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1.
BMC Pregnancy Childbirth ; 21(1): 511, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1874999

ABSTRACT

BACKGROUND: Although the World Health Organization and health authorities in most countries recommend that pregnant women receive inactivated influenza virus vaccines, coverage remains low. This study aimed to investigate (1) the proportion of pregnant women who received an influenza vaccination and influencing factors and (2) the proportion of obstetrics and gynecology (OBGYN) doctors who routinely recommend influenza vaccination to pregnant women and influencing factors. METHODS: Two separate, anonymized questionnaires were developed for physicians and pregnant and postpartum women and were distributed to multicenters and clinics in South Korea. The proportions of women who received influenza vaccination during pregnancy and OBGYN doctors who routinely recommend the influenza vaccine to pregnant women were analyzed. Independent influencing factors for both maternal influenza vaccination and OBGYN doctors' routine recommendations to pregnant women were analyzed using log-binomial regression analysis. RESULTS: The proportion of self-reported influenza vaccination during pregnancy among 522 women was 63.2%. Pregnancy-related independent factors influencing maternal influenza vaccination were "(ever) received information about influenza vaccination during pregnancy" (OR 8.9, 95% CI 4.17-19.01), "received vaccine information about from OBGYN doctors" (OR 11.44, 95% CI 5.46-24.00), "information obtained from other sources" (OR 4.38, 95% CI 2.01-9.55), and "second/third trimester" (OR 2.41, 95% CI 1.21-4.82).. Among 372 OBGYN doctors, 76.9% routinely recommended vaccination for pregnant women. Independent factors effecting routine recommendation were "working at a private clinic or hospital" (OR 5.33, 95% CI 2.44-11.65), "awareness of KCDC guidelines" (OR 3.11, 95% CI 1.11-8.73), and "awareness of the 2019 national free influenza vaccination program for pregnant women" (OR 4.88, 95% CI 2.34-10.17). OBGYN doctors most commonly chose 'guidelines proposed by the government or public health (108, 46%) and academic committees (59, 25%), as a factor which expect to affect the future recommendation CONCLUSION: This study showed that providing information about maternal influenza vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Closer cooperation between the government and OBGYN academic societies to educate OBGYN doctors might enhance routine recommendations.


Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Physicians/statistics & numerical data , Pregnancy Complications, Infectious/prevention & control , Pregnancy/statistics & numerical data , Vaccination/statistics & numerical data , Adult , Female , Gynecology , Health Knowledge, Attitudes, Practice , Humans , Influenza, Human/immunology , Male , Middle Aged , Obstetrics , Pregnancy Complications, Infectious/immunology , Republic of Korea , Surveys and Questionnaires , Vaccination Coverage/statistics & numerical data
3.
Front Immunol ; 13: 827889, 2022.
Article in English | MEDLINE | ID: covidwho-1731779

ABSTRACT

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans.


Subject(s)
COVID-19/immunology , Immunologic Memory/immunology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Adult , Animals , Antibodies, Viral/immunology , Antibody Formation/immunology , B-Lymphocytes/immunology , Cell Line , Chlorocebus aethiops , Female , Humans , Pregnancy , Pregnant Women , Prospective Studies , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
4.
Sci Transl Med ; 14(634): eabn7842, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1723505

ABSTRACT

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , /immunology
5.
Clin Appl Thromb Hemost ; 28: 10760296211056648, 2022.
Article in English | MEDLINE | ID: covidwho-1685920

