INTRODUCTION — Pregnant people with COVID-19 may be asymptomatic or symptomatic. Symptomatic patients appear to be at increased risk for developing severe sequelae of the disease 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. The clinical care of symptomatic patients depends on illness severity, underlying medical comorbidities that increase the risk for severe disease, coexistent pregnancy complications, and social situation (eg, ability for self-care and follow-up).
This topic will discuss the antepartum care of pregnant people with symptomatic COVID-19. An overview of issues related to COVID-19 in pregnancy and management of labor, birth, and postpartum care are reviewed separately. (See "COVID-19: Overview of pregnancy issues" and "COVID-19: Intrapartum and postpartum issues".)
INITIAL EVALUATION OF SYMPTOMATIC PATIENTS — The initial evaluation (by telehealth and/or in person) of patients with COVID-19 should focus on:
●Assessment of symptoms (eg, types, duration, severity)
●Assessment of risk factors for severe illness (table 1)
Initial evaluation and risk stratification of all adult pregnant or nonpregnant patients with COVID-19, including assessment of dyspnea and oxygenation, need for/site of in-person assessment, and consideration of COVID-19 specific therapy, is discussed in detail separately. (See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and 'Use of antiviral drug and monoclonal antibody therapy' below.)
Although it is desirable see all patients at high risk for severe disease in person, this may not always be possible during a surge when patient volume exponentially increases. In our practice, at a minimum, we have in-person visits for those who are >36 weeks of gestation and those who need antenatal testing.
CANDIDATES FOR HOSPITALIZATION — Inpatient monitoring and care are appropriate for patients with severe or critical illness; however, the criteria may vary with the availability of hospital resources, social factors, and patient-specific clinical and/or social factors that might support earlier hospitalization. (See "COVID-19: Evaluation of adults with acute illness in the outpatient setting", section on 'Criteria for ED evaluation and likely hospital admission'.)
In the United States, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel suggests hospitalization for patients with any of the following :
•Oxygen saturation (SpO2) <94 percent on room air
•Respiratory rate >30 breaths/minute
•Pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) <300 mmHg
•Lung infiltrates >50 percent
Pregnant hospitalized patients with severe disease, an oxygen requirement plus comorbidities, or critical disease should be cared for by a multispecialty team at a level III or IV hospital with obstetric services and an adult intensive care unit (ICU) [2,3]. This team can help determine the most appropriate location (medical or obstetric ward, labor and delivery unit, or ICU). COVID-19 status alone is not necessarily a reason to transfer noncritically ill pregnant patients with suspected or confirmed COVID-19.
INPATIENT EVALUATION AND CARE
Inpatient evaluation — The objective in the evaluation of hospitalized patients with COVID-19 is to evaluate for features associated with severe illness (table 2) and identify organ dysfunction or other comorbidities that could complicate potential therapy. The laboratory and imaging evaluation is the same for pregnant and nonpregnant patients. However, it is important to note that several of the features associated with severe illness in the table are not reliable in pregnancy (C-reactive protein and D-dimer are increased in normal pregnancy (table 3)) and should not be used for consideration of risk of severe disease. (See "COVID-19: Management in hospitalized adults", section on 'Evaluation'.)
A portable chest radiograph is sufficient for initial evaluation of pulmonary complications and extent of lung involvement in hospitalized patients with COVID-19. A single chest radiograph carries a very low fetal radiation dose of 0.0005 to 0.01 milligray (mGy). Computed tomography (CT) should be performed, if clinically indicated, as the fetal radiation dose for a routine chest CT (table 4) is also low and not associated with an increased risk of fetal anomalies or pregnancy loss (see "Diagnostic imaging in pregnant and nursing patients"). Some authorities have advocated lung ultrasound, possibly at the same time as the obstetric scan, for quick diagnosis of pneumonia in symptomatic pregnant people [4,5]. A detailed description of performance of lung ultrasound, which appears to have good diagnostic accuracy and has fewer infection control implications than CT, can be found elsewhere .
Overview — General management of hospitalized adults involves:
●Administration of empiric, prophylactic, and therapeutic drugs. Issues to consider include empiric treatment of influenza or bacterial pneumonia, prevention of venous thromboembolism (VTE), and management of chronic medications
●Management of hypoxemia
●Management of complications (eg, acute respiratory distress syndrome [ARDS], arrhythmias and other cardiac disorders, kidney injury)
Specific issues related to pregnancy are addressed in the following section and summarized in the table (table 6).
Selected issues in the management of hospitalized pregnant patients — The following considerations apply specifically to pregnant patients.
