Rapid establishment of a COVID-19 perinatal biorepository: early lessons from the first 100 women enrolled

Abstract

Background: Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them.

Methods: A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization.

Results: Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001).

Conclusions: Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.

Keywords: Biobank; COVID-19; Immune; Neonatology; Newborn; Obstetrics; Pandemic; Pregnancy; Repository; SARS-CoV-2; Vertical transmission.

Fig. 1

Significant events during establishment of the COVID-19 perinatal biorepository impacting cumulative enrollment of pregnant women over time. a. Timeline of events impacting enrollment of pregnant women into the biorepository. b. Blue line indicates cumulative enrollment of COV19+ pregnant women. Black line indicates cumulative number of all enrolled pregnant women (COV19+ and COV19-). Phase 1 of enrollment is defined as April 2 to May 4, prior to interventions streamlining enrollment including (1) unification of Obstetrics and Neonatology teams, allowing enrollment into maternal and newborn protocols at the same time and (2) expansion of enrollment efforts to non-hospitalized women. Phase 2 is defined as May 4 to June 9. MGH = Massachusetts General Hospital. COV19+ = mother positive for SARS-CoV-2 on RT-PCR of nasopharyngeal swab at any time during pregnancy; COV19- = mother negative for SARS-CoV-2 on RT-PCR of nasopharyngeal swab when tested for COVID-19 symptoms or as part of universal screening protocol

Fig. 2

Samples collected on maternal and newborn participants. a. Maternal samples included: (1) blood, including 10 mLs in EDTA tubes for plasma, peripheral blood mononuclear cell (PBMC) isolation, and granulocyte or neutrophil isolation; 5–7.5 mL in serum separator tube for serum; 2.5 mL in PaxGene tube for RNA; (2) saliva and/or (3) sputum (sputum if patient had productive cough); (4) nasal swab; (5) oropharyngeal swab; (6) maternal and fetal side placental biopsies for RNA extraction, and formalin-fixed paraffin-embedded full thickness placental block for in situ placental histopathology; (7) umbilical cord blood (EDTA, serum separator tube and PaxGene as described above for maternal blood); (8) colostrum or mature breastmilk; (9) vaginal swab; (10) rectal swab; (11) urine; (12) stool. Maternal blood was preferentially collected during a clinical blood draw by the clinical nurse. Placental biopsies and cord blood were collected by the obstetrical care team immediately after delivery, with support from study staff when possible. Women who planned to breastfeed were encouraged to clean the breast per instructions and self-collect any amount of colostrum or mature milk prior to discharge from the hospital. b. Newborn samples included: (1) nasopharyngeal swab; (2) oropharyngeal swab; (3) tracheal aspirate (if relevant); (4) neonatal blood collected into EDTA microtainer via heel-stick with clinical metabolic screen at 24–36 h of life; (5) urine collected using cotton balls placed into diaper; and (6) stool. Figure created with BioRender.com and reproduced with permission

Fig. 3

Flow chart of participant enrollment and cohort in which samples have been collected. *Nine patients admitted to MGH who tested positive for SARS-CoV-2 were not approached for enrollment. Five of nine delivered precipitously and could not be enrolled prior to delivery, and four of nine were admitted and delivered during time periods when study staff were not available to consent the patient. COV19+ = mother positive for SARS-CoV-2 on RT-PCR of nasopharyngeal swab at any time during pregnancy; COV19- = mother negative for SARS-CoV-2 on RT-PCR of nasopharyngeal swab when tested for COVID-19 symptoms or as part of universal screening protocol

Fig. 4

Total number of samples collected on each maternal participant by phase of enrollment and by SARS-Cov-2 status. a. Mean number of samples collected on each maternal participant was greater from women enrolled during Phase 2 compared to Phase 1. b. Mean number of samples collected per maternal participant was greater in SARS-CoV-2 negative than positive women. Data depicted as mean +/− SEM, **P < 0.01,***P < 0.001

Fig. 5

Proportion of samples collected from maternal and newborn participants by COVID status. a. Proportion of women in which maternal blood, placenta, umbilical cord blood, and breastmilk were collected, by COVID status. b. Proportion of women in which urine, stool, vaginal swabs, and rectal swabs were collected, by COVID status. c. Proportion of women in which saliva, sputum, nasal swabs, and oropharyngeal swabs were collected, by COVID status. d. Proportion of newborns in which blood urine and stool were collected by mother’s COVID status. e. Proportion of newborns in which nasopharyngeal, oropharyngeal, and tracheal aspirate samples were collected by mother’s COVID status. COV19+ = mother positive for SARS-CoV-2 on RT-PCR of nasopharyngeal swab at any time during pregnancy; COV19- = mother negative for SARS-CoV-2 on RT-PCR of nasopharyngeal swab when tested for COVID-19 symptoms or as part of universal screening protocol. *P < 0.05, **P < 0.01. The number of maternal and newborn participants providing each sample type by COVID status is presented in Additional file 1, Tables S2 and S3, respectively