ABSTRACT

The progress in the development of various vaccine platforms against SARS-CoV-2 have been rather remarkable owing to advancement in molecular and biologic sciences. Most of the current vaccines and those in development focus on targeting the viral spike proteins by generating antibodies of varying spectrum. These vaccines represent a variety of platforms including whole virus vaccines, viral vector vaccines, nucleic acid vaccines representing RNA, DNA, and their hybrid forms.The therapeutic efficacy of these vaccines varies owing to their pharmacodynamic individualities. COVID-19 variants are capable of inducing different pathologic responses and some of which may be resistant to antibodies generated by current vaccines. The current clinical use of these vaccines has been through emergency use authorization until recently. Moreover, the efficacy and safety of these vaccines have been tested in substantial numbers of individuals but studies in special populations that better reflect the global population are pending results. These specialized populations include young children, immunocompromised patients, pregnant individuals, and other specialized groups. Combination approaches, molecularly modified vaccination approaches, and vaccines conferring longer periods of immunity are being currently being investigated, as well as pharmacovigilance studies.The continual transformation of SARS-CoV-2 and its variants are of concern along with the breakthrough infections. These considerations pose new challenges for the development of vaccination platforms. For this purpose, booster doses, combination vaccine approaches, and other modalities are being discussed. This review provides an updated account of currently available vaccines and those in advanced development with reference to their composition and mechanisms of action.A discussion on the use of vaccines in special populations including immunocompromised patients, pregnant women and other specialized populations are also included.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/prevention & control , SARS-CoV-2/immunology , /methods , Adolescent , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Child , Female , Humans , Immunocompromised Host , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology
6.
Front Immunol ; 12: 808064, 2021.
Article in English | MEDLINE | ID: covidwho-1649357

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Maternal-Fetal Exchange/immunology , SARS-CoV-2/immunology , /adverse effects , /adverse effects , Adoptive Transfer , /immunology , COVID-19/immunology , Female , Humans , Infectious Disease Transmission, Vertical/prevention & control , Milk, Human/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , Spike Glycoprotein, Coronavirus/immunology , Vaccination , /statistics & numerical data
7.
Nat Commun ; 13(1): 320, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1632529

ABSTRACT

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.


Subject(s)
COVID-19/immunology , Immunity/immunology , Infectious Disease Transmission, Vertical , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , COVID-19/blood , COVID-19/virology , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant, Newborn , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Young Adult
8.
Epidemiol Infect ; 150: e28, 2022 01 13.
Article in English | MEDLINE | ID: covidwho-1621175

ABSTRACT

We studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pregnant women in Norway by including all women who were first trimester pregnant (n = 6520), each month from December 2019 through December 2020, in the catchment region of Norway's second-largest hospital. We used sera that had been frozen stored after compulsory testing for syphilis antibodies in antenatal care. The sera were analysed with the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Cobas e801). This immunoassay detects IgG/IgM against SARS-CoV-2 nucleocapsid antigen. Sera with equivocal or positive test results were retested with the Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorin), which detects IgG against the spike (S)1 and S2 protein on the SARS-CoV-2 virus. In total, 98 women (adjusted prevalence 1.7%) had SARS CoV-2 antibodies. The adjusted seroprevalence increased from 0.3% (1/445) in December 2019 to 5.7% (21/418) in December 2020. Out of the 98 seropositive women, 36 (36.7%) had serological signs of current SARS-CoV-2 infection at the time of serum sampling, and the incidence remained low during the study period. This study suggests that SARS CoV-2 was present in the first half of December 2019, 6 weeks before the first case was recognised in Norway. The low occurrence of SARS-CoV-2 infection during 2020, may be explained by high compliance to extensive preventive measures implemented early in the epidemic.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2/immunology , Adult , COVID-19/immunology , Cryopreservation , Female , Humans , Norway/epidemiology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Seroepidemiologic Studies
10.
J Reprod Immunol ; 149: 103464, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561228

ABSTRACT

We studied the T cell response to SARS-CoV-2 spike and non-spike peptide epitopes in eight convalescent pregnant women together with the immune monitoring that included innate tolerogenic dendritic cell populations important to maintain the immunological mother/fetus interface to address a potential risk for the antiviral cellular response in the outcome of pregnancy. Four subjects had pre-existing chronic inflammatory conditions that could have potentially affected the SARS-CoV-2-specific T cell response. Seven of eight subjects responded to SARS-CoV-2 peptides with differences within CD4+ T helper (Th) and CD8+ cytotoxic T cells (CTL). SARS-CoV-2-specific inducible regulatory T cells (iTreg) were numerous in circulation. CD4+ T cell memory included central memory T cells (TCM) and effector memory (TEM). As far as the CD8+ memory repertoire, TCM and TEM were very low or absent in eight of eight subjects and only effector cells that revert to CD45RA+, defined as TEMRA were measurable in circulation. T cells were in the normal range in all subjects regardless of pre-existing inflammatory conditions. The immune phenotype indicated the expansion and activation of tolerogenic myeloid dendritic cells including CD14+ cDC2 and CD4+ ILT-4+ tmDC. In summary, SARS-CoV-2 infection induced a physiological anti-viral T cell response in pregnant women that included SARS-CoV-2-specific iTreg with no negative effects on the tolerogenic innate dendritic cell repertoire relevant to the immune homeostasis of the maternal-fetal interface. All eight subjects studied delivered full-term, healthy infants.


