Testing Multiple Body Sites for Coronavirus Could Lower False Negatives

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, 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.

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 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.

Reference

Wang et al. (2020) Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. DOI: https://doi.org/10.1001/jama.2020.3786

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