Ending Isolation and Precautions for People with COVID-19: Interim Guidance

Summary of Recent Changes

Key Points for Healthcare Professionals

• Children and adults with mild, symptomatic COVID-19: Isolation can end at least 5 days after symptom onset and after fever ends for 24 hours (without the use of fever-reducing medication) and symptoms are improving, if these people can continue to properly wear a well-fitted mask around others for 5 more days after the 5-day isolation period. Day 0 is the first day of symptoms.
• People who are infected but asymptomatic (never develop symptoms): Isolation can end at least 5 days after the first positive test (with day 0 being the date their specimen was collected for the positive test), if these people can continue to wear a properly well-fitted mask around others for 5 more days after the 5-day isolation period. However, if symptoms develop after a positive test, their 5-day isolation period should start over (day 0 changes to the first day of symptoms).
• People who have moderate COVID-19 illness: Isolate for 10 days.
• People who are severely ill (i.e., requiring hospitalization, intensive care, or ventilation support): Extending the duration of isolation and precautions to at least 10 days and up to 20 days after symptom onset, and after fever ends (without the use of fever-reducing medication) and symptoms are improving, may be warranted.
• People who are moderately or severely immunocompromised might have a longer infectious period: Extend isolation to 20 or more days (day 0 is the first day of symptoms or a positive viral test). Use a test-based strategy and consult with an infectious disease specialist to determine the appropriate duration of isolation and precautions.
• Recovered patients: Patients who have recovered from COVID-19 can continue to have detectable SARS-CoV-2 RNA in upper respiratory specimens for up to 3 months after illness onset. However, replication-competent virus has not been reliably recovered from such patients, and they are not likely infectious.

Recommendation for Ending Isolation

For people who are mildly ill with a laboratory-confirmed SARS-CoV-2 infection and not moderately or severely immunocompromised:

• Isolation can be discontinued at least 5 days after symptom onset (day 1 through day 5 after symptom onset, with day 0 being the first day of symptoms), and after resolution of fever for at least 24 hours (without the use of fever-reducing medications) and with improvement of other symptoms.
• Loss of taste and smell may persist for weeks or months after recovery and need not delay the end of isolation​.
• These people should continue to properly wear a well-fitted mask around others at home and in public for 5 additional days (day 6 through day 10 after symptom onset) after the 5-day isolation period.
• People who cannot properly wear a mask, including children < 2 years of age and people of any age with certain disabilities, should isolate for 10 days. In certain high-risk congregate settings that have high risk of secondary transmission and where it is not feasible to cohort people, CDC recommends a 10-day isolation period for residents.

For people who test positive, are asymptomatic (never develop symptoms) and not moderately or severely immunocompromised:

• Isolation can be discontinued at least 5 days after the first positive viral test (day 0 through day 5, with day 0 being the date their specimen was collected for the positive test).
• These people should continue to properly wear a well-fitted mask around others at home and in public for 5 additional days (day 6 through day 10) after the 5-day isolation period. Day 0 is the date their specimen was collected for the positive test and day 1 is the first full day after the specimen was collected for the positive test.
• If a person develops symptoms after testing positive, their 5-day isolation period should start over (day 0 changes to the first day of symptoms).
• People who cannot properly wear a mask, including children < 2 years of age and people of any age with certain disabilities, should isolate for 10 days. In certain high-risk congregate settings that have high risk of secondary transmission and where it is not feasible to cohort people, CDC recommends a 10-day isolation period for residents.

For people who are moderately ill and not moderately or severely immunocompromised:

• Isolation and precautions can be discontinued 10 days after symptom onset (day 1 through day 10, with day 0 being the first day of symptoms).

For people who are severely ill and not moderately or severely immunocompromised:

• A test-based strategy can be considered in consultation with infectious disease experts.
• Some people with severe illness (e.g., requiring hospitalization, intensive care, or ventilation support) may produce replication-competent virus beyond 10 days that may warrant extending the duration of isolation and precautions for up to 20 days after symptom onset (with day 0 being the first day of symptoms) and after resolution of fever for at least 24 hours (without the use of fever-reducing medications) and improvement of other symptoms.

