Last updated: September 3, 2020
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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.
A key intervention to prevent community transmission of SARS-CoV-2 is the prompt isolation of people with active COVID-19 infection. To be most effective at controlling spread, these strategies should be followed with contact tracing and a 14-day quarantine of those deemed to have been exposed (CDC, May 2020).
Healthcare settings use similar mitigation strategies, but with the addition of administrative and engineering controls such as dedicated clinical in-patient units of single negative pressure rooms with frequent air exchanges for patients known or suspected to have COVID-19, personal protective equipment for healthcare workers also plays an important role (CDC, July 2020).
Transmission-based studies in people with SARS-CoV2 virus provide important information about duration of infectiousness and transmission risk (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 and decrease precipitously after symptom onset. In patients with mild to moderate disease, the virus has not been cultured 10-12 days post symptom onset, even in setting of positive molecular RNA amplification test, indicating viral RNA present but no longer replication competent. In one unpublished study of 129 patients with severe to critical COVID-19, 5 patients had positive cultures at 15 days post symptom-onset or beyond, while one patient had a positive viral culture at 20 days. For additional details about SARS-CoV-2 viral dynamics, see the RT-PCR testing section.
Based on the evidence, CDC recommends the following symptom- and severity-based strategies for discontinuing isolation and precautions (as opposed to testing-based strategies):
- For most patients, isolation and precautions can be discontinued 10 days after symptom onset, resolution of fever for at least 24 hours (without antipyretics), and improvement in other symptoms.
- For some patients with severe disease or severe immunosupression, consider waiting 20 days after symptom onset to discontinue isolation.
- For asymptomatic patients, isolation can be discontinued 10 days after a positive SARS-CoV-2 RT-PCR test.
- A testing strategy requiring one or two consecutive SARS-CoV-2 PCR tests may be used in severely immunocompromised patients to discontinue or prolong transmission-based precautions
Here we describe data on viral RNA shedding of SARS-CoV-2 and contact tracing of known cases; 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.
Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR (Lu, June 2020).
- 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.
- To characterize re-positive patients with COVID-19.
- 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.
- 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
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.
Shedding of infectious virus in hospitalized patients with coronavirus disease-2019 (COVID-19): duration and key determinants (vanKampen, June 2020)
- 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.
- Duration and determinants of infectious virus shedding (defined by positive viral culture).
- 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.
- 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.
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%.
Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset (Cheng, May 2020).
- 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.
- 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).
- 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%]).
- 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.
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.
Findings from investigation and analysis of re-positive cases (Korea Centers for Disease Control and Prevention, May 2020).
- 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.
- Epidemiological and virological investigation.
- 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).
- 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.
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.
Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon (Li, April 2020).
- 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.
- To describe the clinical characteristics of patients with confirmed COVID-19 who shed viral RNA for 30 days or more.
- 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.
- 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.
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.
Prospective Evaluation of SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients (Zou, March 2020).
- 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.
- Viral load measurements via RT-PCR.
- 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.
- 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.
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.