Target SpO2 — Many experts suggest maintaining maternal peripheral oxygen saturation (SpO2) at ≥95 percent, which is in excess of the oxygen delivery needs of the mother [6,7]. If SpO2 falls below 95 percent, an arterial blood gas may be obtained to measure the partial pressure of oxygen (PaO2): Maternal PaO2 greater than 70 mmHg is desirable to maintain a favorable oxygen diffusion gradient from the maternal to the fetal side of the placenta. The World Health Organization (WHO) suggests maintaining maternal SpO2 ≥92 to 95 percent once the patient is stable . Others have proposed maintaining SpO2 between 92 and 96 percent for patients with acute respiratory failure who require supplemental O2, as long as fetal status is reassuring, because a lower target SpO2 may prevent unnecessary invasive interventions .
●Prone position — In the intensive care unit (ICU), severely ill patients with COVID-19 are often managed in the prone position; the left lateral position is an alternative but may not be as effective. Some ICUs have extended this approach to pregnant patients, although even a semiprone position can be a difficult position in which to place a pregnant person in the last half of pregnancy [10-12]. Padding above and below the gravid uterus >24 weeks is desirable to offload the uterus and avoid aortocaval compression . Permissive hypercapnia (partial pressure of carbon dioxide [PCO2] <60 mmHg) and extracorporeal membrane oxygenation (ECMO), if indicated for management of ARDS, do not appear to be harmful to the fetus, but data are limited [11-14]. High positive end-expiratory pressure strategies (>10 mmHg), if considered, require close ongoing maternal and fetal monitoring because they decrease preload and cardiac output .
●Other respiratory support measures – Noninvasive respiratory support of the critically ill COVID-19 patient, timing and procedure of intubation, and management of the hospitalized and the intubated patient are reviewed separately. Most aspects of these interventions are identical for pregnant and nonpregnant patients. An exception is that minute ventilation should be adjusted to maintain the PaCO2 between 30 to 32 mmHg because significant respiratory alkalosis may decrease uterine blood flow. (See "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)" and "COVID-19: Management of the intubated adult".)
In some situations (eg, refractory COVID-19-related respiratory failure), maternal ECMO may be necessary and delivery on ECMO can be performed safely [12-16]. If ECMO is not available, transporting the patient to a facility where it is available should be considered. Both femoral and jugular cannulation sites have been used in pregnancy. In a systematic review of 29 pre-COVID-19 cases of ECMO during pregnancy, the rate of complications was as high as 57 percent . (See "COVID-19: Extracorporeal membrane oxygenation (ECMO)".)
Venous thromboembolism prophylaxis — Prophylactic-dose anticoagulation is recommended for pregnant patients hospitalized because of COVID-19, if there are no contraindications to its use, and generally discontinued when the patient is discharged to home. Intermittent pneumatic compression is suggested when pharmacologic prophylaxis is contraindicated. (See "Use of anticoagulants during pregnancy and postpartum".)
Unfractionated heparin is generally preferred for pregnant patients who might be proximate to delivery because it is more readily reversed than low molecular weight heparin (LMWH). For these patients and those who have a contraindication to LMWH, prophylactic unfractionated heparin can be used:
●Unfractionated heparin 5000 units in the first trimester, 7500 to 10,000 units in the second trimester, and 10,000 units in the third trimester, administered subcutaneously every 12 hours (reduce the dose if the activated partial thromboplastin time is elevated).
For pregnant patients who are unlikely to be delivered within a few days, prophylactic- or intermediate-dose LMWH is reasonable. For example,
●Enoxaparin 40 mg subcutaneously daily or 1 mg/kg (commonly rounded to the nearest 10 mg) subcutaneously every 24 hours.
Pregnant patients with COVID-19 who do not warrant hospitalization for the infection or who are asymptomatic or mildly symptomatic and hospitalized for reasons other than COVID-19 (eg, labor, preterm prelabor rupture of membranes) do not require anticoagulation, unless antithrombotic therapy had been prescribed during pregnancy for another indication (eg, previous VTE). They should be encouraged to stay hydrated and ambulate. However, decisions regarding VTE prophylaxis in the pregnant and postpartum patient should be individualized, considering concomitant VTE risk factors and timing of delivery. (See "COVID-19: Hypercoagulability" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention".)
We do not prescribe low-dose aspirin for individuals with COVID-19 except for standard indications (preeclampsia prophylaxis). Aspirin does not appear to improve COVID-19 outcomes.
