Data challenges for international health emergencies: lessons learned from ten international COVID-19 driver projects.

The COVID-19 pandemic highlighted the importance of international data sharing and access to improve health outcomes for all. The International COVID-19 Data Alliance (ICODA) programme enabled 12 exemplar or driver projects to use existing health-related data to address major research questions relating to the pandemic, and developed data science approaches that helped each research team to overcome challenges, accelerate the data research cycle, and produce rapid insights and outputs. These approaches also sought to address inequity in data access and use, test approaches to ethical health data use, and make summary datasets and outputs accessible to a wider group of researchers. This Health Policy paper focuses on the challenges and lessons learned from ten of the ICODA driver projects, involving researchers from 19 countries and a range of health-related datasets. The ICODA programme reviewed the time taken for each project to complete stages of the health data research cycle and identified common challenges in areas such as data sharing agreements and data curation. Solutions included provision of standard data sharing templates, additional data curation expertise at an early stage, and a trusted research environment that facilitated data sharing across national boundaries and reduced risk. These approaches enabled the driver projects to rapidly produce research outputs, including publications, shared code, dashboards, and innovative resources, which can all be accessed and used by other research teams to address global health challenges.

Defining and reporting adverse events of special interest in comparative maternal vaccine studies: a systematic review.

Introduction: The GAIA (Global Alignment on Immunisation Safety Assessment in Pregnancy) consortium was established in 2014 with the aim of creating a standardised, globally coordinated approach to monitoring the safety of vaccines administered in pregnancy. The consortium developed twenty-six standardised definitions for classifying obstetric and infant adverse events. This systematic review sought to evaluate the current state of adverse event reporting in maternal vaccine trials following the publication of the case definitions by GAIA, and the extent to which these case definitions have been adopted in maternal vaccine safety research. Methods: A comprehensive search of published literature was undertaken to identify maternal vaccine research studies. PubMed, EMBASE, Web of Science, and Cochrane were searched using a combination of MeSH terms and keyword searches to identify observational or interventional studies that examined vaccine safety in pregnant women with a comparator group. A two-reviewer screening process was undertaken, and a narrative synthesis of the results presented. Results: 14,737 titles were identified from database searches, 435 titles were selected as potentially relevant, 256 were excluded, the remaining 116 papers were included. Influenza vaccine was the most studied (25.0%), followed by TDaP (20.7%) and SARS-CoV-2 (12.9%).Ninety-one studies (78.4%) were conducted in high-income settings. Forty-eight (41.4%) utilised electronic health-records. The majority focused on reporting adverse events of special interest (AESI) in pregnancy (65.0%) alone or in addition to reactogenicity (27.6%). The most frequently reported AESI were preterm birth, small for gestational age and hypertensive disorders. Fewer than 10 studies reported use of GAIA definitions. Gestational age assessment was poorly described; of 39 studies reporting stillbirths 30.8% provided no description of the gestational age threshold. Conclusions: Low-income settings remain under-represented in comparative maternal vaccine safety research. There has been poor uptake of GAIA case definitions. A lack of harmonisation and standardisation persists limiting comparability of the generated safety data.

Seroepidemiology of SARS-CoV-2 in a cohort of pregnant women and their infants in Uganda and Malawi.

BACKGROUND: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. OUTCOME: Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. METHODS: The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. RESULTS: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes.

Using electronic medical records to understand the impact of SARS-CoV-2 lockdown measures on maternal and neonatal outcomes in Kampala, Uganda.

Kawempe National Referral Hospital (KNRH) is a tertiary facility with over 21,000 pregnant or postpartum women admitted annually. The hospital, located in Kampala, Uganda, uses an Electronic Medical Records (EMR) system to capture patient data. Used since 2017, this readily available electronic health record (EHR) has the benefit of informing real-time clinical care, especially during pandemics such as COVID-19. We investigated the use of EHR to assess risk factors for adverse pregnancy and infant outcomes that can be incorporated into a data visualization dashboard for real time decision making during pandemics. This study analysed data from the UgandaEMR collected at pre-, during- and post-lockdown timepoints of the COVID-19 pandemic to determine its use in monitoring risk factors for adverse pregnancy and neonatal outcomes. Logistic regression models were used to identify the risk factors for adverse pregnancy and maternal outcomes including prematurity, obstetric complications, still births and neonatal deaths. Pearson chi-square test was used for pair-wise comparison of the outcomes at the various stages of the pandemic. Data analysis was performed in R, within the International COVID-19 Data Alliance (ICODA) workbench. A visualisation dashboard was developed based on the risk factors, to support decision making and improved healthcare delivery. Comparison of pre-and post-lockdown variables showed an increased risk of pre-term birth (adjusted Odds Ratio (aOR = 1.67, 95% confidence interval (CI) 1.38-2.01)); obstetric complications (aOR = 2.77, 95% CI: 2.53-3.03); immediate neonatal death (aOR = 3.89, 95% CI 2.65-5.72) and Caesarean section (aOR = 1.22, 95% CI 1.11-1.34). The significant risk factors for adverse outcomes were younger maternal age and gestational age <32weeks at labour. This study demonstrates the feasibility of using EHR to identify and monitor at-risk subpopulation groups accessing health services in real time. This information is critical for the development of timely and appropriate interventions in outbreaks and pandemic situations.

COVID-19 disease and vaccination in pregnancy: understanding knowledge, perceptions and experiences among pregnant women and community leaders in Uganda.

