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      SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis of clinical features and pregnancy outcomes

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          Abstract

          Background

          Perform a systematic review and meta-analysis of SARS-CoV-2 infection and pregnancy.

          Methods

          Databases (Medline, Embase, Clinicaltrials.gov, Cochrane Library) were searched electronically on 6th April and updated regularly until 8th June 2020. Reports of pregnant women with reverse transcription PCR (RT-PCR) confirmed COVID-19 were included. Meta-analytical proportion summaries and meta-regression analyses for key clinical outcomes are provided.

          Findings

          86 studies were included, 17 studies (2567 pregnancies) in the quantitative synthesis; other small case series and case reports were used to extract rarely-reported events and outcome. Most women (73.9%) were in the third trimester; 52.4% have delivered, half by caesarean section (48.3%). The proportion of Black, Asian or minority ethnic group membership (50.8%); obesity (38.2%), and chronic co-morbidities (32.5%) were high. The most commonly reported clinical symptoms were fever (63.3%), cough (71.4%) and dyspnoea (34.4%). The commonest laboratory abnormalities were raised CRP or procalcitonin (54.0%), lymphopenia (34.2%) and elevated transaminases (16.0%). Preterm birth before 37 weeks’ gestation was common (21.8%), usually medically-indicated (18.4%). Maternal intensive care unit admission was required in 7.0%, with intubation in 3.4%. Maternal mortality was uncommon (~1%). Maternal intensive care admission was higher in cohorts with higher rates of co-morbidities (beta=0.007, p<0.05) and maternal age over 35 years (beta=0.007, p<0.01). Maternal mortality was higher in cohorts with higher rates of antiviral drug use (beta=0.03, p<0.001), likely due to residual confounding. Neonatal nasopharyngeal swab RT-PCR was positive in 1.4%.

          Interpretation

          The risk of iatrogenic preterm birth and caesarean delivery was increased. The available evidence is reassuring, suggesting that maternal morbidity is similar to that of women of reproductive age. Vertical transmission of the virus probably occurs, albeit in a small proportion of cases.

          Funding

          N/A

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          Most cited references88

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

            Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.
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              Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020

