Interim Guidance on Ending Isolation and Precautions for Adults with COVID-19

Summary of Recent Changes

Accumulating evidence supports ending isolation and precautions for adults with laboratory-confirmed COVID-19 using a symptom-based strategy. This update incorporates recent evidence to inform the duration of isolation and precautions recommended to prevent transmission of SARS-CoV-2 to others, while limiting unnecessary prolonged isolation and unnecessary use of laboratory testing resources. This interim guidance is based upon information available to date and will be updated as new information becomes available.

Summary of Key Findings

1. Concentrations of SARS-CoV-2 RNA in upper respiratory specimens decline after onset of symptoms. ^{(39,56,61,63,64,66)}
2. The likelihood of recovering replication-competent virus also declines after onset of symptoms. For patients with mild to moderate COVID-19, replication-competent virus has not been recovered after 10 days following symptom onset. ^{(1,8,31,36,42,61,66)} 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 cases were immunocompromised. ⁽⁵⁶⁾ 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 severely immunocompromised patients (e.g., patients with chronic lymphocytic leukemia and acquired hypogammaglobulinemia, lymphoma and immunochemotherapy, hematopoietic stem-cell transplant, chimeric antigen receptor T-cell therapy, or AIDS) beyond 20 days, and as long as 143 days after a positive SARS-CoV-2 test result. ^{(2,6,7,14,74)}
3. In a large contact tracing study, no contacts at high risk of exposure developed infection if their exposure to a case patient started 6 days or more after the case patient’s infection onset. ⁽¹²⁾
4. Recovered patients can continue to have SARS-CoV-2 RNA detected in their upper respiratory specimens for up to 12 weeks after symptom onset. ^(31,33,34) Investigation of 285 “persistently positive” adults, which included 126 adults who had developed recurrent symptoms, found no secondary infections among 790 contacts to these case patients. Efforts to isolate replication-competent virus from 108 of these 285 case patients were unsuccessful. ⁽³¹⁾
5. To date, reports of reinfection have been infrequent.  Similar to other human coronaviruses where studies have demonstrated reinfection, the probability of SARS-CoV-2 reinfection is expected to increase with time after recovery from initial infection because of waning immunity and the possibility of exposure to virus variants.  Circulation of variant viruses (such as the B.1.1.7 variant ⁽²⁰⁾ or B.1.1.28 variant ^(67,68)) has been reported in several countries. Reinfection with a SARS-CoV-2 variant virus has been reported in Brazil, ^(69,70,71) the U.K., ⁽⁷²⁾ and South Africa. ⁽⁷³⁾ The risk of reinfection may be increased in the future with exposure to SARS-CoV-2 variant virus strains that are not neutralized by immune antisera, such as one recently described in South Africa. ⁽⁶⁰⁾ The risk of reinfection also depends on the likelihood of re-exposure to infectious cases of COVID-19. Continued widespread transmission makes it more likely that reinfections will occur. Use of prevention strategies can prevent and slow transmission.

The current evidence includes the following limitations:

• In a study of skilled nursing facility workers followed prospectively for asymptomatic infection, one of 48 staff infected with SARS-CoV-2 had a nasopharyngeal swab that was weakly positive on a single-passage plaque assay (and therefore contained live virus) more than 20 days after initial diagnosis. However, the specimen was not subjected to serial passage to demonstrate the presence of replication-competent virus; ⁽⁴⁶⁾ in other words, it is not known if the person was actually infectious.
• In one case report, an adult with mild illness provided specimens that yielded replication-competent virus for up to 18 days after symptom onset. ⁽³⁴⁾
• More data are needed concerning viral shedding in some situations, including in immunocompromised adults.
• Data currently available are from adults; comparable data from children and infants on the character of viral shedding or risk for reinfection are not presently available.

Assessment

Duration of Isolation and Precautions

Available data indicate that adults with mild to moderate COVID-19 remain infectious no longer than 10 days after symptom onset. Most adults with more severe to critical illness or severe immunocompromise likely remain infectious no longer than 20 days after symptom onset; however, there have been several reports of people shedding replication-competent virus beyond 20 days due to severe immunocompromise. ^{(2,6,7,14,74)} Recovered adults can continue to shed detectable but non-infectious SARS-CoV-2 RNA in upper respiratory specimens for up to 3 months after illness onset, albeit at concentrations considerably lower than during illness, in concentration ranges where replication-competent virus has not been reliably recovered and infectiousness is unlikely. 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, so that adults who are no longer infectious are not kept unnecessarily isolated and excluded from work or other responsibilities.

