Chinese researchers have isolated live COVID-19 virus from the feces of patients who died from the disease, according to a report published yesterday in Emerging Infectious Diseases.
In the same journal, a separate group of Chinese researchers reported detection of RNA from SARS-CoV-2, the virus that causes COVID-19, on surfaces in hotel rooms used to quarantine people suspected of having the disease.
Aerosolized feces possible disease vector
In the first study, researchers describe the case of a 78-year-old COVID-19 patient who had recently traveled to Wuhan, China, and was hospitalized in Guangzhou, China, on Jan 17. The man had a cough, sporadic fevers, and abnormal chest computed tomography (CT) findings.
On Jan 22, the patient was placed on a ventilator after his conditioned worsened. Reverse transcription-polymerase chain reaction (RT-PCR) detected SARS-CoV-2 RNA in four feces specimens collected from Jan 27 to Feb 7. Antigens to the virus were also found on gastrointestinal surface cells collected from a biopsy sample. The patient died on Feb 20.
Fecal samples contained higher loads of virus DNA than did respiratory specimens collected 17 to 28 days after symptom onset.
The researchers couldn’t isolate live virus from fecal samples collected at later time points, although RT-PCR continued to detect viral RNA, “indicating only RNA fragments, not infectious virus, in feces of this patient,” they wrote.
When the researchers negatively stained residue from a culture and visualized it using transmission electron microscopy, they saw spherical viral particles with spike proteins characteristic of SARS-CoV-2.
They also collected fecal specimens from 27 other patients, 11 of whom tested positive for virus RNA at least once. They were able to isolate live SARS-CoV-2 from two of them, “indicating that infectious virus in feces is a common manifestation of COVID-19,” they said.
The authors said that their findings show the need for hospital personnel to carefully clean surfaces after the release or death of a patient with severe disease to avoid potential spread of the virus from feces.
They noted a 2004 study suggesting that faulty sewage lines led to the aerosolization of feces contaminated with SARS-CoV-1, the virus that causes severe acute respiratory syndrome (SARS), in a residential building in Hong Kong during the 2003 outbreak of that disease. Of 329 residents who were sickened, 42 died.
“Isolation of infectious SARS-CoV-2 in feces indicates the possibility of fecal–oral transmission or fecal–respiratory transmission through aerosolized feces,” they wrote.
Pillowcases, sheets most heavily contaminated
In the second study, researchers found SARS-CoV-2 RNA on 8 of 22 surfaces (36%) and bedding sampled in two hotel rooms after two presymptomatic former guests were confirmed to have COVID-19.
The guests were Chinese students who returned to China after studying overseas on Mar 19 and 20. Although they were asymptomatic, they were to be quarantined in the hotel for 14 days but tested positive for COVID-19 on RT-PCR 2 days into quarantine.
After the two were hospitalized, nose-throat, sputum, and fecal samples all demonstrated high loads of SARS-CoV-2 RNA. They both developed a fever and cough, and one had abnormal chest CT findings.
About 3 hours after the patients tested positive, the researchers sampled the door handles, light switches, faucet handles, thermometers, TV remotes, pillowcases, duvet covers, sheets, towels, bathroom door handles, and toilets of the two hotel rooms and one room that had stayed unoccupied. Because the hotel had been closed Jan 24 to Mar 18, only the two students had stayed there.
Six (55%) of 11 samples from one patient’s hotel room tested positive for SARS-CoV-2 RNA, including the sheet, duvet cover, pillowcase, and towel; the pillowcase and sheet, with whom the patient had prolonged contact, had a high viral load. The pillowcase in the other patient’s hotel room also tested positive.
“Presymptomatic patients with high viral load shedding can easily contaminate the environment in a short period,” the authors wrote, acknowledging that they didn’t isolate live virus from the samples.
They advised that used linens not be shaken when they are removed from beds and that they should be thoroughly cleaned and dried before reuse.
As the coronavirus disease 2019 (COVID-19) pandemic continues to evolve, the number of cases and the death toll continue to rise, posing a substantial threat to global public health. As of April 23, 2020, the United States (US) has the highest number of COVID-19 cases (31.5%) and deaths (22.8%) in the world.1
Both clinicians and hospitalized patients are facing complications including limited resources, workforce, and information, thus making infection control an even higher priority.
The median basic reproduction number (R0) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is estimated to be 5.7 (95% confidence interval, 3.8–8.9);2 this value holds great significance as, theoretically, an infection will continue to spread as long as R0 >1.
With growing concern, the focus needs to shift toward strategies to mitigate the spread of infection in both hospital and community settings alike. We believe the current isolation guidelines need to be revisited and clinicians should counsel patients with COVID-19 to practice contact precautions for longer duration, given the new evidence suggesting the possibility of a fecal-oral route of transmission.
