Special Clinical Considerations

Pregnancy and Recent Pregnancy

Pregnant and recently pregnant people (for at least 42 days following the end of pregnancy) are at increased risk of severe illness from COVID-19, including hospital admission, intensive care unit admission, receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, and death, compared to people who are not pregnant.^47,48 Race and ethnicity,^48-50 older maternal age, occupation in healthcare, and number and type of underlying conditions are associated with severe COVID-19 illness among pregnant people.^48,51,52

Data from meta-analyses^53-56 and observational studies^29,52,57 suggest that pregnant people with COVID-19 (compared to pregnant people without COVID-19) are at increased risk of preterm birth and stillbirth and might be at increased risk of pregnancy complications, including pre-eclampsia.

Increased risk for postpartum complications, including hospital readmission, has been observed among recently pregnant people with COVID-19 compared to recently pregnant people without COVID-19.^58,59 However, methods for defining the period of recent pregnancy vary from study to study. While some studies include people with COVID-19 immediately after delivery, others include people up to at least 42 days (6 weeks) after a live birth or pregnancy loss.

In general, the therapeutic management of pregnant people with COVID-19 is the same as management of people who are not pregnant. The COVID-19 Treatment Guidelines Panel recommends against withholding treatment for COVID-19 from pregnant or lactating individuals because of theoretical safety concerns. For more information on the treatment of COVID-19 in pregnant people, see the NIH Treatment Guidelines on Special Considerations in Pregnancy.

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Pediatric Populations

The initial clinical presentation of COVID-19 in children can include fever, cough, or other respiratory symptoms; many children also experience gastrointestinal symptoms, including nausea, vomiting, or diarrhea.^60,61 Viral tests are recommended for diagnosing COVID-19 in children. Children who develop severe illness can develop abnormal vital signs and markers of severe inflammation once hospitalized.⁶² A study of over 10,000 hospitalized children found that lower blood pressure, higher heart and respiratory rates, and abnormal markers of inflammation, including D-dimers and ferritin, were associated with severe illness in children.⁶²

Studies suggest that many children experience asymptomatic or mild illness, but some children can experience severe COVID-19 illness requiring admission to the hospital or ICU, or use of invasive mechanical ventilation, and some die.^63,64 Like adults, children with underlying medical conditions, including obesity, diabetes, and cardiac, lung, and neurologic disorders have increased risk of severe COVID-19.^62,63,65,66 Studies of hospitalized children with COVID-19 found that having more than one comorbidity is associated with an increased risk of severe illness.^66,67

While increasing age is the strongest risk factor for severe COVID-19 illness among adults,²⁸ among children, infants (<12 months of age) may be at increased risk for severe illness.^68,69 In addition to individual risk factors, the COVID-19 variant that is circulating at the time of infection could have an impact on disease severity. Compared to prior periods, studies of COVID-19 in the pediatric population during the Delta predominant period found increased rates of hospitalization.^70,71 Further increases in overall number of pediatric hospitalizations were observed during the Omicron predominant period, particularly for children under the age of 5 years. Despite this, pediatric patients experienced less severe disease than in previous waves.^69,72,73

Some of the medications authorized for the treatment of COVID-19 in adults have been authorized for use in children. More information on medications that are authorized for use in children in ambulatory and hospital settings and recommendations for clinical management can be found in the NIH COVID-19 Treatment Guidelines and the American Academy of Pediatrics Management Strategies in Children and Adolescents with Mild to Moderate COVID-19.

People who are Moderately or Severely Immunocompromised

People with immunocompromising conditions and people who take immunosuppressive medications or therapies are at increased risk for severe outcomes with COVID-19, including hospitalization, intensive care unit admission, mechanical ventilation, and death.^74,75 Studies show that people with a hematologic or solid organ cancer, hematopoetic stem cell or solid organ transplant, or who are taking immunosuppressive medications, can experience lower vaccine effectiveness than those who are immunocompetent.^76-78 However, studies suggest that administration of a third vaccine dose as part of the primary series and booster doses increase immune response and protection against severe illness.^79-81

Additionally, several therapeutics, including the oral antiviral medication nirmatrelvir with ritonavir (Paxlovid), the intravenous antiviral remdesivir, and the oral antiviral molnupiravir (Lagevrio) are beneficial in this population for early treatment of COVID-19. Treatment is best if initiated as soon as possible after diagnosis and within 5 to 7 days after illness onset.

