INTRODUCTION — Pregnant people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be asymptomatic or symptomatic. Those who are symptomatic appear to be at increased risk for developing severe sequelae of coronavirus disease 2019 (COVID-19) compared with nonpregnant reproductive-aged females. They also may be at increased risk for developing some pregnancy complications (eg, preterm birth) compared with uninfected or asymptomatic pregnant people. In utero transmission is rare, rates of miscarriage and congenital anomalies do not appear to be increased in pregnancies affected by COVID-19, and neonatal outcome is generally good.
Vaccination reduces the risk of developing COVID-19 and reduces the severity of disease if a breakthrough infection occurs. All available evidence supports the safety of administering currently available SARS-CoV-2 vaccines before, during, and after pregnancy.
Most issues related to COVID-19 are the same for pregnant and nonpregnant people, but there are a few exceptions. This topic will provide an overview of these issues, provide links to UpToDate content that is relevant to both pregnant and nonpregnant people, and discuss aspects of the disease that are specific to pregnancy. Antepartum management of pregnant patients with COVID-19 and management of labor and birth during the pandemic are reviewed separately. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection" and "COVID-19: Intrapartum and postpartum issues".)
Information about the virus and COVID-19 continues to accrue, and interim guidance by multiple organizations is constantly being updated and expanded. Links to society and government-sponsored guidelines from selected countries and regions around the world are also provided separately. (See 'Society guideline links' below.)
VIROLOGY AND VARIANTS OF CONCERN — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus that causes COVID-19. The host receptor for cell entry is the angiotensin-converting enzyme 2 (ACE2) receptor, which is found mostly in alveolar epithelial and stromal cells.
Variants of the SARS-CoV-2 have evolved over time. "Variants of concern" are those with clinical and/or public health implications and are described in the table (table 1). (See "COVID-19: Epidemiology, virology, and prevention", section on 'Virology'.)
DEMOGRAPHICS — Racial and ethnic minority groups comprise a disproportionately high number of infections and deaths due to COVID-19 in the United States and United Kingdom, likely related to underlying disparities in the social determinants of health.
REPRODUCTIVE DECISION-MAKING DURING THE PANDEMIC — The COVID-19 pandemic has prompted questions about whether couples should consider postponing pregnancy because of potential virus-related risks to maternal and newborn health. Given the information in the following sections of this topic, we believe that reproductive decisions (eg, pregnancy planning, pregnancy termination) should not be based primarily on health-related COVID-19 concerns. As others have pointed out, increasing evidence suggests that absolute pregnancy-related risks of SARS-CoV-2 infection are not high or substantially above the risk associated with other conditions or exposures that are fairly common among pregnant people, and pregnancy-related risks can be reasonably minimized or mitigated by standard preventive measures, including vaccination .
TRANSMISSION — Routes of transmission (direct person-to-person transmission is the primary means of SARS-CoV-2 transmission), period of infectiousness, immune responses, and risk for reinfection are the same for pregnant and nonpregnant individuals. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Transmission'.)
Vertical transmission is an additional concern in pregnant and recently pregnant people and is discussed below. (See 'Risk of vertical transmission' below.)
PREVENTION OF INFECTION
●Vaccination – Vaccine types (table 2); dosing and administration; safety, efficacy, side effects, and patient counseling; and contraindications and precautions in the general population are reviewed separately. (See "COVID-19: Vaccines".)
Vaccine administration, safety, and benefits in pregnancy are discussed below. (See 'Vaccination in people planning pregnancy and pregnant or recently pregnant people' below.)
●Personal preventive measures (eg, masks, distancing, frequent hand washing with soap and water or use of hand sanitizer with at least 60 percent alcohol). Sexual transmission has not been reported. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'.)
●Measures for pregnant people with children. (See "COVID-19: Management in children", section on 'Prevention of transmission' and "COVID-19: Clinical manifestations and diagnosis in children", section on 'Do children transmit SARS-CoV-2 to others?'.)
●Occupational health measures, including for pregnant health care workers. (See "COVID-19: Occupational health issues for health care personnel".)
●Infection control measures in the healthcare setting, including strategies for screening and preventing transmission in different patient groups. (See "COVID-19: General approach to infection prevention in the health care setting".)
Infection control measures on the labor and delivery unit are reviewed separately. (See "COVID-19: Intrapartum and postpartum issues".)
●Pre-exposure prophylaxis, specifically with the monoclonal antibody combination tixagevimab-cilgavimab, is an option for individuals (including pregnant people) with a moderate to severe immunocompromising condition that may result in a suboptimal immune response to vaccination (table 3) or who cannot receive a recommended series of a COVID-19 vaccine because of a severe adverse reaction to the vaccines or their components. However, the drug is in short supply. Selection of candidates for pre-exposure prophylaxis, drug choice and administration, and efficacy are reviewed separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Pre-exposure prophylaxis'.)
Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier. Nonclinical reproductive toxicity studies for tixagevimab and cilgavimab have not been conducted, although a tissue cross-reactivity study assessing off-target binding to human fetal tissues found no binding of clinical concern . Potential concerns regarding fetal exposure to monoclonal antibodies are discussed separately. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Antiviral drugs and other COVID-19-specific therapies'.)
●Post-exposure management and prophylaxis — Postexposure management may include testing, self-monitoring for symptoms, self-quarantine or isolation, and drug prophylaxis. Criteria for close contact and potential exposure, quarantine versus isolation, duration of precautions, candidates for prophylaxis, and drug administration (casiriviman-imdevimab or bamlanivimab) are reviewed in detail separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Post-exposure management'.)
Pregnant people are potential candidates for prophylaxis if they have had close contact with an individual with COVID-19 or are at high risk of exposure to individuals with infection in an institutional setting and they are expected to have an inadequate immune response to COVID-19 vaccination (eg, patients who have immunocompromising conditions or are taking immunosuppressive agents), or they have not been fully vaccinated (ie, have not received a complete primary vaccine series at least two weeks before exposure). However, the drug is in short supply. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Post-exposure prophylaxis for selected individuals'.)
