Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation is associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of FcγR signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.

Background: Elderly patients with coronavirus disease 2019 (COVID-19) have a high disease severity and mortality. However, the use of the frailty scale and severity score to predict in-hospital mortality in the elderly is not well established. Therefore, in this study, we investigated the use of these scores in COVID-19 cases in the elderly. Methods: This multicenter retrospective study included severe COVID-19 patients admitted to seven hospitals in Republic of Korea from February 2020 to February 2021. We evaluated patients' Acute Physiology and Chronic Health Evaluation (APACHE) II score; confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older (CURB-65) score; modified early warning score (MEWS); Sequential Organ Failure Assessment (SOFA) score; clinical frailty scale (CFS) score; and Charlson comorbidity index (CCI). We evaluated the predictive value using receiver operating characteristic (ROC) curve analysis. Results:The study included 318 elderly patients with severe COVID-19 of whom 237 (74.5%) were survivors and 81 (25.5%) were non-survivors. The non-survivor group was older and had more comorbidities than the survivor group. The CFS, CCI, APACHE II, SOFA, CURB-65, and MEWS scores were higher in the non-survivor group than in the survivor group. When analyzed using the ROC curve, SOFA score showed the best performance in predicting the prognosis of elderly patients (area under the curve=0.766, P < 0.001). CFS and SOFA scores were associated with in-hospital mortality in the multivariate analysis. Conclusions:The SOFA score is an efficient tool for assessing in-hospital mortality in elderly patients with severe COVID-19.

Background The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO2/FiO2 ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO2/FiO2 ratio as predictors of failure in COVID-19 patients who received HFNC. Methods This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO2/FiO2 ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure. Results Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO2/FiO2 ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679–0.846]). The AUCs of SpO2/FiO2 ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640–0.826), 0.697 (0.597–0.798), and 0.682 (0.583–0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged <70 years (HR 3.367 [1.358–8.349], p = 0.009). The SpO2/FiO2 ratio (HR 0.983 [0.972–0.994], p = 0.003) at 1 h was significantly associated with HFNC failure. Conclusions The SpO2/FiO2 ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO2/FiO2 ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

SARS-CoV-2 infection was confirmed by reverse-transcriptase polymerase chain reaction assay; an oxygen saturation level of 94% or less on room air or a need for oxygen support was defined as severe .Background/Aims: Secondary infection with influenza virus occurs in critically ill patients and is associated with substantial morbidity and mortality; however, there is limited information about it in patients with severe coronavirus disease 2019 . Thus, we investigated the clinical outcomes of and risk factors for secondary infections in patients with severe COVID-19. Methods: This study included patients with severe COVID-19 who were admitted to seven hospitals in South Korea between February 2020 to February 2021. Multivariate logistic regression analyses were performed to assess factors associated with the risk of secondary infections. Results: Of the 348 included patients, 104 (29.9%) had at least one infection. There was no statistically significant difference in the 28-day mortality (17.3% vs. 12.3%, p = 0.214), but in-hospital mortality was higher (29.8% vs. 15.2%, p = 0.002) in the infected group than in the non-infected group. The risk factors for secondary infection were a high frailty scale (odds ratio [OR], 1.314; 95% confidence interval [CI], 1.123 to 1.538; p = 0.001), steroid use (OR, 3.110; 95% CI, 1.164 to 8.309; p = 0.024), and the application of mechanical ventilation (OR, 4.653; 95% CI, 2.533 to 8.547; p < 0.001). Conclusions: In-hospital mortality was more than doubled in patients with severe COVID-19 and secondary infections. A high frailty scale, the use of steroids and application of mechanical ventilation were risk factors for secondary infection.

BackgroundAntiphospholipid antibody syndrome (APS), an important cause of acquired thrombophilia, is diagnosed when vascular thrombosis or pregnancy morbidity occurs with persistently positive antiphospholipid antibodies (aPL). APS is a risk factor for unprovoked recurrence of pulmonary embolism (PE). Performing laboratory testing for aPL after a first unprovoked acute PE is controversial. We investigated if a specific phenotype existed in patients with unprovoked with acute PE, suggesting the need to evaluate them for APS.MethodsWe retrospectively reviewed patients with PE and APS (n=24) and those with unprovoked PE with aPL negative (n=44), evaluated 2006–2016 at the Asan Medical Center. We compared patient demographics, clinical manifestations, laboratory findings, and radiological findings between the groups.ResultsOn multivariate logistic regression analysis, two models of independent risk factors for APS-PE were suggested. Model I included hemoptysis (odds ratio [OR], 12.897; 95% confidence interval [CI], 1.025–162.343), low PE severity index (OR, 0.948; 95% CI, 0.917–0.979), and activated partial thromboplastin time (aPTT; OR, 1.166; 95% CI, 1.040–1.307). Model II included age (OR, 0.930; 95% CI, 0.893–0.969) and aPTT (OR, 1.104; 95% CI, 1.000–1.217).ConclusionWe conclude that patients with first unprovoked PE with hemoptysis and are age <40; have a low pulmonary embolism severity index, especially in risk class I–II; and/or prolonged aPTT (above 75th percentile of the reference interval), should be suspected of having APS, and undergo laboratory testing for aPL.