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      SARS‐CoV‐2—Placental effects and association with stillbirth

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          Abstract

          SARS‐CoV‐2 has had a significant impact on pregnancy outcomes due to the effects of the virus and the altered healthcare environment. Stillbirth has been relatively hidden during the COVID‐19 pandemic, but a clear link between SARS‐CoV‐2 and poor fetal outcome emerged in the Alpha and Delta waves. A small minority of women/birthing people who contracted COVID‐19 developed SARS‐CoV‐2 placentitis. In many reported cases this was linked to intrauterine fetal death, although there are cases of delivery just before imminent fetal demise and we shall discuss how some cases are sub‐clinical. What is surprising, is that SARS‐CoV‐2 placentitis is often not associated with severe maternal COVID‐19 infection and this makes it difficult to predict. The worst outcomes seem to be with diffuse placental disease which occurs within 21 days of COVID‐19 diagnosis. Poor outcomes are often pre‐dated by reduced fetal movements but are not associated with ultrasound changes. In some cases, there has also been maternal thrombocytopenia, or coagulation abnormalities, which may provide a clue as to which pregnancies are at risk of fetal demise if a further variant of concern is to emerge. In future, multidisciplinary collaboration and cross‐boundary working must be prioritised, to identify quickly such a phenomenon and provide clinicians with clear guidance for reducing fetal death and associated poor outcomes. While we wait to see if COVID‐19 brings a future variant of concern, we must focus on appropriate future management of women who have had SARS‐CoV‐2 placentitis. As a placental condition with an infectious aetiology, SARS‐CoV‐placentitis is unlikely to recur in a subsequent pregnancy and thus a measured approach to subsequent pregnancy management is needed.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Detection of SARS-CoV-2 in Different Types of Clinical Specimens

            This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.
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              Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

              Abstract 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 26 June 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 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 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 (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19. Conclusion Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease. 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.
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                Author and article information

                Contributors
                Journal
                BJOG: An International Journal of Obstetrics & Gynaecology
                BJOG
                Wiley
                1470-0328
                1471-0528
                March 2024
                November 20 2023
                March 2024
                : 131
                : 4
                : 385-400
                Affiliations
                [1 ] Centre for Women's Health Research, Department of Women's and Children's Health University of Liverpool Liverpool UK
                [2 ] Liverpool Women's Hospital Liverpool UK
                [3 ] Department of Pathology Cork University Hospital Cork Ireland
                [4 ] Pregnancy Loss Research Group, Department of Obstetrics and Gynaecology University College Cork Cork Ireland
                [5 ] Cork University Maternity Hospital Cork Ireland
                Article
                10.1111/1471-0528.17698
                37984971
                613c2bbb-9713-4021-9e84-a56c4adf5b87
                © 2024

                http://creativecommons.org/licenses/by/4.0/

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