RESUMO
As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.
Assuntos
COVID-19 , Reinfecção , Animais , Humanos , Macaca mulatta , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
BACKGROUND: Ambulatory oxygen is frequently prescribed for patients with chronic obstructive pulmonary disease (COPD) who have oxygen desaturation =88% during exercise. The 6-min walk test (6MWT) with continuous pulse oximetry monitoring is a common method to document this oxygen desaturation, but the reproducibility of this test in determining the need for ambulatory oxygen in patients with COPD is not well documented. OBJECTIVE: The aim of this study was to establish the reproducibility of the 6MWT in determining the need for ambulatory oxygen prescription in stable COPD patients using the Centers for Medicare and Medicaid (CMS) criteria for ambulatory oxygen prescription. METHODS: The study was designed as a prospective observational study in an academic health center and associated pulmonary rehabilitation program. Eighty-eight COPD patients referred to pulmonary rehabilitation underwent continuous pulse oximetry while performing standard 6MWT on 3 separate days. RESULTS: Fifty-one (58%) of these patients desaturated by continuous pulse oximetry to an SpO(2) < or = 88% on a least one of the 6MWTs. Only 26 patients (30%) demonstrated consistency in meeting the criteria for ambulatory oxygen set forth by the CMS on all three 6MWT with a kappa statistic of 0.62. The percent agreement between 6MWTs for ambulatory oxygen prescription was 72% and the paired observation was 51%. CONCLUSIONS: The 6MWT distance is simple and widely used as a consistent measure of functional capacity in patients with COPD; however, the 6MWT oxygen saturation has only modest reproducibility in determining the need for ambulatory oxygen in stable COPD patients undergoing pulmonary rehabilitation.