The fetal safety of anti-SARS-CoV-2 monoclonal antibodies is discussed separately. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Antiviral drugs and other COVID-19-specific therapies'.)
Vaccination in people planning pregnancy and pregnant or recently pregnant people
Candidates — We recommend that all unvaccinated people planning pregnancy or those who are pregnant or recently pregnant undergo COVID-19 vaccination, and those who are vaccinated should receive booster doses, when eligible, in agreement with major medical organizations and public health authorities. This recommendation is based on data showing vaccine safety and efficacy in pregnant people and data that pregnancy itself is associated with an increased risk of severe infection (Centers for Disease Control and Prevention [CDC] tier 1c vaccine allocation). (See 'Safety and efficacy' below.)
Safety and efficacy — None of the vaccines in the following table (table 2) contain virus that replicates; thus, they do not cause disease, but nonspecific side effects from activation of the immune system may occur. Rare serious side effects (thrombosis with thrombocytopenia syndrome, myocarditis and pericarditis, Guillain-Barré syndrome) can also occur. (See "COVID-19: Vaccines", section on 'Patient counseling' and "COVID-19: Vaccines", section on 'Specific safety concerns' and "COVID-19: Vaccines", section on 'General efficacy issues'.)
Although pregnant and breastfeeding people were not included in the initial large vaccine trials, subsequent data from vaccinated pregnant people demonstrated safety and efficacy before pregnancy, during pregnancy, postpartum, and during lactation:
●Safety – No evidence of direct or indirect harmful effects on fertility, embryo/fetal development, pregnancy outcome, parturition, or postnatal development of offspring [3-16].
•Reduction in maternal SARS-CoV-2 infection.
•Reduction in maternal COVID-19 of any severity (including severe and critical disease).
•Reduction of perinatal death.
•Reduction of COVID-19 hospitalization among infants up to six months of age. Maternal antibodies cross the placenta and are transferred into breast milk, conferring passive immunity against SARS-CoV-2 in newborns. Protective antibodies have been documented in cord blood 15 days after the first maternal mRNA vaccination and appear to persist and protect the infant for at least six months.
The following large studies are examples of safety and efficacy data:
●Over 187,000 participants in the CDC's V-safe After Vaccination Health Checker have indicated that they were pregnant at the time of vaccination. The V-safe COVID-19 Vaccine Pregnancy Registry has data on 827 completed pregnancies (mostly among people vaccinated in the third trimester), with no obvious safety signals with respect to miscarriage, congenital anomalies, fetal growth, preterm birth, stillbirth, or neonatal death .
●The CDC's Vaccine Adverse Event Reporting System (VAERS) has data on 154 pregnancies. No excess in side effects or adverse events were observed in these early data compared with the CDC national birth data. The CDC's Vaccine Safety Datalink (VSD) and the Clinical Immunization Safety Assessment (CISA) have collected data from over 40,000 pregnancies . Most of these data were for Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273, but early data from developmental and reproductive toxicity (DART) studies of the Janssen Ad26.COV2.S or JNJ-78436735 have also not demonstrated adverse outcomes.
●In addition, among 2456 pregnant persons who received an mRNA COVID-19 vaccine preconception or prior to 20 weeks of gestation, the age-standardized cumulative risk of miscarriage was 12.8 percent, which is similar to the expected rate in the general obstetric population . In another study including over 92,000 ongoing pregnancies and 13,000 miscarriages, patients who experienced miscarriage had similar odds of exposure to a COVID-19 vaccine (BNT162b2, mRNA-1273, or Ad26.COV.2.S) in the prior 28 days as those with ongoing pregnancies (adjusted odds ratio [aOR] 1.02, 95% CI 0.96-1.08); 8 to 9 percent of these patients were exposed to a COVID-19 vaccine during this period . Results were consistent for mRNA-1273 and BNT162b2 exposure, but it was not possible to assess risks specific to Ad26.COV.2.S exposure because of the small number of patients in this group.
Similar safety data have been reported for the ChAdOx1 nCoV-19 (AZD1222) vaccine, which has been administered outside of the United States .
●At least one study has reported worse pregnancy outcomes in unvaccinated infected patients. In a study of pregnant patients with COVID-19 in Scotland, 77.4 percent of COVID-19 associated hospital admissions (ie, date of onset of infection occurred during a hospital admission or within 14 days before admission), 98 percent of COVID-19 associated critical care admissions (date of onset of infection occurred during a critical care admission or within 21 days before admission), and 100 percent of perinatal deaths (stillbirths and neonatal deaths) occurred in pregnant patients who were unvaccinated at the time of COVID-19 diagnosis . Among vaccinated patients with COVID-19, the perinatal death rate was similar to background rates and rates among pregnancies without confirmed infection. The authors did not have access to clinical records to determine whether COVID-19 directly or indirectly contributed these outcomes.
●According to data from 20 pediatric hospitals in the United States during a period of Delta and Omicron variant circulation, maternal completion of both doses of a primary mRNA COVID-19 vaccination series during pregnancy was associated with reduced risk for COVID-19 hospitalization among infants <6 months of age (vaccine efficacy 61 percent) . Protection was higher among infants whose mothers were vaccinated later in pregnancy.
Among infants with COVID-19 who were admitted to the ICU, 88 percent were born to mothers who were not vaccinated before or during pregnancy and the only infant who died was born to a mother who was not vaccinated.
Choice of vaccine — If both a mRNA and a vector-based COVID-19 vaccine are available (table 2), a mRNA vaccine is preferred. If a mRNA vaccine is not available or convenient for administration or a contraindication to this vaccine exists, patients are advised to select a vector-based vaccine rather than avoid/defer vaccination. This recommendation is based on reports of rare cases of thrombosis associated with thrombocytopenia following vaccination with vector-based vaccines, with females appearing to be at higher risk than males. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)".).