              On March 18, 2020, this report was posted online as an MMWR Early Release. Globally, approximately 170,000 confirmed cases of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) have been reported, including an estimated 7,000 deaths in approximately 150 countries ( 1 ). On March 11, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic ( 2 ). Data from China have indicated that older adults, particularly those with serious underlying health conditions, are at higher risk for severe COVID-19–associated illness and death than are younger persons ( 3 ). Although the majority of reported COVID-19 cases in China were mild (81%), approximately 80% of deaths occurred among adults aged ≥60 years; only one (0.1%) death occurred in a person aged ≤19 years ( 3 ). In this report, COVID-19 cases in the United States that occurred during February 12–March 16, 2020 and severity of disease (hospitalization, admission to intensive care unit [ICU], and death) were analyzed by age group. As of March 16, a total of 4,226 COVID-19 cases in the United States had been reported to CDC, with multiple cases reported among older adults living in long-term care facilities ( 4 ). Overall, 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths associated with COVID-19 were among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. In contrast, no ICU admissions or deaths were reported among persons aged ≤19 years. Similar to reports from other countries, this finding suggests that the risk for serious disease and death from COVID-19 is higher in older age groups. Data from cases reported from 49 states, the District of Columbia, and three U.S. territories ( 5 ) to CDC during February 12–March 16 were analyzed. Cases among persons repatriated to the United States from Wuhan, China and from Japan (including patients repatriated from cruise ships) were excluded. States and jurisdictions voluntarily reported data on laboratory-confirmed cases of COVID-19 using previously developed data collection forms ( 6 ). The cases described in this report include both COVID-19 cases confirmed by state or local public health laboratories as well as those with a positive test at the state or local public health laboratories and confirmation at CDC. No data on serious underlying health conditions were available. Data on these cases are preliminary and are missing for some key characteristics of interest, including hospitalization status (1,514), ICU admission (2,253), death (2,001), and age (386). Because of these missing data, the percentages of hospitalizations, ICU admissions, and deaths (case-fatality percentages) were estimated as a range. The lower bound of these percentages was estimated by using all cases within each age group as denominators. The corresponding upper bound of these percentages was estimated by using only cases with known information on each outcome as denominators. As of March 16, a total of 4,226 COVID-19 cases had been reported in the United States, with reports increasing to 500 or more cases per day beginning March 14 (Figure 1). Among 2,449 patients with known age, 6% were aged ≥85, 25% were aged 65–84 years, 18% each were aged 55–64 years and 45–54 years, and 29% were aged 20–44 years (Figure 2). Only 5% of cases occurred in persons aged 0–19 years. FIGURE 1 Number of new coronavirus disease 2019 (COVID-19) cases reported daily*,† (N = 4,226) — United States, February 12–March 16, 2020 * Includes both COVID-19 cases confirmed by state or local public health laboratories, as well as those testing positive at the state or local public health laboratories and confirmed at CDC. † Cases identified before February 28 were aggregated and reported during March 1–3. The figure is a histogram, an epidemiologic curve showing 4,226 coronavirus disease 2019 (COVID-19) cases, by date of case report, in the United States during February 12–March 16, 2020. Figure 2 Coronavirus disease 2019 (COVID-19) hospitalizations,* intensive care unit (ICU) admissions, † and deaths, § by age group — United States, February 12– March 16, 2020 * Hospitalization status missing or unknown for 1,514 cases. † ICU status missing or unknown for 2,253 cases. § Illness outcome or death missing or unknown for 2,001 cases. The figure is a bar chart showing the number of coronavirus disease 2019 (COVID-19) hospitalizations, intensive care unit admissions, and deaths, by age group, in the United States during February 12– March 16, 2020. Among 508 (12%) patients known to have been hospitalized, 9% were aged ≥85 years, 36% were aged 65–84 years, 17% were aged 55–64 years, 18% were 45–54 years, and 20% were aged 20–44 years. Less than 1% of hospitalizations were among persons aged ≤19 years (Figure 2). The percentage of persons hospitalized increased with age, from 2%–3% among persons aged ≤19 years, to ≥31% among adults aged ≥85 years. (Table). TABLE Hospitalization, intensive care unit (ICU) admission, and case–fatality percentages for reported COVID–19 cases, by age group —United States, February 12–March 16, 2020 Age group (yrs) (no. of cases) %* Hospitalization ICU admission Case-fatality 0–19 (123) 1.6–2.5 0 0 20–44 (705) 14.3–20.8 2.0–4.2 0.1–0.2 45–54 (429) 21.2–28.3 5.4–10.4 0.5–0.8 55–64 (429) 20.5–30.1 4.7–11.2 1.4–2.6 65–74 (409) 28.6–43.5 8.1–18.8 2.7–4.9 75–84 (210) 30.5–58.7 10.5–31.0 4.3–10.5 ≥85 (144) 31.3–70.3 6.3–29.0 10.4–27.3 Total (2,449) 20.7–31.4 4.9–11.5 1.8–3.4 * Lower bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group; upper bound of range = number of persons hospitalized, admitted to ICU, or who died among total in age group with known hospitalization status, ICU admission status, or death. Among 121 patients known to have been admitted to an ICU, 7% of cases were reported among adults ≥85 years, 46% among adults aged 65–84 years, 36% among adults aged 45–64 years, and 12% among adults aged 20–44 years (Figure 2). No ICU admissions were reported among persons aged ≤19 years. Percentages of ICU admissions were lowest among adults aged 20–44 years (2%–4%) and highest among adults aged 75–84 years (11%–31%) (Table). Among 44 cases with known outcome, 15 (34%) deaths were reported among adults aged ≥85 years, 20 (46%) among adults aged 65–84 years, and nine (20%) among adults aged 20–64 years. Case-fatality percentages increased with increasing age, from no deaths reported among persons aged ≤19 years to highest percentages (10%–27%) among adults aged ≥85 years (Table) (Figure 2). Discussion Since February 12, 4,226 COVID-19 cases were reported in the United States; 31% of cases, 45% of hospitalizations, 53% of ICU admissions, and 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years. These findings are similar to data from China, which indicated >80% of deaths occurred among persons aged ≥60 years ( 3 ). These preliminary data also demonstrate that severe illness leading to hospitalization, including ICU admission and death, can occur in adults of any age with COVID-19. In contrast, persons aged ≤19 years appear to have milder COVID-19 illness, with almost no hospitalizations or deaths reported to date in the United States in this age group. Given the spread of COVID-19 in many U.S. communities, CDC continues to update current recommendations and develop new resources and guidance, including for adults aged ≥65 years as well as those involved in their care ( 7 , 8 ). Approximately 49 million U.S. persons are aged ≥65 years ( 9 ), and many of these adults, who are at risk for severe COVID-19–associated illness, might depend on services and support to maintain their health and independence. To prepare for potential COVID-19 illness among persons at high risk, family members and caregivers of older adults should know what medications they are taking and ensure that food and required medical supplies are available. Long-term care facilities should be particularly vigilant to prevent the introduction and spread of COVID-19 ( 10 ). In addition, clinicians who care for adults should be aware that COVID-19 can result in severe disease among persons of all ages. Persons with suspected or confirmed COVID-19 should monitor their symptoms and call their provider for guidance if symptoms worsen or seek emergency care for persistent severe symptoms. Additional guidance is available for health care providers on CDC’s website (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html). This report describes the current epidemiology of COVID-19 in the United States, using preliminary data. The findings in this report are subject to at least five limitations. First, data were missing for key variables of interest. Data on age and outcomes, including hospitalization, ICU admission, and death, were missing for 9%–53% of cases, which likely resulted in an underestimation of these outcomes. Second, further time for follow-up is needed to ascertain outcomes among active cases. Third, the initial approach to testing was to identify patients among those with travel histories or persons with more severe disease, and these data might overestimate the prevalence of severe disease. Fourth, data on other risk factors, including serious underlying health conditions that could increase risk for complications and severe illness, were unavailable at the time of this analysis. Finally, limited testing to date underscores the importance of ongoing surveillance of COVID-19 cases. Additional investigation will increase the understanding about persons who are at risk for severe illness and death from COVID-19 and inform clinical guidance and community-based mitigation measures.* The risk for serious disease and death in COVID-19 cases among persons in the United States increases with age. Social distancing is recommended for all ages to slow the spread of the virus, protect the health care system, and help protect vulnerable older adults. Further, older adults should maintain adequate supplies of nonperishable foods and at least a 30-day supply of necessary medications, take precautions to keep space between themselves and others, stay away from those who are sick, avoid crowds as much as possible, avoid cruise travel and nonessential air travel, and stay home as much as possible to further reduce the risk of being exposed ( 7 ). Persons of all ages and communities can take actions to help slow the spread of COVID-19 and protect older adults. † Summary What is already known about this topic? Early data from China suggest that a majority of coronavirus disease 2019 (COVID-19) deaths have occurred among adults aged ≥60 years and among persons with serious underlying health conditions. What is added by this report? This first preliminary description of outcomes among patients with COVID-19 in the United States indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years. What are the implications for public health practice? COVID-19 can result in severe disease, including hospitalization, admission to an intensive care unit, and death, especially among older adults. Everyone can take actions, such as social distancing, to help slow the spread of COVID-19 and protect older adults from severe illness.
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                Author and article information

