Important update: Healthcare facilities
CDC has updated select ways to operate healthcare systems effectively in response to COVID-19 vaccination. Learn more
UPDATE
Given new evidence on the B.1.617.2 (Delta) variant, CDC has updated the guidance for fully vaccinated people. CDC recommends universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status. Children should return to full-time in-person learning in the fall with layered prevention strategies in place.
UPDATE
The White House announced that vaccines will be required for international travelers coming into the United States, with an effective date of November 8, 2021. For purposes of entry into the United States, vaccines accepted will include FDA approved or authorized and WHO Emergency Use Listing vaccines. More information is available here.

Special Clinical Considerations

Special Clinical Considerations
Updated Apr. 12, 2024
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People who are Moderately or Severely Immunocompromised

Risk

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.30,31 Studies show that people with a hematologic or solid organ cancer, hematopoietic stem cell or solid organ transplant, or who are taking immunosuppressive medications can experience lower vaccine effectiveness than those who are immunocompetent.32-34 However, studies suggest that administration of a third vaccine dose as part of the primary series and additional doses of updated vaccine increases immune response and protection against severe illness.35-37

Pre-exposure prophylaxis (prevention) medication is available for some people who are moderately or severely immunocompromised for additional protection against COVID-19.

Pemivibart (Pemgarda™) is a monoclonal antibody for COVID-19 pre-exposure prophylaxis in people who are moderately or severely immunocompromised and unlikely to mount an adequate immune response to COVID-19 vaccination and who meet the FDA-authorized conditions for use.

Pemivibart may provide another layer of protection against COVID-19 in addition to the protection provided through vaccination and can be given at least 2 weeks after receiving a COVID-19 vaccine.

Pemivibart is administered as a single intravenous infusion, over 60 minutes at a doctor’s office or healthcare facility. If continued protection is needed, additional doses should be administered every 3 months. Pemivibart is still being studied and there is limited information about the safety and effectiveness of pemivibart in preventing COVID-19.  

Pre-exposure prophylaxis helps prevent COVID-19 but does not take the place of vaccination in people who are eligible to receive an updated COVID-19 vaccine. Everyone ages 6 months and older should stay up-to-date with COVID-19 vaccine. For more information, please see the FDA Fact Sheet for Providers.

Treatment

Several therapeutics, including the oral antiviral medication ritonavir-boosted nirmatrelvir (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 emergency use authorization 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 Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 also provides recommendations on who should be considered for this treatment.

Management

Clinical information on the treatment of patients with immunocompromising conditions can be found on the Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. There are additional guidelines about COVID-19 vaccines, and prioritization for therapies specific to this population.

See related pages

Pregnancy and Recent Pregnancy

Risk

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.3,4 Race and ethnicity,4-6 older maternal age, occupation in healthcare, and number and type of underlying conditions are associated with severe COVID-19 illness among pregnant people.4,7,8

Data from meta-analyses9-12 and observational studies2,8,13 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-19.14,15 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 with COVID-19 up to at least 42 days (6 weeks) after a live birth or pregnancy loss.

Treatment

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.

Management

In general, the therapeutic management of pregnant people with COVID-19 is the same as management of people who are not pregnant.

Multisystem Inflammatory Syndrome

Risk

Multisystem inflammatory syndrome (MIS) is a rare but serious condition usually occurring 2-6 weeks after SARS-CoV-2 infection. MIS is characterized by systemic inflammation that may affect the heart, lungs, kidneys, brain, skin, eyes, gastrointestinal, or other organ systems. MIS can occur in children (MIS-C) or adults (MIS-A). The Council for State and Territorial Epidemiologists and CDC have developed surveillance case definitions for MIS-C, with an updated CDC case definition [PDF – 13 pages] for MIS-C effective January 1, 2023.47

Adults

CDC provides a case definition for MIS-A. Patients with MIS-A are often young adults who present with fever, elevated laboratory markers of inflammation, hypotension or shock, cardiac dysfunction, shortness of breath, and gastrointestinal symptoms.40-42

Diagnosing MIS-A can be challenging as patients may have experienced an unrecognized asymptomatic or mild initial SARS-CoV-2 infection. Additionally, the signs and symptoms of MIS-A overlap substantially with other conditions such as acute COVID-19 in adults.41,42 When evaluating for MIS-A it is important to consider alternative diagnoses.

Treatment

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.40-42 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. For more information, see CDC’s MIS-A Information for Healthcare Providers.