Role of Viral Diagnostic Testing after Discontinuation of Isolation or Precautions

The duration and robustness of immunity to SARS-CoV-2 remains under investigation. Among other human coronaviruses, reinfection appears to occur variably over time after onset of infection. ^(19,30) However, for SARS-CoV-2, reinfection appears to be uncommon during the initial 90 days after symptom onset of the preceding infection (Annex: Retesting and Quarantine of Adults Recovered from Laboratory-diagnosed SARS-CoV-2 Infection with Subsequent Re-Exposure). Thus, for adults recovered from SARS-CoV-2 infection, a positive SARS-CoV-2 RT-PCR result without new symptoms during the 90 days after illness onset more likely represents persistent shedding of viral RNA than reinfection.

• If such an adult remains asymptomatic during this 90-day period, then any viral retesting is unlikely to yield useful information, even if the adult had close contact with an infected person.
• If such an adult becomes symptomatic during this 90-day period, and an evaluation fails to identify a diagnosis other than SARS-CoV-2 infection (e.g., influenza), then the adult likely warrants evaluation for SARS-CoV-2 reinfection in consultation with an infectious disease or infection control expert. Isolation might be warranted before and during this evaluation, particularly if symptoms developed after close contact with an infected person or in association with an outbreak setting. Isolation might also be warranted to prevent transmission of any other potentially transmissible respiratory infections (e.g., that might be confirmed by pending cultures or additional testing).

Correlates of immunity to SARS-CoV-2 infection have not been established. Although a positive serologic test result may indicate resolving or previous infection, a positive test result is unlikely to indicate the onset of acute infection in lieu of a positive viral test result except in rare circumstances (i.e., a positive serologic test result 7 days to 3 weeks following acute illness onset in adults with a previous negative serologic test result). Therefore, only under a rare circumstance such as the one described could a serologic test be used to establish a diagnosis date for the purposes of assessing both the interval between past diagnosis and any new exposure and whether or not testing is indicated.

CDC will continue to closely monitor the evolving science for information that would warrant reconsideration of these recommendations.

Recommendations

1. Duration of isolation and precautions
   • For most adults with COVID-19 illness, isolation and precautions can be discontinued 10 days after symptom onset^* and after resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms.
     • Some adults with severe illness may produce replication-competent virus beyond 10 days that may warrant extending duration of isolation and precautions for up to 20 days after symptom onset; severely immunocompromised patients^** may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts.
   • For adults who never develop symptoms, isolation and other precautions can be discontinued 10 days after the date of their first positive RT-PCR test result for SARS-CoV-2 RNA.
2. Role of viral diagnostic testing (RT-PCR or antigen)^***to discontinue isolation or precautions
   • For adults who are severely ill or severely immunocompromised, a test-based strategy could be considered in consultation with infectious diseases experts.
   • For all others, who are not severely ill or severely immunocompromised, a test-based strategy is not recommended, and isolation and precautions should be maintained for at least 10 days as outlined in Part 1 above.
3. Viral diagnostic testing (RT-PCR or antigen)^***and quarantine after discontinuation of isolation or precautions
   • For adults previously diagnosed with symptomatic laboratory-confirmed COVID-19 who remain asymptomatic after recovery, retesting or quarantine is not recommended if another exposure occurs or might have occurred within 90 days after the date of symptom onset from the initial SARS-CoV-2 infection.
   • For adults who develop new symptoms consistent with COVID-19 during the 90 days after the date of initial symptom onset, if an alternative etiology cannot be readily identified by a healthcare provider, then the adult likely warrants retesting. Consultation with infectious disease or infection control experts is recommended, especially in the event that symptoms develop within 14 days after close contact with a person infected with SARS-CoV-2. Adults being evaluated for reinfection with SARS-CoV-2 or any potentially transmissible respiratory infection should be isolated under recommended precautions before and during evaluation. If reinfection is confirmed or remains suspected, they should remain under the recommended SARS-CoV-2 isolation period until they meet the criteria for discontinuation of precautions – for most adults, this would be 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms.
   • For adults with past laboratory-confirmed SARS-CoV-2 who have never had symptoms and have had a subsequent exposure or possible exposure, the date of first positive viral diagnostic test result (RT-PCR or antigen) for SARS-CoV-2 should be used in place of the date of symptom onset to determine the interval between past infection and the recent exposure. This interval can then be used to inform decisions about testing for the recent exposure.
   • Adults who have  a past history of symptoms consistent with COVID-19 but who did not have laboratory confirmation of COVID-19 with a viral diagnostic test (RT-PCR or antigen) and who present with new symptoms consistent with COVID-19 should  be tested and undergo quarantine.
   • For children and infants, the data pertaining to the risk of reinfection within 90 days following laboratory-confirmed diagnosis are extremely limited. However, in the context of a pandemic, children and infants should be managed as recommended for adults above. CDC will continue to monitor closely the evolving science for information that would warrant reconsideration of these recommendations for this population.
4. Role of serologic testing
   • Although serologic testing indicating the presence of SARS-CoV-2 antibodies may signify resolving or previous infection, it should not generally be used to establish the presence or absence of acute SARS-CoV-2 infection. In addition, the date of a positive serologic test should not generally be used to determine the start of the 90-day period following SARS-CoV-2 infection for which retesting or quarantine is not recommended. However, if no positive viral diagnostic test (RT-PCR or antigen) indicating infection is available, a positive serologic test 7 days to 3 weeks following acute illness onset in an adult with a history of a previous negative serologic test can be used to establish the presence of absence of infection and the start date of the 90-day period.