                Contributors
                Journal
                EClinicalMedicine
                EClinicalMedicine
                EClinicalMedicine
                The Author(s). Published by Elsevier Ltd.
                2589-5370
                3 July 2020
                3 July 2020
                : 100446
                Affiliations
                [a ]Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, Blackshaw Road, London SW17 0QT, UK
                [b ]Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, UK
                [c ]Department of Statistics, Middle East Technical University, Ankara, Turkey
                [d ]The Royal College of Obstetricians and Gynaecologists, London, UK
                [e ]University College London Hospitals NHS Foundation Trust, London, UK
                [f ]Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK
                [g ]North Bristol NHS Trust Department of Women's Health, Westbury on Trym, UK
                [h ]Institute of Metabolism and Systems Research, WHO Collaborating Centre for Women's Health, University of Birmingham, Birmingham, UK
                [i ]Paediatric Infectious Diseases Research Group and Vaccine Institute, Institute of Infection and Immunity, St George's University of London, London, UK
                [j ]Immunisation and Countermeasures Division, Public Health England, UK
                [k ]British Paediatric Surveillance Unit, Royal College of Pediatrics and Child Health, UK
                [l ]School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
                Author notes
                [* ]Corresponding author at: Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St. George's University Hospitals NHS Foundation Trust, Blackshaw Road, London SW17 0QT, UK. akhalil@ 123456sgul.ac.uk asma@ 123456hscfw.co.uk
                Article
                S2589-5370(20)30190-5 100446
                10.1016/j.eclinm.2020.100446
                7334039
                32838230
                436117b4-3b0e-41c3-acbb-5ee1f216632a
                © 2020 The Author(s)

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 13 May 2020
                : 25 May 2020
                : 15 June 2020
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