Subject(s)
COVID-19/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Female , Humans , Pregnancy , Prospective Studies
11.
Breastfeed Med ; 16(12): 987-994, 2021 12.
Article in English | MEDLINE | ID: covidwho-1560382

ABSTRACT

Objective: To evaluate the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in colostrum from women who tested positive for the virus. Methods: Between March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Four of 15 women provided liquid colostrum, which was used for validating results obtained from spot cards. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre-coronavirus disease 2019 (COVID-19) controls. All samples were tested for reactivity to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein using an enzyme-linked immunosorbent assay that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM and for levels of 10 inflammatory cytokines (interferon-gamma [IFN-γ], tumor necrosis factor-alpha, interleukin [IL]-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13) using a multiplex electrochemiluminescent sandwich assay. Results: Our validation studies indicate that the levels of SARS-CoV-2-specific antibodies and the associated cytokines measured in liquid colostrum are comparable to levels eluted from spot cards. Bilateral colostrum samples from 73%, 73%, and 33% of the 15 COVID-19 mothers exhibited IgA, IgG, and IgM reactivity to RBD, respectively. In addition, symptomatic COVID-19 mothers had statistically significant elevated levels of 4 of the 10 inflammatory markers (IFN-γ, IL-4, IL-6, and IL-12) compared to asymptomatic COVID-19 mothers. Conclusions: A strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.


Subject(s)
COVID-19 , Colostrum/immunology , Immunity, Cellular , Immunity, Humoral , Pregnancy Complications, Infectious , Breast Feeding , COVID-19/immunology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Spike Glycoprotein, Coronavirus
12.
Front Immunol ; 12: 775168, 2021.
Article in English | MEDLINE | ID: covidwho-1555043

ABSTRACT

COVID-19 is characterized by virus-induced injury leading to multi-organ failure, together with inflammatory reaction, endothelial cell (EC) injury, and prothrombotic coagulopathy with thrombotic events. Complement system (C) via its cross-talk with the contact and coagulation systems contributes significantly to the severity and pathological consequences due to SARS-CoV-2 infection. These immunopathological mechanisms overlap in COVID-19 and pre-eclampsia (PE). Thus, mothers contracting SARS-CoV-2 infection during pregnancy are more vulnerable to developing PE. SARS-CoV-2 infection of ECs, via its receptor ACE2 and co-receptor TMPRSS2, can provoke endothelial dysfunction and disruption of vascular integrity, causing hyperinflammation and hypercoagulability. This is aggravated by bradykinin increase due to inhibition of ACE2 activity by the virus. C is important for the progression of normal pregnancy, and its dysregulation can impact in the form of PE-like syndrome as a consequence of SARS-CoV-2 infection. Thus, there is also an overlap between treatment regimens of COVID-19 and PE. C inhibitors, especially those targeting C3 or MASP-2, are exciting options for treating COVID-19 and consequent PE. In this review, we examine the role of C, contact and coagulation systems as well as endothelial hyperactivation with respect to SARS-CoV-2 infection during pregnancy and likely development of PE.