^* Symptom onset is defined as the date on which symptoms first began, including non-respiratory symptoms.

^** The studies used to inform this guidance did not clearly define severe immunocompromise. For the purposes of this guidance, CDC defines severe immunocompromise as certain conditions, such as being on chemotherapy for cancer, untreated HIV infection with CD4 T lymphocyte count <200, combined primary immunodeficiency disorder, and receipt of prednisone >20mg/day for more than 14 days, that may cause a higher degree of immunocompromise and therefore should inform decisions regarding the duration of isolation. Other factors, such as advanced age, diabetes mellitus, or end-stage renal disease, may pose a much lower degree of immunocompromise and do not clearly affect decisions about duration of isolation. Ultimately, the degree of immunocompromise for the patient is determined by the treating provider, and preventive actions should be tailored to each patient.

^*** RT-PCR testing is defined as the use of an RT-PCR assay to detect the presence of SARS-CoV-2 RNA.

Annex: Interim Guidance on Retesting and Quarantine of Adults Recovered from Laboratory-diagnosed SARS-CoV-2 Infection with Subsequent Re-exposure

Accumulating evidence supports the recommendation that people who have recovered from laboratory-confirmed COVID-19 do not need to undergo repeat testing or quarantine in the case of another SARS-CoV-2 exposure within 90 days of their initial diagnosis. Evidence does not indicate the definitive absence of re-infection during this period, only that risks of potential SARS-CoV-2 transmission from recovered persons are likely outweighed by the personal and societal benefits of avoiding unnecessary quarantine. CDC recommends that all people, regardless of symptoms, and regardless of whether or not they have had laboratory-confirmed COVID-19 in the past, continue to use all recommended prevention strategies to prevent SARS-CoV-2 transmission (e.g., wear masks, stay at least 6 feet away from others who do not live with you, avoid crowds, and wash hands regularly). This interim guidance is based upon information available to date and will be updated as new information becomes available.

