The age-standardized incidence, mortality, and case fatality rates of COVID-19 in 79 countries: a cross-sectional comparison and their correlations with associated factors.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, crude incidence and mortality rates have been widely reported; however, age-standardized rates are more suitable for comparisons. In this study, we estimated and compared the age-standardized incidence, mortality, and case fatality rates (CFRs) among countries and investigated the relationship between these rates and factors associated with healthcare resources: gross domestic product per capita, number of hospital beds per population, and number of doctors per population. METHODS: The incidence, mortality, and CFRs of 79 countries were age-standardized using the World Health Organization standard population. The rates for persons 60 years or older were also calculated. The relationships among the rates were analysed using trend lines and coefficients of determination (R2). Pearson correlation coefficients between the rates and the healthcare resource-related factors were calculated. RESULTS: The countries with the highest age-standardized incidence, mortality, and CFRs were Czechia (14,253 cases/100,000), Mexico (182 deaths/100,000), and Mexico (6.7%), respectively. The R2 between the incidence and mortality rates was 0.852 for all ages and 0.945 for those 60 years or older. The healthcare resources-related factors were associated positively with incidence rates and negatively with CFRs, with weaker correlations among the elderly. CONCLUSIONS: Compared to age-standardized rates, crude rates showed greater variation among countries. Medical resources may be important in preventing COVID-19-related deaths; however, considering the small variation in fatality among the elderly, preventive measures such as vaccination are more important, especially for the elderly population, to minimize the mortality rates.

Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19.

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 T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are 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 Fcγ receptor (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.

Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability.

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.