Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies.

INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.

CONTEXT.­: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.­: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.­: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.­: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.­: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Maternal Death by COVID-19 Associated with Elevated Troponin T Levels.

Cardiomyocyte injury and troponin T elevation has been reported within COVID-19 patients and are associated with a worse prognosis. Limited data report this association among COVID-19 pregnant patients. OBJECTIVE: We aimed to analyze the association between troponin T levels in severe COVID-19 pregnant women and risk of viral sepsis, intensive care unit (ICU) admission, or maternal death. METHODS: We performed a prospective cohort of all obstetrics emergency admissions from a Mexican National Institute. All pregnant women diagnosed by reverse transcription-polymerase chain reaction (RT-qPCR) for SARS-CoV-2 infection between October 2020 and May 2021 were included. Clinical data were collected, and routine blood samples were obtained at hospital admission. Seric troponin T was measured at admission. RESULTS: From 87 included patients, 31 (35.63%) had severe COVID-19 pneumonia, and 6 (6.89%) maternal deaths. ROC showed a significant relationship between troponin T and maternal death (AUC 0.979, CI 0.500-1.000). At a cutoff point of 7 ng/mL the detection rate for severe pneumonia was 83.3% (95%CI: 0.500-0.100) at 10% false-positive rate. CONCLUSION: COVID-19 pregnant women with elevated levels of troponin T present a higher risk of death and severe pneumonia.

Maternal and Neonatal Outcomes of Critically Ill Pregnant and Puerperal Patients Diagnosed with COVID-19 Disease: Retrospective Comparative Study.

BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19). METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU. RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred. CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.

Clinical characteristics and outcomes of pregnant women with COVID-19 and comparison with control patients: A systematic review and meta-analysis.

In a large-scale study, 128176 non-pregnant patients (228 studies) and 10000 pregnant patients (121 studies) confirmed COVID-19 cases included in this Meta-Analysis. The mean (confidence interval [CI]) of age and gestational age of admission (GA) in pregnant women was 33 (28-37) years old and 36 (34-37) weeks, respectively. Pregnant women show the same manifestations of COVID-19 as non-pregnant adult patients. Fever (pregnant: 75.5%; non-pregnant: 74%) and cough (pregnant: 48.5%; non-pregnant: 53.5%) are the most common symptoms in both groups followed by myalgia (26.5%) and chill (25%) in pregnant and dysgeusia (27%) and fatigue (26.5%) in non-pregnant patients. Pregnant women are less probable to show cough (odds ratio [OR] 0.7; 95% CI 0.67-0.75), fatigue (OR: 0.58; CI: 0.54-0.61), sore throat (OR: 0.66; CI: 0.61-0.7), headache (OR: 0.55; CI: 0.55-0.58) and diarrhea (OR: 0.46; CI: 0.4-0.51) than non-pregnant adult patients. The most common imaging found in pregnant women is ground-glass opacity (57%) and in non-pregnant patients is consolidation (76%). Pregnant women have higher proportion of leukocytosis (27% vs. 14%), thrombocytopenia (18% vs. 12.5%) and have lower proportion of raised C-reactive protein (52% vs. 81%) compared with non-pregnant patients. Leucopenia and lymphopenia are almost the same in both groups. The most common comorbidity in pregnant patients is diabetes (18%) and in non-pregnant patients is hypertension (21%). Case fatality rate (CFR) of non-pregnant hospitalized patients is 6.4% (4.4-8.5), and mortality due to all-cause for pregnant patients is 11.3% (9.6-13.3). Regarding the complications of pregnancy, postpartum hemorrhage (54.5% [7-94]), caesarean delivery (48% [42-54]), preterm labor (25% [4-74]) and preterm birth (21% [12-34]) are in turn the most prevalent complications. Comparing the pregnancy outcomes show that caesarean delivery (OR: 3; CI: 2-5), low birth weight (LBW) (OR: 9; CI: 2.4-30) and preterm birth (OR: 2.5; CI: 1.5-3.5) are more probable in pregnant woman with COVID-19 than pregnant women without COVID-19. The most prevalent neonatal complications are neonatal intensive care unit admission (43% [2-96]), fetal distress (30% [12-58]) and LBW (25% [16-37]). The rate of vertical transmission is 5.3% (1.3-16), and the rate of positive SARS-CoV-2 test for neonates born to mothers with COVID-19 is 8% (4-16). Overall, pregnant patients present with the similar clinical characteristics of COVID-19 when compared with the general population, but they may be more asymptomatic. Higher odds of caesarean delivery, LBW and preterm birth among pregnant patients with COVID-19 suggest a possible association between COVID-19 infection and pregnancy complications. Low risk of vertical transmission is present, and SARS-CoV-2 can be detected in all conception products, particularly placenta and breast milk. Interpretations of these results should be done cautiously due to the heterogeneity between studies; however, we believe our findings can guide the prenatal and postnatal considerations for COVID-19 pregnant patients.

