Transmission & Isolation

Last updated: February 8, 2022

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• Overview
• Key Literature 
• Resources 
• Multimedia

The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.

Overview

In the context of the rapid rise in COVID-19 cases due to the Omicron variant, CDC has updated U.S. isolation and quarantine recommendations for the general population as well as health care workers.

As COVID-19 transmission levels rise, CDC recommends a multi-pronged approach to decreasing transmission among the public, including universal face mask use, physical distancing, avoiding nonessential indoor spaces, increasing testing, prompt quarantine of exposed people, safeguarding those at increased risk for severe illness or death, protecting essential workers, postponing travel, enhancing ventilation and hand hygiene and achieving widespread COVID-19 vaccination coverage (Honein, December 2020). 

Health care settings use similar mitigation strategies, but with the addition of administrative and engineering controls such as dedicated clinical inpatient units of single negative pressure rooms with frequent air exchanges for patients known or suspected to have COVID-19, personal protective equipment for health care workers also plays an important role (CDC, July 2020).   

Transmission-based studies in people with SARS-CoV-2 virus provide important information about duration of infectiousness and transmission risk (Meyerowitz, January 2021; Wolfel, April 2020; Lu, June 2020; Young, April 2020; Kujawski, April 2020; van Kampen, June 2020; Bullard, May 2020; Zou, March 2020; Cheng, May 2020). In these studies, the highest viral loads are detected in the upper respiratory tract several days before symptom onset, then decrease precipitously, usually by day 8 after symptom onset (Meyerowitz, January 2021). Much of this work has been done using prior SARS-CoV-2 variants. Work on infections due to the Omicron variant suggests that on average there may be a shorter incubation period of about two to four days (Jansen, December 2021; Brandal, December 2021; Lee, December 2021). For additional details about SARS-CoV-2 viral dynamics, see the RT-PCR testing section.  

CDC recommends the following strategies for discontinuing isolation and precautions (as opposed to testing-based strategies):   

• If a person tests positive for COVID-19 or has symptoms, regardless of vaccination status, isolate at home for at least five days.
• A well-fitted mask should be worn around others until day 10, and travel should be avoided as well as being around others who are considered high-risk.
• If the individual has experienced symptoms, they may end isolation after five full days if they have been fever-free for 24 hours without the use of fever-reducing medication and other symptoms have improved.
• If the individual experienced no symptoms, they may end isolation after at least five days but should wear a well-fitting mask around others for at least 10 days.
• If an individual develops symptoms after testing positive, their 5-day isolation period should start over. The first day of symptoms is day 0.

Regarding exposure to COVID-19:

CDC guidance states that individuals who are exposed to COVID-19 and not up-to-date on COVID-19 vaccination should quarantine for at least five days and get tested.

• These individuals should get tested and stay home for five days.
• Until day 10 take all precautions including wearing a mask, avoiding travel and avoiding high-risk people; if symptoms develop, isolate.
• Re-test on day five, if possible.

CDC guidance states that individuals with a suspected or confirmed COVID-19 exposure who are up to date on COVID-19 vaccination or have had confirmed COVID-19 within the past 90 days (i.e., tested positive using a viral test) are not initially required to quarantine.

• These individuals should get tested and, if symptoms develop, should isolate.
• Until day 10 they should avoid travel, wear a mask and avoid people who may be high risk.
• Re-test on day five, if possible.

With the growing number of COVID-19 cases from the Omicron variant, and consistent with current understanding of the disease trajectory, CDC has updated specific guidance for isolation and quarantine for health care workers, and released guidance for contingency and crisis management during significant health care worker shortages. These updates provide health care facilities with strategies to limit the effects of staff shortages caused by COVID-19 on patient care and note that health care workers who have received all recommended COVID-19 vaccine doses, including a booster, do not need to quarantine at home following high-risk exposures.

For information on transmission prevention in the healthcare setting, including a discussion of the potential routes of SARS-CoV-2 transmission, please see the Personal Protective Equipment in Medical Settings section.