●Risk of VTE — Direct data on risk of VTE related to COVID-19 are limited but suggest an increased risk in infected pregnant patients compared with uninfected pregnant patients (0.2 versus 0.1 percent; adjusted odds ratio [OR] 3.43, 95% CI 2.01-5.82 ) [18-20]. Pregnancy, reduced mobility, and dehydration can contribute to this risk. In a systematic review including >1000 pregnant patients with COVID-19, there were three cases of venous thrombosis (0.28 percent, 95% CI 0.0-0.6), one case of arterial thrombosis, seven cases of disseminated intravascular coagulation (DIC; 0.66 percent, 95% CI 0.17-1.1), and a further three cases of coagulopathy without meeting the criteria for DIC (0.28 percent, 95% CI 0.0-0.6) . VTE occurs primarily in hospitalized patients with severe or critical illness: in one series of 1219 pregnant patients with COVID-19, the incidence of VTE was 6 percent (95% CI 2-11) among those with severe-critical illness, 0.2 percent with mild-moderate illness, and 0 in asymptomatic patients .
Use of dexamethasone — Dexamethasone 6 mg daily for 10 days or until discharge is recommended for severely ill nonpregnant patients who are on supplemental oxygen or ventilatory support. Glucocorticoids may also have a role in the management of refractory shock in critically ill patients with COVID-19. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids' and "COVID-19: Management of the intubated adult", section on 'Use of glucocorticoids for non-COVID-19 reasons'.)
In pregnant patients who meet criteria for use of glucocorticoids for maternal treatment of COVID-19 and also meet criteria for use of antenatal corticosteroids to induce fetal maturity, we suggest:
●Administer the usual doses of dexamethasone (four doses of 6 mg intravenously 12 hours apart) to induce fetal maturation, and
●Continue maternal treatment to complete the course of dexamethasone (6 mg orally or intravenously daily for 10 days or until discharge, whichever is shorter)
Our approach is the same as that of the Society for Maternal-Fetal Medicine . After the initial four doses of dexamethasone, some guidelines switch to hydrocortisone or methylprednisolone to minimize fetal glucocorticoid exposure beyond the standard used for fetal lung maturation.
Glucose levels should be monitored closely in patients with gestational or pregestational diabetes as hyperglycemia will usually occur after administration of dexamethasone. We check fasting and two-hour postprandial glucose levels and attempt to maintain standard pregnancy targets (fasting <95 mg/dL [5.3 mmol/L], two-hour postprandial <120 mg/dL [6.7 mmol/L]). One option is to begin an insulin infusion, especially for severely ill patients who are not eating well. Another option is to adjust the subcutaneous insulin dose by preemptively increasing their daily dose by about 20 percent 8 to 12 hours after the first dexamethasone administration and then making further adjustments based on blood glucose levels. In patients without diabetes, the need for glucose monitoring is unclear, but frequent maternal glucose levels >180 mg/dL (10 mmol/L) are undesirable as they lead to fetal hyperglycemia and hyperinsulinemia, which increase fetal oxygen requirements.
Criteria for glucocorticoid administration in COVID-19 and efficacy data for different steroids are reviewed separately. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids' and "COVID-19: Management of the intubated adult", section on 'Use of glucocorticoids for non-COVID-19 reasons'.)
Use of NSAIDs and acetaminophen — Nonsteroidal anti-inflammatory drugs (NSAIDs) can be administered to COVID-19 patients when clinically indicated. The lowest effective dose is used, ideally for less than 48 hours and guided by gestational age-related potential fetal toxicity (eg, oligohydramnios, premature closure of the ductus arteriosus). Low-dose aspirin for prevention of preeclampsia is safe throughout pregnancy. (See "Inhibition of acute preterm labor", section on 'Fetal side effects' and "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)
We use acetaminophen as the preferred antipyretic and analgesic agent, if possible. In patients with abnormal liver chemistries secondary to COVID-19, hepatic toxicity is a potential concern of acetaminophen use. However, doses less than 2 grams per day are likely safe in the absence of severe or decompensated hepatic disease. (See "COVID-19: Management in hospitalized adults", section on 'NSAID use'.)
Use of acetaminophen in pregnancy, including in the first trimester, has been shown overall to be safe and may attenuate the pregnancy risks associated with fever exposure. Hyperthermia, which is common in COVID-19, is a theoretical concern as elevation of maternal core temperature from a febrile illness during organogenesis in the first trimester may be associated with an increased risk of congenital anomalies, especially neural tube defects, or miscarriage; however, an increased incidence of these outcomes has not been observed. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management", section on 'Fever/hyperthermia'.)
Antiviral drugs and other COVID-19-specific therapies — Selection of COVID-19-specific therapy in adults who have severe disease requiring oxygen supplementation is shown in the algorithm (algorithm 1). The safety, efficacy, and use of antiviral and other drugs for treatment of COVID-19 is reviewed in detail separately. (See "COVID-19: Management in hospitalized adults", section on 'COVID-19-specific therapy'.)
