Convalescent Plasma For Coronavirus Disease 2019 In Pregnancy: A Case Report And Review

Pregnant women with coronavirus disease 2019 (COVID-19) show overall similar clinical features as that of nonpregnant adults with COVID-19, except perhaps for higher risk of admission to the intensive care unit (ICU) and mechanical ventilation.1Center for Disease Control and PreventionData on COVID-19 during pregnancy.https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19.htmlGoogle Scholar Among pregnant women with COVID-19, more than 85% to 90% have no or mild symptoms, 5% to 10% have symptoms severe enough to warrant hospitalization and at times oxygen therapy but no mechanical ventilation, and 1% to 2% develop critical disease requiring mechanical ventilation and at times leading even to death.1Center for Disease Control and PreventionData on COVID-19 during pregnancy.https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19.htmlGoogle Scholar Most promising therapeutic possibilities for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy include currently remdesivir and convalescent plasma (CP). In this study, we present a case of a pregnant woman treated with CP at the city hospital of Mantova in Italy. This study involved a 29-year-old gravida 2, para 1 patient (previous preterm birth at 36 4/7 weeks of gestation) with a body mass index of 31 and with a singleton gestation who presented at the emergency room on April 9, 2020 at 24 2/7 weeks of gestation with worsening cough and fever, which started approximately 7 days before. At presentation, she was febrile (38.0°C) and normotensive, with a respiratory rate of 20 bpm and an O2 saturation (SpO2) of 95%. Laboratory tests showed normal white blood cell and procalcitonin values, a C-reactive protein concentration of 58.6 mg/L, and normal arterial blood gas values. The polymerase chain reaction (PCR) nasopharyngeal (NP) test for SARS-CoV-2 returned positive. Initial chest X-ray revealed a parenchymal thickening of the upper right lobe. Fetal well-being was assessed by obstetrical ultrasound and nonstress test, the latter not detecting uterine contractions. Antibiotic therapy (ceftriaxone and azithromycin) and prophylactic low-molecular-weight heparin (LMWH) were started. The following day, the patient showed a mild clinical worsening, with persistent dry cough, fatigue, dyspnea, fever (38.5°C), and lymphopenia; her SpO2 was 95% on room air. Following a pneumological evaluation, considering gestational age, the patient was transfused with 300 mL of CP, with no adverse effects. Antepartum testing for fetal well-being was reassuring both before and after the transfusion. The following day, a clinical worsening was observed, with persistently high fever (39.5°C), tachypnoea (30 bpm), hypotension (90/60 mm Hg), and an SpO2 of 91% on room air. Lymphopenia, elevated interleukin-6, and serum ferritin level were reported as well. However, it should be noted that her PCR NP test for SARS-CoV-2 returned negative. Chest ultrasound revealed bilateral pleural thickening with nodulations and several B lines (>4/field). Obstetrical ultrasound showed regular fetal biometry with normal umbilical arterial Doppler assessment. Because of the rapid worsening of her clinical condition and laboratory values (Figure), the patient was transferred to the ICU were she was given oxygen therapy via a nasal cannula (4 L/min). She was initiated on hydroxychloroquine, LMWH at a therapeutic dose, and methylprednisolone. The peak of severity was reached 2 days after admission to the ICU, when she developed acute respiratory distress syndrome. The ratio of the partial pressure of arterial oxygen to the percentage of inspired oxygen (PaO2/FiO2) fell to a minimum value of 223. She was supported with oxygen therapy via nasal cannula over noninvasive ventilation (FiO2, 36%) without the need for intubation. Obstetrical ultrasound showed a normal umbilical artery pulsatility index (UA-PI) and fetal ductus venosus with an observed a wave. The middle cerebral artery peak systolic velocity (MCA-PSV) was >1.5 multiples of median, with diastolic reverse flow. As a result, the patient was again transfused with 300 mL of CP on day 12 from onset of symptoms, with no adverse reactions. The patient’s clinical condition rapidly improved as shown by normalization of laboratory tests and vital signs within 3 days of the second CP transfusion (Figure). In particular, we observed a rapid normalization in body temperature and SpO2 and a prompt resolution of dyspnea. The PCR NP test for SARS-CoV-2 was repeated on days 15 and 17 with both tests returning with negative results. The patient was discharged 13 days after admission. The mother’s chest ultrasound showed near-complete resolution of bilateral pneumonia. Fetal Doppler assessment was normal, with UA-PI and MCA-PSV within the normal range for gestational age. The outpatient examinations, performed every week for 1 month, showed a complete recovery of pulmonary function. Pregnancy continued to be monitored after hospital discharge by fetal ultrasonography with Doppler assessment every 2 weeks. In the study, fetal biometry results were consistent with gestational age (34 weeks of gestation). Comparing our patient with those in a US cohort of pregnant women with severe COVID-19,2Pierce-Williams R.A.M. Burd J. Felder L. et al.Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study.Am J Obstet Gynecol MFM. 2020; ([Epub ahead of print])PubMed Google Scholar the clinical course was similar, with hospital admission on day 7 after onset of symptoms, initiation of O2 therapy on day 9, peak respiratory support on day 10, hydroxychloroquine treatment started on day 9, and symptom resolution on day 15. The rationales for the use of CP in our patient were to prevent the mother’s condition from worsening, to avoid a possible cesarean delivery at a gestational age of severe prematurity, and to reduce potential maternal and fetal risk associated with the administration of various drugs utilized for COVID-19. In 1 published randomized controlled trial, there is evidence that CP can be used effectively as a therapy for severe COVID-19 in nonpregnant adults, shortening time to clinical improvement by 5 days, and with trends for improvement in other outcomes, including death, without causing severe adverse events.3Li L. Zhang W. Hu Y. et al.Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial.JAMA. 2020; ([Epub ahead of print])Crossref Scopus (909) Google Scholar Regarding SARS-CoV-2 infection in pregnancy, pregnancy is not a contraindication to blood component transfusion, and 2 other cases of pregnancies managed using CP have been reported (Table).4Zhang B. Liu S. Tan T. et al.Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome coronavirus 2 infection.Chest. 2020; 158: e9-e13Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar,5Anderson J. Schauer J. Bryant S. Graves C.R. The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: a case report.Case Rep Womens Health. 2020; ([Epub ahead of print])Crossref Scopus (62) Google Scholar In a single report, CP administration was associated with survival of the mother but resulted to death of the newborn.4Zhang B. Liu S. Tan T. et al.Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome coronavirus 2 infection.Chest. 2020; 158: e9-e13Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar In the second case report, CP therapy in association with remdesivir successfully managed a critically ill obstetrical patient.5Anderson J. Schauer J. Bryant S. Graves C.R. The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: a case report.Case Rep Womens Health. 2020; ([Epub ahead of print])Crossref Scopus (62) Google Scholar The case in this study is the first treated with CP without antiviral drugs with a favorable outcome for both the mother and fetus.TableClinical course of 3 pregnant women affected by COVID-19 treated with CPAuthorGestational ageSeverity of diseaseInvasive proceduresComorbidityCP dose (units)Other medicationsOutcomeZhang et al4Zhang B. Liu S. Tan T. et al.Treatment with convalescent plasma for critically ill patients with severe acute respiratory syndrome coronavirus 2 infection.Chest. 2020; 158: e9-e13Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar35 wk and 2 dSevere ARDSMechanical ventilation—1Lopinavir and ritonavirMaternal well-beingSeptic shockCRRTRibavirinNewborn death because of intrauterine asphyxiaMOFECMOImipenemCesarean deliveryVancomycinAnderson et al5Anderson J. Schauer J. Bryant S. Graves C.R. The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: a case report.Case Rep Womens Health. 2020; ([Epub ahead of print])Crossref Scopus (62) Google Scholar22 wk and 2 dSevere ARDSMechanical ventilationType 2 DM1RemdesivirMaternal well-beingAsthmaCeftriaxoneNormal ongoing pregnancyClass III obesityAzithromycinHydroxychloroquineHydrocortisoneLMWHGrisolia et al (present study)24 wk and 2 dMild ARDS—Class I obesity2CeftriaxoneMaternal well-beingAzithromycinNormal ongoing pregnancyHydroxychloroquineMethylprednisoloneLMWHARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; CP, convalescent plasma; CRRT, continuous renal replacement therapy; DM, diabetes mellitus; ECMO, extracorporeal membrane oxygenation; LMWH, low-molecular-weight heparin; MOF, multiorgan failure.Grisolia. Convalescent plasma for coronavirus disease 2019 in pregnancy. AJOG MFM 2020. Open table in a new tab ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; CP, convalescent plasma; CRRT, continuous renal replacement therapy; DM, diabetes mellitus; ECMO, extracorporeal membrane oxygenation; LMWH, low-molecular-weight heparin; MOF, multiorgan failure. Grisolia. Convalescent plasma for coronavirus disease 2019 in pregnancy. AJOG MFM 2020. This case report has several limitations, including the short follow-up (the patient was at 34 weeks of gestation and well) and the concomitant use of other medications that may confound the evaluation of CP effectiveness. Nevertheless, the close temporal association between CP transfusion and improvement in clinical and laboratory parameters represents an encouraging finding.