Summary of Key Findings:

1. There are few overall reports of reinfection that have been confirmed through the detection of phylogenetic differences between viruses isolated during the initial and reinfection episodes. Some of these reports demonstrate reinfection occurring at least 90 days after infection onset, ^{(15,21,23,50,54,55)} although other reports suggest that reinfection is possible as early as 45 days after infection onset. ^{(4,32,41,44,52,53)}
2. An increasing number of published studies suggest that >90% of recovered COVID-19 patients develop anti-SARS-CoV-2 antibodies. ^{(17,22,28,57-58)} Additional studies also demonstrate antibody response, including neutralizing antibodies and antibody response following mild or asymptomatic infection, can be durable for 6 months or more. ^{(13,16,24,43)} This evidence must be interpreted cautiously, as anti-SARS-CoV-2 antibodies have not been definitively correlated with protection from SARS-CoV-2 infection, and it is unclear what antibody titer would be associated with protection.
3. Some studies have also noted lower titers and faster waning of anti-SARS-CoV-2 antibodies in mild or asymptomatic cases of COVID-19. ^{(26,35,40,43,49,51,59)}
4. It is important to note that antibodies are only one component of human immunity and that immunity may be achieved through other mechanisms such as virus-specific memory T and B cells. ^{(10,29,47,48)} Studies suggest that the memory T and B cell response can be durable for 6 months or more. ^(16,24,65) However, one study found that T cell responses were 50% higher among symptomatic adults compared with asymptomatic adults at 6 months post-infection. ⁽⁶⁵⁾
5. Animal challenge studies with SARS-CoV-2 ^(11,18) and investigations of seropositive adults in outbreak settings ^(5,45) provide initial evidence of protection against reinfection after prior infection with SARS-CoV-2. Serological surveys have also provided evidence linking antibody presence to protection against reinfection, ^(4,25,37) and an additional animal challenge study demonstrated that exogenously administered anti-SARS-CoV-2 antibodies protected against reinfection in a dose-dependent manner. ⁽³⁸⁾

Assessment

Despite millions of SARS-CoV-2 infections worldwide, including the United States, to date, surveillance and investigations have thus far demonstrated few confirmed cases of reinfection. Currently, it is unknown if recovered adults are definitively immune to SARS-CoV-2 reinfection because biologic markers of immunity have not been correlated with protection from infection. However, available evidence suggests that most recovered adults would have a degree of immunity for at least 90 days following initial diagnosis of laboratory-confirmed COVID-19. If the present guidance is implemented with current prevention strategies to prevent SARS-CoV-2 transmission (i.e., wear masks, stay at least 6 feet away from others who do not live with you, avoid crowds, and wash hands regularly), the risks of potential SARS-CoV-2 transmission from recovered adults is generally too low to justify retesting and quarantine.

However, there could be scenarios in which the risk of reinfection and potential transmission may be deemed high enough to warrant retesting and quarantine of the exposed individual who has recovered from laboratory-confirmed SARS-CoV-2 infection; this can include settings where there is low tolerance for introduction of SARS-CoV-2, such as certain congregate settings.

Circulation of variant viruses (such as the B.1.1.7 variant ⁽²⁰⁾ or B.1.1.28 variant ^(67,68)) has been reported in several countries. Reinfection with a SARS-CoV-2 variant virus has been reported in Brazil, ^(69,70,71) the U.K., ⁽⁷²⁾ and South Africa. ⁽⁷³⁾ The risk of reinfection may be increased in the future with exposure to SARS-CoV-2 variant virus strains that are not neutralized by immune antisera, such as one recently described in South Africa. ⁽⁶⁰⁾ This guidance will be updated as additional evidence emerges regarding the reinfection risk that new variants may pose.

Recommendation

If an adult has a new exposure to someone with suspected or confirmed COVID-19 and:

1. Has recovered from illness due to laboratory-confirmed (RT-PCR or antigen) SARS-CoV-2 infection and has already met criteria to end isolation, and
2. Is within the first 90 days following the onset of symptoms of their initial laboratory-confirmed SARS-CoV-2 infection or within the first 90 days of their first positive SARS-CoV-2 test result if they were asymptomatic during initial infection, and
3. Has remained asymptomatic since the new exposure,

then that adult does not require repeat testing or quarantine for SARS-CoV-2 in the context of this new exposure.

If an adult has a new exposure to a person with suspected or confirmed COVID-19 and meets the first two above criteria, but has or develops new symptoms consistent with COVID-19 within 14 days of the new exposure, consultation with a health care provider is recommended, and consultation with infectious disease or infection control experts may be necessary. If an alternative cause of the symptoms cannot be readily identified, retesting for SARS-CoV-2 infection may be warranted. In the absence of clinical evaluation to rule out SARS-CoV-2 reinfection, this adult should be isolated for the duration recommended in the memo above – for most adults, this would be 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms. Transmission-based precautions should be used as currently recommended in adults with suspected respiratory infection.

