Viral Shedding

Clinical Question

What is the duration of viral shedding in COVID-19?

Key Findings

  • Viral shedding typically reaches peak soon after symptom onset and the persistence of virals shedding/viral loads appears to be correlated with disease severity
  • There is evidence of high viral shedding in both symptomatic and asymptomatic individuals
  • Viral shedding was present in nasopharyngeal, oropharyngeal, pulmonary and fecal samples with fecal swabs persisting longer than oral swabs; however, only throat and pulmonary samples appeared to have infectivity.
  • More studies are showing that viral clearance occurs by day 21 after symptom onset, viral loads peak near symptom onset, and greatly decline by day 7 which is in agreement with prior literature.[1][2][3][4]

Summary of Information

Viral shedding from nasopharyngeal swabs and posterior oropharyngeal swabs

Virus shedding reports and research have shown varying results. A summary of notable results from different studies are below:

  1. Virus shedding has been detected for as long as 34 days from illness onset. This period does not seem to shorten after treatment with antivirals (lopinavir/ritonavir).[5]
    In a report[6] by the European Center for Disease Control and Prevention they cite that studies have shown the following: Positive Viral RNA can be detected 1-2 days before symptom onset and can persist up to 14 days.[7]
  2. Viral shedding from nasopharyngeal aspirates up to 24 days after symptoms onset.[8]
  3. Positive Posterior Oropharyngeal swabs occurred 20+ days post-symptom onset in ⅓ of patients. Up to day 25 post-symptom onset in one patient.[2]
  4. Viral load often peaks shortly after presentation of symptoms, this is a high infectivity period no matter what the severity of symptoms.[1][2]
  5. Viral load/peaks are correlated with disease severity. Liu et al. reported in their cohort study that 90% of mild cases repeat tested negative 10 days post-symptom onset but 100% of severe cases repeat tested positive 10 days post-symptom onset.[9]

In aggregate, the number of days before repeat Viral RNA negatives are seen in respiratory tract swab testing is contingent on disease severity. Amongst severe cases though, 10 days is often the absolute minimum number of days required before repeat negatives are seen but repeat positive tests are often seen for much longer periods of times, stretching to as long as 34 days. Viral load peaks typically occur 0-2 days post symptom-onset.

Other considerations:

  • Peak viral load measurements are strongly correlated with to age (and comorbidities) of the patient.[2]
  • Self-collected Posterior Oropharyngeal Saliva (a confluence point for URT [upper respiratory tract], LRT [lower respiratory tract], and salivary gland secretions) Testing may be the most non-invasive, reduced-transmission risk method of sample collection.[2] This method is limited because it does not determine URT vs LRT predilection[2] and has been shown to test negative even while other tests remain positive in at least one patient.[1]
  • Viral Rebound (through Posterior Oropharyngeal Saliva) has been demonstrated in patients (negative day 21 and 22, positive day 23 and 24)[2]

Viral shedding & viral load from non-respiratory diagnostic testing

Fecal swabs seem to stay positive longer than oral swab tests. Fan et al. demonstrated that the oropharyngeal specimens show negative result for SARS‐CoV‐2 14 days after the onset of illness while anal swabs remain positive 28 days after illness onset.[10] In the aforementioned European Center for Disease Control and Prevention report[6], they cite that studies show:

  • Viral RNA has been detected in feces for up to 4-5 weeks but the significance of this is unclear[7]
  • Viral shedding has been seen in convalescent children with mild infections for 22 days and more than a month in feces[8]

A study of 57 patients from Guangzhou Eigth People’s Hospital demonstrated that Serum and Anal Swab Positives are correlated with higher disease severity, which is important for disease prediction.[11]

Amongst 23 patients from two Hong Kong hospitals, Antibody Response [IgG and IgM to internal Nucleoprotein & surface spike protein receptor binding domain (RBD) ] often increased at roughly 10 days post-symptom onset. Seroconversion occured in most patients within 3 weeks.[2]

A study of 17 patients in Singapore shows that there is no viral shedding from tears regardless of the stage of the disease (disease in these patients confirmed by RT-PCR of nasopharyngeal swabs).[12]

Viral shedding in symptomatic and asymptomatic patients

There is evidence that symptomatic and asymptomatic patients can carry high viral loads. This is true for children and adults.[13][14][15] Studies have constructed timelines to demonstrate how asymptomatic persons transmit the disease during the virus’s incubation period.[13][14] Additionally, it’s been shown that asymptomatic patients can have viral loads similar to symptomatic patients (cycle threshold [Ct] values 22-28 from nasal swabs and 30-32 from throat swabs; Ct values of 30.76, 27.67, 24.56, and 21.48 correspond to 1.5×104, 1.5×105, 1.5×106, and 1.5×107 copies per milliliter).[15]

