Variations of COVID-19 mortality are affected by economic disparities across countries.

BACKGROUND: When the COVID-19 case number reaches a maximum in a country, its capacity and management of health system face greatest challenge. METHODS: We performed a cross-sectional study on data of turning points for cases and deaths for the first three waves of COVID-19 in countries with more than 5000 cumulative cases, as reported by Worldometers and WHO Coronavirus (COVID-19) Dashboard. We compared the case fatality rates (CFRs) and time lags (in unit of day) between the turning points of cases and deaths among countries in different development stages and potential influence factors. As of May 10, 2021, 106 out of 222 countries or regions (56%) reported more than 5000 cases. Approximately half of them have experienced all the three waves of COVID-19 disease. The average mortality rate at the disease turning point was 0.038 for the first wave, 0.020 for the second wave, and 0.023 for wave 3. In high-income countries, the mortality rates during the first wave are higher than that of the other income levels. However, the mortality rates during the second and third waves of COVID-19 were much lower than those of the first wave, with a significant reduction from 5.7% to 1.7% approximately 70%. At the same time, high-income countries exhibited a 2-fold increase in time lags during the second and the third waves compared to the first wave, suggesting that the periods between the cases and deaths turning point extended. High rates in the first wave in developed countries are associated to multiple factors including transportation, population density, and aging populations. In upper middle- and lower middle-income countries, the decreasing of mortality rates in the second and third waves were subtle or even reversed, with increased mortality during the following waves. In the upper and lower middle-income countries, the time lags were about 50% of the durations observed from high-income countries. INTERPRETATION: Economy and medical resources affect the efficiency of COVID-19 mitigation and the clinical outcomes of the patients. The situation is likely to become even worse in the light of these countries' limited ability to combat COVID-19 and prevent severe outcomes or deaths as the new variant transmission becomes dominant.

MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program.

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.

A cost-effective plan for global testing - an infection rate stratified, algorithm guided, multiple-level, continuously pooled testing strategy.

The most effective measure to prevent or stop the spread of infectious diseases is the early identification and isolation of infected individuals through comprehensive screening. At present, in the COVID-19 pandemic, such screening is often limited to isolated regions as determined by local governments. Screening of potentially infectious individuals should be conducted through coordinated national or global unified actions. Our current research focuses on using resources to conduct comprehensive national and regional regular testing with a risk rate based, algorithmic guided, multiple-level, pooled testing strategy. Here, combining methodologies with mathematical logistic models, we present an analytic procedure of an overall plan for coordinating state, national, or global testing. The proposed plan includes three parts 1) organization, resource allocation, and distribution; 2) screening based on different risk levels and business types; and 3) algorithm guided, multiple level, continuously screening the entire population in a region. This strategy will overcome the false positive and negative results in the polymerase chain reaction (PCR) test and missing samples during initial tests. Based on our proposed protocol, the population screening of 300,000,000 in the US can be done weekly with between 15,000,000 and 6,000,000 test kits. The strategy can be used for population screening for current COVID-19 and any future severe infectious disease when drugs or vaccines are not available.

Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: An epidemiological study from a fever clinic in Wuhan, China.

BACKGROUND: Since the outbreak of 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) pneumonia, thousands of patients with fever or cough were flocked into fever clinic of designated hospitals in Wuhan, China. To date, no data have ever been reported to reflect the prevalence of coronavirus disease 2019 (COVID-19) among these outpatients. Moreover, it is almost unknown to discriminate COVID-19 and nucleic acid negative patients based on clinical features in the fever clinics. METHODS: The infectious status of SARS-CoV-2 was estimated among the outpatients. The epidemiological and clinical characteristics were compared between COVID-19 and nucleic acid negative patients. RESULTS: The nucleic acid positive rate for SARS-CoV-2 in the outpatients from our fever clinic was 67·1%, while the majority of patients with COVID-19 were mild cases. The predominant initial symptom in those patients with COVID-19 was fever (78.2%), followed by cough (15.6%). Very significantly lower number of eosinophils was characterized in patients with COVID-19 as compared with that of nucleic acid negative patients. More importantly, the proportion of subjects with eosinophil counts lower than normal levels in patients with COVID-19 was much higher than that of nucleic acid negative patients. Fever combined with bilateral ground-glass opacities in computed tomography imaging and eosinophil count below the normal level are probably a valuable indicator of COVID-19 infection in those outpatients. CONCLUSIONS: Those findings may provide critical information for the regions, such as Europe and United States that are facing the same situation as Wuhan experienced, and could be valuable to prevent those nucleic acid negative patients from misdiagnosis before antibody testing.

Obesity predisposes to the risk of higher mortality in young COVID-19 patients

BACKGROUND: Although emerging data demonstrated mortality of young COVID-19 patients, but no data reported the risk factors of mortality for those young patients, and whether obesity is a risk for young COVID-19 patients remains unknown. METHODS: We conducted a retrospective study including 13 young patients died of COVID-19 and 40 matched survivors. Logistic regression was employed to characterize the risk factors of mortality in young obese COVID-19 patients. RESULTS: Most of the young deceased COVID-19 patients were mild cases at the time of admission, but the disease progressed rapidly featured by the higher severity of Patchy shadows (100.00% vs. 48.70%, P = 0.006), pleural thickening (61.50% vs. 12.80%, P = 0.012), mild pericardial effusion (76.90% vs. 0.00%, P < 0.001). Most importantly, the deceased patients manifested higher BMI (OR = 1.354, 95% CI = 1.075-1.704, P = 0.010), inflammatory-related index CRP (OR = 1.014, 95% CI = 1.003-1.025, P = 0.014), cardiac injury biomarker hs-cTnI (OR = 1.420, 95% CI = 1.112-1.814, P = 0.005), and increased coagulation activity biomarker D-Dimer (OR = 418.7, P = 0.047), as compared to that of survivors. CONCLUSIONS: Our data support that obesity could be a risk factor associated with high mortality in young COVID-19 patients, while aggravated inflammatory response, enhanced cardiac injury and increased coagulation activity are likely to be the mechanisms contributing to the high mortality. This article is protected by copyright. All rights reserved.