BACKGROUND: We investigated pregnant women and community leaders' knowledge, perceptions and experiences of the coronavirus disease 2019 (COVID-19) vaccination program during pregnancy in Uganda and how this changed over the course of the pandemic. METHODS: We conducted 20 in-depth interviews (IDIs) and two group discussions (GDs) with pregnant women and four GDs with community leaders in Kawempe division of Kampala, Uganda. The first round of IDIs/GDs were carried out in March 2021. In July 2021, telephone IDIs were conducted with 7 pregnant women and 10 community leaders randomly selected from first-round interview participants. Themes were analysed deductively drawing codes from the topic guides. RESULTS: In the first round, the majority of participants thought COVID-19 was not real because of misconceptions around government messaging/motivation and beliefs that Africans would not be affected. In the second round, participants recognised COVID-19 disease, because of rising case numbers and fatalities. There was increased awareness of the benefits of the vaccine. However, pregnant women remained unsure of vaccine safety and quality, citing side effects like fevers and general body weakness. Role models and coherent public health messaging and healthcare workers were key enablers of vaccine uptake. CONCLUSIONS: Targeted and sustained COVID-19 communication and engagement strategies are needed, especially for pregnant women and others in their communities, to improve vaccine confidence during outbreaks.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

Understanding the diagnosis and management of multisystem inflammatory syndrome in adults (MIS-A) in the UK: results of a national Delphi process.

Infection with SARS-CoV-2 may trigger a delayed hyper-inflammatory illness in children called paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS). A similar syndrome is increasingly recognised in adults termed multisystem inflammatory syndrome in adults (MIS-A) and may present acutely to medical or surgical specialties with severe symptoms, such as acute abdominal pain or cardiogenic shock. No national guidelines exist in the UK for the management of MIS-A and there is limited evidence to guide treatment plans. We undertook a national Delphi process to elicit opinions from experts in hyperinflammation about the diagnosis and management of MIS-A with the dual aim of improving recognition and producing a management guideline. Colleagues in paediatrics successfully initiated a national consensus management document that facilitated regional multidisciplinary referral and follow-up pathways for children with PIMS-TS, and we propose a similar system be developed for adult patients across the UK. This would facilitate better recognition and treatment of MIS-A across the multiple specialties to which it may present as well as enable follow-up with specialty services post-discharge.

Vaccinating Children against SARS-CoV-2: A Literature Review and Survey of International Experts to Assess Safety, Efficacy and Perceptions of Vaccine Use in Children.

Introduction: The balance of risks and benefits of COVID-19 vaccination in children is more complex than in adults with limited paediatric data resulting in no global consensus on whether all healthy children should be vaccinated. We sought to assess the safety, efficacy, and effectiveness of childhood vaccination against SARS-CoV-2, as well as better understanding perceptions of vaccination in parents and vaccine experts. Methods: We performed a literature review for COVID-19 vaccine safety, efficacy, effectiveness, and perceptions. We searched international safety databases for safety data and developed an electronic survey to elicit country-specific COVID-19 immunisation data, including vaccine regulations, policies, rates, and public attitudes solicited from vaccine experts. Results: Nine studies were included in the final safety analysis. Local reactions were frequently reported across all studies and vaccine types. Adverse events reported to surveillance systems tended to be non-serious, and commonly included injection site reactions and dizziness. Twenty-three studies reported immunogenicity, efficacy, and effectiveness data. There were nine randomised control trials of six different vaccine types, which showed seroconversion of neutralising antibodies in vaccinated children ranging from 88% to 100%. The vaccine efficacy for Pfizer and Moderna vaccines ranged from 88% to 100%. There were 118 survey responses representing 55 different countries. Reported vaccination rates ranged from <1% to 98%. Most respondents described "mixed opinions" regarding paediatric vaccination policies in their country. By region, a more positive public attitude towards vaccination correlated with higher vaccination rates. Discussion: In this mixed-methods review, we have found evidence that vaccination against COVID-19 in children is safe, efficacious, and effective. Overall, the combined evidence from both the literature review and survey highlights the need for further data on both the safety and effectiveness of COVID-19 vaccinations in children.

Can PIMS-TS lead to a facial nerve palsy?

Paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2 (PIMS-TS) is a recently described syndrome. We describe the case of a 17-year-old man presenting with a recent illness consistent with COVID-19 who presented with fever, chest pain and anterior uveitis. He was treated with aspirin, pulsed methylprednisolone and tocilizumab followed by oral steroids. On day 16 from initial presentation, he developed a facial nerve palsy. He was managed with ongoing steroids and the addition of valaciclovir. PIMS-TS is an under-recognised condition among adult physicians and may not be well known in adult neurology. It is important for adult physicians and neurologists to be aware of PIMS-TS and its possible sequelae.

The Value of Perfusion Fluid Culture Analysis in Deceased Donor Renal Transplants: A 10-Year Single-Center Experience.

Microbiological analysis of kidney perfusion/transport solution is not routinely performed in all transplant centers. This paper gives a 10-year descriptive single-center experience of the routine culture of perfusion fluid in deceased donor renal transplant recipients as well as the prophylactic treatment of certain organisms if identified. Data were collected retrospectively on all deceased donor transplants performed between 2009 and 2018. Organisms detected were classified as either pathologic, of uncertain pathogenicity, or contaminants. Treatment was guided by the microbiology team. A total of 661 specimens were analyzed. Organisms were cultured in 168 of 661 (25.4%) of these samples. The most frequent organisms identified were skin and oral flora (n = 95, 42%). The majority of organisms identified (131 of 226, 58%) necessitated prophylactic treatment on the advice of our microbiology department. On 7 (4.2%) occasions, the perfusion fluid cultures grew organisms not covered by the routine antimicrobial prophylaxis, and on 15 occasions Candida albicans was isolated. Candida isolates were treated preemptively with 1 month of antifungal treatment. There were no infective sequelae in this group.