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.

Perinatal outcomes of pregnant women having SARS-CoV-2 infection.

OBJECTIVES: Aim of this study is to evaluate the prognosis of pregnant women having SARS-CoV-2 infection and investigate whether there was a difference in perinatal outcomes between pregnant women who had SARS-CoV-2 infection and those who did not. MATERIALS AND METHODS: This prospective observational study was conducted with 116 singleton pregnancies. Cases enrolling in the study were divided into two groups. While those in the first group had a history of SARS-CoV-2 infection (n = 46) the second group consisted of healthy pregnant women (n = 70). RESULTS: Emergency Cesarean section was performed on three SARS-CoV-2 infected pregnancies (30, 33 and 34 gestational weeks). Intensive care unit admission was required for all three cases after delivery and two of them died. Among the pregnancies that had an infection in the third trimester, 71.4% (n = 20) of them had delivery in 14 days after diagnosis and 17.4% (n = 8) of their newborns were followed up at newborn intensive care unit. Overall, only one newborn had a positive swab test result for SARS-CoV-2. There was no statistically significant difference between groups regarding their delivery week (37.02 ± 5.85 vs 38.5 ± 2.33). Similarly, there was no significant difference between groups, concerning mean age, parity, and birth weight (P = 0.707, P = 0.092, P = 0.334; P < 0.05). Furthermore, the difference between SARS-CoV-2 infected pregnancies that were followed up as inpatient or outpatient with respect to the delivery week and birth weight was not significant (p > 0.05). Also, APGAR 5 scores of hospitalized women (9.3 ± 1.1) were found to be lower than the outpatient group (9.8 ± 0.8) (P = 0.043; p < 0.05). CONCLUSION: No significant difference was detected between groups in terms of the delivery week, birth weight, and APGAR scores. The inpatient group was found to have lower APGAR 5 scores.

Maternal and Neonatal Complications, Outcomes and Possibility of Vertical Transmission in Iranian Women with COVID-19.

BACKGROUND: The emergence and fast spread of coronavirus disease 2019 (COVID-19) threatens the world as a new public health crisis. Little is known about its effects during pregnancy. This study aimed to investigate the clinical manifestations of COVID-19 on maternal and neonatal outcomes. METHODS: In this systematic review, PubMed, Scopus, Web of Science, and Google Scholar databases were searched focusing on pregnancy and perinatal outcomes of COVID-19. RESULTS: The initial search yielded 1236 articles, from which finally 21 unique studies, involving 151 pregnant women and 17 neonates, met the criteria. Mean ± SD age of included mothers and mean ± SD gestational age at admission were 30.6 ± 6.2 years and 30.8 ± 8.9 weeks, respectively. The common symptoms were fever, cough, fatigue, dyspnea and myalgia. The mortality rates of pregnant women and neonates were 28 out of 151 (18.5%) and 4 out of 17 (23.5%), respectively. Most of the neonates were preterm at the time of delivery. Three neonates had positive RT-PCR test on the first day after birth and three others on day two. On the average, neonate's PCR became positive on day 4 for the first time. CONCLUSION: Early diagnosis of COVID-19 is crucial due to the possibility of the prenatal complications. Strict prevention strategies may reduce the risk of mother to infant transmission.