According to current Centers for Disease Control and Prevention (CDC) recommendations, discontinuation of transmission-based precautions as per the test-based strategy in patients with COVID-19 is warranted after all of the following:
(1) resolution of fever without the use of fever-reducing medications;
(2) improvement in respiratory symptoms; and
(3) two consecutive negative reverse transcriptase polymerase chain reaction (rRT-PCR) results of nasopharyngeal swabs obtained at least 24 h apart.3
For asymptomatic individuals, contact precautions can be discontinued seven days after diagnosis; should they remain asymptomatic three days after the discontinuation, individuals should still practice social distancing and nasal/oral barrier protection.3
To date, COVID-19 has been thought to be transmitted via respiratory droplets, with most patients commonly presenting with fever, cough, or dyspnea. However, studies have also reported gastrointestinal manifestations including diarrhea, nausea, vomiting, and abdominal discomfort in addition to respiratory symptoms.4
When selectively tested, 28 of 42 patients were positive for SARS-CoV-2 viral RNA on rRT-PCR in both nasopharyngeal and fecal specimens.5 Detecting extrapulmonary viral RNA does not necessarily confirm the presence of infectious virions; however, active infection cannot be excluded.
Studies have found that viral shedding of SARS-CoV-2 RNA in feces occurred even after testing negative in nasopharyngeal swabs, having lasted for approximately seven days.4 , 5 In a study from China, 41 of 74 patients had both fecal and respiratory samples tested positive for SARS-CoV-2 RNA, with stool samples showing positive results for longer periods than respiratory samples (days after onset of first symptom, 27.9 ± 10.7 versus 16.7 ± 6.7).6
In a case series conducted examining the first 12 patients with COVID-19 in the US, SARS-CoV-2 RNA was detected in the stool sample of 7 of 10 patients.7 Furthermore, a recent case reported an asymptomatic patient with COVID-19 who retested positive for SARS-CoV-2 despite being discharged after two negative consecutive respiratory nucleic acid tests at least 24 h apart, raising concern for inadequate discharge protocol.
Notably, he was found to have a weakly positive stool sample test during his observation. Should these patients remain contagious and prematurely discontinue self-isolation, they may disrupt current infection control.8
Moreover, to date, one study has successfully cultured live SARS-CoV-2 from a fecal specimen, with implications that stool samples may contaminate hands, food, water, and so on.9
The resilience of SARS-CoV-2 plays a role in its virulence and pathogenesis. Owing to its hard outer shell, the virus can remain active for extended periods of time and may be more resistant to antimicrobial and digestive enzymes in body fluids.10
In addition, as per nucleocapsid and membrane protein analysis, SARS-CoV-2 has been classified as category B, which means it has intermediate grades of both respiratory and fecal-oral transmission potentials.10 A study suggested that the half-life of the aerosolized form of SARS-CoV-2 is approximated to be 1.1–1.2 h.
However, it was found to remain viable on wooden and metal surfaces for up to 72 h, supporting a concern for indirect transmission beyond respiratory particles.11
Given the possibility of fecal-oral transmission, evidence noting the occurrence of viral RNA shedding in feces for up to a month, and the current state of the pandemic, we believe it is reasonable to extend the duration of contact isolation precautions as currently outlined by the CDC for patients with COVID-19 in efforts to strengthen infection control.
If patients with COVID-19 were discharged home or to a nursing home facility based solely on two negative respiratory samples, it could put families, close contacts, and/or healthcare providers at risk because of the yet unknown full transmission potential of COVID-19. Healthcare providers should also exercise additional precautions when transferring patients with COVID-19 within the hospital or de-escalating levels of care.
However, with current limitations in the supply of personal protective equipment, prolonged self-isolation may prove beneficial for adequate infection control while conserving resources. The consideration of testing for viral RNA by PCR in fecal samples, in addition to respiratory samples, to confirm recovery of active COVID-19, may offer clinicians guidance as to the duration of isolation precautions for patients on discharge.
What recommendations should clinicians provide patients amid the COVID-19 pandemic? Those exhibiting gastrointestinal symptoms with high probability of COVID-19 infection should practice extended periods of contact precautions for at least 4 weeks, given the data that suggest that viral RNA sheds in feces beyond a month.
They should also be educated on contact precautions and preventive measures to minimize fecal-oral transmission until further definitive evidence arises confirming or disproving such a route. Clinicians should emphasize education as a non-invasive means of infection control. Patients should be advised that close contacts are at high risk and that they may be at risk of reinfection themselves.
The World Health Organization recommends effective preventive measures in the community including frequent hand hygiene using an alcohol-based solution or soap and water; avoiding touching the eyes, nose, and mouth; practicing respiratory hygiene; and maintaining social distance.12
Currently, time and resources are limited, but our efforts should not be. The COVID-19 pandemic is a public health emergency, and clinicians need to act accordingly. With consideration of its high virulence, high infectivity, and the concern for a fecal-oral route of transmission, we suggest modifying guidelines to extend isolation and/or contact precautions in the best interest of patients, healthcare workers, and the global community as a whole.
University of Minnesota
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