Very few trials of drugs for treatment of COVID-19 have included pregnant people (eg, SOLIDARITY trial , RECOVERY trial ). Decisions about use of COVID-19-specific therapies during pregnancy should involve shared decision-making, considering severity of maternal status, underlying risk factors, gestational age, potential maternal benefit, likelihood of placental transfer and potential mechanisms for fetal harm, and lack of information on fetal and newborn risks. The following drugs are used in hospitalized patients.
●Remdesivir – Remdesivir is a novel nucleotide analog that inhibits RNA-dependent RNA polymerase. It has been used in pregnancy without reported fetal toxicity in some patients with Ebola and Marburg virus disease . (See "COVID-19: Management in hospitalized adults", section on 'Remdesivir'.)
●Baricitinib, tofacitinib – Placental transfer of baricitinib (a Janus kinase [JAK] inhibitor) may be expected based on its molecular weight. Information on use of baricitinib in pregnancy is limited to a case report and registry data of inadvertent administration during pregnancy . These limited human data are insufficient to inform a drug-associated risk for major birth defects or miscarriage. Embryo-fetal toxicity, such as skeletal anomalies and reduced fertility, have been observed in animals dosed in excess of the maximum human exposure. Tofacitinib is another JAK inhibitor and similar considerations apply. The drug has been used in 33 pregnancies for non-COVID-19 disorders and pregnancy outcomes were similar to the general population . (See "COVID-19: Management in hospitalized adults", section on 'Baricitinib and JAK inhibitors'.)
●Tocilizumab, sarilumab, siltuximab – Markedly elevated inflammatory markers (eg, D-dimer, ferritin) and elevated pro-inflammatory cytokines (including interleukin [IL]-6) are associated with critical and fatal COVID-19, and blocking the inflammatory pathway may prevent disease progression . Several agents that target the IL-6 pathway have been evaluated in randomized trials for treatment of COVID-19; these include the IL-6 receptor blockers tocilizumab and sarilumab and the direct IL-6 inhibitor siltuximab. Tocilizumab is a recombinant humanized monoclonal IgG1 antibody that interrupts IL-6. A review of tocilizumab use in pregnancy included 610 cases (20 with COVID-19, most of the others for rheumatological diseases) and did not reveal clear serious safety signals, but the available data had significant limitations . There is even less information about use of sarilumab and siltuximab in pregnancy . (See "COVID-19: Management in hospitalized adults", section on 'IL-6 pathway inhibitors (eg, tocilizumab)' and 'Use of antiviral drug and monoclonal antibody therapy' below.)
Fetal monitoring — A specific management issue in pregnant patients is monitoring fetuses who are at a viable gestational age (ie, gestational age when delivery for fetal indications and neonatal resuscitation would be considered). The need for and frequency of fetal testing depend on gestational age, stability of maternal vital signs and oxygenation, other maternal comorbidities, and discussions with the patient and the family that consider the possibly increased risks of stillbirth and perinatal morbidities in the absence of testing.
For hospitalized patients, a Bluetooth-enabled external fetal monitor can transmit the fetal heart rate tracing to the obstetric team. The monitor can be used continuously in severely ill hospitalized patients in whom emergency cesarean birth would be performed for a persistent nonreassuring fetal heart rate pattern. An abnormal tracing might also help guide maternal oxygen therapy. In patients with stable SpO2, a nonstress test can be performed once or twice daily, as one option.
Monitoring for preterm labor — Monitoring pregnant patients for signs and symptoms of preterm labor is a routine component of obstetric care and should be a component of maternal monitoring of pregnant patients admitted to nonobstetric hospital units. (See "Preterm labor: Clinical findings, diagnostic evaluation, and initial treatment".)
OUTPATIENT CARE OF PATIENTS WITH MILD OR MODERATE ILLNESS — Most (at least 86 percent ) pregnant patients with known or suspected COVID-19 have mild disease (no shortness of breath) that does not warrant hospital-level care in the absence of obstetric problems (eg, preterm labor), concern for rapid deterioration, inability to promptly return to the hospital, or, possibly, inability to self-isolate. It is important to note, however, that infection with SARS-CoV-2 may cause catastrophic illness in any patient, even among those without risk factors for severe disease. In a prospective cohort study, 90 percent of 1326 COVID-19 infections (March 18, 2020 to September 30, 2021) in pregnant patients were asymptomatic or mild; 10 percent of 436 initially asymptomatic patients developed symptoms; and of patients with asymptomatic or mild symptoms at diagnosis, 4 percent of first, 5 percent of second, and 6 percent of third-trimester patients developed moderate, severe, or critical illness .
Home care — Home care is generally supportive, similar to that advised for other acute viral illnesses. Hydration, adequate rest, and frequent ambulation with more advanced activity as soon as tolerated are advised. Specific issues discussed in detail separately include:
●The supportive and medical care of ambulatory COVID-19 patients. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Symptom management and recovery expectation'.)