Vaccination of Pregnant Women Against COVID-19.

Pregnant women are at increased risk for severe morbidity and mortality following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading some countries to recommend vaccination of pregnant women against coronavirus disease 2019 (COVID-19). These recommendations are based on studies conducted early in the pandemic, and thus, the pregnant women in these studies most likely did not have pre-existing immunity to SARS-CoV-2 at the time of infection. The susceptibility of pregnant women and their infants to SARS-CoV-2 and the severity of infection may be attenuated as the pandemic progresses and an increasing number of women will have pre-existing immunity (following natural infection or vaccination prior to pregnancy) during pregnancy. The reactogenicity, immunogenicity and efficacy of COVID-19 vaccines administered in pregnancy may also be affected by the pre-existing immunity of pregnant women. Maternal vaccine trials should be evaluated in the context of their timing in the pandemic and interpreted based on the pre-existing immunity of pregnant women.

Third trimester stillbirth during the first wave of the SARS-CoV-2 pandemic: Similar rates with increase in placental vasculopathic pathology.

Whether early SARS-CoV-2 definitively increases the risk of stillbirth is unknown, though studies have suggested possible trends of stillbirth increase during the pandemic. This study of third trimester stillbirth does not identify an increase in rates during the first wave of the pandemic period, however investigation of the placental pathology demonstrates trends towards more vascular placental abnormalities.

Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic.

Importance: Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. Objective: To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. Design, Setting, and Participants: This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. Exposures: The presence of a COVID-19 diagnosis using ICD-10. Main Outcomes and Measures: Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2. Results: Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non-COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25]; P < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P < .001), and in-hospital mortality (24 women [0.1%] vs 71 [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001). Conclusions and Relevance: This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.

Death from COVID-19 in a Hispanic postpartum woman and review of the literature.

There is still much we do not know about the impact of COVID-19 on the health of pregnant and postpartum women and pregnancy outcomes. Current evidence suggests that there is biological plausibility for worse outcomes among this population. This case report details the clinical care given to a postpartum Hispanic and obese woman diagnosed with COVID-19 in April 2020. We report the care she and her newborn received and her progression through the virus. We discuss the current knowledge surrounding COVID-19 among pregnant and postpartum women. While research supports COVID-19 outcomes being comparable to the general population, there is limited research in this area. Clinical trials, acting on the side of caution, have tended to exclude pregnant women from participation. Therefore, there is a need for further research that can inform evidence-based policy decisions related to COVID-19 in pregnant and postpartum women.

The Contrast of Color: Why the Black Community Continues to Suffer Health Disparities.

The evidence of racial health disparities is profound. Much attention has been given to the disparity in maternal morbidity and mortality experienced by Black mothers. The disparity in Black lives lost from coronavirus disease 2019 (COVID-19) has further highlighted the disparity in health outcomes for Black people. Although COVID-19 is a new disease, the reason for the health disparity is the same as in maternal morbidity and mortality: implicit bias and structural racism. Implicit bias among health care professionals leads to disparities in how health care is delivered. Generations of structural racism perpetuated through racial residential segregation, economic suppression, and health care inequality have normalized the poorer health outcomes for Black Americans. It is easy to dismiss these issues as someone else's problem, because health care professionals often fail to acknowledge the effect of implicit bias in their own practices. We all need to be highly critical of our own practices and look introspectively for implicit bias to find the cure. Health care organizations must invest time and resources into investigating the structural racism that exists within our own walls.

Pregnancy and COVID-19.

The continuing impact of the pandemic on pregnant women and obstetric care.

Perinatal outcomes of pregnancies resulting from assisted reproduction technology in SARS-CoV-2-infected women: a prospective observational study.