For people who are moderately or severely immunocompromised (regardless of COVID-19 symptoms or severity):

• Moderately or severely immunocompromised patients may produce replication-competent virus beyond 20 days. For these people, CDC recommends an isolation period of at least 20 days, and ending isolation in conjunction with a test-based strategy and consultation with an infectious disease specialist to determine the appropriate duration of isolation and precautions.
• The criteria for the test-based strategy are:
  • Results are negative from at least two consecutive respiratory specimens collected ≥ 24 hours apart (total of two negative specimens) tested using an antigen test or nucleic acid amplification test.
  • Also, if a moderately or severely immunocompromised patient with COVID-19 was symptomatic, there should be resolution of fever for at least 24 hours (without the use of fever-reducing medication) and improvement of other symptoms. Loss of taste and smell may persist for weeks or months after recovery and need not delay the end of isolation​.
• Re-testing for SARS-CoV-2 infection is suggested if symptoms worsen or return after ending isolation and precautions based on this test-based strategy for moderately or severely immunocompromised people.⁽¹⁾
• If a patient has persistently positive nucleic acid amplification tests beyond 30 days, additional testing could include molecular studies (e.g., genomic sequencing) or viral culture, in consultation with an infectious disease specialist.
• For the purposes of this guidance, moderate to severely immunocompromising conditions include, but might not be limited to, those defined in the interim clinical considerations for people with moderate to severe immunocompromise due to a medical condition or receipt of immunosuppressive medications or treatments.
  • Other factors, such as end-stage renal disease, likely pose a lower degree of immunocompromise, and there might not be a need to follow the recommendations for those with moderate to severe immunocompromise.
  • Ultimately, the degree of immunocompromise for the patient is determined by the treating provider, and preventive actions should be tailored to each patient and situation.

Assessment for Duration of Isolation

Available data suggest that patients with mild-to-moderate COVID-19 remain infectious no longer than 10 days after symptom onset. More information is available at What We Know About Quarantine and Isolation.

Most patients with more severe-to-critical illness likely remain infectious no longer than 20 days after symptom onset.

There have been numerous reports of moderately or severely immunocompromised people shedding replication-competent virus beyond 20 days.^{(examples: 1-33)} A higher SARS-CoV-2 viral load and longer duration of infection among moderately or severely immunocompromised people may favor emergence of SARS-CoV-2 variants.^{(5,14,19,30,34,35)} Strategies that reduce SARS-CoV-2 transmission to and from people at increased risk of long-term infections could slow the emergence and spread of new variants.^(34,35)

Patients who have recovered from COVID-19 can continue to have detectable SARS-CoV-2 RNA in upper respiratory specimens for up to 3 months after illness onset in concentrations considerably lower than during illness; however, replication-competent virus has not been reliably recovered from such patients, and they are not likely infectious. The circumstances that result in persistently detectable SARS-CoV-2 RNA have yet to be determined. Studies have not found evidence that clinically recovered adults with persistence of viral RNA have transmitted SARS-CoV-2 to others. These findings strengthen the justification for relying on a symptom-based rather than test-based strategy for ending isolation of most patients.