●Options for and safety of over-the-counter medications in pregnancy. (See "COVID-19: Management in hospitalized adults", section on 'NSAID use' and "Treatment of respiratory infections in pregnant patients", section on 'The common cold'.)
●The importance of infection control and self-isolation. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Infection prevention in the home setting'.)
Ideally, government and community organizations and social service agencies will provide dedicated housing units to isolate and care for patients experiencing homelessness.
When to call the provider — Outpatients should be followed closely for progression to severe or critical disease and given instructions for infection control, symptom management, warning symptoms, and obstetric follow-up (at least once within two weeks of COVID-19 diagnosis ). In general, pregnant outpatients should call their provider (or seek emergency medical care) if they experience any of the following [2,6,32]:
●Respiratory rate ≥20 to 24 breaths/minute and/or heart rate >100 beats per minute
●Oxygen saturation (SpO2) <95% (if the patient has access to an over-the-counter pulse oximeter)
●Unremitting fever >39°C despite appropriate use of acetaminophen
●Inability to tolerate oral hydration and medications
●Persistent pleuritic chest pain
●Confusion or other alterations in mentation
●Obstetric complications (eg, preterm contractions, vaginal bleeding, rupture of membranes)
●Decreased fetal movement
Fetal monitoring — COVID-19 alone is not an indication for nonstress tests or biophysical profiles. The US Food and Drug Administration (FDA) has expanded its approval for use of noninvasive fetal monitoring devices in the home for patients who require fetal monitoring for standard obstetric indications unrelated to COVID-19 . This can help reduce patient and health care provider contact and potential exposure to COVID-19 during the pandemic.
Use of antiviral drug and monoclonal antibody therapy — Pregnant and recently pregnant people with mild to moderate COVID-19 are potential candidates for COVID-19-specific therapy because they are at increased risk for progression to severe disease and treatment can substantially reduce the risk of progression to severe illness and hospitalization (and with some interventions, mortality). In our practice, we suggest this therapy to pregnant patients with additional risk factors for severe disease (table 1) or who are unvaccinated, after discussion of the benefits/risks and drug-drug interaction potential. We provide it to patients who request therapy but have no risk factors for severe disease other than pregnancy. Limited supplies may warrant prioritization of COVID-19-specific therapy to those at the highest risk of severe disease using the tiered approach shown in the table (table 7). A detailed discussion of the use of antiviral drugs and monoclonal antibodies is available separately. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Treatment with COVID-19-specific therapies'.)
In the United States, treatment of confirmed cases, preferably with nirmatrelvir-ritonavir, or a monoclonal antibody therapy active against prevalent variants (table 8), or remdesivir, is initiated as soon as possible after symptom onset. The maximum allowable time window for administration varies from 5 to 7 days after symptom onset, depending on the agent. High-titer convalescent plasma is an option if nirmatrelvir-ritonavir, a monoclonal antibody therapy active against prevalent variants (table 8), or remdesivir is not available.
Molnupiravir is not preferred because it may be less effective and in pregnant patients the potential for fetoplacental toxicity is a concern. The drug choice depends upon local availability, ease of prompt access to treatment, susceptibility to prevalent viral variants (table 8), ease of administration, safety during pregnancy and lactation (discussed in the following bulleted sections), and specific patient factors (eg, comorbid conditions, potential drug-drug interactions [eg, nirmatrelvir-ritonavir]).
●Nirmatrelvir-ritonavir – Nirmatrelvir-ritonavir has received an emergency use authorization (EUA) in the United States, including for pregnant patients . The dose is 300 mg nirmatrelvir (two 150 mg tablets) with one 100 mg ritonavir tablet taken together orally twice daily for five days. It should be initiated as soon as possible following COVID-19 diagnosis and within five days of symptom onset (symptom onset is day 0). Minimal reproductive safety data from animal studies are available for nirmatrelvir (eg, reduced fetal body weights in rabbits when exposed to doses 10-fold higher and for a longer proportion of gestational days than authorized human maternal doses, which was attributed to lower maternal gestational body weight gain) . However, extensive data are available for ritonavir in patients with HIV and no increased risk of overall teratogenic effects was observed following first-trimester exposure.
Potential drug interactions are a particular concern in patients taking nirmatrelvir-ritonavir (eg, in postpartum patients, ergot derivatives should be avoided and opioids used with caution). Consult a reliable prescribing reference to determine if nirmatrelvir-ritonavir use is appropriate or if risk can be safely mitigated with alteration of the patient's medication regimen. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Nirmatrelvir-ritonavir'.)
