Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity.

IMPORTANCE: The Omicron subvariants have substantially evaded host-neutralizing antibodies and adopted an endosomal route of entry. The virus has acquired several mutations in the receptor binding domain and N-terminal domain of S1 subunit, but remarkably, also incorporated mutations in S2 which are fixed in Omicron sub-lineage. Here, we found that the mutations in the S2 subunit affect the structural and biological properties such as neutralization escape, entry route, fusogenicity, and protease requirement. In vivo, these mutations may have significant roles in tropism and replication. A detailed understanding of the effects of S2 mutations on Spike function, immune evasion, and viral entry would inform the vaccine design, as well as therapeutic interventions aiming to block the essential proteases for virus entry. Thus, our study has identified the crucial role of S2 mutations in stabilizing the Omicron spike and modulating neutralization resistance to antibodies targeting the S1 subunit.

Effectiveness of convalescent plasma in Indian patients with COVID-19.

BACKGROUND: Convalescent plasma (CP) is being used as a treatment option in hospitalized patients with COVID-19. Till date, there is conflicting evidence on efficacy of CP in reducing COVID-19 related mortality. OBJECTIVE: To evaluate the effect of CP on 28-day mortality reduction in patients with COVID-19. METHODS: We did a multi-centre, retrospective case control observational study from 1st May 2020 to 31st August 2020. A total of 1079 adult patients with moderate and severe COVID-19 requiring oxygen, were reviewed. Of these, 694 patients were admitted to ICU. Out of these, 333 were given CP along with best supportive care and remaining 361 received best supportive care only. RESULTS: In the overall group of 1079 patients, mortality in plasma vs no plasma group was statistically not significant (22.4% vs 18.5%; p = 0.125; OR = 1.27, 95% CI: 0.94--1.72). However, in patients with COVID-19 admitted to ICU, mortality was significantly lower in plasma group (25.5% vs 33.2%; p = 0.026; OR = 0.69, 95%CI: 0.50-0.96). This benefit of reduced mortality was most seen in age group 60 to 74 years (26.7% vs 43.0%; p = 0.004; OR = 0.48, 95% CI: 0.29-0.80), driven mostly by females of this age group (23.1% vs 53.5%; p = 0.013; OR = 0.26, 95% CI: 0.09-0.78). Significant difference in mortality was observed in patients with one comorbidity (22.3% vs 36.5%; p = 0.004; OR = 0.50, 95% CI: 0.31-0.80). Moreover, patients on ventilator had significantly lower mortality in the plasma arm (37.2% vs 49.3%; p = 0.009; OR = 0.61, 95% CI: 0.42-0.89); particularly so for patients on invasive mechanical ventilation (63.9% vs 82.9%; p = 0.014; OR = 0.37, 95% CI: 0.16-0.83). CONCLUSION: The use of CP was associated with reduced mortality in COVID-19 elderly patients admitted in ICU, above 60 years of age, particularly females, those with comorbidities and especially those who required some form of ventilation.

Policy implementation and recommended actions to create healthy food environments using the Healthy Food Environment Policy Index (Food-EPI): a comparative analysis in South Asia.

Background: The increasing prevalence of diet-related non-communicable diseases (NCDs) in South Asia is concerning, with type 2 diabetes projected to rise to 68%, compared to the global increase of 44%. Encouraging healthy diets requires stronger policies for healthier food environments. Methods: This study reviewed and assessed food environment policies in Bangladesh, India, Pakistan, and Sri Lanka from 2020 to 2022 using the Healthy Food Environment Policy Index (Food-EPI) and compared them with global best practices. Seven policy domains and six infrastructure support domains were considered, employing 47 good practice indicators to prevent NCDs. Stakeholders from government and non-governmental sectors in South Asia (n = 148) were invited to assess policy and infrastructure support implementation using the Delphi method. Findings: Implementation of food environment policies and infrastructure support in these countries was predominantly weak. Labelling, monitoring, and leadership policies received a moderate rating, with a focus on food safety, hygiene, and quality rather than obesity prevention. Key policy gaps prioritized for attention included front-of-pack labelling, healthy food subsidies, unhealthy food taxation, restrictions on unhealthy food promotion, and improvements in school nutrition standards to combat NCDs. Interpretation: Urgent action is required to expand food policies beyond hygiene and food security measures. Comprehensive strategies targeting NCD prevention are crucial to combat the escalating burden of NCDs in the region. Funding: This research was funded by the NIHR (16/136/68 and 132960) with aid from the UK Government for global health research. Petya Atanasova also acknowledges funding from the Economic and Social Research Council (ESRC) (ES/P000703/1). The views expressed are those of the authors and not necessarily of the NIHR, the UK government or the ESRC.