The FDA has issued an EUA to permit the emergency use of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting. For more information, please see the FDA Fact Sheet for Providers. The NIH COVID-19 Treatment Guidelines also provide recommendations on who should be considered for this treatment.

Clinical information on the treatment of patients with immunocompromising conditions can be found on the NIH Treatment Guidelines for Non-hospitalized Adults. There are additional guidelines about COVID-19 vaccines, prioritization for therapies, and treatment, specific to this population.

Pre-Exposure Prophylaxis

EVUSHELD^TM, a monoclonal antibody combination that was used for pre-exposure prophylaxis to protect against SARS-CoV-2 infection, is not currently authorized for emergency use in the United States because it is unlikely to be active against certain SARS-CoV-2 variants. According to the most recent CDC Nowcast data, these variants are projected to be responsible for more than 90% of current infections in the U.S. This means that Evusheld is not expected to provide protection against developing COVID-19 if exposed to those variants. Healthcare facilities and providers with EVUSHELD^TM should retain all products in the event that SARS-CoV-2 variants that are neutralized by EVUSHELD^TM become more prevalent in the U.S. in the future. For more information, see FDA’s announcement.

Management of Conditions Presenting after Acute Illness

Multisystem Inflammatory Syndrome

Multisystem inflammatory syndrome is a rare but serious post-acute condition that generally occurs 2-6 weeks after SARS-CoV-2 infection and is characterized by systemic inflammation which may affect the heart, lungs, kidneys, brain, skin, eyes, gastrointestinal or other organ systems. Multisystem inflammatory syndrome occurs in children (MIS-C) and adults (MIS-A).

Multisystem Inflammatory Syndrome in Children (MIS-C)

CDC, the World Health Organization (WHO), and the Brighton Collaboration have developed surveillance case definitions for MIS-C, with an updated CDC case definition for MIS-C effective January 1, 2023. Common features of these case definitions include clinical criteria including fever, multisystem organ involvement, elevated laboratory markers of inflammation, and history of SARS-CoV-2 infection or exposure to a known COVID-19 case.

Patients with MIS-C present with fever often accompanied by mucosal or cutaneous lesions, vomiting, diarrhea, abdominal pain, conjunctival hyperemia or injection, and less commonly cough and shortness of breath.^82,83 The elevated inflammatory state can lead to severe organ dysfunction⁶⁴; in a study of 4,470 pediatric patients with MIS-C in the United States, 80% of patients experienced severe cardiovascular symptoms, 74% mucocutaneous symptoms, 60% severe hematologic symptoms, 44% severe respiratory symptoms, and 25% severe gastrointestinal symptoms.⁸³ Severity of MIS-C has decreased since the Omicron predominance began.^83,84

Diagnosing MIS-C can be difficult. The presentation of MIS-C may overlap with that of other conditions, including Kawasaki Disease, toxic shock syndrome, and severe acute COVID-19.^64,85 It is important to consider alternative diagnoses when evaluating children suspected of having MIS-C and to pursue testing to evaluate multisystem involvement as indicated.

Treatment for patients with MIS-C continues to evolve.  A study of over 4,000 patients with MIS-C found that treatment typically includes supportive care and stabilization of the patient, immunomodulatory treatment (including intravenous immunoglobulin (IVIG), steroids, and/or other medications), and anticoagulant and antiplatelet therapy.⁸⁶ Clinical treatment guidelines for MIS-C that describe diagnosis and clinical treatment options have been developed by the American College of Rheumatology, the National Institutes of Health, and the American Academy of Pediatrics. For clinical information to assist providers in speaking with patients and families about MIS-C, see Talking with Families and Caregivers.

COVID-19 vaccination has been shown to be protective against MIS-C,^87-89 and according to expert opinion, COVID-19 vaccination may benefit children who have had MIS-C by reducing risk of severe disease and potential recurrence of MIS-C after re-infection. For more information on vaccination recommendations for patients with a history of MIS-C, see CDC’s Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States.

CDC and the Council of State and Territorial Epidemiologists (CSTE) recommend that clinicians report cases of MIS-C to their local, state, or territorial health department, and that all jurisdictions conduct case surveillance and reporting of MIS-C (as of January 1, 2023, this will be using the 2023 case definition). Data concerning health department-reported cases of MIS-C in the United States are available in CDC COVID Data Tracker.