●Anti-SARS-CoV-2 monoclonal antibodies can be used for treatment or postexposure prophylaxis, as described in the table (table 9). The choice of monoclonal antibody depends on the variant prevalent in the community (table 8). These drugs are generally administered as a single intravenous (IV) dose; dosing information is available separately. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Monoclonal antibodies'.)
Pregnancy implications of anti-SARS-CoV-2 monoclonal antibody therapy are not well defined, but they appear to reduce the risk of severe disease and no significant adverse maternal or perinatal outcomes have been noted [28,37-40]. Humanized monoclonal antibodies (IgG1) cross the placenta beginning as early as 13 weeks of gestation, with increasing transport as the pregnancy progresses and the largest amount transferred in the third trimester . A concern is that the transferred antibody may affect immune responses in utero in the exposed fetus. Nonclinical reproductive toxicity studies have not been performed, and there is minimal information regarding whether the potential transfer of these drugs provides any treatment benefit or risk to the developing fetus.
●Remdesivir – The need for IV administration daily for three days (200 mg IV on day 1, followed by 100 mg IV daily on days 2 and 3) is a disadvantage in outpatients; however, remdesivir may have a better fetal safety profile than available oral agents (nirmatrelvir-ritonavir, and particularly molnupiravir [relatively contraindicated in pregnancy] discussed below). (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Remdesivir'.)
Pregnancy considerations are addressed above. (See 'Antiviral drugs and other COVID-19-specific therapies' above.)
●High-titer convalescent plasma – High-titer convalescent plasma is an alternative option for COVID-19-specific therapy for symptomatic outpatients with risk for progression to severe disease if nirmatrelvir-ritonavir, or a monoclonal antibody therapy active against prevalent variants, or remdesivir is unavailable or inappropriate. Safety and efficacy during pregnancy have not been evaluated in clinical trials; however, pathogen-specific immunoglobulins have been administered safely during pregnancy to prevent maternal varicella zoster virus and rabies virus infections and in trials to reduce symptomatic congenital cytomegalovirus (CMV) infection in offspring of mothers with primary CMV infection . The maximum allowable time window for the transfusion is 8 days after symptom onset. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'High-titer convalescent plasma'.)
●Molnupiravir – Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis. It has an EUA for treatment of mild to moderate COVID-19 in nonpregnant adults at risk for progression to severe disease. Because of its mechanism of action , possible adverse effects on the developing fetus and placenta are a concern. It is generally not recommended for pregnant patients due to concerns about instances of fetal toxicity in animal studies; however, when other therapies are not available (eg, nirmatrelvir-ritonavir), pregnant people with COVID-19 who are at high risk of progressing to severe disease, especially those beyond the time of embryogenesis (ie, >10 weeks' gestation), may reasonably choose molnupiravir therapy after being fully informed of the risks . The discussion of the risks and benefits and the patient's choice should be documented. The manufacturer advises nonpregnant individuals of childbearing potential to use effective contraception correctly and consistently, as applicable, during treatment and for four days after the last dose . (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Molnupiravir'.)
Drugs of limited or uncertain benefit and drugs that are not recommended are reviewed separately. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies that we do not recommend' and "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies of limited or uncertain benefit' and "COVID-19: Management of adults with acute illness in the outpatient setting".)
Discontinuation of infection precautions — Guidelines are summarized in the table (table 10) and discussed in more detail separately. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Discontinuation of precautions'.)
Time to recovery — The time to recovery from COVID-19 is highly variable and depends on age and preexisting comorbidities in addition to illness severity. Individuals with mild infection are expected to recover relatively quickly (eg, within two weeks) whereas many individuals with severe disease have a longer time to recovery (eg, two to three months). The most common persistent symptoms include fatigue, dyspnea, chest pain, cough, and cognitive deficits (table 11).
Prenatal care and follow-up after recovery
●Initial follow-up – Hospitalized patients with COVID-19 ideally should have outpatient follow-up through telehealth or an in-person visit within one week but no later than two to three weeks after discharge from the hospital. They should call their provider if they develop new or worsening symptoms. Follow-up medical care is similar to that in nonpregnant patients, of whom up to 10 to 20 percent require rehospitalization. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")" and "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Post-discharge management'.)
●Prenatal care – Prenatal care in asymptomatic and recovering/recovered patients is mostly routine. The risk of preterm birth in patients with resolved asymptomatic or symptomatic antepartum infection generally appears to be similar to that in those without infection; however, two studies reported that patients with first- or second-trimester COVID-19 experienced a modest increase in risk of adverse pregnancy outcome (eg, preterm birth, perinatal death, hypertensive disorders of pregnancy) later in pregnancy [46,47].
