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worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01-0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period.

Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality.

Bayer AG, Merck Sharp & Dohme.

Bayer AG, Merck Sharp & Dohme.

Although the first wave of the COVID-19 pandemic progressed more slowly in Africa than the rest of the world, by December, 2020, the second wave appeared to be much more aggressive with many more cases. To date, the pandemic situation in all 55 African Union (AU) Member States has not been comprehensively reviewed. We aimed to evaluate reported COVID-19 epidemiology data to better understand the pandemic’s progression in Africa.

We did a cross-sectional analysis between Feb 14 and Dec 31, 2020, using COVID-19 epidemiological, testing, and mitigation strategy data reported by AU Member States to assess trends and identify the response and mitigation efforts at the country, regional, and continent levels. We did descriptive analyses on the variables of interest including cumulative and weekly incidence rates, case fatality ratios (CFRs), tests per case ratios, growth rates, and public health and social measures in place.

As of Dec 31, 2020, African countries had reported 2 763 421 COVID-19 cases and 65 60s the importance of examining multiple epidemiological variables down to the regional and country levels over time. These country-specific and regional results informed the implementation of continent-wide initiatives and supported equitable distribution of supplies and technical assistance. Monitoring and analysis of these data over time are essential for continued situational awareness, especially as Member States attempt to balance controlling COVID-19 transmission with ensuring stable economies and livelihoods.

None.

None.

Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study.

We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19e phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001’s safety and efficacy.

National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.

For the Chinese translation of the abstract see Supplementary Materials section.

For the Chinese translation of the abstract see Supplementary Materials section.Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces the disease-associated metabolite hydrogen sulfide. Here, we present a 2.7 Å resolution X-ray structure of wild-type IslA from Bilophila wadsworthia with isethionate bound. In comparison with other GREs, alternate positioning of the active site β strands allows for distinct residue positions to contribute to substrate binding. These structural differences, combined with sequence variations, create a highly tailored active site for the binding of the negatively charged isethionate substrate. Through the kinetic analysis of 14 IslA variants and computational analyses, we probe the mechanism by which radical chemistry is used for C-S bond cleavage. This work further elucidates the structural basis of chemistry within the GRE superfamily and will inform structure-based inhibitor design of IsIA and thus of microbial hydrogen sulfide production.

Parents have faced substantial social and economic challenges during the COVID-19 pandemic. GSK1070916 in vitro Preliminary cross-sectional research has demonstrated increases in mental health problems in mothers during the COVID-19 pandemic compared with pre-pandemic estimates. We aimed to study an existing longitudinal cohort of mothers to assess changes in the prevalence of maternal depression and anxiety symptoms as a result of the COVID-19 pandemic over time and at the individual level.

In this longitudinal observational study, women who took part in the All Our Families pregnancy cohort in Canada were invited to complete a COVID-19 impact survey between May 20 and July 15, 2020. Women who had not agreed to additional research, had discontinued, were lost to follow-up, or who were not contactable via email were excluded. Maternal depression and anxiety symptoms during the COVID-19 pandemic were compared with three previous estimates collected at 3, 5, and 8-year timepoints (between April, 2012, and October, 2019). Depression symptoms were assessed using the 10-item Center for Epidemiological Studies Depression scale and anxiety symptoms were assessed using the short form of the Spielberger State-Trait Anxiety Inventory.