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BackgroundMutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. MethodsWe enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). ResultsThe casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature ([≥] 38{degrees}C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). ConclusionThis real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge. SummaryThis real-world retrospective study demonstrates the contribution of treatment with casirivimab-imdevimab to the prevention of deterioration in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) even during the Delta variant pandemic.
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BACKGROUNDDue to the dissemination of vaccination against severe acute respiratory syndrome coronavirus 2 in the elderly, the virus-susceptible subjects have shifted to unvaccinated non-elderlies. The risk factors of COVID-19 deterioration in non-elderly patients without respiratory failure have not yet been determined. This study was aimed to create simple predicting method to identify such patients who have high risk for exacerbation. METHODSWe analyzed the data of 1,675 patients aged under 65 years who were admitted to hospitals with mild-to-moderate COVID-19. For validation, 324 similar patients were enrolled. Disease progression was defined as administration of medication, oxygen inhalation and mechanical ventilator starting one day or longer after admission. RESULTSThe patients who exacerbated tended to be older, male, had histories of smoking, and had high body temperatures, lower oxygen saturation, and comorbidities such as diabetes/obesity and hypertension. Stepwise logistic regression analyses revealed that comorbidities of diabetes/obesity, age [≥] 40 years, body temperature [≥] 38{degrees}C, and oxygen saturation < 96% (DOATS) were independent risk factors of worsening COVID-19. As a result two predictive scores were created: DOATS score, which includes all the above risk factors; and DOAT score, which includes all factors except for oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve of the DOATS and DOAT scores were 0.789 and 0.771, respectively. In the validation, the areas were 0.702 and 0.722, respectively. CONCLUSIONWe established two simple prediction scores that can quickly evaluate the risk of progression of COVID-19 in non-elderly, mild/moderate patients. SummaryThe risk stratification models using independent risks, namely comorbidity of diabetes or obesity, age [≥] 40 years, high body temperature [≥] 38{square}, and oxygen saturation < 96%, DOATS and DOAT scores, predicted worsening COVID-19 in patients with mild-to-moderate cases.
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To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