•Obstetric ultrasound – In the absence of robust data, authorities have suggested that pregnant persons with confirmed infection should have at least one ultrasound assessment of fetal growth, scheduled in the third trimester (eg, 30 to 32 weeks) or at least 14 days after symptom resolution or >21 days from prior fetal biometry ultrasound, depending on timing of maternal infection . For those with first- or early second-trimester infection, the standard fetal anatomy scan at 18 to 23 weeks of gestation is performed.
Development of fetal growth restriction is a theoretic concern and has been described with other SARS infections [48,49]. The very limited COVID-19-specific data on fetal growth after maternal infection are reassuring [50,51]. Although significant placental histopathologic changes are not universally present, suboptimal fetal growth due to placental insufficiency is plausible because maternal COVID-19 has been associated with vascular and inflammatory placental lesions, which appear to persist after recovery [52-54]. These lesions, termed SARS placentitis, could be caused by COVID-19-related coagulopathy, placental hypoxia during the acute maternal illness, placental viral infection, or a combination of these factors. (See "Placental development and physiology", section on 'SARS-CoV-2' and "COVID-19: Intrapartum and postpartum issues", section on 'Placenta'.)
•Fetal surveillance – Antenatal fetal testing (nonstress test, biophysical profile) is typically reserved for standard obstetric indications . (See "Overview of antepartum fetal assessment", section on 'Indications for fetal assessment'.)
TIMING OF DELIVERY — Timing of delivery is individualized based on maternal status, concurrent disorders, gestational age, and shared decision-making with the patient or health care proxy.
Postnatal transmission in the delivery room is not a major concern because the risk is very low in the setting of infection control. It should be noted that maternal antibody production and, in turn, passive newborn immunity may not have had time to develop when maternal symptoms are acute. Maternal immunoglobulin G (IgG) levels increase soon after the maternal infection and peak >30 days after onset of symptoms . High placental transfer efficiency is achieved when infection onset is at least 60 days prior to birth ; however, the factors affecting transplacental antibody transfer, such as disease severity, have not been clearly elucidated [56,58,59].
Patients with severe or critical COVID-19 — For patients who are severely ill, timing of delivery is individualized as multiple maternal and fetal factors must be considered, including [2,60]:
●Gestational age and plans for neonatal resuscitation
●Severity of hypoxemia
●Rate of disease progression
●Response to escalating therapy
●Results of tests of fetal well-being
●Whether a course of antenatal corticosteroids has been completed (for pregnancies between 23 and 34 weeks of gestation)
In general, we deliver pregnancies in which fetal testing suggests compromise (eg, bradycardia or repetitive late decelerations), and standard in utero resuscitative measures are unsuccessful, and the fetus is a candidate for neonatal resuscitation (if required), as long as delivery is unlikely to compromise a critically ill mother.
Maternal indications for delivery are more complicated. We avoid delivery in patients with oxygen saturation (SpO2) ≥95 percent. In patients with ongoing hypoxemia, timing of delivery is based on the factors described above. We have a low threshold for delivering pregnancies that have reached at least 32 to 34 weeks of gestation when the mother's disease is worsening. For pregnancies above the lower limit of viability but less than 30 to 32 weeks of gestation, the threshold for delivery is higher, such that as long as maternal health is not jeopardized by continuing the pregnancy, we avoid delivery because of the fetal benefits of prolonging the gestation. Decision-making in these cases must be individualized based on factors such as the specific gestational age and plans for neonatal resuscitation, severity of hypoxemia, rate of disease progression, response to escalating therapy, and comorbidities. However, refractory hypoxemic respiratory failure or worsening critical illness is generally an indication for delivery. In critically ill patients, although the stress of delivery could exacerbate the maternal condition, limited data also suggest that delivery sometimes improves maternal hypoxemia . In these cases, delivery reverses pregnancy-related increased oxygen consumption and reduced functional residual capacity, thus improving oxygenation . Patients with excessive uterine distension because of multiple gestation or severe polyhydramnios in the third trimester would benefit most.
Patients with nonsevere (or asymptomatic) COVID-19 — A positive test for COVID-19 is not a reason to postpone a planned delivery in these patients.
●For patients with nonsevere (or asymptomatic) COVID-19 at ≥39 weeks of gestation, delivery can be considered to decrease the risk of worsening maternal status before the onset of spontaneous labor ; however, most patients do not go on to develop severe COVID-19 .
Patients who had planned a week 39 induction of labor may proceed with the induction, if resources permit.
●For most patients <39 weeks with COVID-19 and nonsevere (or asymptomatic) illness who have no medical/obstetric indications for prompt delivery, intervention is not indicated; ideally, birth will occur sometime after recovery. Induction and cesarean birth are performed for standard obstetric indications.
