Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Major databases between December 2019 and January 2023. STUDY SELECTION: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. QUALITY ASSESSMENT, DATA EXTRACTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. RESULTS: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). CONCLUSION: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO REGISTRATION NUMBER: CRD42020178076.

Viral shedding of SARS-CoV-2 in body fluids associated with sexual activity: a systematic review and meta-analysis.

OBJECTIVE: To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion). ELIGIBILITY: All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs. INFORMATION SOURCES: The WHO COVID-19 database from inception to 20 April 2022. RISK OF BIAS ASSESSMENT: The National Institutes of Health tools. SYNTHESIS OF RESULTS: The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models. INCLUDED STUDIES: A total of 182 studies with 10 023 participants. RESULTS: The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces. LIMITATIONS: Scarcity of longitudinal studies with follow-up until negative results. INTERPRETATION: SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed. PROSPERO REGISTRATION NUMBER: CRD42020204741.

Evidence of Zika Virus Reinfection by Genome Diversity and Antibody Response Analysis, Brazil.

We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events.

Detection and persistence of Zika virus in body fluids and associated factors: a prospective cohort study.

This study aimed to analyze the detection and duration of the Zika virus (ZIKV) in plasma, urine, saliva, sweat, rectal swabs, vaginal secretions, breast milk, and semen and to explore risk factors associated with prolonged viral persistence. A prospective cohort study of symptomatic patients and their household contacts was conducted in Brazil from July 2017 to June 2019. A total of 260 individuals (184 women and 76 men) with confirmed ZIKV infection were enrolled and followed up for 12 months. ZIKV RNA was present in all body fluid specimens and detectable for extended periods in urine, sweat, rectal swabs, and semen. The longest detection duration was found in semen, with high viral loads in the specimens. ZIKV RNA clearance was associated with several factors, including age, sex, education level, body mass index, non-purulent conjunctivitis, joint pain, and whether the participant had a history of yellow fever vaccination. The influence of each of these factors on the low or fast viral clearance varied according to the specific body fluid under investigation. Recurrent ZIKV detection events after total viral clearance were observed in the cohort. Our findings provide valuable insights into the persistence and potential recurrence of ZIKV infection, highlighting the need for continued monitoring and follow-up of individuals infected with ZIKV and for effective prevention measures to reduce the risk of transmission.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Myopericarditis associated with acute Zika virus infection: a case report.

BACKGROUND: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection. CASE PRESENTATION: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year. CONCLUSIONS: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection.

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.

Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis.

OBJECTIVE: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes. DATA SOURCES: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020. STUDY ELIGIBILITY CRITERIA: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions. STUDY APPRAISAL AND SYNTHESIS METHODS: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37 weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH < 7.0) and Apgar scores (<8 after 5 min). Study quality assessment was performed. RESULTS: From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I2 = 0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I2 = 0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I2 = 0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation. CONCLUSIONS: We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately.

Treatment administered to newborns with congenital syphilis during a penicillin shortage in 2015, Fortaleza, Brazil.

BACKGROUND: Between 2014 and 2016, Brazil experienced a severe shortage in penicillin supply, resulting in a lack of treatment among some pregnant women and newborns with syphilis and the use of non-evidence-based regimens. This study evaluated all live births in Fortaleza reported with CS in 2015 in order to identify the different therapeutic regimens used in newborns during this period of penicillin shortage. METHODS: A retrospective cross-sectional study design was conducted using manually extracted data from medical chart review of maternal and infant cases delivered in 2015 from all public maternity hospitals in the city of Fortaleza. Data collection occurred from June 2017 to July 2018. RESULTS: A total of 575 congenital syphilis cases were reported to the municipality of Fortaleza during 2015 and 469 (81.5%) were analyzed. Of these, only 210 (44.8%) were treated with a nationally-recommended treatment. As alternative therapeutic options, ceftriaxone was used in 65 (13.8%), Cefazolin in 15 (3.2%) and the combination of more than one drug in 179 (38.2%). Newborns with serum VDRL titers ≥1:16 (p = 0.021), who had some clinical manifestation at birth (p = 0.003), who were born premature (p <  0.001), with low birth weight (p = 0.010), with jaundice indicative of the need for phototherapy (p = 0.019) and with hepatomegaly (p = 0.045) were more likely to be treated with penicillin according to national treatment guidelines compared to newborns treated with other regimens. CONCLUSION: During the period of shortage of penicillin in Fortaleza, less than half of the infants reported with CS were treated with a nationally-recommended regimen, the remaining received treatment with medications available in the hospital of birth including drugs that are not part of nationally or internationally-recommended treatment recommendations.

An initiative of cooperation in Zika virus research: the experience of the ZIKABRA study in Brazil.

