Researchers have detected COVID-19 viral RNA and live virus in specimens other than nose-throat swabs and sputum samples, raising the possibility that the disease may spread through additional routes.

In a research letter published yesterday in JAMA, Chinese scientists describe testing lung wash (bronchoalveolar lavage), lung biopsy, nasal, sputum, and blood samples for live virus in 1,070 specimens from 205 infected patients in three hospitals in China from Jan 1 to Feb 17.

In related news, a research letter today in Emerging Infectious Diseases, highlights a cluster of COVID-19 cases linked to a shopping mall in Wenzhou, China. The study's authors said that an analysis of their findings can't rule out indirect transmission of the pandemic novel coronavirus, such as via inanimate objects or aerosolization.

Testing various sites could lower false-negatives

Using real-time reverse transcriptase polymerase chain reaction (RT-PCR), investigators detected COVID-19 RNA in lung wash (14 of 15 samples; 93%), sputum (72 of 104; 72%), nasal swabs (5 of 8; 63%), lung biopsy (6 of 13; 46%), throat swabs (126 of 398; 32%), feces (44 of 153; 29%), and blood (3 of 307; 1%). The 72 urine specimens all tested negative.

Twenty patients had two to six specimens collected at the same time. Viral RNA was detected in single specimens from six patients (respiratory specimens, feces, or blood). Seven patients shed live virus in respiratory specimens, 5 in feces (2 of whom did not have diarrhea), and 2 in blood.

"Testing of specimens from multiple sites may improve the sensitivity and reduce false-negative test results," the authors wrote, citing two smaller studies that reported COVID-19 in anal and oral swabs and in blood in 16 patients and viral load throughout disease progression in throat swabs and sputum from 17 infected patients.

The highest viral loads in the JAMA study were found in sputum, the authors note, with moderate loads in nose-throat swabs, the most common way to confirm infection. Four fecal samples had high viral loads.

Multiple routes may speed transmission

The findings imply that the coronavirus may be transmitted through feces and invade the circulatory system, the researchers said. "A small percentage of blood samples had positive PCR test results, suggesting that infection sometimes may be systemic," they wrote. "Transmission of the virus by respiratory and extrarespiratory routes may help explain the rapid spread of disease."

The patients' mean age was 44 years old (range, 5 to 67), and 68% were male. In the study, throat swabs were collected from most patients 1 to 3 days after hospital admission. Blood, sputum, feces, urine, and nasal samples were collected throughout the illness. Lung wash and biopsy specimens were taken from patients with severe illness or who were on mechanical ventilation.

The authors cautioned that the number of some types of samples in the study was small and that data couldn't be correlated with disease symptoms or course because clinical information in some patients was limited. "Further investigation of patients with detailed temporal and symptom data and consecutively collected specimens from different sites is warranted," they wrote.

Indirect spread likely in mall cluster

In the 34-person COVID-19 mall cluster, researchers from Wenzhou, elsewhere in China, and in the United States say that the virus appears to have been transmitted indirectly, through the touching of contaminated surfaces, viral aerosolization in a confined space, or through contact with infected people who had no symptoms.

The investigators monitored and traced close contacts and analyzed clinical and lab data using RT-PCR. They also drew the eight-floor shopping mall showing the floors where the COVID-19 patients worked or shopped, dates of onset, potential incubation periods, symptom durations, and times of positive diagnosis and hospital release.

Except for those who had visited floor 7, no patients reported close contact with the other patients. "The possibility of customers being infected from other sources cannot be excluded. However, most customers reported early symptom onset in a concentrated time frame," the authors wrote. "Our findings appear to indicate that low intensity transmission occurred without prolonged close contact in this mall; that is, the virus spread by indirect transmission."

Scientists are exploring whether COVID-19 is spread mainly through respiratory droplets and close contact with infected people, and research is lacking on how long the virus survives outside the body. The authors point out, however, that the Middle East respiratory syndrome coronavirus (MERS-CoV) can survive outside the body and stay infectious for as long as 60 minutes after aerosolization.

"Hence, the rapid spread of SARS-CoV-2 [the COVID-19 virus] in our study could have resulted from spread via fomites (e.g., elevator buttons or restroom taps) or virus aerosolization in a confined public space (e.g., restrooms or elevators)," they wrote.