Subject(s)
COVID-19/immunology , Complement System Proteins/immunology , Pre-Eclampsia/immunology , Pregnancy Complications, Infectious/immunology , COVID-19/drug therapy , COVID-19/physiopathology , Complement Inactivator Proteins/therapeutic use , Endothelium/immunology , Female , Humans , Pre-Eclampsia/physiopathology , Pre-Eclampsia/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2 , Thrombosis/immunology
13.
J Clin Invest ; 131(23)2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546629

ABSTRACT

BackgroundSARS-CoV-2 infection in pregnancy is associated with a higher risk of pregnancy-related complications and neonatal respiratory distress and hospitalization. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known.MethodsAll women with confirmed pregnancy who presented to the national referral hospital in Qatar between December 20, 2020, and May 30, 2021, with at least 1 SARS-CoV-2 test and not testing prior to pregnancy were included. We determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection during pregnancy using both cohort and test-negative case-control designs. Analyses were adjusted for age group, nationality, and gestational age.ResultsAmong 4534 pregnant women, there were 407 vaccinated and 407 unvaccinated women in the matched cohort analysis. Vaccine effectiveness was 87.6% (95%CI 44.1%-97.2%) at least 14 days after the second dose. There were 386 test-positive and 834 matched women in the test-negative case control analysis. Vaccine effectiveness was 86.8% (95%CI 47.5%-98.5%) at least 14 days after the second dose. Adjustment for age, nationality, and gestational age yielded similar results for both designs. In the test-negative analysis, vaccine effectiveness at least 14 days after the first dose but before the second dose was 40.8% (95% CI 0.0%-80.4%). Of the 386 test-positive pregnant women, 74 cases were Alpha variant, 163 cases were Beta variant, and 156 cases were variants of unknown status. There were 9 severe or critical disease cases and no deaths in the test-positive pregnant women, all of whom were unvaccinated.ConclusionThe mRNA vaccines provide a high level of protection against documented SARS-CoV-2 infection, which supports the inclusion of pregnant women in vaccination campaigns.FUNDINGHamad Medical Corporation, Weill Cornell Medicine Qatar, and the Ministry of Public Health Qatar.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2/immunology , Vaccination , Vaccines, Synthetic/administration & dosage , Adult , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/adverse effects , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/immunology , Vaccines, Synthetic/adverse effects
14.
Prenat Diagn ; 41(8): 1018-1035, 2021 07.
Article in English | MEDLINE | ID: covidwho-1544371

ABSTRACT

There are over 50 SARS-CoV-2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolled out for use in different countries. Due to concerns of potential teratogenicity or adverse effect on maternal physiology, pregnancy has been a specific exclusion criterion for most vaccine trials with only two trials not excluding pregnant women. Thus, other than limited animal studies, gradually emerging development and reproductive toxicity data, and observational data from vaccine registries, there is a paucity of reliable information to guide recommendations for the safe vaccination of pregnant women. Pregnancy is a risk factor for severe COVID-19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity. We discuss the major SARS-CoV-2 vaccines, their mechanisms of action, efficacy, safety profile and possible benefits to the maternal-fetal dyad to create a rational approach towards maternal vaccination while anticipating and mitigating vaccine-related complications. Pregnant women with high exposure risks or co-morbidities predisposing to severe COVID-19 infection should be prioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly. It is essential to support patient autonomy by shared decision-making involving a risk-benefit discussion with the pregnant woman.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2/immunology , COVID-19/immunology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/immunology , Vaccination/ethics
15.
Int J Med Sci ; 18(3): 763-767, 2021.
Article in English | MEDLINE | ID: covidwho-1524479

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19's during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age. Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.


Subject(s)
COVID-19/epidemiology , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19/therapy , COVID-19/transmission , Female , Humans , Infant, Newborn , Maternal Exposure , Middle East Respiratory Syndrome Coronavirus/immunology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , SARS Virus/immunology , SARS-CoV-2/isolation & purification , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index
16.
Placenta ; 115: 146-150, 2021 11.
Article in English | MEDLINE | ID: covidwho-1514252

ABSTRACT

There is inadequate screening for SARS-COV-2 during pregnancy. We aimed to determine the impact of maternal and neonatal cord blood SARS-COV-2 antibodies and placental transfer ratios in a region with a low screening plan. We performed a blind study in one of the SARS-CoV-2 epicenters in South America. 32% of pregnant women were serological positive. Importantly, there is an efficient passive immunization of the fetus to SARS-CoV-2. We report high incidence of SARS-CoV-2 infection during pregnancy, which is higher than officially reported. Therefore the need of active immunization to enhance maternal protection and fetal passive immunization.


