Serological Responses up to 9 Months following COVID-19 mRNA Vaccination in Residents and Health-Care Workers of Long-Term Care Facilities: A Multicenter Prospective Cohort Study in Northern Italy

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Abstract

Long-term care facilities (LTCFs) were severely affected by COVID-19, in particular in Northern Italy. We aimed to assess antibody responses among residents and healthcare workers (HCWs) of 13 LTCFs through serum samples collected at three time points: prior to, two weeks, and 9 months after receiving Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine (respectively t0, t1, and t2). IgG antibodies targeted towards the S1 domain of the spike protein were measured, and results were expressed in binding antibody units (BAU/mL). Friedman’s average rank test was performed to compare antibody titres between the three time points. Two logistic regression models were built to identify independent predictors of (1) developing and (2) maintaining a significant antibody response to vaccination, using a previously identified threshold. In total, 534 subjects were enrolled (371 HCWs and 163 residents). The antibody titres at t1 were the highest; at t2, the IgG titres significantly decreased, remaining however 10 times higher compared to titres at t0. Previous infection was the only significant predictor of developing and maintaining a response over threshold in both models. Results of this study provided further insights on the humoral response elicited by vaccination, and on host factors determining variations in its magnitude and kinetics.

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Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Yapeng Su, Dan Yuan, Daniel G. Chen … (2022)

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

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Why does COVID-19 disproportionately affect older people?

Amber L. Mueller, Maeve S. McNamara, David A Sinclair (2020)

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection and effectively regulate immune responses.

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Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19

Yapeng Su, Daniel Chen, Dan Yuan … (2020)

We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.