Expert Review of Global Real-World Data on COVID-19 Vaccine Booster Effectiveness & Safety During the Omicron-dominant Phase of the Pandemic (preprint)

Introduction COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron (B.1.1.529) variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently-available vaccines and prompted debate about potential future vaccination strategies.Areas covered Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE data were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently-available COVID-19 vaccines.Expert opinion Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that time. The positive risk-benefit ratio of these vaccines is well established, thus increasing confidence in administering additional doses as required. Future vaccination strategies will likely include a combination of schedules based on a person’s risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Expert Review of Global Real-World Vaccine Effectiveness Against SARS-CoV-2 (preprint)

IntroductionCOVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses.Areas coveredWe reviewed 79 studies in the publicly available International Vaccine Access Center (IVAC) VIEW-hub platform on vaccine effectiveness (VE) after primary immunizations with two-dose schedules. VE data were reported for SARS-CoV-2 infection, COVID-19-related hospitalizations and deaths, and stratified across variants of concern (VOC), age, study design and prior SARS-CoV-2 infection for mRNA vaccines (BNT162b2, mRNA-1273 and combinations of both), vector vaccines (AstraZeneca, AZD1222 “Vaxzevria”) and inactivated virus vaccines (CoronaVac).Expert opinionThe most-studied COVID-19 vaccines provide consistently high (>90%) protection against serious clinical outcomes like hospitalizations and deaths, regardless of variant. Additionally, this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of local Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalizations and deaths on healthcare systems worldwide, encouraging vaccination strategies that can reduce this burden is more relevant than attempting to prevent broader but milder infections with specific variants, including Omicron.Article highlights - VE was high and comparable for both AZD1222 and mRNA vaccine types (91%-93%) in protecting against hospitalization and death from COVID-19, regardless of age.- VE against symptomatic infections trended higher (though not significantly) for mRNA-based vaccines compared to AZD1222.- Waning of VE since time of vaccination was observed for symptomatic infections but was limited for serious COVID-19 outcomes. A sub-analysis of studies with comparative arms evaluating the VE of different vaccines in the same settings also confirmed these observations for all VOC assessed, with all vaccines conferring a high level of protection against serious outcomes.- For Omicron, there is limited comparative data within the IVAC dataset, however, expert review of emerging data suggests that VE against all outcomes is lower for all COVID-19 vaccines, than for the Delta variant.- Data from the UK indicate that VE improves with a booster dose and that VE continues to be very similar, irrespective of the type of vaccine used.- Importantly, all COVID-19 vaccines evaluated here have favorable benefit/risk profiles.- Although many SEA countries have high rates of primary vaccination, there are still challenges to achieving high booster dose coverage. The results of this analysis suggest that the most effective way to achieve vaccine booster targets, particularly in resource-limited settings, would simply be to consider any vaccines which have good safety and comparable effectiveness profiles, particularly against severe outcomes, and that are accessible and optimal for the local situation.- This review reinforces the value of real-world evidence to support efforts advocating for the completion of primary series and booster vaccinations where appropriate, especially to restore VE against emerging VOC such as Omicron. However, data gaps still persist, given the lag between the emergence of new variants, updated vaccine schedules and VE data to inform their impact. 

Genome sequencing and detection of Philippine SARS-CoV-2 infections with viruses classified under the B.1.1.7 lineage (preprint)

We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in the Philippines identified to be caused by viruses under the B.1.1.7 lineage (UK variant). Genome sequences obtained from these samples carry the lineage-defining mutations associated with the said variant of concern.

Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines (preprint)

The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.35 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

Impact of COVID-19 on Routine Immunisation in South-East Asia and Western Pacific: Disruptions and Solutions (preprint)

Background: Data on COVID-19-induced disruption to routine vaccinations in the South-East Asia and Western Pacific regions (SEAR/WPR) have been sparse. This study aimed to quantify the impact of COVID-19 on routine vaccinations by country, antigen, and sector (public or private), up to 1 June 2020, and to identify the reasons for disruption and possible solutions. Methods: Sanofi Pasteur teams from 19 countries in SEAR/WPR completed a structured questionnaire reporting on COVID-19 disruptions for 13–19 routinely delivered antigens per country, based on sales data, government reports, and regular physician interactions. Data were analysed descriptively, disruption causes ranked, and solutions evaluated using a modified public health best practices framework. Findings: 95% (18/19) of countries reported vaccination disruption. When stratified by country, a median of 91% (interquartile range 77–94) of antigens were impacted. Infancy and school-entry age vaccinations were most impacted. Both public and private sector healthcare providers experienced disruptions. Vaccination rates had not recovered for 39% of impacted antigens by 1 June 2020. Fear of infection, movement/travel restrictions, and limited healthcare access were the highest-ranked reasons for disruption. Highest-scoring solutions were separating vaccination groups from unwell patients, non-traditional vaccination venues, virtual engagement, and social media campaigns. Many of these solutions are under-utilised. Interpretation: COVID-19-induced disruption of routine vaccination was more widespread than previously reported. Adaptable solutions were identified which could be implemented in SEAR/WPR and elsewhere. Governments and private providers need to act urgently to improve coverage rates and plan for future waves of the pandemic, to avoid a resurgence of vaccine-preventable diseases. Funding: Sanofi Pasteur.Declaration of Interests: At the time of the preparation of this work, Rebecca C Harris, Yutao Chen, Pierre Côte, Antoine Ardillon, Maria Carmen Nievera, Kiruthika Velan Kandasamy, Kuharaj Mahenthiran, Ta-Wen Yu, Changshu Huang, Clotilde El Guerche-Séblain, Juan C Vargas-Zambrano, Ayman Chit, and Gopinath Nageshwaran were employees of Sanofi Pasteur and might be shareholders of Sanofi. Anna Ong-Lim and Somasundaram Aiyamperumal have no disclosures. Poh Chong Chan reports speaker fees and other fees for involvement in clinical trial from Sanofi Pasteur.Ethics Approval Statement: As the study did not gather patient or individual level data orinvolve any interventions, formal ethical approval was not sought. Data were mostly open source or company data, and informed consent was sought from those filling in the survey