Some inactivated COVID-19 vaccines contain an adjuvant. Two adjuvants have been widely used in vaccines administered in pregnancy (eg, insoluble aluminum salts in Tdap, AS03-adjuvanted influenza vaccines) and have a documented good safety profile . Vaccines with novel adjuvants are generally avoided in pregnancy because of a lack of safety data, but this theoretic concern should be balanced with the risk of an ongoing pandemic and the known risks of severe COVID-19, including death, during pregnancy.
Timing — We advise that unvaccinated people planning pregnancy and pregnant or recently pregnant people become fully vaccinated as soon as possible, regardless of gestational age or breastfeeding status. Booster injections are advised when the individual is eligible; timing depends on the particular vaccine administered for primary immunization. The booster vaccine can be different from the vaccine administered for primary vaccination. Issues related to booster vaccines are the same for pregnant and nonpregnant people. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'.)
The following issues relate specifically to people planning pregnancy and pregnant or recently pregnant people:
●Early versus late pregnancy – Primary vaccine administration earlier rather than later in gestation provides the most maternal benefit as it reduces the maternal risk of hospitalization because of COVID-19, death from COVID-19, and COVID-19 related pregnancy complications during more weeks of the pregnancy. Although fetal and newborn antibody levels appear to be higher with primary vaccination later in pregnancy , this potential benefit does not outweigh the overall pregnancy (maternal, fetal, newborn) benefits of vaccination as soon as possible or account for the effects of booster doses when eligible .
●Periconception – Currently available vaccines for prevention of COVID-19 do not affect fertility or success of infertility treatment [24-26], pregnancy testing is not a requirement prior to receiving any approved COVID-19 vaccine, and it is not necessary to delay pregnancy after vaccination . (See "In vitro fertilization: Overview of clinical issues and questions", section on 'No proven effect'.)
If an individual becomes pregnant after receiving the first dose of a two-dose COVID-19 vaccine series, the second dose should be administered at the same time specified by the manufacturer for nonpregnant persons.
●Administration of non-COVID-19 vaccines and anti-D immunoglobulin – COVID-19 vaccines may be administered at the same time as other vaccines routinely administered in pregnancy (eg, influenza, Tdap); a separation period between vaccinations is unnecessary .
Anti-D immunoglobin does not interfere with the immune response to vaccines, so timing of administration for prevention of alloimmunization is based on standard clinical protocols. (See "COVID-19: Vaccines", section on 'Administration'.)
●Breastfeeding – Breastfeeding should not influence timing of vaccination [29,30]. Maternal SARS-CoV-2 antibodies induced by vaccination can pass into breast milk and may offer passive protection to the infant [31,32]. Although breastfeeding people were not included in the initial large vaccine trials, available vaccines are unlikely to pose a risk to the breastfeeding child as they do not contain infectious virus and the minimal amount of vaccine that crosses into breast milk [33,34] and ingested by the infant is likely to be inactivated by the infant's digestive system.
CLINICAL MANIFESTATIONS AND COURSE OF INFECTION
Overview — General issues regarding the incubation period, clinical presentation and course, spectrum of clinical findings (table 4), risk factors for severe illness (table 5), and laboratory and imaging findings are primarily discussed in the following topic (see "COVID-19: Clinical features"), and briefly below. (See 'Maternal clinical findings of COVID-19' below.)
The course of infection appears to be more severe in pregnant people. Infection, particularly when symptomatic, is associated with an increased risk for some pregnancy complications. (See 'Maternal course' below and 'Pregnancy and newborn outcomes' below.)
Maternal clinical findings of COVID-19 — Asymptomatic cases are common, but the proportion of these cases is not well defined. In a systematic review, 7 percent of pregnant people universally screened for COVID-19 tested positive, 73 percent of these individuals were asymptomatic, and pregnant people were more likely to be asymptomatic than nonpregnant people of reproductive age with COVID-19 . In another systematic review, 95 percent of COVID-19 infections in pregnant people were asymptomatic, and 59 percent (95% CI 49-68 percent) remained asymptomatic through follow-up .
Symptoms and signs of COVID-19 during pregnancy appear to be similar to those in nonpregnant individuals (table 4) [37,38] (see "COVID-19: Clinical features"). Some of the clinical manifestations of COVID-19 overlap with symptoms of normal pregnancy (eg, fatigue, shortness of breath, nasal congestion, nausea/vomiting), which should be considered during evaluation of afebrile symptomatic pregnant people. (See 'Other disorders to consider' below.)
Laboratory and imaging findings are generally similar to those in nonpregnant people. However, some laboratory findings of COVID-19 also overlap with those caused by pregnancy-related disorders (eg, thrombocytopenia and elevated liver chemistries in preeclampsia with severe features). (See "COVID-19: Clinical features", section on 'Laboratory findings' and "COVID-19: Clinical features", section on 'Imaging findings'.)
Other disorders to consider
●Other infections – Early symptoms of COVID-19 can be similar to those of multiple other viral and bacterial respiratory infections (eg, influenza, respiratory syncytial virus, adenovirus, Haemophilus influenzae pneumonia, Mycoplasma pneumoniae pneumonia). In a systematic review including over 64,000 pregnant and recently pregnant people with suspected or confirmed COVID-19, 28 percent of symptomatic people tested positive for SARS-CoV-2; thus, most had other etiologies for their symptoms .
If influenza is prevalent in the community, it is reasonable to also test for influenza when testing for SARS-CoV-2 as this could have management implications. Detection of another pathogen does not necessarily rule out SARS-CoV-2 in locations where there is widespread transmission as coinfection with SARS-CoV-2 and other respiratory viruses, including influenza, has been described. Coinfection with tuberculosis has also been reported and should be considered in patients with impaired immunity or at increased risk for exposure to Mycobacterium tuberculosis.
●Preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome – In pregnant people, some COVID-19-related laboratory abnormalities (elevated liver enzyme levels, thrombocytopenia) are identical to those that occur in preeclampsia with severe features and HELLP syndrome. Autoimmune hemolysis; prolonged prothrombin time; elevated D-dimer, procalcitonin, and C-reactive protein (CRP) levels; positive lupus anticoagulant screen; and low fibrinogen levels may also be observed in complicated COVID-19 cases (note the normal reference ranges for D-dimer, CRP, and fibrinogen levels are higher in pregnant people) [35,39]. Symptoms also overlap: Headache, acute cerebrovascular disease, and seizures can be neurologic manifestations of COVID-19, as well as findings in preeclampsia with severe features/eclampsia.
The diagnosis of preeclampsia with severe features or HELLP syndrome should be considered in the differential diagnosis of persons under investigation for COVID-19, as well as in patients with confirmed COVID-19 as these pregnancy-related disorders may coexist with the infection [40-42]. The presence of acute hypertension can be helpful as it is a common finding in patients with preeclampsia or HELLP syndrome and not a feature of COVID-19 (chronic hypertension is a risk factor for severe illness) (see "Hypertensive disorders in pregnancy: Approach to differential diagnosis"). In patients with SARS-CoV-2 pneumonia plus clinical findings that have been associated with both severe COVID-19 and preeclampsia, we suggest maternal-fetal medicine consultation. (See "COVID-19: Neurologic complications and management of neurologic conditions" and "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension".)
Although acute kidney injury can occur as a severe complication of COVID-19 and can also be a severe complication of obstetric disorders, such as preeclampsia with severe features, abruptio placentae, or hemorrhagic shock, uterine bleeding is a prominent feature of the last two disorders but not for COVID-19 or preeclampsia.
Maternal course — The body of evidence suggests that pregnancy does not increase susceptibility to SARS-CoV-2 infection but appears to worsen the clinical course of COVID-19 (increased risks for intensive care unit [ICU] admission, need for mechanical ventilation and ventilatory support, death) compared with nonpregnant females of the same age [35,37,43-48]. However, at least one study has reported a higher rate of SARS-CoV-2 infection in pregnant people compared with similarly aged adults  and three did not find an increased risk of severe COVID-19 or mortality in pregnancy compared with nonpregnant female patients of reproductive age [50-52]. Limitations of available data include difficulties in distinguishing behavioral from biological determinants of infection susceptibility and differences in infection assessment.
Although most (>90 percent) infected pregnant people recover without undergoing hospitalization, rapid clinical deterioration can occur, and symptomatic pregnant people appear to be at increased risk of severe disease and death compared with symptomatic nonpregnant females of reproductive age [35,37,44,53-57]. Risk factors for severe disease and death in pregnancy include older age (especially ≥35 years), obesity, preexisting medical comorbidities (particularly hypertension and diabetes or more than one comorbidity), and being unvaccinated [57-59]. For example, among the 15 maternal deaths from COVID-19 in Mississippi (nine deaths per 1000 SARS-CoV-2 infections in pregnant patients versus 2.5 deaths per 1000 SARS-CoV-2 infections in nonpregnant females of reproductive age), 14 of the 15 patients had comorbidities and zero of the 15 patients was fully vaccinated . (See "COVID-19: Clinical features", section on 'Acute course and complications'.)
The following examples show the spectrum of the clinical course of COVID-19 in pregnant people in three large datasets:
●In a systematic review of 192 studies including over 64,000 pregnant and recently pregnant people with suspected or confirmed COVID-19 :
•17.4 percent had pneumonia.
•17.1 percent received oxygen by cannula.
•13.4 percent had acute respiratory distress syndrome (ARDS).
•11.3 percent had severe disease.
•3.3 percent were admitted to an ICU, and the risk was higher in pregnant people compared with nonpregnant females of reproductive age with COVID-19 (odds ratio [OR] 2.13) and pregnant people without COVID-19 (OR 19).
•1.6 percent received invasive ventilation.
•0.11 percent received extracorporeal membrane oxygenation (ECMO).
•0.8 percent died.
However, these findings have many limitations. For example, the primary studies included people with both suspected and confirmed infection; largely consisted of pregnant people who required visits to the hospital, such as for childbirth, thus affecting the generalizability of the estimates; often did not indicate timing of assessment of the clinical manifestations of disease; used different definitions of symptoms, tests, and outcomes; generally did not provide adequate information to distinguish iatrogenic effects from the true impact of the disease; and the findings for some outcomes were based on one or two studies.
●In a report from the Centers for Disease Control and Prevention (CDC) COVID-19 Response Pregnancy and Infant Linked Outcomes Team that included over 23,000 pregnant people and over 386,000 nonpregnant females of reproductive age with symptomatic laboratory-confirmed SARS-CoV-2 infection, pregnant people had a higher risk of :
•ICU admission (10.5 versus 3.9 per 1000 cases, adjusted risk ratio [aRR] 3.0, 95% CI 2.6-3.4)
•Receiving invasive ventilation (2.9 versus 1.1 per 1000 cases, aRR 2.9, 95% CI 2.2-3.8)
•Receiving ECMO (0.7 versus 0.3 per 1000 cases, aRR 2.4, 95% CI 1.5-4.0)
•Death (1.5 versus 1.2 per 1000 cases, aRR 1.7, 95% CI 1.2-2.4)
Pregnant people with comorbidities and older pregnant persons appeared to be at particularly elevated risk of adverse maternal outcome. Some limitations of the study included ascertainment biases; lack of information on pregnancy status in over one-half of reported cases; and lack of information for the reason for hospital admission in many cases, limiting the ability to distinguish between admissions solely for labor and delivery and those for COVID-19-related illness.