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Key Literature

In summary: Knowledge is evolving on the duration of infectivity of patients with COVID-19; current data suggests people begin to transmit SARS-CoV-2 a few days prior to symptom onset, that non-immune-compromised hosts with non-critical illness are unlikely to be infectious 10 days after symptom onset and that individuals with critical illness or significant immune compromise are unlikely to be infectious 15 days after symptom onset. Peak transmission likely occurs around symptom onset, when viral RNA load is at its highest. While prolonged viral RNA shedding can occur, in most cases SARS-CoV-2 cannot be cultured after 8-12 days; whether viral culture directly correlates to a lack of infectivity is not known, but epidemiologic data suggests it may be a reasonable surrogate marker.

Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools — Georgia, November 16–December 11, 2020 (Gettings, May 2021).  

Study population:  

• Students at 169 elementary schools in the state of Georgia. 

Primary endpoint:  

• COVID-19 incidence amid staff and children at these elementary schools.

Key findings:  

• This was a study of elementary schools in the state of Georgia with varying school-based infection prevention measures, including physical barriers in the classroom, social distancing, reductions in class size, cohorting of students, increased handwashing stations, mandated masking and ventilation strategies.  
• The study found that COVID-19 rates were 39% lower in schools that introduced ventilation strategies and 37% lower in schools that mandated masking for staff and teachers.    

Limitations:  

• Infections were self-reported.  
• Compliance with infection prevention measures such as masking was not measured. 
• Response rate was low at 11.6%. 
• Infection control practices were not standardized across all sites. 
  

Risk Factors Associated With SARS-CoV-2 Seropositivity Among U.S. Health Care Personnel (Jacob, March 2021).  

Study population:  

• 24,749 health care personnel in 3 U.S. states. 

Primary endpoint:  

• SARS-CoV-2 seropositivity.

Key findings:  

• In this cross-sectional study, community exposures (e.g., community contact, community cumulative incidence) were associated with seropositivity to SARS-CoV-2, but workplace factors were not.  
• These results suggest that current infection prevention practices in health care settings such as hospitals, rehabilitation facilities and skilled nursing facilities are effective in preventing transmission of SARS-CoV-2 from patients to health care personnel.  

Limitations:  

• Laboratory methods differed across sites. 
• Questionnaires were not standardized at each site. 
• Risk factors included in the authors’ multivariable model were limited to those that could be mapped from all sites. 
• Infection control practices were not standardized across all sites, and the practices changed during the study period. 
• This study included mostly urban/metropolitan settings. 

 

The household secondary attack rate of SARS-CoV-2: A rapid review (Fung, October 2020).

Overall, in this review of 22 published and pre-published studies, testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases.  This suggests that studies with less intensive testing may have missed cases and underestimated the household secondary attack rate.

Study population:

• 22 published and pre-published studies with data from 20,291 household contacts in 10 countries, 3,151 of whom (15.5%) tested positive for SARS-CoV-2.
• Household contacts are defined as people living in the same residence as the index case.
• The household secondary attack rate was defined as the percentage of all household contacts who were reported to have tested positive for SARS-CoV-2 by RT-PCR.

Primary endpoint:

• To evaluate estimates of the SARS-CoV-2 household secondary attack rate and explore their variation.

Key findings:

• The number of household contacts per study ranged from 11 to 10,592.
• 4 of the studies were classified as high quality, 14 as moderate quality and 4 as low quality.
• The overall pooled random-effects estimate of the household secondary attack rate was 17.1% (95% CI, 13.7-21.2%).
• In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, >2 tests), SAR estimates were 9.2% (95% CI, 6.7-12.3%), 17.5% (95% CI, 13.9-21.8%) and 21.3% (95% CI, 13.8-31.3%), respectively.
• Household secondary attack rate tended to be higher among older adult contacts and among contacts of symptomatic cases.

Limitations:

• Household size and composition, contact patterns and testing and isolation practices all vary substantially geographically.

