Delayed production of neutralizing antibodies correlates with fatal COVID-19.
Carolina LucasJonathan KleinMaria E SundaramFeimei LiuPatrick WongJulio SilvaTianyang MaoJi Eun OhSubhasis MohantyJiefang HuangMaria TokuyamaPeiwen LuArvind VenkataramanAnnsea ParkBenjamin IsraelowChantal B F VogelsM Catherine MuenkerC-Hong ChangArnau Casanovas-MassanaAdam J MooreJoseph ZellJohn B Fourniernull nullChantal B F VogelsMelissa CampbellAlfred I LeeHyung J ChunNathan D GrubaughWade L SchulzShelli F FarhadianCharles Dela CruzAaron M RingAlbert C ShawAdam V WisnewskiInci YildirimAlbert I KoSaad B OmerAkiko IwasakPublished in: Nature medicine (2021)
Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.
Keyphrases
- coronavirus disease
- immune response
- sars cov
- end stage renal disease
- ejection fraction
- newly diagnosed
- cross sectional
- cardiovascular disease
- metabolic syndrome
- risk factors
- young adults
- machine learning
- big data
- patient reported outcomes
- dendritic cells
- inflammatory response
- high intensity
- transcription factor
- insulin resistance
- weight loss
- skeletal muscle
- living cells
- adipose tissue
- fluorescent probe
- binding protein
- molecular dynamics