Among children and infants, data pertaining to the risk of reinfection following laboratory-confirmed diagnosis are extremely limited. However, in the context of a pandemic, children and infants should be managed as recommended for adults above.

There also may be circumstances (such as certain congregate settings) where there is increased concern for SARS-CoV-2 transmission. Under these circumstances, repeat testing for SARS-CoV-2 or quarantine can be considered if a new exposure occurs more than 90 days after recovery from a prior infection. As above, the decision to retest or quarantine should be made in consultation with a healthcare provider; consultation with infectious disease or infection control experts may also be necessary.

References

1. Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 2020 May 28;382(22):2081-2090. doi:10.1056/NEJMoa2008457external icon
2. Aydillo T, Gonzalez-Reiche AS, Aslam S, de Guchte AV, Khan Z, Obla A, et al. Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer. N Engl J Med 2020. DOI: 10.1056/NEJMc2031670external icon
3. Abu-Raddad LJ, Chemaitelly H, Coyle P, et al. SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks. Preprint. bioRxiv. 2021;2021.01.15.21249731. Published 2021 January 15. doi:10.1101/2021.01.15.21249731external icon
4. Abu-Raddad LJ, Chemaitelly H, Malek JA, et al. Assessment of the risk of SARS-CoV-2 reinfection in an intense re-exposure setting [published online ahead of print, 2020 Dec 14]. Clin Infect Dis. 2020;ciaa1846. doi:10.1093/cid/ciaa1846external icon
5. Addetia A, Crawford KHD, Dingens A, et al. Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate. J Clin Microbiol. 2020;58(11):e02107-20. Published 2020 Oct 21. doi:10.1128/JCM.02107-20external icon
6. Avanzato AA, Matson MJ, Seifert SN, Pryce R, Williamson BN, Anzick SL, et al. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell 2020 December 23;183(1–12).external icon
7. Baang JH, Smith C, Mirabelli C, Valesano AL, Manthei DM, Bachman MA, et al. Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient. The Journal of Infectious Diseases 2020.external icon
8. Bullard J, Durst K, Funk D, Strong JE, Alexander D, Garnett L, et al. Predicting Infectious SARS-CoV-2 From Diagnostic Samples. Clin Infect Dis 2020 May 22.  doi: 10.1093/cid/ciaa638external icon
9. Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105(2):435-446. doi:10.1017/s0950268800048019external icon
10. Cervia C, Nilsson J, Zurbuchen Y, et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19 [published online ahead of print, 2020 Nov 20]. J Allergy Clin Immunol. 2020;S0091-6749(20)31623-7. doi:10.1016/j.jaci.2020.10.040external icon
11. Chandrashekar A, Liu J, Martinot AJ, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science. 2020;369(6505):812-817. doi:10.1126/science.abc4776external icon
12. Cheng HW, Jian SW, Liu DP, Ng TC, Huang WT, Lin HH, et al. Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med 2020 May 1; doi:10.1001/jamainternmed.2020.2020external icon
13. Choe PG, Kim KH, Kang CK, et al. Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection [published online ahead of print, 2020 Dec 22]. Emerg Infect Dis. 2020;27(3):10.3201/eid2703.204543. doi:10.3201/eid2703.204543
14. Choi B, Choudhary MC, Regan J, Sparks JA, Padera RF, Qiu X, et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N Engl J Med. 2020 Dec 3;383(23):2291-2293external icon
15. Colson P, Finaud M, Levy N, Lagier JC, Raoult D. Evidence of SARS-CoV-2 re-infection with a different genotype [published online ahead of print, 2020 Nov 15]. J Infect. 2020;S0163-4453(20)30706-4. doi:10.1016/j.jinf.2020.11.011external icon
16. Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection [published online ahead of print, 2021 Jan 6]. Science. 2021;eabf4063. doi:10.1126/science.abf4063external icon
17. Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020;6(6):CD013652. Published 2020 Jun 25. doi:10.1002/14651858.CD013652external icon
18. Deng W, Bao L, Liu J, et al. Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Science. 2020;369(6505):818-823. doi:10.1126/science.abc5343external icon
19. Edridge AWD, Kaczorowska J, Hoste ACR, et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med. 2020;26(11):1691-1693. doi:10.1038/s41591-020-1083-1external icon
20. Galloway SE, Prabasaj P, MacCannell DR, et al. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021. MMWR Morb Mortal Wkly Rep. 2021;ePub. Published 2021 Jan 15. doi:10.15585/mmwr.mm7003e2
21. Goldman JD, Wang K, Roltgen K, et al. Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report. Preprint. medRxiv. 2020;2020.09.22.20192443. Published 2020 Sep 25. doi:10.1101/2020.09.22.20192443external icon
22. Gudbjartsson DF, Norddahl GL, Melsted P, et al. Humoral Immune Response to SARS-CoV-2 in Iceland. N Engl J Med. 2020;383(18):1724-1734. doi:10.1056/NEJMoa2026116external icon
23. Gupta V, Bhoyar RC, Jain A, et al. Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2 [published online ahead of print, 2020 Sep 23]. Clin Infect Dis. 2020;ciaa1451. doi:10.1093/cid/ciaa1451external icon
24. Hartley GE, Edwards ESJ, Aui PM, et al. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence. Sci Immunol. 2020;5(54):eabf8891. doi: 10.1126/sciimmunol.abf8891external icon
25. Harvey RA, Rassen JA, Kabelac CA, et al. Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection. Preprint. medRxiv. 2020;2020.12.18.20248336. Published 2020 Dec 20. doi:10.1101/2020.12.18.20248336external icon
26. Ibarrondo FJ, Fulcher JA, Goodman-Meza D, et al. Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19 [published correction appears in N Engl J Med. 2020 Jul 23;:]. N Engl J Med. 2020;383(11):1085-1087. doi:10.1056/NEJMc2025179external icon
27. Isho B, Abe KT, Zuo M, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020;5(52):eabe5511. doi:10.1126/sciimmunol.abe5511external icon
28. Iyer AS, Jones FK, Nodoushani A, et al. Dynamics and significance of the antibody response to SARS-CoV-2 infection. Preprint. medRxiv. 2020;2020.07.18.20155374. Published 2020 Jul 20. doi:10.1101/2020.07.18.20155374external icon
29. Kaneko N, Kuo HH, Boucau J, et al. Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19. Cell. 2020;183(1):143-157.e13. doi:10.1016/j.cell.2020.08.025external icon
30. Kiyuka PK, Agoti CN, Munywoki PK, Njeru R, Bett A, Otieno JR, et al. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. J Infect Dis 2018 May 5;217(11):1728-1739. doi: 10.1093/infdis/jiy098external icon
31. Korea Centers for Disease Control and Prevention. Findings from Investigation and Analysis of re-positive cases. May 19, 2020.external icon
32. Larson D, Brodniak SL, Voegtly LJ, et al. A Case of Early Re-infection with SARS-CoV-2 [published online ahead of print, 2020 Sep 19]. Clin Infect Dis. 2020;ciaa1436. doi:10.1093/cid/ciaa1436external icon
33. Li N, Wang X, Lv T. Prolonged SARS-CoV-2 RNA Shedding: Not a Rare Phenomenon. J Med Virol 2020 Apr 29. doi: 10.1002/jmv.25952external icon
34. Liu WD, Chang SY, Wang JT, Tsai MJ, Hung CC, Hsu CL, et al. Prolonged Virus Shedding Even After Seroconversion in a Patient With COVID-19. J Infect 2020 Apr 10;S0163-4453(20)30190-0.  doi: 10.1016/j.jinf.2020.03.063external icon
35. Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26(8):1200-1204. doi:10.1038/s41591-020-0965-6external icon
36. Lu J, Peng J, Xiong Q, et al. Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR. EBioMedicine. 2020;59:102960. doi:10.1016/j.ebiom.2020.102960external icon
37. Lumley SF, O’Donnell D, Stoesser NE, et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers [published online ahead of print, 2020 Dec 23]. N Engl J Med. 2020;10.1056/NEJMoa2034545. doi:10.1056/NEJMoa2034545external icon