 

Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR (Lu, June 2020). 

Overall, 14% of patients in this study were positive for SARS-CoV-2 on RT-PCR.  In a subsample of specimens, viral culture was attempted but not successful.

Study population: 

•  619 COVID-19 cases who were discharged between 23 January and 19 February, isolated in hotels, and underwent repeat testing on day 7 and 14 after discharge.  

Primary endpoint: 

• To characterize re-positive patients with COVID-19. 

Key findings: 

• 87 of the 618 people tested became positive for SARS-CoV-2 on repeat RT-PCR testing. 
• All re-positive cases had mild or moderate symptoms in initial diagnosis, with a mean age of 30.4 years. 
• 137 swabs and 59 serum samples from 70 re-positive cases were collected. 
• Neutralization antibodies (NAbs) titer distributions of the 59 serum samples were similar to other COVID-19 cases (n=150) parallel-tested in the study.  
• Viral culture was attempted on 33 repeat positive cases; successful isolation did not occur, and no full-length viral genomes could be sequenced.  

Limitations: 

• Successively collected samples were not collected, resulting in bias towards the summarized duration from the discharge to firstly re-positive result for viral RNA as well as the time of the re-positive RNA to negative.  
• The corresponding samples were not collected during the acute infection for re-positive cases; therefore, genetic differences remain for SARS-CoV-2 viruses sampled in an acute infection phase and a re-positive phase. 
• Antibody testing and viral culture was not attempted on the majority of repeat positive cases    

Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants (vanKampen, June 2020). 

Overall, in this prospective study, the median duration of shedding of culturable virus was 8 days; after approximately 15 days of viral RNA shedding, the probability of being able to isolate virus on culture dropped below 5%.

Study population: 

• 129 hospitalized patients with COVID-19 in the Netherlands. 89 (69%) were admitted to the ICU, and 81 required mechanical ventilation. 
• Neutralizing antibody titers from 112 serum samples from 27 patients were available. 
• 690 respiratory samples from the 129 patients were tested for viral culture. 

Primary endpoint:  

• Duration and determinants of infectious virus shedding (defined by positive viral culture). 

Key findings: 

• 14.7% of patients were moderately or severely immunocompromised. 
• Infectious virus shedding was present in 23 of the 129 patients (17.8%).  
• The median duration of infectious virus shedding was 8 days post onset of symptoms (IQR 5-11). 
• The probability of detecting infectious virus dropped below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4-17.2).  
• Multivariate analyses identified viral loads > 7 log10 RNA copies/mL (odds ratio [OR]; CI 14.7 (3.57-58.1; p<0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract.  
• A serum neutralizing antibody titer of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p<0.001) was independently associated with non-infectious SARS-CoV-2. 

Limitations: 

• Positive viral culture was used as a marker of infectiousness, but whether this is the best surrogate, given the poor sensitivity of viral culture, is unclear. 
• The study only included patients with severe disease; the findings may not be generalizable to asymptomatic or mild-moderate patients. 
• Samples for virologic assessment were not collected at predefined timepoints.  

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset (Cheng, May 2020). 

Overall, in this prospective study of patients with COVID-19 and their close contacts, the overall clinical secondary attack rate was 0.7%. This increased if the contact occurred within 5 days of symptom onset in the index case, implying increased risk of transmission around the time of symptom onset.  

Study population: 

• Prospective case-ascertained study of 100 patients in Taiwan with confirmed COVID-19 and 2761 close contacts. 
• All close contacts were quarantined at home for 14 days after their last exposure to the index case. 
• During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of close contacts triggered RT-PCR testing 
• For high-risk contacts, including household and hospital contacts, RT-PCR was performed regardless of symptoms (ie, once when they were listed as a close contact). If the initial COVID-19 test result was negative, further testing would only be performed if a close contact developed symptoms during quarantine.

Primary endpoint: 

• Secondary clinical attack rate (symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). 

