ABSTRACT
Interpretation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveillance studies is limited by poorly defined performance of antibody assays over time in individuals with different clinical presentations. We measured antibody responses in plasma samples from 128 individuals over 160 days using 14 assays. We found a consistent and strong effect of disease severity on antibody magnitude, driven by fever, cough, hospitalization, and oxygen requirement. Responses to spike protein versus nucleocapsid had consistently higher correlation with neutralization. Assays varied substantially in sensitivity during early convalescence and time to seroreversion. Variability was dramatic for individuals with mild infection, who had consistently lower antibody titers, with sensitivities at 6 months ranging from 33 to 98% for commercial assays. Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on infection severity, timing, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.
ABSTRACT
Serosurveillance studies are critical for estimating SARS-CoV-2 transmission and immunity, but interpretation of results is currently limited by poorly defined variability in the performance of antibody assays to detect seroreactivity over time in individuals with different clinical presentations. We measured longitudinal antibody responses to SARS-CoV-2 in plasma samples from a diverse cohort of 128 individuals over 160 days using 14 binding and neutralization assays. For all assays, we found a consistent and strong effect of disease severity on antibody magnitude, with fever, cough, hospitalization, and oxygen requirement explaining much of this variation. We found that binding assays measuring responses to spike protein had consistently higher correlation with neutralization than those measuring responses to nucleocapsid, regardless of assay format and sample timing. However, assays varied substantially with respect to sensitivity during early convalescence and in time to seroreversion. Variations in sensitivity and durability were particularly dramatic for individuals with mild infection, who had consistently lower antibody titers and represent the majority of the infected population, with sensitivities often differing substantially from reported test characteristics (e.g., amongst commercial assays, sensitivity at 6 months ranged from 33% for ARCHITECT IgG to 98% for VITROS Total Ig). Thus, the ability to detect previous infection by SARS-CoV-2 is highly dependent on the severity of the initial infection, timing relative to infection, and the assay used. These findings have important implications for the design and interpretation of SARS-CoV-2 serosurveillance studies.
ABSTRACT
BACKGROUND: The purpose of this study was to identify the incidence and types of complications after revision total hip arthroplasty (THA) within the first year, and determine the relative risk factors for these complications and of re-revision. METHODS: The sample size of 5% Medicare claims data from 1998-2011 was studied. Primary THA patients who underwent subsequent revision were identified using ICD-9-CM codes. Outcomes and complications after revision THA were assessed. Multivariate Cox regression was used to evaluate the effect of patient demographic characteristics on the adjusted complication risk for revision THA patients. RESULTS: Of the 64,260 primary THA patients identified between 1998 and 2011, 3555 patients (5.71%) underwent revision THA. Etiology of primary hip failure included mechanical complications such as loosening and wear (40.7%), dislocation (14.0%), and infection (11.3%). Complications after revision THA included infection and redo revision, 17.3% and 15.8% followed by venous thromboembolic disease (VTE) at 11.1%, dislocation at 5.43%, PE at 3.24%, and death at 2.11%. The rate of "new" infections after an aseptic revision was 8.13%. Patients in the 85+-year-old age group had a 100% greater adjusted risk of VTE (P < .001) and 406% higher adjusted risk of death (P < .001) than those in the 65-69 years-old age group. Patients with higher Charlson scores had higher adjusted risks of VTE (P < .001), infection (P < .001), death (P = .002), and re-revision THA (P = .011). CONCLUSION: Advanced age is a clear risk factor for VTE and mortality, but not for dislocation, infection, or re-revision. Higher Charlson index was found to be a risk factor for every complication after revision except dislocation. Greater attention is required to address the high rate of infection and re-do revision after revision THA (17.3% and 15.8%).