●A prospective cohort study that compared 5183 pregnant with 175,905 nonpregnant people with COVID-19 reported the following crude morbidity rates and propensity score-matched risks :
•Death (1.5 versus 1.5 percent; OR 1.84, 95% CI 1.26-2.69)
•Pneumonia (9.9 versus 6.5 percent; OR 1.86, 95% CI 1.60-2.16)
•ICU admission (13 versus 6.9 percent; OR 1.86, 95% CI 1.41-2.45)
Potential complications of COVID-19 in adults — Complications of COVID-19 include, but are not limited to, the following:
●Respiratory disorders – Pneumonia, respiratory failure, ARDS (see "COVID-19: Management in hospitalized adults", section on 'Management of hypoxemia, ARDS, and other complications')
●Cardiac disorders (arrhythmias, acute cardiac injury) (see "COVID-19: Cardiac manifestations in adults")
●Thromboembolic complications (see "COVID-19: Hypercoagulability")
●Secondary infections (see "COVID-19: Clinical features", section on 'Acute course and complications')
●Neurologic disorders – Headache, dizziness, myalgia, alteration of consciousness, disorders of smell and taste, weakness, strokes, seizures (see "COVID-19: Neurologic complications and management of neurologic conditions")
●Cutaneous disorders – Morbilliform rash; urticaria; pernio-like, acral lesions; livedo-like, vascular lesions; and vesicular, varicella-like eruption (see "COVID-19: Cutaneous manifestations and issues related to dermatologic care")
●Gastrointestinal and liver disorders (see "COVID-19: Issues related to gastrointestinal disease in adults" and "COVID-19: Issues related to liver disease in adults")
●Psychiatric illness (eg, anxiety disorders, depressive disorders, insomnia disorder, posttraumatic stress disorder) (see "COVID-19: Psychiatric illness")
It is known that some patients with severe COVID-19 have laboratory evidence of an exaggerated inflammatory response (similar to cytokine release syndrome), which has been associated with critical and fatal illnesses. Whether the normal immunologic changes of pregnancy affect the occurrence and course of this response is unknown. (See "COVID-19: Clinical features", section on 'Acute course and complications'.)
DIAGNOSIS — Diagnostic tests for COVID-19 (table 6) and making a diagnosis are the same, regardless of pregnancy status (algorithm 1). The diagnostic approach, including whom to test, choice of test and specimen collection, factors affecting test performance, test interpretation, follow-up/repeat testing, and use of serology to identify prior/late infection are discussed separately. (See "COVID-19: Diagnosis".)
Classification of disease severity — In the United States, the National Institutes of Health (NIH) have categorized degrees of disease severity in nonpregnant persons as follows :
●Asymptomatic or presymptomatic infection – Positive test for SARS-CoV-2 but no symptoms.
●Mild illness – Any signs and symptoms (eg, fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnea, or abnormal chest imaging.
●Moderate illness – Evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SaO2) ≥94 percent on room air at sea level.
●Severe illness – Respiratory frequency >30 breaths per minute, SaO2 <94 percent on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300, or lung infiltrates >50 percent.
●Critical illness – Respiratory failure, septic shock, and/or multiple organ dysfunction.
Disease severity has also been categorized (Wu classification) as :
●Mild – No or mild symptoms (fever, fatigue, cough, and/or less common features of COVID-19).
●Severe – Tachypnea (respiratory rate >30 breaths per minute), hypoxia (oxygen saturation ≤93 percent on room air or PaO2/FiO2 <300 mmHg), or >50 percent lung involvement on imaging).
●Critical (eg, with respiratory failure, shock, or multiorgan dysfunction).
Other definitions of severity exist (eg, severe = maternal peripheral oxygen saturation [SpO2] ≤94 percent on room air, requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]) and are discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Defining disease severity'.)
PREGNANCY AND NEWBORN OUTCOMES — Pregnancy outcome data are derived from systematic reviews and large series of cases published before the surge of the Omicron variant in late 2021. Omicron has been associated with less risk for severe disease in nonpregnant people, but robust data on its effect on pregnancy outcomes are not yet available. Preliminary data suggest that infection with the Delta-variant during pregnancy may be associated with a higher risk of placental dysfunction and fetal compromise than previous variants .
Risk of vertical transmission — The extent of vertical transmission (in utero, intrapartum, early postnatal period) remains unclear. Although the overall rate of congenital infection has been reported to be approximately 2 percent of maternal infections [64-67], only a few well-documented cases of probable in utero transmission have been published [68-70]. Many reports of congenital infection in the setting of maternal infection in the third trimester may be related to transmission in the delivery room or from caregivers.
In utero transmission typically occurs via a hematogenous route but sometimes via the ascending route. Viremia rates in patients with COVID-19 appear to be low (1 percent in one study  but higher in severe disease  and possibly with the Delta variant ) and transient, suggesting placental seeding and in utero transmission would not be common . Most placentas studied so far had no evidence of infection, but the virus has been identified in a few cases [68,69,74-76]. At least four patients with a positive vaginal swab and one patient with a positive vaginal swab and amniotic fluid have been reported, suggesting the ascending route of infection and intrapartum transmission from contact with vaginal secretions are rare [68,69,77]. On the other hand, viral shedding in maternal feces is common, so fecal contamination of the perineum could theoretically be a source of intrapartum transmission, although there is no evidence of protective effect of cesarean. Postnatal transmission could occur from ingestion of breast milk or, more likely, from an infected mother (or other caregiver) to the infant through respiratory or other infectious secretions. (See "COVID-19: Intrapartum and postpartum issues", section on 'Breastfeeding and formula feeding'.)