Key findings: 

• Of the 2761 close contacts, 22 people became infected; 4 of these were asymptomatic. 
• The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%).  
• The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%).  
• The 299 contacts with only presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]).  
• The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and non-household (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings.  
• The attack rates were higher among those aged 40-59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged > 60 (0.9% [95% CI, 0.3%-2.6%]). 

Limitations: 

• Universal testing was performed in high-risk contacts, but not for others; this may have missed some secondary cases. 
• Contacts were not completely examined prior to symptom onset of the index cases; therefore, there may be an underestimation of early transmission from the index case. In addition, it is possible the contacts were infected from a source other than the index case. 
• Increased transmissibility in the early stage of COVID-19 may be due to the effect of household and non-household family contacts. 

 

Findings from investigation and analysis of re-positive cases (Korea Centers for Disease Control and Prevention, May 2020). 

Overall, in this unpublished epidemiologic study of re-positive patients with COVID-19 in South Korea, no secondary infections appeared to have occurred. SARS-CoV-2 was unable to be isolated from these patients, supporting the idea that viral RNA shedding was not associated with infectivity (assuming viral culture is a reasonable surrogate for infectiousness. 

Study population: 

• 477 patients in South Korea with RT-PCR-confirmed SARS-CoV-2 infection who were hospitalized and then discharged with negative RT-PCRs, and then became positive again after isolation was discontinued. 
• Successful contact tracing and epidemiologic investigation was completed on 285 of the 477 repeat positives. 
• 790 contacts, including 351 family members, were identified and followed for 14 days from exposure. 

Primary endpoint: 

• Epidemiological and virological investigation. 

Key findings: 

• 126 (44.2%) of 285 individuals with re-positive PCR tests had developed new upper respiratory tract symptoms.  
• On average, it took 44.9 days (range: 8-82 days) from initial symptom onset date to re-testing positive after discharge. 
• On average, it took 14.3 days (range: 1-37 days) from discharge to testing positive.  
• Respiratory viral cultures were attempted in 108 of the repeat positive cases; none resulted in isolation of SARS-CoV-2. 
• Of the 23 re-positive cases from whom the first and the second serum samples were obtained, 96% were positive for neutralizing antibodies. 
• Three of the 790 contacts developed COVID-19 infection, and none were clearly related to the index case (all 3 infections were traced to the Shincheonji religious group outbreak or a different family member).  

Limitations: 

• Roughly 40% of the repeat positive patients did not undergo complete contact investigation; whether the findings in the contacts of these patients would have been different is not known. 
• Contacts were only followed for 14 days from exposure. 
• Serology was not performed on all patients.   

Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon (Li, April 2020). 

Overall, in this cohort of 378 patients with mild COVID-19, prolonged viral RNA shedding of SARS-CoV-2 for 30 days or more was noted in 36 patients; the median duration of viral RNA shedding was 53.5 days, and IgG and IgM antibodies were detected. Most of these patients had comorbidities.

Study population: 

• 36 patients with confirmed COVID-19 via RT-PCR on samples collected from the respiratory tract in China who had viral RNA shedding for 30 days or more. 

Primary endpoint: 

• To describe the clinical characteristics of patients with confirmed COVID-19 who shed viral RNA for 30 days or more. 

Key findings: 

• The median age of patients was 57.5 years (IQR 52‐65); 11.1% were <40 years old.  
• Most patients had comorbidities (22 [61.1%]), including cardiovascular diseases (16 [44.4%]), metabolic diseases such as diabetes and gout (7 [19.4%]), and chronic respiratory diseases (3 [8.3%]).  
• On admission, 33 (91.7%) and 3 (8.3%) patients had mild and severe COVID‐19, respectively. 
• The median duration of viral RNA shedding was 53.5 days (IQR 47.75‐60.5).  
• IgG and IgM were detected in the patients, and at week 9 their mean values were 150 and 50 AU/mL, respectively 
• Compared to patients that had late-onset symptoms, patients with early‐onset symptoms had longer durations of viral shedding and more severe illnesses. 