Key Findings from Transmission Literature

1. Concentrations of SARS-CoV-2 RNA in upper respiratory specimens decline after onset of symptoms.^{(36-39, 40-43)} Infectiousness peaks around one day before symptom onset and declines within a week of symptom onset, with an average period of infectiousness and risk of transmission between 2-3 days before and 8 days after symptom onset.^(42,44)
2. Several studies have found similar concentrations of SARS-CoV-2 RNA in upper respiratory specimens from children and adults.^(45-52)
   • To date, most studies of SARS-CoV-2 transmission have found that children and adults have a similar risk of transmitting SARS-CoV-2 to others.
   • One study reported that children were more likely to transmit SARS-CoV-2 than adults >60 years old.⁽⁵³⁾
3. Certain SARS-CoV-2 variants of concern are more transmissible than the wild type virus or other variants, resulting in higher rates of infection. For example, people infected with the Delta variant, including people who are up to date with their vaccines with symptomatic breakthrough infections, can transmit infection to others. However, like other variants, the amount of virus produced by Delta breakthrough infections in people who are up to date with their vaccines decreases faster than in people who are not up to date with their vaccines.
4. The likelihood of recovering replication-competent (infectious) virus is very low after 10 days from onset of symptoms, except in people who have severe COVID-19 or who are moderately or severely immunocompromised.
   • For patients with mild COVID-19 who are not moderately or severely immunocompromised, replication-competent virus has not been recovered after 10 days following symptom onset for most patients.^{(38,39,54-58)} With the recommended shorter isolation period for asymptomatic and mildly ill people with COVID-19, it is critical that people continue to properly wear well-fitted masks and take additional precautions for 5 days after leaving isolation.^(59,60) Modeling data suggest that close to one-third of people remain infectious after day 5 and can potentially transmit the virus.⁽⁶¹⁾ Outliers exist; in one case report, an adult with mild illness provided specimens that yielded replication-competent virus for up to 18 days after symptom onset.⁽⁶²⁾
   • Recovery of replication-competent virus between 10 and 20 days after symptom onset has been reported in some adults with severe COVID-19; some of these people were immunocompromised.⁽³⁷⁾ However, in this series of patients, it was estimated that 88% and 95% of their specimens no longer yielded replication-competent virus after 10 and 15 days, respectively, following symptom onset.
   • Detection of sub-genomic SARS-CoV-2 RNA or recovery of replication-competent virus has been reported in moderately or severely immunocompromised patients beyond 20 days, and as long as >140 days after a positive SARS-CoV-2 test result.^{(examples: 1-33)} Immunocompromising conditions that have been associated with shedding of replication-competent virus beyond 20 days include active treatment for solid tumor and hematologic malignancies, solid organ transplant and taking immunosuppressive therapy, receipt of CAR-T-cell therapy or hematopoietic cell transplant (HCT) (within 2 years of transplantation or taking immunosuppression therapy), moderate or severe primary immunodeficiency, and active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, and other biologic agents that are immunosuppressive or immunomodulatory.^{(examples: 1-33)}
   • Prolonged detection of replication-competent virus may be associated with other factors. For example, a 13-year-old immunocompetent male was hospitalized for injuries received in a motor vehicle crash. He required intubation, developed pulmonary infiltrates, and tested positive for SARS-CoV-2. Viral cultures of upper and lower respiratory tract specimens were positive for SARS-CoV-2 on days 47 and 54 of his hospitalization.⁽⁶³⁾
5. The risk of SARS-CoV-2 transmission to others varies based upon several factors including time after symptom onset, virus variant, virus levels in the upper respiratory tract, and disease status (asymptomatic, pre-symptomatic, or symptomatic).
   • In a large contact tracing study, no contacts developed SARS-CoV-2 infection if their exposure to a COVID-19 case patient occurred 6 days or more after the case patient’s symptom onset.⁽⁶⁴⁾
   • One study reported that 59% of SARS-CoV-2 transmission originated from index cases that were asymptomatic or pre-symptomatic.⁽⁶⁵⁾
   • A meta-analysis found that the secondary attack rate for asymptomatic (never develop symptoms) index cases was 1.9%, but was 9.3% for pre-symptomatic and 13.6% for symptomatic index cases.⁽⁶⁶⁾ Therefore, people with SARS-CoV-2 infection without symptoms pose a transmission risk and should isolate based upon CDC’s quarantine and isolation recommendations.
6. People who have recovered from COVID-19 may have prolonged detection of SARS-CoV-2 RNA.⁽⁶⁷⁾ However, prolonged detection of viral RNA does not necessarily mean that such people are a transmission risk.⁽⁶⁸⁾ Studies of patients who were hospitalized and recovered indicate that SARS-CoV-2 RNA can be detected in upper respiratory tract specimens for up to 3 months (12 weeks) after symptom onset.^(58,62,69)
   • Investigation of 285 “persistently SARS-CoV-2 RNA positive” adults, which included 126 adults who had developed recurrent symptoms, found no secondary infections among 790 contacts. Efforts to isolate replication-competent virus were attempted for 108 of these 285 case patients, and SARS-CoV-2 was not recovered in viral culture from any of the 108 specimens.⁽⁵⁸⁾
7. The probability of SARS-CoV-2 reinfection may increase with time after recovery, consistent with other human coronaviruses, because of waning immunity and the possibility of exposure to viral variants.^(70-78) The risk of reinfection also depends on host susceptibility, vaccination status, and the likelihood of re-exposure to infectious cases of COVID-19. Continued widespread transmission makes it more likely that reinfections will occur.
8. Loss of taste and smell may continue for weeks or months after recovery.⁽⁷⁹⁾ The presence of these symptoms does not mean that the isolation period must be extended.

Limitations of Current Evidence

• Studies referenced in this document may have differences compared to the current epidemiology of COVID-19 in the United States. Specifically, many of these references involve non-US populations, homogenous populations, virus transmission prior to the availability of vaccination for COVID-19, and infection prior to the known circulation of SARS-CoV-2 current variants of concern, such as the Delta or Omicron variant. More studies are needed to fully understand virus transmission related to the Delta variant, Omicron variant, and other SARS-CoV-2 variants among people who are up to date with their vaccines.
• Studies have used viral culture to attempt to grow SARS-CoV-2 from clinical samples from patients who tested positive for SARS-CoV-2 to determine infectiousness. Because viral culture must be done in very specialized laboratories, these studies are more limited in number compared to studies using other test methods to detect SARS-CoV-2 infection.
• Many studies that assessed the duration of SARS-CoV-2 infectiousness have been conducted in adults. More studies are needed, especially in children with SARS-CoV-2 infection.
• More data are needed to understand the frequency and duration of infectious SARS-CoV-2 shedding among the spectrum of mild to severely immunocompromised people, including both asymptomatic and symptomatic people.
• More data are needed to fully understand the risk of recovery of replication-competent virus in people with severe COVID-19. There was variation in how studies defined severe illness with COVID-19. Some studies defined severe disease as cases requiring hospitalization or mechanical ventilation while other researchers used the definition of severityexternal icon from the COVID-19 Treatment Guidelines published by National Institutes of Health (NIH).

References

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