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BackgroundPassive antibody therapy with convalescent plasma (CP) represents a promising alternative for the treatment of SARS-CoV-2 infection. The efficacy of CP therapy has been associated with high titers of neutralizing antibodies (nAbs) in the plasma of recovered patients, but the assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti-SARS-CoV-2 immunoassays and the clinical characteristics of the CP potential donors. MethodsTwo hundred and fourteen CP donors were enrolled and tested for the presence of anti-SARS-CoV-2 antibodies using two commercial immunoassays (IA): Anti-SARS-CoV-2 ELISA IgG EUROIMMUN and Anti-SARS-CoV-2 Chemiluminescence IgG Abbott. In parallel, quantification of neutralizing antibodies (nAbs) was performed using the Cytopathic effect-based virus neutralization test (CPE-VNT). Three criteria for identifying donors with high titers of nAbs ([≥]1:160) were tested: - Criterion1: Curve ROC Method; - Criterion 2: Conditional decision tree considering only the results from the IA and -Criterion 3: Conditional decision tree including both the IA results and the clinical variables. ResultsThe performance of Abbott and EUROIMMUN immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers [≥] 1:160. Regarding the three studied criteria for identifying CP donors with high nAbs titers ([≥] 1:160): 1) Criterion 1 showed 76.1% accuracy when the S/CO cut-off of 4.65 was used, 2) Criterion 2 presented 76.1% accuracy if the S/CO [≥] 4.57 was applied and 3) Criterion 3 had 71.6% accuracy if either S/CO [≥] 4.57 or S/CO between 2.68 and 4.57 and the last COVID-19-related symptoms occurred less than 19 days from donor recruiting were used. ConclusionThe results of SARS-CoV-2 immunoassays (S/CO) can be used to predict high nAbs titers of potential CP donors. This study has proposed three different criteria for identifying donors with [≥] 1:160 nAbs titer based on either solely S/CO results or S/CO together with clinical variables, all with high efficacy and accuracy.
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The herd immunity threshold is the proportion of a population that must be immune to an infectious disease, either by natural infection or vaccination such that, in the absence of additional preventative measures, new cases decline and the effective reproduction number falls below unity. This fundamental epidemiological parameter is still unknown for the recently-emerged COVID-19, and mathematical models have predicted very divergent results. Population studies using antibody testing to infer total cumulative infections can provide empirical evidence of the level of population immunity in severely affected areas. Here we show that the transmission of SARS-CoV-2 in Manaus, located in the Brazilian Amazon, increased quickly during March and April and declined more slowly from May to September. In June, one month following the epidemic peak, 44% of the population was seropositive for SARS-CoV-2, equating to a cumulative incidence of 52%, after correcting for the false-negative rate of the antibody test. The seroprevalence fell in July and August due to antibody waning. After correcting for this, we estimate a final epidemic size of 66%. Although non-pharmaceutical interventions, plus a change in population behavior, may have helped to limit SARS-CoV-2 transmission in Manaus, the unusually high infection rate suggests that herd immunity played a significant role in determining the size of the epidemic.
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BACKGROUND: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients. In this study, we compared the efficacy of voriconazole containing regimen vs non-voriconazole containing regimen in patients with IA. METHODS: In this retrospective study, we reviewed the medical records of all immunocompromised cancer patients diagnosed with proven or probable IA between February 2012 and March 2018. This trial included 26 patients from the American University of Beirut, Lebanon, 20 patients from Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil, and 10 patients from St. Luke's International Hospital Tokyo, Japan. RESULTS: A total of 56 patients were analyzed. They were divided into 2 groups voriconazole containing regimen and non-voriconazole containing regimen (90% Amphotericin B based regimen). Both groups had similar characteristic, age, gender, and immunocompromised status. The majority of patients had underlying leukemia (63%), followed by lymphoma (20%), myeloma (16%) and other hematologic malignancy (1%). Antifungal primary therapy with voriconazole-containing regimen was associated with better response to treatment (p = 0.003). Survival analysis showed that primary therapy with a voriconazole containing regimen was significantly associated with improved survival (p =0.006). By multivariate logistic regression analysis, mechanical ventilation was a predictor of worse outcomes (poor response to therapy and increased mortality within 6 months), whereas primary treatment with voriconazole containing regimen was associated with improved outcomes including response to primary therapy (OR=18.1, p=0.002) and 6-month mortality (OR=0.14, p=0.011). CONCLUSIONS: Based on international experience in immunocompromised cancer patients with IA, primary therapy with voriconazole-containing regimen is associated with improved response and survival compared with non-voriconazole amphotericin B based regimen.