Pediatric Populations

Risk

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.16,17 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.18 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.18

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.19,20 Like adults, children with underlying medical conditions, including obesity, diabetes, and cardiac, lung, and neurologic disorders, have increased risk of severe COVID-19.18,19,21,22 Studies of hospitalized children with COVID-19 found that having more than one comorbidity is associated with an increased risk of severe illness.22,23

While increasing age is the strongest risk factor for severe COVID-19 illness among adults,1 among children, infants (<12 months of age) may be at increased risk for severe illness.24,25 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.26,27 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 during the Omicron period than in previous waves.25,28,29

Treatment

Some of the medications authorized for the treatment of COVID-19 in adults have been authorized for use in children. For information on medications that are authorized for use in children in ambulatory and hospital settings, see Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19.

Management

For information on recommendations for clinical management, see the American Academy of Pediatrics Management Strategies in Children and Adolescents with Mild to Moderate COVID-19.

Table of Contents

References

  1. Kompaniyets L, Pennington AF, Goodman AB, et al. Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020-March 2021. Preventing chronic disease. Jul 1 2021;18:E66. doi:10.5888/pcd18.210123
  2. Ko JY, Danielson ML, Town M, et al. Risk Factors for COVID-19-associated hospitalization: COVID-19-Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance System. Clin Infect Dis. Sep 18 2020;doi:10.1093/cid/ciaa1419
  3. Zambrano LD, Ellington S, Strid P, et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status – United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. Nov 6 2020;69(44):1641-1647. doi:10.15585/mmwr.mm6944e3
  4. Jamieson DJ, Rasmussen SA. An update on COVID-19 and pregnancy. Am J Obstet Gynecol. Feb 2022;226(2):177-186. doi:10.1016/j.ajog.2021.08.054
  5. Barbero P, Mugüerza L, Herraiz I, et al. SARS-CoV-2 in pregnancy: characteristics and outcomes of hospitalized and non-hospitalized women due to COVID-19. The Journal of Maternal-Fetal & Neonatal Medicine. 2020:1-7. doi:10.1080/14767058.2020.1793320
  6. Grechukhina O, Greenberg V, Lundsberg LS, et al. Coronavirus disease 2019 pregnancy outcomes in a racially and ethnically diverse population. Am J Obstet Gynecol MFM. Nov 2020;2(4):100246. doi:10.1016/j.ajogmf.2020.100246
  7. Galang RR, Newton SM, Woodworth KR, et al. Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection – Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021. medRxiv. 2021:2021.02.27.21252169. doi:10.1101/2021.02.27.21252169
  8. Jering KS, Claggett BL, Cunningham JW, et al. Clinical Characteristics and Outcomes of Hospitalized Women Giving Birth With and Without COVID-19. JAMA Intern Med. Jan 15 2021;doi:10.1001/jamainternmed.2020.9241
  9. Matar R, Alrahmani L, Monzer N, et al. Clinical Presentation and Outcomes of Pregnant Women With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. Clin Infect Dis. Feb 1 2021;72(3):521-533. doi:10.1093/cid/ciaa828
  10. Dubey P, Thakur B, Reddy S, et al. Current trends and geographical differences in therapeutic profile and outcomes of COVID-19 among pregnant women – a systematic review and meta-analysis. BMC Pregnancy Childbirth. Mar 24 2021;21(1):247. doi:10.1186/s12884-021-03685-w
  11. Wei SQ, Bilodeau-Bertrand M, Liu S, Auger N. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. Cmaj. Apr 19 2021;193(16):E540-e548. doi:10.1503/cmaj.202604
  12. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. Sep 1 2020;370:m3320. doi:10.1136/bmj.m3320
  13. DeSisto CL, Wallace B, Simeone RM, et al. Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization – United States, March 2020-September 2021. MMWR Morb Mortal Wkly Rep. Nov 26 2021;70(47):1640-1645. doi:10.15585/mmwr.mm7047e1