●For most patients <39 weeks with COVID-19 and nonsevere (or asymptomatic) illness who also have medical/obstetric complications (eg, prelabor rupture of membranes, preeclampsia, pregestational diabetes), the timing of delivery is, in general, determined by usual protocols for the specific medical/obstetric disorder. Induction of labor or cesarean birth performed for appropriate medical/obstetric indications should not be postponed or rescheduled in such patients.
ROUTE OF DELIVERY, INTRAPARTUM AND POSTPARTUM MANAGEMENT — Route of delivery, management of labor and delivery, and postpartum maternal and infant care are reviewed separately. (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".)
SUMMARY AND RECOMMENDATIONS
●Initial evaluation – The initial evaluation (by telehealth and/or in person) of patients with COVID-19 should focus on assessment of symptoms (eg, types, duration, severity) and risk factors for severe illness (table 1). (See 'Initial evaluation of symptomatic patients' above.)
●Triage – Inpatient care is generally required for patients with respiratory compromise (see 'Candidates for hospitalization' above):
•Oxygen saturation (SpO2) <94 percent on room air
•Respiratory rate >30 breaths/minute
•Pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) <300 mmHg
•Lung infiltrates >50 percent
●Inpatient management – Management of inpatients with severe COVID-19 includes:
•Possible empiric treatment for influenza or bacterial pneumonia. (See "COVID-19: Management in hospitalized adults", section on 'Empiric treatment for influenza during influenza season' and "COVID-19: Management in hospitalized adults", section on 'Empiric treatment for bacterial pneumonia in select patients'.)
•Prevention of venous thromboembolism (VTE). (See 'Venous thromboembolism prophylaxis' above.)
•Administration of dexamethasone for maternal treatment and, in pregnancies at 23 to 34 weeks, to induce fetal maturation. In patients with diabetes, glucose levels should be monitored and insulin dose adjusted to maintain euglycemia. (See 'Use of dexamethasone' above.)
•Administration of COVID-19-specific therapy (algorithm 1). (See 'Antiviral drugs and other COVID-19-specific therapies' above.)
•Fetal monitoring. Initiation and frequency depend on gestational age, stability of maternal vital signs and oxygenation, other maternal comorbidities, and discussions with the patient and family that consider the possibly increased risks of stillbirth and perinatal morbidities in the absence of testing. (See 'Fetal monitoring' above.)
●Outpatient management – Most patients are asymptomatic or have nonsevere COVID-19 and can be managed at home. Outpatients should be followed closely for progression to severe or critical disease and given instructions for infection control, symptom management, warning symptoms, and obstetric follow-up (at least once within two weeks of COVID-19 diagnosis). (See 'Home care' above and 'When to call the provider' above.)
•COVID-19-specific therapy – Pregnant patients are candidates for COVID-19-specific therapy, if available, especially if they have comorbidities in addition to pregnancy (table 1) or are unvaccinated. The benefit/risk balance is unclear in vaccinated patients when pregnancy is the only risk factor for severe disease. (See 'Use of antiviral drug and monoclonal antibody therapy' above.)
Nirmatrelvir-ritonavir, or a monoclonal antibody therapy active against prevalent variants (table 8), or remdesivir initiated as soon as possible after symptom onset are the preferred drugs for pregnant patients. Molnupiravir is not preferred because it may be less effective and in pregnant patients the potential for fetoplacental toxicity is a concern. (See 'Use of antiviral drug and monoclonal antibody therapy' above.)
•Guidelines for discontinuation of isolation are summarized in the table (table 10). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Discontinuation of precautions'.)
●Timing of delivery
•In patients with severe COVID-19, we deliver pregnancies in which fetal testing suggests compromise (eg, bradycardia or repetitive late decelerations), and standard in utero resuscitative measures are unsuccessful, and the fetus is a candidate for neonatal resuscitation (if required), as long as delivery is unlikely to compromise a critically ill mother.
Maternal indications for delivery are more complicated. We avoid delivery in patients with SpO2 ≥95 percent. In patients with ongoing hypoxemia, we have a low threshold for delivering pregnancies that have reached at least 32 to 34 weeks of gestation when the mother's condition is worsening. For pregnancies above the lower limit of viability but less than 30 to 32 weeks of gestation, the threshold for delivery is higher, such that as long as maternal health is not jeopardized by continuing the pregnancy, we avoid delivery because of the fetal benefits of prolonging the gestation. Although decision-making in these cases must be individualized based on multiple factors, refractory hypoxemic respiratory failure or worsening critical illness is generally an indication for delivery.
•In patients with nonsevere COVID-19, timing of delivery is based on standard obstetric indications. COVID-19 is not a reason to postpone a planned delivery. (See 'Patients with nonsevere (or asymptomatic) COVID-19' above.)