Immunisation against COVID-19 in Pregnancy and of Women Planning Pregnancy

Following reports of the first human SARS-CoV2 infection in December 2019 from Wuhan Province, China, there was such rapid spread that by March 2021, the World Health Organization (WHO) had declared a pandemic. Over 6.5 million people have died from this infection worldwide, although this is most likely an underestimate. Until vaccines became available, mortality and severe morbidity were costly in terms of life lost as well as the cost of supporting the severely and acutely ill. Vaccination changed the landscape, and following worldwide adoption, life has gradually been returning to normal. The speed of production of the vaccines was unprecedented and undoubtedly ushered in a new era in the science of fighting infections. The developed vaccines were on the already known platforms for vaccine delivery: inactivated virus, virus vector, virus-like particles (VLP) subunit, DNA and mRNA. The mRNA platform was used for the first time to deliver vaccines to humans. An understanding of these platforms and the pros and cons of each are important for clinicians who are often challenged by the recipients on the advantages and risks of these vaccines. These vaccines have so far and reassuringly been shown to be safe in reproduction (with no effect on gametes) and pregnancy (not associated with congenital malformations). However, safety remains paramount and continuing vigilance is critical, especially against rare fatal complications such as vaccine-induced thrombocytopenia and myocarditis. Finally, the waning immunity months after vaccination means repeated immunisation is likely to be ongoing, but just how often and how many such revaccinations should be recommended remains uncertain. Research into other vaccines and alternate delivery methods should continue as this infection is likely to be around for a long time.

[1]  P. Karnaki,et al.  The impact of Covid-19 vaccines on fertility-A systematic review and metanalysis , 2022, Vaccine.

[2]  S. Rasmussen,et al.  Covid-19 vaccination in pregnancy , 2022, BMJ.

[3]  H. Shulha,et al.  Safety of COVID-19 vaccines in pregnancy: a Canadian National Vaccine Safety (CANVAS) network cohort study , 2022, The Lancet Infectious Diseases.

[4]  E. McDonald,et al.  Cardiovascular Complications of Pregnancy-Associated COVID-19 Infections , 2022, JACC: Advances.

[5]  G. Alter,et al.  COVID-19 booster dose induces robust antibody response in pregnant, lactating, and nonpregnant women , 2022, American Journal of Obstetrics and Gynecology.

[6]  D. Satar,et al.  Investigation of the effect of COVID‐19 on sperm count, motility, and morphology , 2022, Journal of medical virology.

[7]  A. Salami,et al.  Risk Markers of COVID-19, a Study from South-Lebanon , 2022, COVID.

[8]  M. Craina,et al.  The Benefits of Vaccination against SARS-CoV-2 during Pregnancy in Favor of the Mother/Newborn Dyad , 2022, Vaccines.

[9]  W. Klockenbusch,et al.  Assessment of Neonatal Cord Blood SARS-CoV-2 Antibodies after COVID-19 Vaccination in Pregnancy: A Prospective Cohort Study , 2022, Geburtshilfe und Frauenheilkunde.

[10]  E. Miller,et al.  Association of COVID-19 Vaccination During Early Pregnancy With Risk of Congenital Fetal Anomalies. , 2022, JAMA pediatrics.

[11]  H. Gjessing,et al.  Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes. , 2022, JAMA.

[12]  Christopher A Gravel,et al.  Association of COVID-19 Vaccination in Pregnancy With Adverse Peripartum Outcomes. , 2022, JAMA.

[13]  Noah Whited,et al.  Antibodies Against SARS-CoV-2 in Human Breast Milk After Vaccination: A Systematic Review and Meta-Analysis. , 2022, Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine.

[14]  Gheyath K Nasrallah,et al.  Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar , 2022, The New England journal of medicine.

[15]  S. Gharbia,et al.  Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant , 2022, The New England journal of medicine.

[16]  Joshua I. Rosenbloom,et al.  Safety of SARS-CoV-2 vaccination during pregnancy- obstetric outcomes from a large cohort study , 2022, BMC Pregnancy and Childbirth.

