptom onset in 73% of the individuals, in the absence of any evidence of re-exposure. Pre-existing antibodies to alpha- HCoV were lower in individuals who subsequently seroconverted for SARS-CoV-2. IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease. Most of the health care workers from this cohort have already been immunized with COVID-19 vaccines and antibody responses will be analyzed in relation to previous SARS-CoV-2 exposure and immune responses.
In conclusion, antibody levels and neutralizing capacity are generally maintained up to 7.7 months after infection, and in a substantial number of individuals antibody levels increase after some months. Importantly, previous exposure to HCoVs could have a protective effect against SARS-CoV-2 infection and symptoms development, and may explain in part the differential susceptibility to disease in the population.
Gemma Moncunill is an immunologist (PhD Universitat Autònoma de Barcelona) with over 10 years of experience in immunology of infectious diseases and vaccinology. Currently, she is an Assistant Research Professor in the Malaria Immunology group at ISGlobal, where she works on mechanisms of susceptibility and immunity to malaria and other infectious diseases, including COVID-19.
Her research career started in 2004 at IrsiCaixa AIDS Research Institute, where she received a PhD degree in Immunology in 2009, working on new anti-HIV agents. Afterward, she moved to ISGlobal (Barcelona Institute for Global Health), where she worked as a postdoctoral fellow on malaria immunology (2009-2013) and performed studies at FM-CISM (Mozambique). She elucidated mechanisms of acquired immunity to malaria and vaccine-induced immunity. Later she moved to Dr. McElrath lab at the Fred Hutchinson Cancer Research Center (USA, 2013-2014) where she worked on immune responses to vaccines. In 2015, she moved to the lab of Prof. Kollmann at the University of British Columbia (Canada), where she described immune alterations due to malaria and HIV exposure in pregnant women and their newbons. In 2017 she returned at ISGlobal, with the goal to decode the immune responses that determine infection and vaccine outcomes to develop more effective vaccines and immunotherapies.
Recently, the scope of her research has expanded to include COVID-19. She is currently leading and a multicentric immunology study to assess the strength and duration of the immune responses in African adults with mild-to-moderate COVID-19 or asymptomatic infection. In addition, she has conducted seroprevalence and immune studies in different Catalan cohorts, including a Health Care workers cohort from the Hospital Clinic de Barcelona, subject of this seminar.
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