38. McMahan K, Yu J, Mercado NB, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques [published online ahead of print, 2020 Dec 4]. Nature. 2020;10.1038/s41586-020-03041-6. doi:10.1038/s41586-020-03041-6external icon
39. Midgley CM, Kujawski SA, Wong KK, Collins, JP, Epstein L, Killerby ME, et al. (2020). Clinical and Virologic Characteristics of the First 12 Patients with Coronavirus Disease 2019 (COVID-19) in the United States. Nat Med 2020 Jun;26(6):861-868. doi: 10.1038/s41591-020-0877-5external icon
40. Milani GP, Dioni L, Favero C, et al. Serological follow-up of SARS-CoV-2 asymptomatic subjects. Sci Rep. 2020;10(1):20048. Published 2020 Nov 18. doi:10.1038/s41598-020-77125-8external icon
41. Mulder M, van der Vegt DSJM, Oude Munnink BB, et al. Reinfection of SARS-CoV-2 in an immunocompromised patient: a case report [published online ahead of print, 2020 Oct 9]. Clin Infect Dis. 2020;ciaa1538. doi:10.1093/cid/ciaa1538external icon
42. Personal communication with Young BE first author of preprint of: Young BE, Ong SW, Ng LF, Anderson DE, Chia WN, Chia PY, et al. Immunological and Viral Correlates of COVID-19 Disease Severity: A Prospective Cohort Study of the First 100 Patients in Singapore. (Preprint) SSRN. 2020. doi:10.2139/ssrn.3576846external icon
43. Pradenas E, Trinité B, Urrea V, et al. Stable neutralizing antibody levels six months after mild and severe COVID-19 episode. Preprint. bioRxiv. 2020;2020.11.22.389056. Published 2020 Nov 24. doi:10.1101/2020.11.22.389056external icon
44. Prado-Vivar B, Becerra-Wong M, Guadalupe JJ, et al. A case of SARS-CoV-2 reinfection in Ecuador [published online ahead of print, 2020 Nov 23]. Lancet Infect Dis. 2020;S1473-3099(20)30910-5. doi:10.1016/S1473-3099(20)30910-5external icon
45. Pray IW, Gibbons-Burgener SN, Rosenberg AZ, et al. COVID-19 Outbreak at an Overnight Summer School Retreat – Wisconsin, July-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(43):1600-1604. Published 2020 Oct 30. doi:10.15585/mmwr.mm6943a4
46. Quicke K, Gallichote E, Sexton N, Young M, Janich A, Gahm G, et al. Longitudinal Surveillance for SARS-CoV-2 RNA Among Asymptomatic Staff in Five Colorado Skilled Nursing Facilities: Epidemiologic, Virologic and Sequence Analysis. (Preprint) Medrxiv. 2020. doi:10.1101/2020.06.08.20125989external icon
47. Rodda LB, Netland J, Shehata L, et al. Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19 [published online ahead of print, 2020 Nov 23]. Cell. 2020;S0092-8674(20)31565-8. doi:10.1016/j.cell.2020.11.029external icon
48. Sekine T, Perez-Potti A, Rivera-Ballesteros O, et al. Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19. Cell. 2020;183(1):158-168.e14. doi:10.1016/j.cell.2020.08.017external icon
49. Self WH, Tenforde MW, Stubblefield WB, et al. Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Adultnel in a Multistate Hospital Network – 12 States, April-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(47):1762-1766. Published 2020 Nov 27. doi:10.15585/mmwr.mm6947a2
50. Selhorst P, Van Ierssel S, Michiels J, et al. Symptomatic SARS-CoV-2 reinfection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response [published online ahead of print, 2020 Dec 14]. Clin Infect Dis. 2020;ciaa1850. doi:10.1093/cid/ciaa1850external icon
51. Seow J, Graham C, Merrick B, et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol. 2020;5(12):1598-1607. doi:10.1038/s41564-020-00813-8external icon
52. Shastri J, Parikh S, Agarwal S, et al.. Whole genome sequencing confirmed SARS-CoV-2 reinfections among healthcare workers in India with increased severity in the second episode. Preprint. SSRN. 2020;ssrn.3688220. Published 2020 Sep 21. doi:10.2139/ssrn.3688220external icon
53. Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021;21(1):52-58. doi:10.1016/S1473-3099(20)30764-7external icon