[17]  A. Randolph,et al.  Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19–Associated Hospitalization in Infants Aged <6 Months — 17 States, July 2021–January 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[18]  J. Kuint,et al.  Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes. , 2022, JAMA pediatrics.

[19]  I. Sas,et al.  Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester , 2022, Viruses.

[20]  C. Fuller,et al.  Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth — Eight Integrated Health Care Organizations, United States, December 15, 2020–July 22, 2021 , 2022, MMWR. Morbidity and mortality weekly report.

[21]  P. Pannaraj,et al.  Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination. , 2022, Pediatrics.

[22]  Chao-Min Cheng,et al.  Evaluation of Transplacental Antibody Transfer in SARS-CoV-2-Immunized Pregnant Women , 2022, Vaccines.

[23]  G. Alter,et al.  Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms , 2021, Nature Communications.

[24]  R. Aitken,et al.  Rapid impact of COVID-19 infection on semen quality: a case report , 2021, Translational andrology and urology.

[25]  OUP accepted manuscript , 2022, Clinical Infectious Diseases.

[26]  Iman A. Mohammed,et al.  Association of Gestational Age at Coronavirus Disease 2019 (COVID-19) Vaccination, History of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, and a Vaccine Booster Dose With Maternal and Umbilical Cord Antibody Levels at Delivery , 2021, Obstetrics and gynecology.

[27]  O. Lavie,et al.  Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy. , 2021, JAMA pediatrics.

[28]  Y. Yogev,et al.  The association of maternal SARS‐CoV‐2 vaccination‐to‐delivery interval and the levels of maternal and cord blood antibodies , 2021, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[29]  K. Järvinen,et al.  Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination. , 2021, JAMA pediatrics.

[30]  M. Makris,et al.  Vaccine-induced immune thrombotic thrombocytopenia , 2021, The Lancet Haematology.

[31]  S. Porat,et al.  Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study , 2021, Clinical Microbiology and Infection.

[32]  A. Wilcox,et al.  Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage , 2021, The New England journal of medicine.

[33]  D. Lauffenburger,et al.  COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women , 2021, Science Translational Medicine.

[34]  J. Biggio,et al.  Maternal Outcomes After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Vaccinated Compared With Unvaccinated Pregnant Patients , 2021, Obstetrics and gynecology.

[35]  E. Schleußner,et al.  Newborns’ passive humoral SARS-CoV-2 immunity following heterologous vaccination of the mother during pregnancy , 2021, American Journal of Obstetrics and Gynecology.

[36]  M. Neeman,et al.  Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. , 2021, Journal of Clinical Investigation.

[37]  J. Lessing,et al.  Titers of SARS CoV-2 antibodies in cord blood of neonates whose mothers contracted SARS CoV-2 (COVID-19) during pregnancy and in those whose mothers were vaccinated with mRNA to SARS CoV-2 during pregnancy , 2021, Journal of Perinatology.

[38]  L. Sagi‐Dain,et al.  COVID-19 vaccination safety and efficiency during pregnancy: a prospective observational study , 2021, Vaccine.

[39]  S. Grisaru-Granovsky,et al.  Covid‐19 vaccination during the third trimester of pregnancy: rate of vaccination and maternal and neonatal outcomes, a multicentre retrospective cohort study , 2021, BJOG : an international journal of obstetrics and gynaecology.

[40]  Y. Yinon,et al.  Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy , 2021, American Journal of Obstetrics & Gynecology MFM.

[41]  A. Wilcox,et al.  Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion , 2021, The New England journal of medicine.

[42]  K. Vesco,et al.  Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. , 2021, JAMA.

[43]  T. Wainstock,et al.  Prenatal maternal COVID-19 vaccination and pregnancy outcomes , 2021, Vaccine.

[44]  A. Roman,et al.  High antibody levels in cord blood from pregnant women vaccinated against COVID-19 , 2021, American Journal of Obstetrics & Gynecology MFM.

[45]  P. MacAry,et al.  Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees , 2021, NPJ vaccines.

[46]  A. Roman,et al.  COVID-19 vaccination in pregnancy: early experience from a single institution , 2021, American Journal of Obstetrics & Gynecology MFM.

