A Retrospective Case Series Analysis of Pregnancy and COVID-19 Based on a Global Postmarketing COVID-19 Surveillance Program.

PURPOSE: To document and characterize COVID-19 cases involving pregnancy in the context of exposure to pharmaceutical products. METHODS: This retrospective case series analysis leveraged the Pfizer safety database containing worldwide adverse event data related to use of Pfizer products between October 1, 2019 and November 3, 2022. Selected Medical Dictionary for Drug Regulatory Activities (Version 25.0) Preferred Terms and subsequent clinical review were used to identify COVID-19 cases involving female patients who received Pfizer products during pregnancy and infants with intrauterine exposure to Pfizer products. FINDINGS: As of November 3, 2022, 504 pregnancy cases (426 maternal; 78 infants) were identified. Most maternal cases reported COVID-19 during the third trimester, and (when known) 52% of cases involved presentation or progression of severe COVID-19 with associated complications requiring hospitalization, and often intensive management (eg, mechanical ventilation, oxygen support) and emergent delivery. Twenty-three maternal cases were fatal; patients developed severe COVID-19 disease involving multisystem deterioration (eg, cardiopulmonary injury/decompensation, coagulopathies, septic/hemorrhagic shock) and frequently required risk-benefit decisions regarding maintaining/prolonging pregnancies to improve fetal viability while attempting to improve or stabilize maternal conditions or electing to either terminate pregnancies or induce emergent deliveries. Approximately 40% of maternal cases reported medical history involving at least one underlying condition (eg, diabetes, respiratory disorders, renal/hepatic disease, cardiac disease, obesity, autoimmune conditions) considered potentially associated with susceptibility to infection/adverse outcome of infection, or twin/triplet pregnancy, which may further complicate COVID-19 disease. Most cases with known fetal outcomes reported normal newborns including preterm/low birth weight infants, which occurred in many cases involving emergent preterm delivery due to deteriorating maternal conditions. The remaining smaller proportion of cases involved abnormal newborn/perinatal/postperinatal complications (eg, premature births, respiratory distress, alveolar damage, meconium aspiration with hypoxic-ischemic encephalopathy), intrauterine/neonatal death (due to multiple concurrent complications such as neonatal sepsis, hypoxemia/acute respiratory distress, potential cardiac damage, mucormycosis) and congenital anomaly (eg, intrauterine growth restriction in association with contracting COVID-19). Among infants tested within our dataset, 28 cases involved reference to infants who tested positive for COVID-19 infection at birth or shortly thereafter, with vertical transmission suspected only in 2 infants. IMPLICATION: This large retrospective case series provides additional perspectives regarding potential impact of COVID-19 on pregnancy outcomes, and its characterization of this case volume may contribute to the current information landscape related to COVID-19 in pregnancy. Further studies may be warranted to confirm the generalizability of our findings to the general pregnant patient population infected with COVID-19.

Reporting of COVID-19 Reinfection and Potential Role of Immunosuppressant/Immunomodulating Agents: A Cross-Sectional Observational Analysis Based on a Spontaneous Reporting Database.

BACKGROUND: The enduring presence of COVID-19 and subsequent increasing incidence of COVID-19 reinfection has prompted evaluation of associated risk factors, particularly the role of immunosuppression. OBJECTIVE: The objective of this study was to characterize cases indicative of COVID-19 reinfection with respect to their reported use of immunosuppressant/immunomodulating agents. METHODS: This cross-sectional observational study leveraged the Pfizer global safety database (SDB) containing adverse event data collected in association with use of Pfizer products between 1 October 2019, and 30 June 2022. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA®) Preferred Terms were used to identify COVID-19 cases; the search was further refined to comprise cases that subsequently reported events potentially indicative of COVID-19 reinfection. RESULTS: Of the cumulative total of 218,242 COVID-19 cases reported into the SDB, 4590 cases (2.1%) involving potential COVID-19 reinfection were identified. Of these 4590 cases of potential Covid-19 reinfection, a total of 134 cases reported COVID-19 specifically during treatment with pharmaceutical products, of which approximately 16% (21/134) of cases reported use of immunosuppressant/immunomodulating agents. Likewise, in the overall dataset (213,652 cases; excluding the 4590 cases involving potential COVID-19 recurrence), the percentage of reported immunosuppressant/immunomodulating agents was low (12%). In applying similar parameters to a dataset that excludes COVID-19 vaccine cases, 18% of cases reported use of immunosuppressant/immunomodulating agents (similar to the aforementioned 16% of cases reported from the overall total dataset that was inclusive of vaccine cases). CONCLUSION: This pharmacovigilance study provides a characterization of cases indicative of COVID-19 reinfection with respect to reported use of immunosuppressant/immunomodulating agents. The observations generated from this cross-sectional observational analysis may prompt further research into the role of immunosuppression in COVID-19 reinfection, in an effort to better inform clinical practice and patient management.

Global Safety Database Summary of COVID-19-Related Drug Utilization-Safety Surveillance: A Sponsor's Perspective.

INTRODUCTION: Evidence-based clinical data on coronavirus disease 2019 (COVID-19) pharmacotherapies are scarce. OBJECTIVE: This study documented and characterized COVID-19 cases reported in individuals receiving treatment with Pfizer pharmaceutical products and cases that reported use of Pfizer pharmaceutical products for COVID-19 treatment. METHODS: This retrospective observational review leveraged the Pfizer safety database containing adverse event data collected in association with use of Pfizer products between 1 October, 2019, and 25 June, 2020; the database includes worldwide adverse event data from various sources. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA®) Preferred Terms and subsequent clinical review were used to characterize COVID-19 cases. RESULTS: Over 1500 relevant cases were identified over an 8-month period. In cases that reported COVID-19, immunosuppressant/immunomodulating agents, followed by anticoagulant/antithrombic agents and corticosteroids, were the most frequently reported agents. The frequent reporting of immunosuppressant/immunomodulating agents among cases of COVID-19 suggests increased vulnerability to infection among treated patients, either because of immunosuppressive effects of certain agents or the nature of the underlying treated condition. In cases involving off-label pharmacotherapy use for the treatment of COVID-19-related conditions, the most frequently reported therapeutic classes included antibiotics, antimalarial agents, antivirals/antiretroviral agents, immunosuppressant/immunomodulating agents, corticosteroids, anticoagulants, and immunoglobulin/interferons. The most frequently reported pharmacotherapeutic agents were azithromycin and chloroquine/hydroxychloroquine, followed by lopinavir-ritonavir, ceftriaxone, and tofacitinib. The most frequently reported clinical adverse events associated with azithromycin (as sole therapy or combined with chloroquine/hydroxychloroquine) include electrocardiogram QT prolonged, drug interaction, hepatitis, diarrhea, and hepatitis acute. Regarding cardiac-related events, 19% (120/645) of azithromycin cases reported events associated with QT prolongation/torsade de pointes (which included seven fatal cardiac events). The most frequently reported clinical adverse events associated with other commonly used agents are also presented. CONCLUSIONS: This pharmacovigilance surveillance study provides a unique characterization of cases in which a broad range of pharmaceutical products was reported in relation to COVID-19.