Multisystem Inflammatory Syndrome in Adults (MIS-A)

As with MIS-C, diagnosing MIS-A can be challenging because patients may have experienced an asymptomatic or mild initial SARS-CoV-2 infection, which may have been undiagnosed, and signs and symptoms of MIS-A overlap substantially with those of acute COVID-19 in adults.^91,92  Similar to MIS-C, it is important to consider alternative diagnoses and to evaluate for multisystem involvement.

Treatment recommendations have not yet been developed for MIS-A; however, studies have reported the use of steroids, intravenous immunoglobulins (IVIG), other immunomodulatory medications, and supportive care for treatment.^90-92

Vaccination is also considered beneficial for patients who have had MIS-A. For more information on vaccination recommendations for patients with a history of MIS-A, see CDC’s Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States.

Consider reporting cases of MIS-A to your local, state, or territorial health department. CDC COVID Data Tracker.
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Post-COVID Conditions or Long COVID

Commonly reported symptoms can include fatigue, post-exertional malaise, dyspnea, anxiety or psychological distress, joint or muscle pain, cough, chest pain, cognitive impairment, and headache.^93-95 Patients with post-COVID conditions can also be diagnosed with new conditions, including diabetes and mental health concerns.⁹⁶ Assessment of patients with post-COVID conditions can be difficult because the symptoms are associated with many medical conditions and patients may experience multiple symptoms and conditions. Clinicians can consult CDC’s General Clinical Considerations for suggestions on initial diagnostic and follow-up evaluation when caring for patients with post-COVID conditions. When patients experience symptoms 4 weeks or more after SARS-CoV-2 infection, clinicians may consider alternative diagnoses, as well as post-COVID conditions, and complete additional follow-up visits as indicated by on-going need. Patients who experience post-COVID conditions are not infectious, and isolation, which is recommended for patients with acute COVID-19, is not recommended for these patients, unless they experience reinfection.

Several factors, including severity of initial COVID-19 infection, pre-existing medical conditions, older age, infection without vaccination, female sex, and predominant variant in circulation have been found to be associated with an increased occurrence of post-COVID conditions.^97-99 Estimates of the proportion of people who had COVID-19 that go on to experience post-COVID conditions range widely; in studies of post-COVID conditions that use uninfected comparison groups, estimates are typically lower than in studies that do not include uninfected comparison groups.^93-95 Clinicians should be aware that COVID-19 vaccination is recommended for everyone ages 6 months and older, including people with post-COVID conditions. Growing epidemiologic evidence indicates that vaccination following SARS-CoV-2 infection further increases protection from subsequent infection and hospitalization and may, as a consequence of preventing severe illness, prevent cases of post-COVID conditions, including in the setting of increased circulation of more infectious SARS-CoV-2 strains.^100,101 An alternate hypothesis is that vaccination may accelerate clearance of virus or decrease the exaggerated inflammatory response associated with PCC.¹⁰⁰  Further, some studies suggest that vaccination may reduce PCC symptoms in those who receive vaccination after onset of PCC.¹⁰⁰ For more information on vaccination recommendations for patients with post-COVID conditions, see CDC’s Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States.

Children experience post-COVID conditions, but they appear to be affected less frequently than adults. Estimates of the proportion of children who experience COVID-19 and later develop post-COVID conditions range widely.^102,103 Many studies suggest that older adolescence, female sex, and underlying medical conditions are frequently associated with persistent symptoms.^103,104  Studies of post-COVID conditions in children report varying symptoms and conditions^103-105, and many studies report symptoms in similar frequencies between children who were infected with SARS-CoV-2 and those who were not infected.^102,106 Commonly reported symptoms can include fatigue, smell and taste disturbances, and myalgia or arthralgia.^103-105

Many patients diagnosed with post-COVID conditions slowly improve over several months, but some studies suggest that patients can experience prolonged illness lasting more than 6 months.^107,108

Post-COVID conditions are challenging to study because they include a wide range of physical and mental health consequences that are new, returning, or ongoing. Studies to date include different patient populations and case definitions, and assessments at varying points of time after acute infection; many studies include only one assessment or do not include control groups; and the severity and impact of symptoms on quality of life or daily activities have not been consistently reported. For more information on post-COVID conditions see Post-COVID Conditions: Information for Healthcare Providers and Post-COVID Conditions: CDC Science.

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