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Mechanisms underlying the detrimental immune responses and disease severity remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated a total of 137 APs infected with SARS\u2010CoV\u20102. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD\u2010, S1\u2010, SSA\/Ro\u2010 and dsDNA\u2010specific IgG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection\u2010induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID\u201019 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal an immune mechanism that controls SARS\u2010CoV\u20102\u2010induced detrimental B cell responses and COVID\u201019 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1025","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T17:54:53Z","timestamp":1663178093000},"source":"Crossref","is-referenced-by-count":11,"title":["Mitochondrial regulation of acute extrafollicular B\u2010cell responses to COVID\u201019 severity"],"prefix":"10.1002","volume":"12","author":[{"given":"Tianyu","family":"Cao","sequence":"first","affiliation":[{"name":"AIDS Institute, Li Ka Shing Faculty of Medicine The University of Hong 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