  14. Hcini N, Maamri F, Picone O, et al. Maternal, fetal and neonatal outcomes of large series of SARS-CoV-2 positive pregnancies in peripartum period: A single-center prospective comparative study. Eur J Obstet Gynecol Reprod Biol. Feb 2021;257:11-18. doi:10.1016/j.ejogrb.2020.11.068
  15. Prabhu M, Cagino K, Matthews KC, et al. Pregnancy and postpartum outcomes in a universally tested population for SARS-CoV-2 in New York City: a prospective cohort study. Bjog. Nov 2020;127(12):1548-1556. doi:10.1111/1471-0528.16403
  16. Siebach MK, Piedimonte G, Ley SH. COVID‐19 in childhood: Transmission, clinical presentation, complications and risk factors. Pediatric Pulmonology. 2021;56(6):1342-1356. doi:10.1002/ppul.25344
  17. Rubens JH, Akindele NP, Tschudy MM, Sick-Samuels AC. Acute covid-19 and multisystem inflammatory syndrome in children. BMJ. 2021:n385. doi:10.1136/bmj.n385
  18. Martin B, Dewitt PE, Russell S, et al. Characteristics, Outcomes, and Severity Risk Factors Associated With SARS-CoV-2 Infection Among Children in the US National COVID Cohort Collaborative. JAMA Network Open. 2022;5(2):e2143151. doi:10.1001/jamanetworkopen.2021.43151
  19. Kompaniyets L, Agathis NT, Nelson JM, et al. Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. JAMA Netw Open. Jun 1 2021;4(6):e2111182. doi:10.1001/jamanetworkopen.2021.11182
  20. Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA. 2021;325(11):1074. doi:10.1001/jama.2021.2091
  21. Wanga V, Gerdes ME, Shi DS, et al. Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 – Six Hospitals, United States, July-August 2021. MMWR Morb Mortal Wkly Rep. Dec 31 2021;70(5152):1766-1772. doi:10.15585/mmwr.mm705152a3
  22. Woodruff RC, Campbell AP, Taylor CA, et al. Risk Factors for Severe COVID-19 in Children. Pediatrics. 2022;149(1):e2021053418. doi:10.1542/peds.2021-053418
  23. Preston LE, Chevinsky JR, Kompaniyets L, et al. Characteristics and Disease Severity of US Children and Adolescents Diagnosed With COVID-19. JAMA Netw Open. Apr 1 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298
  24. Hobbs CV, Woodworth K, Young CC, et al. Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants. Pediatr Infect Dis J. Mar 1 2022;41(3):e81-e86. doi:10.1097/inf.0000000000003435
  25. Marks KJ, Whitaker M, Agathis NT, et al. Hospitalization of Infants and Children Aged 0-4 Years with Laboratory-Confirmed COVID-19 – COVID-NET, 14 States, March 2020-February 2022. MMWR Morb Mortal Wkly Rep. Mar 18 2022;71(11):429-436. doi:10.15585/mmwr.mm7111e2
  26. Delahoy MJ, Ujamaa D, Whitaker M, et al. Hospitalizations Associated with COVID-19 Among Children and Adolescents – COVID-NET, 14 States, March 1, 2020-August 14, 2021. MMWR Morb Mortal Wkly Rep. Sep 10 2021;70(36):1255-1260. doi:10.15585/mmwr.mm7036e2
  27. Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years – United States, August 2020-August 2021. MMWR Morb Mortal Wkly Rep. Sep 10 2021;70(36):1249-1254. doi:10.15585/mmwr.mm7036e1
  28. Cloete J, Kruger A, Masha M, et al. Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study. The Lancet Child & Adolescent Health. 2022;6(5):294-302. doi:10.1016/s2352-4642(22)00027-x
  29. Torjesen I. Covid-19: Omicron variant is linked to steep rise in hospital admissions of very young children. BMJ. 2022:o110. doi:10.1136/bmj.o110
  30. Fung M, Babik JM. COVID-19 in Immunocompromised Hosts: What We Know So Far. Clin Infect Dis. Jan 27 2021;72(2):340-350. doi:10.1093/cid/ciaa863
  31. Belsky JA, Tullius BP, Lamb MG, Sayegh R, Stanek JR, Auletta JJ. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. The Journal of infection. Mar 2021;82(3):329-338. doi:10.1016/j.jinf.2021.01.022
  32. Di Fusco M, Lin J, Vaghela S, et al. COVID-19 vaccine effectiveness among immunocompromised populations: a targeted literature review of real-world studies. Expert Rev Vaccines. Apr 2022;21(4):435-451. doi:10.1080/14760584.2022.2035222
  33. Lee A, Wong SY, Chai LYA, et al. Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis. Bmj. Mar 2 2022;376:e068632. doi:10.1136/bmj-2021-068632
  34. Embi PJ, Levy ME, Naleway AL, et al. Effectiveness of two-dose vaccination with mRNA COVID-19 vaccines against COVID-19-associated hospitalizations among immunocompromised adults-Nine States, January-September 2021. Am J Transplant. Jan 2022;22(1):306-314. doi:10.1111/ajt.16641
