Changes in the Hospital Standardized Mortality Ratio Before and During the COVID-19 Pandemic: A Disaggregated Analysis by Region and Hospital Type in Korea.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to a global shortage of medical resources; therefore, we investigated whether COVID-19 impacted the quality of non-COVID-19 hospital care in Korea by comparing hospital standardized mortality rates (HSMRs) before and during the pandemic. METHODS: This retrospective cohort study analyzed Korean National Health Insurance discharge claim data obtained from January to June in 2017, 2018, 2019, and 2020. Patients' in-hospital deaths were classified according to the most responsible diagnosis categories. The HSMR is calculated as the ratio of expected deaths to actual deaths. The time trend in the overall HSMR was analyzed by region and hospital type. RESULTS: The final analysis included 2 252 824 patients. In 2020, the HSMR increased nationwide (HSMR, 99.3; 95% confidence interval [CI], 97.7 to 101.0) in comparison to 2019 (HSMR, 97.3; 95% CI, 95.8 to 98.8). In the COVID-19 pandemic zone, the HSMR increased significantly in 2020 (HSMR, 112.7; 95% CI, 107.0 to 118.7) compared to 2019 (HSMR, 101.7; 95% CI, 96.9 to 106.6). The HSMR in all general hospitals increased significantly in 2020 (HSMR, 106.4; 95% CI, 104.3 to 108.5) compared to 2019 (HSMR, 100.3; 95% CI, 98.4 to 102.2). Hospitals participating in the COVID-19 response had a lower HSMR (HSMR, 95.6; 95% CI, 93.9 to 97.4) than hospitals not participating in the COVID-19 response (HSMR, 124.3; 95% CI, 119.3 to 129.4). CONCLUSIONS: This study suggests that the COVID-19 pandemic may have negatively impacted the quality of care in hospitals, especially general hospitals with relatively few beds. In light of the COVID-19 pandemic, it is necessary to prevent excessive workloads in hospitals and to properly employ and coordinate the workforce.

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4+ T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs). Anti-S IgG, IgA, and IgG subclasses 1 and 3 increased after vaccination and correlated with neutralization activity in HCs and patients with oPADs. However, 42% of CVID patients developed such responses after the 2nd dose. A similar pattern was also observed with S-specific CD4+ T-cells as determined by OX40 and 4-1BB expression. Patients with poor anti-S IgG response had significantly lower levels of baseline IgG, IgA, CD19+ B-cells, switched memory B-cells, naïve CD8+ T-cells, and a higher frequency of EM CD8+ T-cells and autoimmunity compared to patients with adequate anti-S IgG responses. Patients with oPADs can develop humoral and cellular immune responses to vaccines similar to HCs. However, a subset of CVID patients exhibit impairment in developing such responses, which can be predicted by the baseline immune profile and history of autoimmunity.

Estimation of Excess All-cause Mortality during COVID-19 Pandemic in Korea.

BACKGROUND: Excess all-cause mortality is helpful to assess the full extent of the health impact, including direct and indirect deaths of coronavirus disease 2019 (COVID-19). The study aimed to estimate overall and regional excess all-cause mortality during the pandemic in Korea. METHODS: We obtained all-cause death data and population statistics from January 2010 to December 2020. The expected mortality in 2020 was estimated using a quasi-Poisson regression model. The model included death year, seasonal variation, cold wave (January), average death counts in the previous month, and population. Excess mortality was defined as the difference between the observed mortality and the expected mortality. Regions were classified into three areas according to the numbers of COVID-19 cases. RESULTS: There was no annual excess all-cause mortality in 2020 at the national and regional level compared to the average death for the previous ten years. The observed mortality in 2020 was 582.9 per 100,000 people, and the expected mortality was 582.3 per 100,000 people (95% confidence interval, 568.3-596.7). However, we found monthly and regional variations depending on the waves of the COVID-19 pandemic in Korea. While the mortality in August, October, and November exceeded the expected range, the mortality in September was lower than the expected range. The months in which excess deaths were identified differed by region. CONCLUSION: Our results show that the mortality in 2020 was similar to the historical trend. However, in the era of the COVID-19 pandemic, it would be necessary to regularly investigate COVID-19-related mortality and determine its direct and indirect causes.

A distinct association of inflammatory molecules with outcomes of COVID-19 in younger versus older adults.

Aging can alter immunity affecting host defense. COVID-19 has the most devastating clinical outcomes in older adults, raising the implication of immune aging in determining its severity and mortality. We investigated biological predictors for clinical outcomes in a dataset of 13,642 ambulatory and hospitalized adult COVID-19 patients, including younger (age < 65, n = 566) and older (age ≥ 65, n = 717) subjects, with in-depth analyses of inflammatory molecules, cytokines and comorbidities. Disease severity and mortality in younger and older adults were associated with discrete immune mechanisms, including predominant T cell activation in younger adults, as measured by increased soluble IL-2 receptor alpha, and increased IL-10 in older adults although both groups also had shared inflammatory processes, including acute phase reactants, contributing to clinical outcomes. These observations suggest that progression to severe disease and death in COVID-19 may proceed by different immunologic mechanisms in younger versus older subjects and introduce the possibility of age-based immune directed therapies.