Publications by Year: 2020

BACKGROUND: The COVID-19 pandemic caused by the SARS-CoV-2 has increased the demand for inpatient healthcare resources; however, approximately 80% of patients with COVID-19 have a mild clinical presentation and can be managed at home.

OBJECTIVE: This study aimed to describe the feasibility and clinical and process outcomes associated with a multidisciplinary telemedicine surveillance model to triage and manage obstetrical patients with known exposures and symptoms of COVID-19.

STUDY DESIGN: We implemented a multidisciplinary telemedicine surveillance model with obstetrical physicians and nurses to standardize ambulatory care for obstetrical patients with confirmed or suspected COVID-19 based on the symptoms or exposures at an urban academic tertiary care center with multiple hospital-affiliated and community-based practices. All pregnant or postpartum patients with COVID-19 symptoms, exposures, or hospitalization were eligible for inclusion in the program. Patients were assessed by means of regular nursing phone calls and were managed according to illness severity. Patient characteristics and clinical and process outcomes were abstracted from the electronic medical record.

RESULTS: A total of 135 patients were enrolled in the multidisciplinary telemedicine model from March 17 to April 19, 2020, of whom 130 were pregnant and 5 were recently postpartum. In this study, 116 of 135 patients (86%) were managed solely in the outpatient setting and did not require an in-person evaluation; 9 patients were ultimately admitted after ambulatory or urgent evaluations, and 10 patients were observed after hospital discharge. Although only 50% of the patients were tested secondary to limitations in ambulatory testing, 1 in 3 of those patients received positive results for SARS-CoV-2 (N=22, 16% of entire cohort). Patients were enrolled in the telemedicine model for a median of 7 days (interquartile range, 4-8) and averaged 1 phone call daily, resulting in 891 nursing calls and 20 physician calls over 1 month.

CONCLUSION: A multidisciplinary telemedicine surveillance model for outpatient management of obstetrical patients with COVID-19 symptoms and exposures is feasible and resulted in rates of ambulatory management similar to those seen in nonpregnant patients. A centralized model for telemedicine surveillance of obstetrical patients with COVID-19 symptoms may preserve inpatient resources and prevent avoidable staff and patient exposures, particularly in centers with multiple ambulatory practice settings.

PROBLEM: Evaluation of Zika virus (ZIKV)-specific humoral and cellular immune response in pregnant women exposed to ZIKV.

METHOD OF STUDY: In this observational, prospective cohort study, we recruited pregnant women presenting for prenatal ultrasound for ZIKV exposure at a single academic teaching hospital in Boston, MA from November 2016 to December 2018. We collected blood, urine, and cervicovaginal swabs antepartum, intrapartum, and postpartum; and cord blood and placenta at delivery. We used experimental assays to calculate quantitative viral loads, ZIKV-specific immunoglobulin titers, and ZIKV-specific T-cell responses.

RESULTS: We enrolled 22 participants, three of which had serologic-confirmed ZIKV infection. No participants demonstrated sustained ZIKV shedding. ZIKV-specific IgG/IgM antibody was sustained throughout pregnancy and postpartum. ZIKV envelope and capsid-specific T-cell responses were also observed, albeit inconsistent. No newborns in this cohort had congenital Zika syndrome. Infant cord blood of infected mothers exhibited ZIKV-specific IgG, but not IgM antibodies.

CONCLUSION: We detected a robust, prolonged maternal humoral immune response to ZIKV during pregnancy and postpartum. We also demonstrated evidence for efficient transplacental antibody transfer from mother to infant at birth, supporting the importance of neonatal passive immunity to ZIKV. Maternal T-cell responses were less consistent among pregnant women infected with ZIKV.

IMPORTANCE: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

OBJECTIVE: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2.

EXPOSURES: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR.

MAIN OUTCOMES AND MEASURES: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta.

RESULTS: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted.

CONCLUSIONS AND RELEVANCE: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.