SARS-CoV-2 cell entry is thought to depend on the angiotensin-converting enzyme 2 receptor and serine protease TMPRSS2, which are minimally coexpressed in the placenta [78,79]. This may account for the infrequent occurrence of placental SARS-CoV-2 infection and fetal transmission. However, SARS-CoV-2 (or maternal) IgM could reach the fetus as a result of ischemic injury to the placenta that compromises the syncytiotrophoblast barrier, without requiring placental cell infection .
●Criteria for diagnosis of congenital infection — In a mother with SARS-CoV-2 infection, we would make a definitive diagnosis of congenital infection in a live born neonate if SARS-CoV-2 is detected by polymerase chain reaction in umbilical cord blood or neonatal blood collected within the first 12 hours of birth or amniotic fluid collected prior to rupture of membranes, in agreement with criteria proposed by Shah et al for confirmed, probable, and possible congenital infection . Others have also published reasonable criteria [72,81].
One barrier to diagnosis of maternal-fetal transmission is that there are no accepted criteria for definitive evidence of congenital infection. Criteria for vertical transmission should distinguish between intrauterine (congenital) versus postnatal transmission of SARS-CoV-2.
Risk of miscarriage — The body of evidence suggests that the frequency of miscarriage is not increased above baseline [67,82-88].
Risk of congenital anomalies — The body of evidence suggests that the frequency of congenital anomalies is not increased above baseline .
Risk of preterm or cesarean birth — Preterm and cesarean birth rates have been increased in many studies but not all [35,54,89-91], likely because initial data were not derived from nationally representative samples, lacked appropriate comparison groups, and were subject to bias . In cohort studies, the increased risk appears to be limited to patients with severe or critical disease [44,47,93], and underlying comorbidities also likely play a role. Fever and hypoxemia may increase the risks for preterm labor, prelabor rupture of membranes, and abnormal fetal heart rate patterns, but preterm births also occur in patients without severe respiratory disease. Increases in preterm births could also be related to higher stress during the pandemic and changes in maternity services . A limitation of many studies is that they do not distinguish between spontaneous and iatrogenic preterm birth. It appears that many third-trimester cases are delivered by planned cesarean because of a bias to intervene catalyzed by the belief that management of severe maternal respiratory disease would be improved by delivery; however, this hypothesis is unproven.
●In three large cohort studies of pregnant patients with COVID-19 in the United States, the overall preterm delivery rates were 7.2 percent (compared with 5.8 percent in patients without COVID-19) , 12.9 percent (compared with a national rate of 10.1 percent ) , and 14.8 percent (compared with 10.2 percent in patients without COVID-19) . The overall rates of cesarean birth were generally similar or modestly higher than the rates in patients without COVID-19 and the overall cesarean rate in the United States (31.8 percent ).
●As of August 2021, the CDC's COVID Data Tracker indicated that among pregnant people in the United States with COVID-19, the preterm birth rate was 11.6 percent (2697 of 23,265) among births with known gestational age and the cesarean birth rate was 33.1 percent (8077 of 24,373) . As noted above, these rates for the overall US population were 10.1 and 31.8, percent, respectively .
Risk of preeclampsia — A meta-analysis of observational studies of SARS-CoV-2 infection during pregnancy found a 62 percent higher odds of developing preeclampsia among patients with COVID-19 (7 versus 4.8 percent; pooled unadjusted odds ratio [OR] 1.62, 95% CI 1.45-1.82, 26 studies, >786,000 patients), which remained elevated after limiting the analysis to the 11 studies with adjustment for confounders and the six studies with a low risk of bias . Preeclampsia; preeclampsia with severe features; eclampsia; and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome were all increased. In contrast to preterm birth, both asymptomatic and symptomatic patients experienced an increased risk, with a higher risk among symptomatic patients (OR 2.11 versus OR 1.59).
In addition to the usual limitations of observational studies, another limitation of these data is that some COVID-19-related laboratory abnormalities (elevated liver enzyme levels, thrombocytopenia) are identical to those that occur in preeclampsia with severe features and HELLP syndrome. (See 'Other disorders to consider' above.)
Risk of stillbirth — Emerging data suggest an association between COVID-19 in pregnancy and stillbirth; however, initial studies were unable to adjust for potential confounders [35,89].
In an analysis of over 1.2 million delivery hospitalizations with over 8000 stillbirths in the United States (March 2020 through September 2021), pregnant patients with COVID-19 were at increased risk for stillbirth compared with pregnant patients without COVID-19 (1.26 versus 0.64 percent of deliveries; adjusted relative risk [aRR] 1.90, 95% CI 1.69–2.15) . The highest risk for stillbirth was during the Delta variant period, July through September 2021 (2.7 versus 0.63 percent; aRR 4.04, 95% CI 3.28–4.97) and in patients with COVID-19 plus comorbidities (eg, chronic hypertension, multiple gestation, adverse cardiac event, abruption, sepsis, shock, acute respiratory distress syndrome (ARDS), mechanical ventilation). Of note, the stillbirth rate among patients without COVID-19 was similar to that in the prepandemic rate (0.59 percent). Despite the study's limitations (eg, gestational age at SARS-CoV-2 infection, vaccination status, and maternal symptom status were not available; criteria for SARS-CoV-2 testing varied across hospitals), these findings provide further support for vaccination.
In some other countries, such as India, a rise in stillbirths has been attributed to disruptions to maternal care and maternal supportive services (eg, food and micronutrient supplements) during the pandemic .
Overall risk of serious maternal morbidity and mortality — A study that evaluated the association of SARS-CoV-2 infection with serious maternal morbidity or mortality (SMM) from common obstetric complications reported an increased risk . The study included over 14,000 patients in the United States of whom 2352 had and 11,752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was associated with:
●Increase in the primary outcome of composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2 (13.4 versus 9.2 percent; aRR 1.41, 95% CI 1.23-1.61). All five maternal deaths were in the SARS-CoV-2 group.
