The care of pregnant women during the COVID-19 pandemic - response of a large health system in metropolitan New York.

The rapid progression of the coronavirus disease 2019 (COVID-19) outbreak presented extraordinary challenges to the US health care system, particularly straining resources in hard hit areas such as the New York metropolitan region. As a result, major changes in the delivery of obstetrical care were urgently needed, while maintaining patient safety on our maternity units. As the largest health system in the region, with 10 hospitals providing obstetrical services, and delivering over 30,000 babies annually, we needed to respond to this crisis in an organized, deliberate fashion. Our hospital footprint for Obstetrics was dramatically reduced to make room for the rapidly increasing numbers of COVID-19 patients, and established guidelines were quickly modified to reduce potential staff and patient exposures. New communication strategies were developed to facilitate maternity care across our hospitals, with significantly limited resources in personnel, equipment, and space. The lessons learned from these unexpected challenges offered an opportunity to reassess the delivery of obstetrical care without compromising quality and safety. These lessons may well prove valuable after the peak of the crisis has passed.

Comparative molecular dynamics simulation of Hepatitis C Virus NS3/4A protease (Genotypes 1b, 3a and 4b) predicts conformational instability of the catalytic triad in drug resistant strains.

The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3) has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan), and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a.