Limitations: 

• This was a small sample size from a single center. 
• Most of the patients received antiviral therapies at different points in their infections; 5.7% received Remdesivir. This may have altered the results. 
• Most patients had mild COVID-19 and were younger; therefore, these results may not be generalizable to severe patient populations and older individuals.  

Prospective Evaluation of SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients (Zou, March 2020). 

Overall, in this small prospective study of patients with COVID-19, detectable virus was present in an asymptomatic patient at levels similar to his symptomatic family members, suggesting the presence of viral shedding and the potential for transmission in asymptomatic individuals. 

Study population: 

• 18 patients within 2 family clusters with COVID-19 from China; 1 person was asymptomatic, while 13 had pneumonia on CT.  
• 72 throat swabs and 72 nasal swabs were collected.  

Primary endpoint: 

• Viral load measurements via RT-PCR. 

Key findings: 

• Two family clusters of infections were identified. After returning from Wuhan, 14 individuals contracted COVID-19 determined to be imported. In addition to the asymptomatic transmission, 4 secondary infections developed.    
• In symptomatic patients, the highest SARS-CoV-2 levels were observed soon after symptom onset, while in the asymptomatic patient the virus was detected for 5 consecutive days.  

Limitations: 

• Small sample size. 
• Patients were part of the same family cluster; viral inoculum may have been higher in this group than in patients who are infected outside of the home.   

Additional Literature

Antibody Responses 8 Months after Asymptomatic or Mild SARS-CoV-2 Infection (Choe, December 2020). Antibody responses of 58 persons 8 months after asymptomatic (N=7) or mildly symptomatic infection (N=51) with SARS-CoV-2 were investigated at Seoul National University Hospital using 4 commercial immunoassays. Rates of antibody positivity according to 3 commercial kits was still high at 8 months after infection, even in asymptomatic or mildly symptomatic participants (69.0%–91.4%). The surrogate virus neutralization test (sVNT) found positive neutralizing activity for 31 (53.4%).

Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence (Hartley, December 2020).  The longevity and immunophenotype of SARS-CoV-2-specific memory T cells and memory B cells (Bmem) in 25 patients with COVID-19 were evaluated using fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP).  Thirty-six blood samples were obtained between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM+ or IgG1+ and continued to rise until 150 days.  Nearly all RBD-specific IgG+ Bmem cells expressed CD27 and their numbers correlated with circulating TFH cells, indicative of long-lived immune memory. 

The Duration of Infectiousness of Individuals Infected with SARS-CoV-2 (Walsh, October 2020). This review summarizes 15 relevant studies, including 13 virus culture and two contact tracing studies. In five of the virus culture studies, the last day on which SARS-CoV-2 was isolated was within 10 days of symptom onset. In another five virus culture studies, SARS-CoV-2 was isolated beyond day 10 for approximately 3% of included patients. The remaining three virus culture studies included patients with severe or critical disease and found that immunocompromised and severe-to-critical patients may be infectious for >10 days. The two contact tracing studies found no evidence of laboratory-confirmed onward transmission of SARS-CoV-2 when close contacts were first exposed more than 5 days after symptom onset in the index case.

Duration of SARS-CoV-2 Infectivity: When is it Safe to Discontinue Isolation? (Rhee, August 2020). In this review summarizing the duration of infectivity of SARS-CoV-2, the authors found the following: median incubation period for SARS-CoV-2 is 5 days, with an IQR of 2-7 days; 98% of patients who develop symptoms do so within 12 days; viral RNA levels peak at symptom onset; asymptomatic and pre-symptomatic individuals transmit prior to symptom onset; sicker patients tend to have detectable RNA for longer periods, but prolonged PCR positivity also occurs in mildly ill and asymptomatic individuals; and persistently positive SARS-CoV-2 RNA PCRs are due to residual viral “debris” rather than replication-competent virus.

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