Huang Y., et al., Calibration of two validated SARS-CoV-2 pseudovirus neutralization assays for COVID-19 vaccine evaluation. with persistent gastrointestinal and neurological symptoms. Longitudinal modeling exhibited significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses. Keywords: COVID-19, SARS-CoV-2, Neutralizing Antibodies, Long COVID, Post-Acute Sequelae of SARS-CoV-2 contamination (PASC) Summary: SARS-CoV-2-specific antibody neutralization of Omicron BA.5 variant approximately 4 months following acute infection with wild-type virus prior to vaccination was independently and significantly associated with greater odds of distinct Long COVID phenotypes. INTRODUCTION Many individuals experience post-acute sequelae of SARS-CoV-2 contamination (PASC), which can affect quality of life and return to health [1C3]. The etiologic drivers of Long COVID (LC), a form of PASC defined by ongoing, often debilitating, symptoms, are poorly comprehended and likely involve multiple mechanisms [2, Dopamine hydrochloride 4, 5]. Proposed mechanisms include aberrant autoreactive immune responses, microvascular dysregulation, and reactivation of latent human herpesviruses which may lead to the systemic inflammatory responses now identified in individuals with Long COVID compared Dopamine hydrochloride to those who fully recovered [6C11]. Furthermore, there is growing evidence that SARS-CoV-2 subgenomic RNA and proteins are present in the tissues of at least a subset of immunocompetent individuals with LC [12C14]. Although those with persistent symptoms tend to have higher levels of SARS-CoV-2 Spike-specific antibody levels [10, 15C18], we and others have previously exhibited that LC is usually associated with adaptive immune dysregulation and exhaustion [15, 18]. SARS-CoV-2 contamination leads to Dopamine hydrochloride rapid development of robust antibody responses, although neutralizing capacity wanes more quickly than total Spike IgG levels over time [17, 19C21]. A higher initial viral burden or Dopamine hydrochloride persistence of viral antigens may lead to observed dysregulated immune phenotypes and higher antibody levels. However, there is a paucity of information regarding the associations between longitudinal dynamics or the breadth of the neutralizing antibody response with various LC phenotypes with some data showing that weaker antibody responses over time being associated with LC [22]. Recent pre-print data suggests that an expanded antibody response against the prior OC43 endemic coronavirus may be associated with Long COVID [23]. This suggests that the breadth of the response to initial contamination may play an important role in the development of LC. Given that the rapid emergence of Omicron variants that evade neutralization result from contamination from older SARS-CoV-2 strains (antibody neutralization of the original SARS-CoV-2 virus and subsequent variants approximately 1 month (A, N=69), 2 months (B, N=115), and 4 months (C, N=119) following acute contamination for all participants. Subgroup analysis of cross-neutralization in an expanded Omicron sub variant panel (N=16) in a subset of participants that had samples across all timepoints with either high or unfavorable neutralization to BA.5 (D). Most Rabbit Polyclonal to C56D2 samples collected prior to SARS-CoV-2 vaccination and prior to the emergence of Delta and Omicron variants. Bars represent mean antibody (Ab) infectious dose 50% (ID50) values and 95% confidence intervals (* P<0.05, ** P<0.01, ***P<0.001 by two-sided Freidman.