A reasoned approach towards administering COVID-19 vaccines to pregnant women.

There are over 50 SARS-CoV-2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolled out for use in different countries. Due to concerns of potential teratogenicity or adverse effect on maternal physiology, pregnancy has been a specific exclusion criterion for most vaccine trials with only two trials not excluding pregnant women. Thus, other than limited animal studies, gradually emerging development and reproductive toxicity data, and observational data from vaccine registries, there is a paucity of reliable information to guide recommendations for the safe vaccination of pregnant women. Pregnancy is a risk factor for severe COVID-19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity. We discuss the major SARS-CoV-2 vaccines, their mechanisms of action, efficacy, safety profile and possible benefits to the maternal-fetal dyad to create a rational approach towards maternal vaccination while anticipating and mitigating vaccine-related complications. Pregnant women with high exposure risks or co-morbidities predisposing to severe COVID-19 infection should be prioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly. It is essential to support patient autonomy by shared decision-making involving a risk-benefit discussion with the pregnant woman.

The Relationship between Inflammatory Cytokines and Coagulopathy in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19), with a broad range of clinical and laboratory findings, is currently the most prevalent medical challenge worldwide. In this disease, hypercoagulability and hyperinflammation, two common features, are accompanied by a higher rate of morbidity and mortality. We assessed the association between baseline inflammatory cytokine levels and coagulopathy and disease outcome in COVID-19. One hundred and thirty-seven consecutive patients hospitalized with COVID-19 were selected for the study. Baseline interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) level were measured at time of admission. At the same time, baseline coagulation parameters were also assessed during the patient's hospitalization. Clinical findings, including development of thrombosis and clinical outcome, were recorded prospectively. Out of 136 patients, 87 (~64%) had increased cytokine levels (one or more cytokines) or abnormal coagulation parameters. Among them, 58 (~67%) had only increased inflammatory cytokines, 12 (~14%) had only coagulation abnormalities, and 17 (19.5%) had concomitant abnormalities in both systems. It seems that a high level of inflammatory cytokines at admission points to an increased risk of developing coagulopathy, thrombotic events, even death, over the course of COVID-19. Early measurement of these cytokines, and timely co-administration of anti-inflammatories with anticoagulants could decrease thrombotic events and related fatal consequences.

SARS-CoV-2 Infection: Modulator of Pulmonary Embolism Paradigm.

Pulmonary embolism (PE) is a life-threatening complication arising from venous thromboembolism with a difficult diagnosis and treatment and is often associated with increased mortality and morbidity. PE had a significantly low incidence prior to the COVID-19 epidemic. This condition saw a sharp surge during the COVID-19 pandemic, indicating an evident viral influence on PE's pathophysiology in COVID-19 patients. The hypercoagulable state induced by the viral load seems to be the major contributor, and the classical causative factors seem to play a lesser role. PE in COVID-19 infection has become a mammoth challenge since the diagnosis is quite challenging due to overlapping symptoms, lack of prior-known predisposing risk factors, limited resources, and viral transmittance risk. Numerous factors arising out of the viral load or treatment lead to an increased risk for PE in COVID-19 patients, besides the fact that certain unknown risk factors may also contribute to the incidence of PE in COVID-19 patients. The management of PE in COVID-19 infection mainly comprises thromboprophylaxis and anticoagulant therapy with mechanical ventilation, depending on the risk stratification of the patient, with a post-COVID-19 management that prevents recurrent PE and complications. This review aims to discuss various aspects of COVID-19-infection-associated PE and major differential aspects from non-COVID-19 PE.

Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2s.

There remain unanswered questions concerning mother-to-child-transmission of SARS-CoV-2. Despite reports of neonatal COVID-19, SARS-CoV-2 has not been consistently isolated in perinatal samples, thus definitive proof of transplacental infection is still lacking. To address these questions, we assessed investigative tools used to confirm maternal-fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. Forty studies of COVID-19 pregnancies reviewed suggest a lack of consensus on diagnostic strategy for congenital infection. Although real-time polymerase chain reaction of neonatal swabs was universally performed, a wide range of clinical samples was screened including vaginal secretions (22.5%), amniotic fluid (35%), breast milk (22.5%) and umbilical cord blood. Neonatal COVID-19 was reported in eight studies, two of which were based on the detection of SARS-CoV-2 IgM in neonatal blood. Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID-19. The paucity of placental co-expression of ACE-2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS-CoV-2, may explain its relative insensitivity to transplacental infection. Viral interactions may utilise membrane receptors other than ACE-2 thus, tissue susceptibility may be broader than currently known. Further spatial-temporal studies are needed to determine the true potential for transplacental migration.

Care of the pregnant woman with coronavirus disease 2019 in labor and delivery: anesthesia, emergency cesarean delivery, differential diagnosis in the acutely ill parturient, care of the newborn, and protection of the healthcare personnel.

Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2, has been declared a pandemic by the World Health Organization. As the pandemic evolves rapidly, there are data emerging to suggest that pregnant women diagnosed as having coronavirus disease 2019 can have severe morbidities (up to 9%). This is in contrast to earlier data that showed good maternal and neonatal outcomes. Clinical manifestations of coronavirus disease 2019 include features of acute respiratory illnesses. Typical radiologic findings consists of patchy infiltrates on chest radiograph and ground glass opacities on computed tomography scan of the chest. Patients who are pregnant may present with atypical features such as the absence of fever as well as leukocytosis. Confirmation of coronavirus disease 2019 is by reverse transcriptase-polymerized chain reaction from upper airway swabs. When the reverse transcriptase-polymerized chain reaction test result is negative in suspect cases, chest imaging should be considered. A pregnant woman with coronavirus disease 2019 is at the greatest risk when she is in labor, especially if she is acutely ill. We present an algorithm of care for the acutely ill parturient and guidelines for the protection of the healthcare team who is caring for the patient. Key decisions are made based on the presence of maternal and/or fetal compromise, adequacy of maternal oxygenation (SpO2 >93%) and stability of maternal blood pressure. Although vertical transmission is unlikely, there must be measures in place to prevent neonatal infections. Routine birth processes such as delayed cord clamping and skin-to-skin bonding between mother and newborn need to be revised. Considerations can be made to allow the use of screened donated breast milk from mothers who are free of coronavirus disease 2019. We present management strategies derived from best available evidence to provide guidance in caring for the high-risk and acutely ill parturient. These include protection of the healthcare workers caring for the coronavirus disease 2019 gravida, establishing a diagnosis in symptomatic cases, deciding between reverse transcriptase-polymerized chain reaction and chest imaging, and management of the unwell parturient.

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy.

The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2-2.5, indicating that 2-3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal-fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.