BACKGROUND: The Zika virus outbreak has triggered a set of local and global actions for a rapid, effective, and timely public health response. A World Health Organization (WHO) initiative, supported by the Department of Chronic Condition Diseases and Sexually Transmitted Infections (DCCI) of the Health Surveillance Secretariat (SVS), Brazil Ministry of Health (MoH) and other public health funders, resulted in the start of the "Study on the persistence of Zika virus in body fluids of patients with ZIKV infection in Brazil - ZIKABRA study". The ZIKABRA study was designed to increase understanding of how long ZIKV persists in bodily fluids and informing best measures to prevent its transmission. Data collection began in July 2017 and the last follow up visit occurred in 06/26/2020. METHODS: A framework for the ZIKABRA Cooperation initiative is provided through a description and analysis of the mechanisms, strategies and the ethos that have guided the models of international governance and technical cooperation in health for scientific exchange in the context of a public health emergency. Among the methodological strategies, we included a review of the legal documents that supported the ZIKABRA Cooperation; weekly documents produced in the meetings and working sessions; technical reports; memorandum of understanding and the research protocol. CONCLUSION: We highlight the importance of working in cooperation between different institutional actors to achieve more significant results than that obtained by each group working in isolation. In addition, we point out the advantages of training activities, ongoing supervision, the construction of local installed research capacity, training academic and non-academic human resources, improvement of laboratory equipment, knowledge transfer and the availability of the ZIKABRA study protocol for development of similar studies, favoring the collective construction of knowledge to provide public health emergency responses. Strategy harmonization; human resources and health services; timing and recruiting particularities and processing institutional clearance in the different sites can be mentioned as challenges in this type of initiative.

Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens.

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.

Cohort profile: Study on Zika virus infection in Brazil (ZIKABRA study).

Zika virus (ZIKV) has been detected in blood, urine, semen, cerebral spinal fluid, saliva, amniotic fluid, and breast milk. In most ZIKV infected individuals, the virus is detected in the blood to one week after the onset of symptoms and has been found to persist longer in urine and semen. To better understand virus dynamics, a prospective cohort study was conducted in Brazil to assess the presence and duration of ZIKV and related markers (viral RNA, antibodies, T cell response, and innate immunity) in blood, semen, saliva, urine, vaginal secretions/menstrual blood, rectal swab and sweat. The objective of the current manuscript is to describe the cohort, including an overview of the collected data and a description of the baseline characteristics of the participants. Men and women ≥ 18 years with acute illness and their symptomatic and asymptomatic household contacts with positive reverse transcriptase-polymerase chain reaction test for ZIKV in blood and/or urine were included. All participants were followed up for 12 months. From July 2017 to June 2019, a total of 786 participants (284 men, 502 women) were screened. Of these, 260 (33.1%) were enrolled in the study; index cases: 64 men (24.6%), 162 (62.3%) women; household contacts: 12 men (4.6%), 22 (8.5%) women. There was a statistically significant difference in age and sex between enrolled and not enrolled participants (p<0.005). Baseline sociodemographic and medical data were collected at enrollment from all participants. The median and interquartile range (IQR) age was 35 (IQR; 25.3, 43) for men and 36.5 years (IQR; 28, 47) for women. Following rash, which was one of the inclusion criteria for index cases, the most reported symptoms in the enrollment visit since the onset of the disease were fever, itching, arthralgia with or without edema, non-purulent conjunctivitis, headache, and myalgia. Ten hospitalizations were reported by eight patients (two patients were hospitalized twice) during follow up, after a median of 108 days following symptom onset (range 7 to 266 days) and with a median of 1.5 days (range 1 to 20 days) of hospital stay. A total of 4,137 visits were performed, 223 (85.8%) participants have attended all visits and 37 (14.2%) patients were discontinued.

Impact of a nurse-led enhanced monitoring, management and contact tracing intervention for chronic hepatitis B in England, 2015-2017.

Around 200,000 people live with chronic hepatitis B in England. Despite national guidance on identification and management of cases and their close contacts, testing rates of close contacts is as low as 43% in high prevalence areas of London. Our study aimed to determine whether a nurse-led enhanced management and contact tracing of chronically infected individuals improved testing uptake, vaccination and onward referral of close contacts. The study was conducted across Greater Manchester and East of England regions between October 2015 and July 2017. All HBV chronically infected individuals registered with a GP and their close contacts were eligible for recruitment. The proportion of contacts who were tested, vaccinated and referred where appropriate were compared before and after the nurse-led intervention. Baseline and outcome information was collected using questionnaires. The intervention improved case referral rates by an additional 14% (from 86% (88/102 cases) to 99.7%; 648/650 cases). The proportion of contacts tested increased from 34% to 72%-94% with 18 new cases of HBV diagnosed. Amongst close contacts tested, vaccination rates of at least three doses increased from 77% (43/56) to 93% (452/491) during the study. Our study has shown that nurse-led enhanced management greatly improves identification, testing and vaccination of close contacts. The identification of new acute and chronic cases is likely to make the intervention cost effective and local health commissioners should consider providing a nurse-led service as part of hepatitis B care pathways.

Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action.

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population.

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 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.

Phase II trial evaluating the clinical efficacy of cefixime for treatment of active syphilis in non-pregnant women in Brazil (CeBra).

BACKGROUND: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis. METHODS: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response. DISCUSSION: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis. TRIAL REGISTRATION: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

Correction to: Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak.

An amendment to this paper has been published and can be accessed via the original article.

Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak.

The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment.Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.

Zika virus RNA excretion in sweat with concomitant detection in other body fluid specimens

We evaluated sweat, blood and urine specimens obtained from an ongoing cohort study in Brazil. Samples were collected at pre-established intervals after the initial rash presentation and tested for Zika virus (ZIKV) RNA presence by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). From 254 participants with confirmed infection, ZIKV RNA was detected in the sweat of 46 individuals (18.1%). Sweat presented a median cycle threshold (Ct) of 34.74 [interquartile range (IQR) 33.44-36.04], comparable to plasma (Ct 35.96 - IQR 33.29-36.69) and higher than urine (Ct 30.78 - IQR 28.72-33.22). Concomitant detection with other specimens was observed in 33 (72%) of 46 participants who had a positive result in sweat. These findings represent an unusual and not yet investigated virus shedding through eccrine glands.