Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform (preprint)

Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine (preprint)

As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN{gamma}+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains. ONE-SENTENCE SUMMARYThe monovalent Omicron XBB.1.5-adapted BNT162b2 mRNA vaccine encodes a prefusion-stabilized spike immunogen that elicits more potent neutralizing antibody responses against homologous XBB.1.5 and other circulating sublineage pseudoviruses compared to the bivalent Wild Type + Omicron BA.4/5 BNT162b2 vaccine, thus demonstrating the importance of annual strain changes to the COVID-19 vaccine.

An evaluation of the introduction of telehealth for remote antenatal and postnatal contacts in Bangladesh and Lao People’s Democratic Republic during the COVID-19 pandemic (preprint)

ABSTRACT From 2020, COVID-19 spread rapidly around the globe and continues to have a major impact on health system functioning, with a disproportionate impact on low- and middle-income countries (LMIC). Reduced service utilisation and coverage of essential childbirth interventions is likely impacting maternal and newborn morbidity and mortality. Telehealth has been identified as an important tool in the continued provision of essential health care services. The aim of this study was to explore the experience and impact of implementing telehealth services for the provision of remote antenatal (ANC) and postnatal (PNC) contacts in regions of Bangladesh and Lao People’s Democratic Republic through 100 semi-structured interviews with health service leaders and providers, and childbearing women who organised, provided, or were the recipients of ANC and PNC telehealth during the COVID-19 pandemic response. The findings showed that a sudden pivot from face-to-face to telehealth services posed health system and care was challenging. Health systems lacked funding to support telehealth and the infrastructure needed for service changes; however, some were able to work with key maternal child health departments within Ministries of Health to find the resources to implement the services. Health providers found telehealth beneficial during the pandemic response but identified a lack of training, guidance, and support as a barrier to changing practice. Childbearing women reported being fearful of accessing care at health services due to COVID-19, and whilst they appreciated the telehealth contacts, many continued to prefer face-to-face delivery of ANC and PNC care. Telehealth, however, was a good alternative in a time when face-to-face care was not possible. Considerations for post-pandemic broader implementation or scale-up of telehealth for routine ante natal and post natal maternity care provision include the need for further research on issues such as accessibility, acceptability, quality of care, and sustainability of service provision.

Effectiveness of whole virus COVID-19 vaccine at protecting health care personnel against SARS-CoV-2 infections in Lima, Peru (preprint)

In February 2021, Peru launched a vaccination campaign among healthcare personnel using BBIBP-CorV inactivated whole virus (BBIBP-CorV) COVID-19 vaccine. Two doses of BBIBP-CorV vaccine are recommended, 21 days apart. Data on BBIBP-CorV vaccine effectiveness will inform the use and acceptance of vaccination with BBIBP-CorV vaccine. We evaluated BBIBP-CorV vaccine effectiveness among an existing multi-year influenza cohort at two hospitals in Lima. We analyzed data on 290 participants followed between February and May 2021. Participants completed a baseline questionnaire and provided weekly self-collected anterior nasal swabs tested for SARS-CoV-2 by rRT-PCR for sixteen weeks. We performed multivariable logistic regression models adjusting for pre-selected characteristics (age, sex, exposure to COVID-19 patients, work in intensive care unit or emergency department, BMI, and exposure time in days). BBIBP-CorV vaccine effectiveness was calculated after the two-week post-vaccination period as (1-Odds Ratio for testing SARS-CoV-2 positive)x100%. SARS-CoV-2 was detected by rRT-PCR among 25 (9%) participants during follow-up (February-May 2021). Follow-up period ranged 1-11 weeks (median: 2 weeks). Among cohort participants who were fully vaccinated the adjusted vaccine effectiveness against SARS-CoV-2 infection was estimated as 95% (95% CI: 70%, 99%) and 100% (95% CI: 88%, 100%) for those partially vaccinated. During the study period, vaccination of healthcare personnel with BBIBP-CorV vaccine was effective at reducing SARS-CoV-2 infections in the weeks immediately following vaccination. This information can be used to support vaccination efforts in the region, especially among those who could be concerned about their effectiveness.