54. To KK, Hung IF, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing [published online ahead of print, 2020 Aug 25]. Clin Infect Dis. 2020;ciaa1275. doi:10.1093/cid/ciaa1275external icon
55. Van Elslande J, Vermeersch P, Vandervoort K, et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain [published online ahead of print, 2020 Sep 5]. Clin Infect Dis. 2020;ciaa1330. doi:10.1093/cid/ciaa1330external icon
56. van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat Commun. 2021;12(1):267. Published 2021 Jan 11. doi:10.1038/s41467-020-20568-4external icon
57. Wajnberg A, Amanat F, Firpo A, et al. SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months. Preprint. medRxiv. 2020; 2020.07.14.20151126. Published 2020 Jul 17. doi:10.1101/2020.07.14.20151126external icon
58. Wajnberg A, Mansour M, Leven E, et al. Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study. Lancet Microbe. 2020;1(7):e283-e289. doi:10.1016/S2666-5247(20)30120-8external icon
59. Wang X, Guo X, Xin Q, et al. Neutralizing Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in Coronavirus Disease 2019 Inpatients and Convalescent Patients. Clin Infect Dis. 2020;71(10):2688-2694. doi:10.1093/cid/ciaa721external icon
60. Wibmer CK, Ayres F, Hermanus T, et al. Preprint. bioRxiv. 2021;2021.01.18.427166. Published 2021 January 19. doi: 10.1101/2021.01.18.427166external icon
61. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature 2020 May;581(7809):465-469. doi:10.1038/s41586-020-2196-xexternal icon
62. Xiao F, Sun J, Xu Y, Li F, Huang X, Li H, et al. Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. Emerg Infect Dis 2020;26(8):10.3201/eid2608.200681. doi:10.3201/eid2608.200681
63. Young BE, Ong SWX, Kalimuddin S, Low JG, Ta, SY, Loh J, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA 2020 Mar 3;323(15):1488-1494. doi:10.1001/jama.2020.3204external icon
64. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. (2020). SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med, 382(12), 1177-1179. doi:10.1056/NEJMc2001737external icon
65. Zuo J, Dowell A, Pearce H, et al. Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection. Preprint. bioRxiv. 2020; 2020.11.01.362319. Published 2020 Nov 2. doi: 1101/2020.11.01.362319external icon
66. CDC, unpublished data, 2020
67. Voloch CM, da Silva F Jr. R, de Almeida LGP, et al. Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil. Preprint. medRxiv 2020. Published 2020 December 26.external icon
68. Sabino EC, Buss LF, Carvalho MPS, et al. Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence. Lancet. 2021 Jan 27:S0140-6736(21)00183-5. doi: 10.1016/S0140-6736(21)00183-5. Online ahead of print.external icon
69. Nonaka CKV, Franco MM, Graf T, et al. Genomic evidence of a SARS-CoV-2 reinfection case with E484K spike mutation in Brazil. Preprints 2021, 2021010132 (doi: 10.20944/preprints202101.0132.v1).external icon
70. Naveca F, da Costa C, Nascimento V, et al. SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil. Preprint. Published 2021 January 18.external icon
71. Resende PC, Bezerra JF, de Vasconcelos RHT, et al. Spike E484K mutation in the first reinfection case confirmed in Brazil, 2020. Preprint. Published 2021 January 10, 2021.external icon
72. Harrington D, Kele B, Pereira S, et al. Confirmed Reinfection with SARS-CoV-2 Variant VOC-202012/01. Clin Infect Dis. 2021 Jan 9:ciab014. doi: 10.1093/cid/ciab014. Online ahead of print.
73. Zucman N, Uhel F, Descamps D, Roux D, Ricard JD. Severe reinfection with South African SARS-CoV-2 variant 501Y.V2: A case report. Clin Infect Dis. 2021 Feb 10:ciab129. doi: 10.1093/cid/ciab129. Online ahead of print.external icon
74. Tarhini H, Recoing A, Bridier-Nahmias A, et al. Long term SARS-CoV-2 infectiousness among three immunocompromised patients: from prolonged viral shedding to SARS-CoV-2 superinfection. J Infect Dis. 2021 Feb 8:jiab075. doi: 10.1093/infdis/jiab075. Online ahead of print.external icon