Subject(s)
COVID-19/epidemiology , Fetal Blood/immunology , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Ecuador/epidemiology , Female , Fetal Blood/metabolism , Humans , Immunization, Passive/statistics & numerical data , Immunoglobulin G/blood , Immunoglobulin M/blood , Incidence , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/immunology , Seroepidemiologic Studies , Young Adult
17.
JAMA Netw Open ; 4(11): e2132563, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1499193

ABSTRACT

Importance: Although several studies have provided information on short-term clinical outcomes in children with perinatal exposure to SARS-CoV-2, data on the immune response in the first months of life among newborns exposed to the virus in utero are lacking. Objective: To characterize systemic and mucosal antibody production during the first 2 months of life among infants who were born to mothers infected with SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study enrolled 28 pregnant women who tested positive for SARS-CoV-2 infection and who gave birth at Policlinico Umberto I in Rome, Italy, from November 2020 to May 2021, and their newborns. Maternal and neonatal systemic immune responses were investigated by detecting spike-specific antibodies in serum, and the mucosal immune response was assessed by measuring specific antibodies in maternal breastmilk and infant saliva 48 hours after delivery and 2 months later. Exposures: Maternal infection with SARS-CoV-2 in late pregnancy. Main Outcomes and Measures: The systemic immune response was evaluated by the detection of SARS-CoV-2 IgG and IgA antibodies and receptor binding domain-specific IgM antibodies in maternal and neonatal serum. The mucosal immune response was assessed by measuring spike-specific antibodies in breastmilk and in infant saliva, and the presence of antigen-antibody spike IgA immune complexes was investigated in breastmilk samples. All antibodies were detected using an enzyme-linked immunosorbent assay. Results: In total, 28 mother-infant dyads (mean [SD] maternal age, 31.8 [6.4] years; mean [SD] gestational age, 38.1 [2.3] weeks; 18 [60%] male infants) were enrolled at delivery, and 21 dyads completed the study at 2 months' follow-up. Because maternal infection was recent in all cases, transplacental transfer of virus spike-specific IgG antibodies occurred in only 1 infant. One case of potential vertical transmission and 1 case of horizontal infection were observed. Virus spike protein-specific salivary IgA antibodies were significantly increased (P = .01) in infants fed breastmilk (0.99 arbitrary units [AU]; IQR, 0.39-1.68 AU) vs infants fed an exclusive formula diet (0.16 AU; IQR, 0.02-0.83 AU). Maternal milk contained IgA spike immune complexes at 48 hours (0.53 AU; IQR, 0.25-0.39 AU) and at 2 months (0.09 AU; IQR, 0.03-0.17 AU) and may have functioned as specific stimuli for the infant mucosal immune response. Conclusions and Relevance: In this cohort study, SARS-CoV-2 spike-specific IgA antibodies were detected in infant saliva, which may partly explain why newborns are resistant to SARS-CoV-2 infection. Mothers infected in the peripartum period appear to not only passively protect the newborn via breastmilk secretory IgA but also actively stimulate and train the neonatal immune system via breastmilk immune complexes.


Subject(s)
COVID-19/immunology , Immunoglobulin A/immunology , Milk, Human/immunology , Pregnancy Complications, Infectious/immunology , Adult , COVID-19/blood , COVID-19/transmission , COVID-19 Serological Testing , Female , Humans , Immunoglobulin A/isolation & purification , Immunoglobulin G/immunology , Immunoglobulin G/isolation & purification , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Male , Pregnancy , Pregnancy Complications, Infectious/blood , Prospective Studies , SARS-CoV-2 , Saliva/immunology , Spike Glycoprotein, Coronavirus/immunology
18.
Int J Mol Sci ; 22(21)2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1488617

ABSTRACT

Since the COVID-19 outbreak was acknowledged by the WHO on 30 January 2020, much research has been conducted to unveil various features of the responsible SARS-CoV-2 virus. Different rates of contagion in adults, children, and pregnant women may guide us to understand the underlying infection conditions of COVID-19. In this study, we first provide a review of recent reports of COVID-19 clinical outcomes in children and pregnant women. We then suggest a mechanism that explains the curious case of COVID-19 in children/pregnant women. The unique stem cell molecular signature, as well as the very low expression of angiotensin-converting enzyme 2 and the lower ACE/ACE2 ratio in stem cells of children/pregnant women compared to adults might be the cause of milder symptoms of COVID-19 in them. This study provides the main molecular keys on how stem cells can function properly and exert their immunomodulatory and regenerative effects in COVID-19-infected children/pregnant women, while failing to replicate their role in adults. This can lay the groundwork for both predicting the pattern of spread and severity of the symptoms in a population and designing novel stem cell-based treatment and prevention strategies for COVID-19.