Cross-National Analysis of Bereavement From COVID-19 and Depressive Symptoms Among Older Adults in Europe

The COVID-19 pandemic has left older adults around the globe grieving the sudden death of relatives and friends. We examine if COVID-19 bereavement corresponds with older adults’ depressive symptoms in 27 countries, and test for variation by gender and country context. We analyzed the Survey of Health, Ageing and Retirement in Europe (SHARE) COVID-19 data collected from N=51,383 older adults (age 50–104) living in 27 countries between June-August 2020, of whom 1,363 reported the death of a relative or friend from COVID-19. We estimated pooled-multilevel logistic regression models to examine if COVID-19 bereavement was associated with depressive symptoms and worsening depressive symptoms for older men and women, and we tested whether the national COVID-19 mortality rate in their country had an additive, or multiplicative, influence. COVID-19 bereavement from the death of a relative or friend is associated with significantly higher odds of reporting depressive symptoms, and reporting that these symptoms have recently worsened since the outbreak of COVID-19. Net of personal loss, living in a country with the highest COVID-19 mortality rate corresponds further with women’s depressive symptoms;however, living in the midst of more COVID-19 deaths does not alter the implications of personal loss for depressive symptoms. COVID-19 deaths have lingering mental health implications for surviving older adults. Even as the collective toll of the crisis is apparent, bereaved older adults are in particular need of mental health support.

Using mobile phone data for epidemic response in low resource settings—A case study of COVID-19 in Malawi

The COVID-19 global pandemic has had considerable health impact, including sub-Saharan Africa. In Malawi, a resource-limited setting in Africa, gaining access to data to inform the COVID-19 response is challenging. Information on adherence to physical distancing guidelines and reducing contacts are nonexistent, but critical to understanding and communicating risk, as well as allocating scarce resources. We present a case study which leverages aggregated call detail records into a daily data pipeline which summarize population density and mobility in an easy-to-use dashboard for public health officials and emergency operations. From March to April 2021, we have aggregated 6-billion calls and text messages and continue to process 12 million more daily. These data are summarized into reports which describe, quantify, and locate mass gatherings and travel between subdistricts. These reports are accessible via web dashboards for policymakers within the Ministry of Health and Emergency Operations Center to inform COVID-19 response efforts and resource allocation.

Impact of the COVID-19 Pandemic on Antimicrobial Resistance (AMR) Surveillance, Prevention and Control: A Global Survey (preprint)

Objectives The COVID-19 pandemic has had a substantial impact on health systems. The WHO Antimicrobial Resistance (AMR) Collaborating Centres Network conducted a survey to assess the effects of COVID-19 on AMR surveillance, prevention and control. Methods From October-December 2020, WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) national focal points completed a questionnaire including Likert-scales and open-ended questions. Data were descriptively analysed, income/regional differences were assessed, and free-text questions were thematically analysed. Results Seventy-three countries across income levels participated. During the COVID-19 pandemic, 67% reported limited ability to work with AMR partnerships; decreases in funding were frequently reported by low- and middle-income countries (LMICs; p<0.01). Reduced availability of nursing, medical and public health staff for AMR was reported by 71%, 69% and 64%, respectively, whereas 67% reported stable cleaning staff availability. The majority (58%) reported reduced reagents/consumables, particularly LMICs (p<0.01). Decreased numbers of cultures, elective procedures, chronically ill admissions and outpatients and increased intensive care unit admissions reported could bias AMR data. Reported overall infection prevention and control (IPC) improvement could decrease AMR rates, whereas increases in selected inappropriate IPC practices and antibiotic prescribing could increase rates. Most did not yet have complete data on changing AMR rates due to COVID-19. Conclusions This was the first survey to explore the global impact of COVID-19 on AMR among GLASS countries. Responses revealed universal patterns but also captured country variability. Although focus is understandably on COVID-19, gains in detecting and controlling AMR, a global health priority, cannot afford to be lost.

Optimizing COVID-19 Health Campaigns: A Person-Centered Approach (preprint)

As the United States continues to be ravaged by COVID-19, it becomes increasingly important to implement effective public health campaigns to improve personal behaviors that help control the spread of the virus. To design effective campaigns, research is needed to understand the current mitigation intentions of the general public, diversity in those intentions, and theoretical predictors of them. COVID-19 campaigns will be particularly challenging because mitigation involves myriad, diverse behaviors. This study takes a person-centered approach to investigate data from a survey (N = 976) of Pennsylvania adults. Latent class analysis revealed five classes of mitigation: one marked by complete adherence with health recommendations (34% of the sample), one by complete refusal (9% of the sample), and three by a mixture of adherence and refusal. Statistically significant covariates of class membership included relatively negative injunctive norms, risk due to essential workers in the household, personal knowledge of someone who became infected with COVID-19, and belief that COVID-19 was a leaked biological weapon. Additionally, trait reactance was associated with non-adherence while health mavenism was associated with adherence. These findings may be used to good effect by local healthcare providers and institutions, and also inform broader policy-making decisions regarding public health campaigns to mitigate COVID-19.