[47]  E. Woo,et al.  Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices — United States, July 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[48]  Alison L. Drake,et al.  Short-term Reactions Among Pregnant and Lactating Individuals in the First Wave of the COVID-19 Vaccine Rollout , 2021, JAMA network open.

[49]  L. Magee,et al.  COVID-19 vaccination during pregnancy: coverage and safety , 2021, American Journal of Obstetrics and Gynecology.

[50]  R. Stebbings,et al.  Developmental and reproductive safety of AZD1222 (ChAdOx1 nCoV-19) in mice , 2021, Reproductive Toxicology.

[51]  B. Fox,et al.  SARS-CoV-2 Antibodies Detected in Mother’s Milk Post-Vaccination , 2021, Journal of human lactation : official journal of International Lactation Consultant Association.

[52]  M. Hernán,et al.  Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy , 2021, Nature Medicine.

[53]  N. Regev,et al.  Short‐term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID‐19 vaccine , 2021, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[54]  R. Ramasamy,et al.  Sperm Parameters Before and After COVID-19 mRNA Vaccination. , 2021, JAMA.

[55]  J. Konje,et al.  Severe acute respiratory syndrome (SARS) coronavirus-2 infection (COVID-19) in pregnancy – An overview , 2021, European Journal of Obstetrics & Gynecology and Reproductive Biology.

[56]  D. Vasireddy,et al.  Review of COVID-19 Variants and COVID-19 Vaccine Efficacy: What the Clinician Should Know? , 2021, Journal of clinical medicine research.

[57]  R. Sellers,et al.  Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine , 2021, Reproductive Toxicology.

[58]  M. Verdecia,et al.  COVID-19 vaccine platforms: Delivering on a promise? , 2021, Human vaccines & immunotherapeutics.

[59]  M. Wick,et al.  Pregnancy and birth outcomes after SARS-CoV-2 vaccination in pregnancy , 2021, American Journal of Obstetrics & Gynecology MFM.

[60]  G. Alter,et al.  Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. , 2021, JAMA.

[61]  R. Nahum,et al.  Does mRNA SARS-CoV-2 vaccine influence patients' performance during IVF-ET cycle? , 2021, Reproductive Biology and Endocrinology.

[62]  L. Riley,et al.  Antibody Response to Coronavirus Disease 2019 (COVID-19) Messenger RNA Vaccination in Pregnant Women and Transplacental Passage Into Cord Blood , 2021, Obstetrics and gynecology.

[63]  H. Fennema,et al.  Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19 , 2021, The New England journal of medicine.

[64]  C. Olson,et al.  Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons , 2021, The New England journal of medicine.

[65]  L. Gianaroli,et al.  Joint IFFS/ESHRE statement on COVID-19 vaccination for pregnant women and those considering pregnancy†,‡ , 2021, Human reproduction open.

[66]  D. Wolf,et al.  Ovarian follicular function is not altered by SARS–CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination , 2021, medRxiv.

[67]  I. Youngster,et al.  SARS-CoV-2-Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. , 2021, JAMA.

[68]  J. Goldstein,et al.  Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy , 2021, American Journal of Obstetrics and Gynecology.

[69]  G. Alter,et al.  Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study , 2021, American Journal of Obstetrics and Gynecology.

[70]  S. Porat,et al.  Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination , 2021, medRxiv.

[71]  K. Järvinen,et al.  Characterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19 , 2021, mBio.

[72]  C. Spong,et al.  COVID-19 Vaccination in Pregnant and Lactating Women. , 2021, JAMA.

[73]  F. Muñoz Can We Protect Pregnant Women and Young Infants From COVID-19 Through Maternal Immunization? , 2021, JAMA pediatrics.

[74]  Nguyen H. Tran,et al.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK , 2020, Lancet.

[75]  J. Mascola,et al.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine , 2020, The New England journal of medicine.

[76]  P. Dormitzer,et al.  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine , 2020, The New England journal of medicine.

[77]  J. Segars,et al.  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) and its effect on gametogenesis and early pregnancy , 2020, American journal of reproductive immunology.