OBJECTIVE: To evaluate the perinatal and maternal outcomes of pregnancies in women infected with SARS-CoV-2, comparing spontaneous and in vitro fertilization (IVF) pregnancies (with either own or donor oocytes). DESIGN: Multicenter, prospective, observational study. SETTING: 78 centers participating in the Spanish COVID19 Registry. PATIENT(S): 1,347 pregnant women with SARS-CoV-2 positive results registered consecutively between February 26 and November 5, 2020. INTERVENTION(S): The patients' information was collected from their medical records, and multivariable regression analyses were performed, controlling for maternal age and the clinical presentation of the infection. MAIN OUTCOME MEASURE(S): Obstetrics and neonatal outcomes, pregnancy comorbidities, intensive care unit admission, mechanical ventilation need, and medical conditions. RESULT(S): The IVF group included 74 (5.5%) women whereas the spontaneous pregnancy group included 1,275 (94.5%) women. The operative delivery rate was high in all patients, especially in the IVF group, where cesarean section became the most frequent method of delivery (55.4%, compared with 26.1% of the spontaneous pregnancy group). The reason for cesarean section was induction failure in 56.1% of the IVF patients. IVF women had more gestational hypertensive disorders (16.2% vs. 4.5% among spontaneous pregnancy women, adjusted odds ratio [aOR] 5.31, 95% confidence interval [CI] 2.45-10.93) irrespective of oocyte origin. The higher rate of intensive care unit admittance observed in the IVF group (8.1% vs. 2.4% in the spontaneous pregnancy group) was attributed to preeclampsia (aOR 11.82, 95% CI 5.25-25.87), not to the type of conception. CONCLUSION(S): A high rate of operative delivery was observed in pregnant women infected with SARS-CoV-2, especially in those with IVF pregnancies; method of conception did not affect fetal or maternal outcomes, except for preeclampsia. CLINICAL TRIAL REGISTRATION NUMBER: NCT04558996.

Maternal death related to COVID-19: A systematic review and meta-analysis focused on maternal co-morbidities and clinical characteristics.

BACKGROUND: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain. OBJECTIVE: To evaluate the characteristics of pregnant women who died due to COVID-19. SEARCH STRATEGY: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021. SELECTION CRITERIA: Studies that compared deceased and survived pregnant women with COVID-19. DATA COLLECTION AND ANALYSIS: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity. MAIN RESULTS: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41-4.36, I2  = 0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77-42.44, I2  = 94%) or asthma (RR 2.05, 95% CI 0.81-5.15, I2  = 0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77-2.89, I2  = 76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00-12.98, I2  = 56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23-1.48, I2  = 95%) or mechanical ventilation (RR 4.34, 95% CI 0.96-19.60, I2  = 58%). CONCLUSION: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Characteristics and outcomes of COVID-19 pneumonia in pregnancy compared with infected nonpregnant women.

OBJECTIVE: To compare the clinical and paraclinical features and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: A multicenter retrospective cohort study of pregnant and nonpregnant women of reproductive age hospitalized between March and October 2020 in Tehran, Iran. Medical records were reviewed and women who tested positive for SARS-CoV-2 on RT-PCR were included. Extracted data were compared and logistic regression performed. RESULTS: A total of 110 pregnant and 234 nonpregnant COVID-19-positive women were included. Frequency of severe disease was higher in nonpregnant women than pregnant women (29% vs 11.8%; P < 0.001). Symptoms including cough, dyspnea, chill, fatigue, and headache were more frequent in nonpregnant women (P < 0.05). Pregnant women had higher oxygen saturation levels and lower lymphocyte count (P = 0.001). Six (5.5%) pregnant and 12 (5.1%) nonpregnant women died (P = 0.80). No significant differences between the groups were found for ICU admission and end organ failure. Significantly more nonpregnant women had acute respiratory distress syndrome (ARDS, 9.4% vs 0%; P = 0.001). Univariate regression indicated association between hypertension and death; oxygen saturation and ARDS; and body mass index and ICU admission. No association was found between pregnancy and death, ICU admission, or ARDS. CONCLUSION: Pregnant women with COVID-19 are not at higher risk of adverse outcomes compared with nonpregnant women.