●A trend towards an increase in cesarean birth (34.7 versus 32.4 percent; aRR 1.05, 95% CI 0.99-1.11).
In particular, moderate or higher COVID-19 severity (586 patients) was significantly associated with the primary outcome (26.1 versus 9.2 percent; aRR, 2.06, 95% CI 1.73-2.46) and cesarean birth (45.4 versus 32.4 percent; aRR 1.17, 95% CI 1.07-1.28), whereas mild or asymptomatic infection (1766 patients) was not.
Newborn outcome — Over 95 percent of newborns of SARS-CoV-2-positive mothers are uninfected and in good condition at birth. Some newborns of infected mothers have developed symptoms of mild infection (ie, not requiring respiratory support), and most of these cases have been attributed to transmission from respiratory droplets postnatally when the neonates were exposed to mothers or other caregivers with COVID-19.
Neonatal morbidity (eg, need for mechanical ventilation) has largely been related to preterm birth and to adverse uterine environments resulting from critical maternal COVID-19 [35,102-106]. In a study that included maternal and infant data for 92 percent of births in Sweden during the pandemic, infants of SARS-CoV-2-positive mothers had a small increase in the rate of any respiratory disorder compared with infants of uninfected mothers (2.8 versus 2 percent, OR 1.42, 95% CI 1.07-1.90) and admission for neonatal care (11.7 versus 8.4 percent, OR 1.47, 95% CI 1.26-1.70) . Preterm delivery, which occurred in 8.8 percent of infected mothers and 5.5 percent of uninfected mothers, could explain approximately 89 percent of the association between maternal infection and neonatal respiratory morbidity. Neonatal mortality and length of hospital stay did not differ significantly between the groups. Interpretation of these data is limited by the lack of information on severity of maternal illness.
An analysis of data from pregnant patients with confirmed or suspected SARS-CoV-2 infection in 12 countries reported all-cause early neonatal death rates of 0.2 to 0.3 percent, which is no higher than expected based on pre-COVID-19 national data . A systematic review also found that the incidence of neonatal death was similar among individuals who tested positive compared with negative for SARS-CoV-2 when admitted to labor and delivery .
Factors potentially affecting outcome
●Severity of maternal disease — The risk of adverse pregnancy outcome is increased in symptomatic patients , especially those with severe/critical disease. Patients with asymptomatic infections appear to have similar outcomes as those without a COVID-19 diagnosis, except for an increased risk for preeclampsia .
•In a study that specifically reported outcome by disease severity, 32 of the 64 pregnant people hospitalized for severe or critical COVID-19 delivered during the course of infection; 9 of 44 people with severe disease and 13 of the 20 people with critical disease were delivered because of the maternal status while only three deliveries were for fetal status . Birth was preterm in 9 percent of people with severe disease and 75 percent of those with critical disease.
•In a similar study, severe-critical COVID-19 was associated with an increased risk of cesarean birth (59.6 versus 34 percent, aRR 1.57, 95% CI 1.30-1.90) and preterm birth (41.8 versus 11.9 percent, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients . Mild and moderate COVID-19 were not associated with adverse perinatal outcomes compared with asymptomatic patients.
●Gestational age at time of infection — In an international retrospective cohort study that compared obstetric and neonatal outcomes of 393 SARS-CoV-2-positive patients according to gestational age at the time of infection, maternal infection after 20 weeks of gestation increased the risk for a composite of adverse obstetric outcomes, and maternal infection after 26 weeks increased the risk for a composite of adverse neonatal outcomes, whereas earlier infection did not increase these risks . These data support vaccination as soon as possible to reduce the risk of acquiring SARS-CoV-2 infection.
Uninfected pregnant patients — The American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and others have issued guidance regarding prenatal care during the COVID-19 pandemic (available at acog.org and SMFM.org and rcog.org) [110-113]. It includes general guidance for testing and preventing spread of COVID-19, a flowchart for outpatient assessment and risk stratification, and suggestions for modifying traditional protocols for prenatal visits. These modifications, which should be tailored for low- versus high-risk patients (eg, multiple gestation, hypertension, diabetes), include :
(Different institutions may mobilize these types of care delivery models at different times depending on prevalence of disease in the community and availability of staffing.)
●Telehealth appointments (telephone or video) for care that does not necessitate physical examination, laboratory/imaging tests, or administration of parenteral medications. For example, a review of symptoms, counseling, and some types of screening (eg, depression) can be conducted virtually (table 7). (See "Telemedicine for adults".)
●Reducing the number of appointments/visits:
•Grouping laboratory tests for the same visit/day (eg, aneuploidy, diabetes, infection screening) when possible. For example, the clinician can order a 75 gram two-hour oral glucose tolerance test (GTT) instead of a glucose challenge test and 100 gram three-hour GTT (in patients with positive results); cell-free DNA screening can be used (at >10 weeks) for Down syndrome screening rather than the combined test (ie, nuchal translucency on ultrasound and serum analytes).
•Grouping indications for indicated obstetric ultrasound examinations to minimize the number of examinations (eg, a single examination at 18 weeks for gestational age, fetal anatomic survey, and placental attachment) when possible
•Revising the timing and frequency of nonstress tests and biophysical profiles when possible
•Home monitoring of weight, blood pressure, glucose levels, and urine protein
●Limiting the number of persons in waiting rooms and physical distancing
●Restricting visitors during visits and tests
●Use of virtual media for encounters other than prenatal visits (eg, tours of the labor and delivery unit, childbirth classes)
●Expanded use of telephone or video helplines and email for patient enquiries
There is limited information on the effects of these modifications on maternal and pregnancy outcomes, but after lockdown, some countries reported increased rates of stillbirth, which may have been related to disruptions in prenatal care and to a higher frequency of home birth [115-118]. Other countries reported no change. (See 'Pregnancy and newborn outcomes' above.)