Subject(s)
COVID-19/diagnosis , Pregnancy Complications, Infectious/diagnosis , SARS-CoV-2/immunology , Stem Cells/physiology , Adult , Age of Onset , COVID-19/epidemiology , COVID-19/immunology , COVID-19/pathology , Child , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Prognosis , Severity of Illness Index
19.
Acta Obstet Gynecol Scand ; 100(12): 2268-2277, 2021 12.
Article in English | MEDLINE | ID: covidwho-1488173

ABSTRACT

INTRODUCTION: Evidence about the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is rapidly increasing; however, data on antibody response and risk of transmission during pregnancy and delivery are still limited. The aim of this study was to evaluate if SARS-CoV-2 is detectable in vaginal swabs and whether antibodies against SARS-CoV-2 are present in maternal and umbilical cord blood of pregnant women with confirmed SARS-CoV-2. MATERIAL AND METHODS: A single-unit prospective cohort study in Denmark including pregnant women with SARS-CoV-2 infection confirmed by a pharyngeal swab between August 20, 2020, and March 1, 2021, who gave birth during the same period. All patients admitted to the maternity ward and antepartum clinic were screened for SARS-CoV-2 infection. A maternal blood sample and vaginal swabs were collected at inclusion. If included antepartum, these samples were repeated intrapartum when an umbilical cord blood sample was also collected. Swabs were analyzed for SARS-CoV-2 and blood samples were analyzed for SARS-CoV-2 total antibodies. Placental and neonatal swabs as well as placental histopathological examinations were performed on clinical indications. RESULTS: We included 28 women, of whom four had serious maternal or fetal outcomes including one case of neonatal death. Within the first 8 days after confirmed SARS-CoV-2 infection, SARS-CoV-2 was detectable in two vaginal swabs (2/28) and SARS-CoV-2 antibodies were detected in 1 of 13 women. From 16 days after confirmed infection, antibodies were observed in 19 of 21 of women. Antibodies in cord blood were not detected during the first 16 days after confirmed infection (n = 7). However, from 26 days, antibodies were present in 16 of 17 cord blood samples of seropositive mothers. Placental examination in two cases of severe fetal outcomes preceded by reduced fetal movements revealed SARS-CoV-2 in swabs and severe histopathological abnormalities. CONCLUSIONS: SARS-CoV-2 was detected in only 2 of 28 vaginal swabs within 8 days after confirmed infection in pregnant women. Our data suggest that maternal seroconversion occurs between days 8 and 16, whereas antibodies in cord blood of seropositive mothers were present in the majority from 26 days after confirmed infection. Additional data are needed regarding timing of seroconversion for the mother and appearance of antibodies in cord blood.


Subject(s)
Antibodies, Viral , COVID-19/immunology , Fetal Blood/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Antibodies , Cohort Studies , Denmark , Female , Humans , Pregnancy , Prospective Studies , Vaginal Smears
20.
Arch Pathol Lab Med ; 145(11): 1328-1340, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1485410

ABSTRACT

CONTEXT.­: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. OBJECTIVE.­: To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. DESIGN.­: Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. RESULTS.­: Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. CONCLUSIONS.­: SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.


Subject(s)
COVID-19/transmission , COVID-19/virology , Infectious Disease Transmission, Vertical , Macrophages/virology , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Adult , COVID-19/immunology , COVID-19/pathology , Cell Proliferation , Endothelium/pathology , Endothelium/virology , Female , Humans , Hyperplasia/pathology , Hyperplasia/virology , Infant, Newborn , Macrophages/pathology , Macrophages/physiology , Male , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Retrospective Studies , SARS-CoV-2/immunology , Stillbirth , Trophoblasts/pathology , Trophoblasts/virology
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