Novel Coronavirus: Study Suggests Multiple Shedding Routes

Nicola M. Parry, DVM

February 21, 2020

The novel coronavirus (2019-nCoV) responsible for the COVID-19 global outbreak may have multiple infection routes, according to a study published online February 17 in Emerging Microbes & Infection.

"We detected the virus in oral swabs, anal swabs, and blood," write Wei Zhang, from Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, and colleagues.

"[T]hus, infected patients can potentially shed this pathogen through respiratory, fecal–oral, or body fluid routes," they write.

But one US infectious disease expert cautions that, overall, the epidemiologic data continue to point to airborne transmission being the driver of the COVID-19 outbreak. "It's almost a rewrite of the influenza playbook," said Michael T. Osterholm, PhD, MPH, Director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis.

To date, oral swabs have been used to test for 2019-nCoV antigen to confirm a diagnosis of COVID-19. And patients who have two sequential negative oral swabs are thought to have cleared the virus and no longer be contagious.

However, according to the authors, many coronaviruses can also undergo fecal–oral transmission.

With this in mind, Zhang and colleagues conducted a study in a hospital in Wuhan to investigate the possibility of alternate routes of transmission of 2019-nCoV.

They collected oral swabs, anal swabs, and blood samples from a total of 178 patients infected with the virus.

In the first part of their study, the researchers examined samples from 39 of the patients who had tested positive for 2019-nCoV based on oral swabs taken at the time of admission to the hospital. They performed molecular testing (quantitative polymerase chain reaction [qPCR]) for 2019-nCoV on blood, oral swabs, and anal swabs.

According to Zhang and colleagues, 15 of these 39 patients still tested positive for the virus even after several days of treatment. Of these, 8 (53.3%) tested positive on oral swabs, 4 (26.7%) on anal swabs, 6 (40%) on blood samples, and 3 (20%) on serum samples.

Notably, the researchers found instances when viral nucleotide was present in anal swabs or blood samples even when oral swabs tested negative.

In the second part of their study, the researchers examined samples from 139 of the 178 patients to investigate changes in the presence of virus in oral and anal swabs over time. In these samples, they tested for the presence of both viral antibody and viral nucleotide.

The authors report detailed characterization of samples from 16 patients. Among those, Zhang and colleagues found that antiviral immunoglobulin (Ig) M and IgG titers were relatively low or undetectable on the first day of sampling. However, by day 5, the titers of both antibodies had risen in most patients. The rate of detection rose from 50% (8/16) on day 0 to 81% (13/16) on day 5 for IgM, and from 81% (13/16) to 100% (16/16) for IgG.

In contrast, on day 0, 8 out of 16 (50%) oral swabs tested positive with qPCR as did 4 anal swabs (25%). By day 5, 25% of oral swabs and 37.5% of anal swabs tested positive for the viral nucleotide.

These findings suggest the potential for patients to transition from testing positive for the virus on oral swabs during early infection to testing positive on anal swabs during late infection.

In an email interview with Medscape Medical News, one of the study's lead authors, Peng Zhou, also from Wuhan Institute of Virology, noted that although the group has not yet tried to isolate the virus from fecal samples from infected patients, other groups have apparently had some success doing this.

"In summary, we provide a cautionary warning that 2019-nCoV may be transmitted through multiple routes," the authors write.

Although gastrointestinal symptoms have been reported in COVID-19, they are infrequent. For example, one case series showed that 8% of patients with 2019-nCoV infection presented with diarrhea at the onset of their illness.

And health officials in Hong Kong recently evacuated residents from one apartment block because they were concerned about transmission of 2019-nCoV via the building's bathroom pipes, according to several news sources. Two people living on different floors of the building had tested positive for the virus. After discovering an unsealed bathroom pipe in one of the patient's bathrooms, officials raised the possibility of stool-based transmission in these two cases.

Because the pipe that carried feces was connected to the ventilation pipe, officials suspected that the virus present in the feces may have been transmitted through the ventilation system into people's apartments.

However, in an interview with Medscape Medical News, Osterholm, CIDRAP's director, said "the question still remains wide open about what role fecal–oral transmission might play in this novel coronavirus disease."

He indicated the need to avoid overinterpreting the data from this latest study, especially because PCR was used to detect the virus in the different patient samples.

Although this confirms that the patients were infected with 2019-nCoV, Osterholm stressed that it does not necessarily mean that the samples contained infectious virus.

He explained that this is similar to the situation in patients with some other infectious diseases. For example, Osterholm described one study in which researchers simultaneously performed PCR and virus isolation on stool samples from patients infected with a related coronavirus that causes Middle East respiratory syndrome (MERS). In that case, although the samples tested PCR-positive for the MERS virus, the researchers were unable to isolate the virus from them.

He clarified that when a sample tests positive with PCR, it indicates the presence of viral nucleotides, which could be a breakdown product from the infection. But it doesn't automatically reflect the presence of viable virus that is infectious and could put other people at risk.

This work was jointly supported by the Mega-Project for Infectious Disease from the Minister of Science and Technology of the People's Republic of China; China Natural Science Foundation for excellent scholars; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS); and the Youth innovation promotion association of CAS. The authors and Osterholm have disclosed no relevant financial relationships.

Emerg Microbes Infect. Published online February 14, 2020. Full text

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