Infectivity in asymptomatic & symptomatic patients

Preprint Study: Study results showed there is a high viral load and virus could be detected in fecal, throat, and lung derived samples during the first week. However, only throat and lung derived samples showed capability for infectivity. Active replication of the virus was detected in the throat for the first five days after symptom onset. Serum conversion was seen 6-12 days after symptom onset but viral load decline did not follow. This demonstrates that viral shedding through sputum continues after the end of symptoms but infectivity during this period was not assessed.[16]

Peak Viral Load can occur before severe disease progression (ie during mild symptom presentation)[1]

Preprint Study: Infectiousness begins ~2-3 days prior to symptom onset (thus informing contact tracing), Infectiousness peaked at 0.6 days post symptom onset. 44% transmissions before symptom onset. Sensitivity Analysis: 4 or 6 days, 0-2 days, 52% or 46%13. New data agrees that infectiousness begins 2.3 days before symptom onset but predicts that peak infectiousness is 0.7 days before symptoms onset.[17]

Factors associated with prolonged viral shedding

New study finds that male sex (OR = 3.24; 95% CI: 1.31–8.02), delayed addmission to hospital (>5 days from symptom onset) (odds ratio [OR] = 1.30; 95% confidence interval [CI]: 1.10-1.54), and invasive mechanical ventilation (OR = 9.88; 95% CI: 1.11-88.02) are independently associated with prolonged viral RNA shedding. Of the 113 patients studied 84 had viral RNA clearance within 21 days and the median duration of viral shedding was 15 days.[3]

Author Information

Authors: Danielle Urman MS1, Andrew Chang MS1; UC San Diego School of Medicine
Completed on: March 27, 2020
Last updated: April 17, 2020

Reviewed by: Marsha-Gail Davis MD
Reviewed on: April 12, 2020

This summary was written as part of the CoRESPOND Earth 2.0 COVID-19 Rapid Response at UC San Diego. For more information about the project, please visit http://earth2-covid.ucsd.edu

References

  1. Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020;382(10):929-936.  [PMID:32004427]
  2. To, Kelvin Kai-Wang, et al. “Temporal Profiles of Viral Load in Posterior Oropharyngeal Saliva Samples and Serum Antibody Responses during Infection by SARS-CoV-2: an Observational Cohort Study.” The Lancet Infectious Diseases, 2020, doi:10.1016/s1473-3099(20)30196-1
  3. Factors associated with prolonged viral RNA shedding in patients with COVID-19 | Clinical Infectious Diseases | Oxford Academic. https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa351/5818308. Accessed April 17, 2020.
  4. He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med. 2020.  [PMID:32296168]
  5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054-1062. doi:10.1016/S0140-6736(20)30566-3
  6. Discharge criteria for confirmed COVID-19 cases. European Centre for Disease Control and Prevention. ECDC Technical Report:5.

  7. World Health Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Geneva: WHO; 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf.
  8. Cai J, Xu J, Lin D, et al. A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis. 2020.  [PMID:32112072]
  9. Liu, Yang, et al. “Viral Dynamics in Mild and Severe Cases of COVID-19.” The Lancet Infectious Diseases, 19 Mar. 2020, doi:10.1016/S1473-3099(20)30232-2
  10. Fan Q, Pan Y, Wu Q, et al. Anal swab findings in an infant with COVID-19. Pediatr Investig. 2020;4(1):48-50.  [PMID:32328338]
  11. Chen W, Lan Y, Yuan X, et al. Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg Microbes Infect. 2020;9(1):469-473.  [PMID:32102625]
  12. Seah IYJ, Anderson DE, Kang AEZ, et al. Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients. Ophthalmology. 2020.  [PMID:32291098]
  13. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020;382(12):1177-1179.  [PMID:32074444]
  14. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020;382(10):970-971.  [PMID:32003551]
  15. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020.  [PMID:32083643]
  16. Woelfel R, Corman VM, Guggemos W, et al. Clinical Presentation and Virological Assessment of Hospitalized Cases of Coronavirus Disease 2019 in a Travel-Associated Transmission Cluster. Infectious Diseases (except HIV/AIDS); 2020. doi:10.1101/2020.03.05.20030502
  17. He, Xi, et al. “Temporal Dynamics in Viral Shedding and Transmissibility of COVID-19.” MedRxiv, 18 Mar. 2020, doi:10.1101/2020.03.15.20036707
  18. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020.  [PMID:32125362]