The differential demographic pattern of Coronavirus Disease 2019 patient fatality outside Hubei and from six hospitals in Hubei, China: a descriptive analysis (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated.Methods: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified.Findings: The overall CFR in China was estimated to be 4.6% (95% CI 4.5%-4.8%). It increased with age and was higher in males than females. The highest CFR observed was in male patients ≥70 years old. Although the outcome of infection is generally worse for males, this adverse effect from male sex decreased as people get old. Differential age/sex CFR patterns across geographical regions were found: the age effect on CFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher CFR was associated with older age, and male sex. Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher CFR.Interpretation: This up-to-date and comprehensive picture of COVID-19 CFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

Reaction Cycles of Halogen Species in the Immune Defense: Implications for Human Health and Diseases and the Pathology and Treatment of COVID-19 (preprint)

There is no vaccine or specific antiviral treatment for COVID-19. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. It is therefore challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.