Prioritizing Pregnant Women for Coronavirus Disease 2019 Vaccination in African Countries.

Coronavirus disease 2019 (COVID-19) in pregnancy is associated with excess maternal and infant morbidity and mortality in both African and higher-resource settings. Furthermore, mounting evidence demonstrates the safety and efficacy of COVID-19 vaccination for pregnant women and infants. However, national guidelines in many African countries are equivocal or lack recommendations on COVID-19 vaccine in pregnancy. We summarize key data on COVID-19 epidemiology and vaccination among pregnant African women to highlight major barriers to vaccination and recommend 4 interventions. First, policymakers should prioritize pregnant women for COVID-19 vaccination, with a target of 100% coverage. Second, empirically supported public health campaigns should be sustainably implemented to inform and support pregnant women and their healthcare providers in overcoming vaccine hesitancy. Third, COVID-19 vaccination for pregnant women should be expanded to include antenatal care, obstetrics/gynecology, and targeted mass vaccination campaigns. Fourth, national monitoring and evaluation of COVID-19 vaccine uptake, safety, surveillance, and prospective outcomes assessment should be conducted.

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis.

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries.

IMPORTANCE: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. OBJECTIVE: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. EXPOSURES: Age, sex, preexisting comorbidities, and region of residence. MAIN OUTCOMES AND MEASURES: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. RESULTS: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. CONCLUSIONS AND RELEVANCE: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project.

INTRODUCTION: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. DISCUSSION: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. CONCLUSIONS: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children.

The Critical Need for Pooled Data on Coronavirus Disease 2019 in African Children: An AFREhealth Call for Action Through Multicountry Research Collaboration.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children and adolescents; and these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of coronavirus disease 2019 (COVID-19) among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and coinfections such as human immunodeficiency virus (HIV), tuberculosis, malaria, sickle cell disease, and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policy-making for COVID-19 while concurrently addressing other major diseases affecting children in African countries.

Effect of SARS-CoV-2 Infection in Pregnancy on Maternal and Neonatal Outcomes in Africa: An AFREhealth Call for Evidence through Multicountry Research Collaboration.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health's COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

Characterising and managing paediatric SARSCoV-2 infection: Learning about the virus in a global classroom.

AIM: This study is a comprehensive review with the purpose of collecting the most relevant data in several sections including current treatment guidelines in the paediatric population. METHODS: Literature was systematically searched in different databases. Results were limited to 2019+ and English, French and Spanish language. RESULTS: Children can exhibit mild and less severe COVID-19 disease than adults and also have asymptomatic carriage of SARS-CoV-2, while severe disease is more frequently noted during infancy (<1 year). SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE-2) receptor; age-, racial-, and gender-specific differences in ACE-2 expression need to be elucidated in order to explain the differential clinical profiles between children and adults. Multisystem inflammatory syndrome in children (MIS-C) is an important condition to recognise in children. The decision to use antiviral or immunomodulatory therapy in a child or adolescent should be individualised based on the clinical scenario. Remdesivir is the only FDA-approved therapy available for children older than 12 years old who require hospitalisation for COVID-19. CONCLUSION: Further studies are urgently required to address prevention and treatment in at-risk and infected children, especially with underlying comorbidities. The chapter on the overall impact of COVID-19 in children has not yet been written. Nevertheless, SARS-CoV-2 has now joined a long list of human pandemics, which may forever change the world's history.

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

INTRODUCTION: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic. METHODS AND ANALYSIS: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo.

Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34-58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9-15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85-23.64), 40-59 years (aHR = 4.45, 95% CI: 1.83-10.79), and ≥ 60 years (aHR = 13.63, 95% CI: 5.70-32.60) compared with those aged 20-39 years, with obesity (aHR = 2.30, 95% CI: 1.24-4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85-15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88-2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35-1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.

OBJECTIVE: To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists. STUDY SELECTION: Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. DATA EXTRACTION: At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. RESULTS: 192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19. CONCLUSION: Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.