[78]  D. Logunov,et al.  Safety and efficacy of the Russian COVID-19 vaccine: more information needed – Authors’ reply , 2020, The Lancet.

[79]  L. Mofenson,et al.  Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis , 2020, BMJ.

[80]  O. Batiha,et al.  Impact of COVID‐19 and other viruses on reproductive health , 2020, Andrologia.

[81]  Wanli Xie,et al.  A comparative overview of COVID-19, MERS and SARS: Review article , 2020, International Journal of Surgery.

[82]  L. Gianaroli,et al.  Assisted reproduction and COVID-19: A joint statement of ASRM, ESHRE and IFFS , 2020, Fertility and Sterility.

[83]  O. Turriziani,et al.  SARS‐CoV‐2 presence in seminal fluid: Myth or reality , 2020, Andrology.

[84]  Diangeng Li,et al.  Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019 , 2020, JAMA network open.

[85]  A. Lenzi,et al.  Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic , 2020, Metabolism.

[86]  M. Cevik,et al.  COVID-19 pandemic—a focused review for clinicians , 2020, Clinical Microbiology and Infection.

[87]  L. Rienzi,et al.  COVID-19 and ART: the view of the Italian Society of Fertility and Sterility and Reproductive Medicine , 2020, Reproductive BioMedicine Online.

[88]  M. Choolani,et al.  Coronavirus disease 2019 (COVID-19) pandemic and pregnancy , 2020, American Journal of Obstetrics and Gynecology.

[89]  Qiang Zhou,et al.  Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 , 2020, Science.

[90]  S. Gurunathan,et al.  The promise of mRNA vaccines: a biotech and industrial perspective , 2020, npj Vaccines.

[91]  P. van Damme,et al.  Vaccination during pregnancy: current and possible future recommendations , 2020, European Journal of Pediatrics.

[92]  Jie Cui,et al.  Origin and evolution of pathogenic coronaviruses , 2018, Nature Reviews Microbiology.

[93]  I. Dieussaert,et al.  Maternal immunization: where are we now and how to move forward? , 2018, Annals of medicine.

[94]  Shuai Jiang,et al.  Recent advances in the production of recombinant subunit vaccines in Pichia pastoris , 2016, Bioengineered.

[95]  A. Kamen,et al.  Large-scale adenovirus and poxvirus-vectored vaccine manufacturing to enable clinical trials. , 2015, Biotechnology journal.

[96]  H. Fausther-Bovendo,et al.  Pre-existing immunity against Ad vectors , 2014, Human vaccines & immunotherapeutics.

[97]  Sarah G. Crist,et al.  Estradiol Reduces Susceptibility of CD4+ T Cells and Macrophages to HIV-Infection , 2013, PloS one.

[98]  P. Oyston,et al.  The current challenges for vaccine development. , 2012, Journal of medical microbiology.

[99]  A. Hill,et al.  Viral vectors as vaccine platforms: deployment in sight. , 2011, Current opinion in immunology.

[100]  Michael J. Davis,et al.  Sensing prokaryotic mRNA signifies microbial viability and promotes immunity , 2011, Nature.

[101]  Nick Andrews,et al.  No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine. , 2009, Vaccine.

[102]  V. Hornung,et al.  Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response. , 2007, Blood.

[103]  Anastasia Vlasova,et al.  Biologic, Antigenic, and Full-Length Genomic Characterization of a Bovine-Like Coronavirus Isolated from a Giraffe , 2007, Journal of Virology.

[104]  J. Gu,et al.  Orchitis: A Complication of Severe Acute Respiratory Syndrome (SARS)1 , 2006, Biology of reproduction.

[105]  S. Weiss,et al.  Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus , 2005, Microbiology and Molecular Biology Reviews.

[106]  M. Loutfy,et al.  Severe Acute Respiratory Syndrome , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[107]  D. Weissman,et al.  HIV Gag mRNA Transfection of Dendritic Cells (DC) Delivers Encoded Antigen to MHC Class I and II Molecules, Causes DC Maturation, and Induces a Potent Human In Vitro Primary Immune Response1 , 2000, The Journal of Immunology.

[108]  H. Rammensee,et al.  In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies , 2000 .