The Multifaceted Role of Glutathione S-Transferases in Health and Disease.

In humans, the cytosolic glutathione S-transferase (GST) family of proteins is encoded by 16 genes presented in seven different classes. GSTs exhibit remarkable structural similarity with some overlapping functionalities. As a primary function, GSTs play a putative role in Phase II metabolism by protecting living cells against a wide variety of toxic molecules by conjugating them with the tripeptide glutathione. This conjugation reaction is extended to forming redox sensitive post-translational modifications on proteins: S-glutathionylation. Apart from these catalytic functions, specific GSTs are involved in the regulation of stress-induced signaling pathways that govern cell proliferation and apoptosis. Recently, studies on the effects of GST genetic polymorphisms on COVID-19 disease development revealed that the individuals with higher numbers of risk-associated genotypes showed higher risk of COVID-19 prevalence and severity. Furthermore, overexpression of GSTs in many tumors is frequently associated with drug resistance phenotypes. These functional properties make these proteins promising targets for therapeutics, and a number of GST inhibitors have progressed in clinical trials for the treatment of cancer and other diseases.

What Is the Impact of Early and Subsequent Epidemic Characteristics on the Pre-delta COVID-19 Epidemic Size in the United States?

It is still uncertain how the epidemic characteristics of COVID-19 in its early phase and subsequent waves contributed to the pre-delta epidemic size in the United States. We identified the early and subsequent characteristics of the COVID-19 epidemic and the correlation between these characteristics and the pre-delta epidemic size. Most (96.1% (49/51)) of the states entered a fast-growing phase before the accumulative number of cases reached (30). The days required for the number of confirmed cases to increase from 30 to 100 was 5.6 (5.1-6.1) days. As of 31 March 2021, all 51 states experienced at least 2 waves of COVID-19 outbreaks, 23.5% (12/51) experienced 3 waves, and 15.7% (8/51) experienced 4 waves, the epidemic size of COVID-19 was 19,275-3,669,048 cases across the states. The pre-delta epidemic size was significantly correlated with the duration from 30 to 100 cases (p = 0.003, r = -0.405), the growth rate of the fast-growing phase (p = 0.012, r = 0.351), and the peak cases in the subsequent waves (K1 (p < 0.001, r = 0.794), K2 (p < 0.001, r = 0.595), K3 (p < 0.001, r = 0.977), and K4 (p = 0.002, r = 0.905)). We observed that both early and subsequent epidemic characteristics contribute to the pre-delta epidemic size of COVID-19. This identification is important to the prediction of the emerging viral infectious diseases in the primary stage.