  35. Tenforde MW, Patel MM, Gaglani M, et al. Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults – United States, August-December 2021. MMWR Morb Mortal Wkly Rep. Jan 28 2022;71(4):118-124. doi:10.15585/mmwr.mm7104a2
  36. Kwon JH, Tenforde MW, Gaglani M, et al. mRNA Vaccine Effectiveness Against Coronavirus Disease 2019 Hospitalization Among Solid Organ Transplant Recipients. J Infect Dis. Sep 13 2022;226(5):797-807. doi:10.1093/infdis/jiac118
  37. Parker EPK, Desai S, Marti M, et al. Response to additional COVID-19 vaccine doses in people who are immunocompromised: a rapid review. Lancet Glob Health. Mar 2022;10(3):e326-e328. doi:10.1016/S2214-109X(21)00593-3
  38. Zambrano LD, Newhams MM, Olson SM, et al. BNT162b2 mRNA Vaccination Against COVID-19 is Associated with Decreased Likelihood of Multisystem Inflammatory Syndrome in U.S. Children Ages 5-18 Years. Clin Infect Dis. Aug 4 2022;doi:10.1093/cid/ciac637
  39. Levy M, Recher M, Hubert H, et al. Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France. Jama. Jan 18 2022;327(3):281-283. doi:10.1001/jama.2021.23262
  40. Nygaard U, Holm M, Hartling UB, et al. Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: a Danish nationwide prospective cohort study. The Lancet Child & adolescent health. Jul 2022;6(7):459-465. doi:10.1016/s2352-4642(22)00100-6
  41. Belay ED, Godfred Cato S, Rao AK, et al. Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination. Clin Infect Dis. Aug 24 2022;75(1):e741-e748. doi:10.1093/cid/ciab936
  42. Patel P, DeCuir J, Abrams J, Campbell AP, Godfred-Cato S, Belay ED. Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults: A Systematic Review. JAMA Network Open. 2021;4(9):e2126456-e2126456. doi:10.1001/jamanetworkopen.2021.26456
  43. Melgar M, Haston J, DeCuir J, et al. Multisystem inflammatory syndrome in adults (MIS-A): case finding through systematic review of electronic medical records. Clin Infect Dis. Apr 20 2022;doi:10.1093/cid/ciac303
  44. Zimmermann P, Pittet LF, Curtis N. The Challenge of Studying Long COVID: An Updated Review. Pediatr Infect Dis J. May 1 2022;41(5):424-426. doi:10.1097/inf.0000000000003502
  45. Pellegrino R, Chiappini E, Licari A, Galli L, Marseglia GL. Prevalence and clinical presentation of long COVID in children: a systematic review. European Journal of Pediatrics. 2022/09/15 2022;doi:10.1007/s00431-022-04600-x
  46. Zimmermann P, Pittet LF, Curtis N. How Common is Long COVID in Children and Adolescents? Pediatr Infect Dis J. Dec 1 2021;40(12):e482-e487. doi:10.1097/inf.0000000000003328
  47. Kompaniyets L, Bull-Otterson L, Boehmer TK, et al. Post-COVID-19 Symptoms and Conditions Among Children and Adolescents – United States, March 1, 2020-January 31, 2022. MMWR Morb Mortal Wkly Rep. Aug 5 2022;71(31):993-999. doi:10.15585/mmwr.mm7131a3
  48. Zavala M, Ireland G, Amin-Chowdhury Z, Ramsay ME, Ladhani SN. Acute and Persistent Symptoms in Children With Polymerase Chain Reaction (PCR)-Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Compared With Test-Negative Children in England: Active, Prospective, National Surveillance. Clin Infect Dis. Aug 24 2022;75(1):e191-e200. doi:10.1093/cid/ciab991
  49. Melgar M, Lee EH, Miller AD, Lim S, Brown CM, Yousaf AR, Zambrano LD, Belay ED, Godfred-Cato S, Abrams JY, Oster ME, Campbell AP. Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection – United States. MMWR Recomm Rep. 2022 Dec 16;71(4):1-14. doi: 10.15585/mmwr.rr7104a1. PMID: 36520808; PMCID: PMC9762894.
  50. Miller AD, Zambrano LD, Yousaf AR, Abrams JY, Meng L, Wu MJ, Melgar M, Oster ME, Godfred Cato SE, Belay ED, Campbell AP; MIS-C Surveillance Authorship Group. Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021. Clin Infect Dis. 2022 Aug 24;75(1):e1165-e1175. doi: 10.1093/cid/ciab1007. Erratum in: Clin Infect Dis. 2022 Apr 27;: PMID: 34864955; PMCID: PMC8689703.
  51. Centers for Disease Control and Prevention Center for Preparedness and Response. Updates on Multisystem Inflammatory Syndrome in Children (MIS-C): Epidemiology, Case Definition, and COVID-19 Vaccination. https://emergency.cdc.gov/coca/ppt/2022/120822_slides.pdf [PDF – 69 pages]. December 8, 2022