Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity.
Clin Transl Med
; 12(9): e1025, 2022 09.
Article
Dans Anglais
| MEDLINE | ID: covidwho-2027333
ABSTRACT
BACKGROUND:
Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive.METHODS:
We investigated a total of 137 APs infected with SARS-CoV-2. 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-, S1-, SSA/Ro- and dsDNA-specific IgG.RESULTS:
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-induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID-19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease.CONCLUSION:
Our results reveal an immune mechanism that controls SARS-CoV-2-induced detrimental B cell responses and COVID-19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.Mots clés
Texte intégral:
Disponible
Collection:
Bases de données internationales
Base de données:
MEDLINE
Sujet Principal:
Vaccins antiviraux
/
COVID-19
Type d'étude:
Études expérimentales
/
Étude pronostique
/
Essai contrôlé randomisé
Les sujets:
Vaccins
Limites du sujet:
Humains
langue:
Anglais
Revue:
Clin Transl Med
Année:
2022
Type de document:
Article
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