The psychological impact of the pandemic should also be recognized and support offered [119-123]. The COVID-19 pandemic may be associated with new onset or exacerbation of subsyndromal psychiatric symptoms as well as full-blown psychiatric disorders, including anxiety disorders, depressive disorders, posttraumatic stress disorder, or substance use disorders. (See "COVID-19: Psychiatric illness".)
Infected pregnant patients
Care of asymptomatic infected patients — Care of asymptomatic patients with confirmed or probable SARS-CoV-2 infection involves self-monitoring for development of COVID-19 symptoms, infection control with self-isolation for the anticipated duration of illness, and appropriate timing of discontinuation of precautions (table 8). (See "COVID-19: Outpatient evaluation and management of acute illness in adults" and "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Discontinuation of precautions'.)
Prenatal care is routine and may utilize telemedicine until discontinuation of precautions. Asymptomatic infected patients do not appear to be at increased risk for pregnancy complications, with the possible exception of preeclampsia, which is evaluated for during routine prenatal care. (See 'Risk of preeclampsia' above.)
Care of symptomatic infected patients — The outpatient evaluation of symptomatic patients with documented or suspected COVID-19 should focus on assessment of risk factors for severe illness (table 5), findings associated with severe illness (table 9), and identification of organ dysfunction or other comorbidities that could complicate potential therapy. Specific issues discussed separately include:
●The initial outpatient evaluation, counseling, outpatient management (home care, COVID-19 specific drug therapy), and instructions on how to prevent transmission to others. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Initial evaluation of symptomatic patients' and "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Home care'.)
●Indications for hospitalization and inpatient management. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Inpatient evaluation and care'.)
●Medical and obstetric care of recovering patients. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Recovering patients'.)
Is it safe to perform invasive fetal procedures? — Invasive procedures for fetal diagnosis and therapy are generally thought to be safe in patients with COVID-19, based on data from invasive procedures in patients with other viral infections that have a low concentration of virus in maternal blood . Therefore, postponement of procedures such as chorionic villus sampling is not required.
TIMING OF DELIVERY — Timing of delivery of asymptomatic and symptomatic patients should be individualized based on maternal status, concurrent disorders, gestational age, and shared decision-making with the patient or health care proxy. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Timing of delivery'.)
LABOR, BIRTH, AND POSTPARTUM CARE — (See "COVID-19: Intrapartum and postpartum issues".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
SUMMARY AND RECOMMENDATIONS
●Overview – The prevention, clinical findings, and diagnosis of COVID-19 are the same for pregnant and nonpregnant people (see 'Transmission' above and 'Prevention of infection' above and 'Clinical manifestations and course of infection' above and 'Diagnosis' above), but some specific concerns exist in pregnancy:
•Course of infection – Pregnancy does not increase susceptibility to SARS-CoV-2 infection; however, it appears to worsen the clinical course of COVID-19 compared with nonpregnant reproductive-aged females. (See 'Maternal course' above.)
•Vertical transmission – Although the overall rate of congenital infection has been reported to be approximately 2 percent of maternal infections, well-documented cases of probable in utero transmission are rare. (See 'Risk of vertical transmission' above.)
●Vaccination – We recommend COVID-19 vaccination for all people planning pregnancy or those who are pregnant or recently pregnant as soon as possible rather than deferring vaccination until after delivery or after breastfeeding (Grade 1B). Vaccination reduces the risk of developing COVID-19 and reduces the severity of disease if a breakthrough infection occurs. All available evidence supports the safety of administering currently available SARS-CoV-2 vaccines before, during, and after pregnancy. (See 'Vaccination in people planning pregnancy and pregnant or recently pregnant people' above.)
If both mRNA and adenoviral vector vaccines are available, we suggest an mRNA vaccine (BNT162b2 or mRNA-1273) rather than Ad26.COV2.S (Grade 2C). All three vaccines are highly effective, but data suggest that the mRNA vaccines may have higher effectiveness against severe disease. The rare adverse effects associated with Ad26.COV2.S appear more severe than those with the mRNA vaccines and thrombotic events associated with thrombocytopenia appear to be more common in reproductive-age females. Nevertheless, Ad26.COV2.S is an effective and safe option for most individuals if mRNA vaccines are unavailable or contraindicated.
●Pregnancy outcomes – Compared with uninfected pregnancies, pregnancies complicated by COVID-19:
•Appear to be at increased risk for preterm birth, cesarean birth, and stillbirth, but the increased risk appears to be limited to patients with severe or critical disease and third-trimester infections. (See 'Risk of preterm or cesarean birth' above and 'Risk of stillbirth' above and 'Factors potentially affecting outcome' above.)
•Appear to be at increased risk for developing preeclampsia, even if the infection is asymptomatic. (See 'Risk of preeclampsia' above.)
●Newborn outcome – Fewer than 5 percent offspring of infected mothers have developed symptoms of mild infection (ie, not requiring respiratory support) in the early neonatal period, and most such cases have been attributed to postnatal transmission from their mothers or other caregivers with COVID-19. (See 'Newborn outcome' above.)
●Prenatal care – The American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and others have issued guidance regarding prenatal care during the COVID-19 pandemic (available at acog.org and SMFM.org and rcog.org), including general guidance for testing and preventing spread of COVID-19, a flowchart for outpatient assessment and risk stratification, and suggestions for modifying traditional protocols for prenatal visits. These modifications should be tailored for low- versus high-risk patients. (See 'Prenatal care' above.)
•Invasive procedures for fetal diagnosis and therapy are generally thought to be safe in patients with COVID-19. (See 'Is it safe to perform invasive fetal procedures?' above.)
●Timing of delivery of asymptomatic and symptomatic patients should be individualized based on maternal status, concurrent disorders, gestational age, and shared decision-making with the patient or health care proxy. (See "COVID-19: Antepartum care of pregnant patients with symptomatic infection", section on 'Timing of delivery'.)