COVID-19 will be around for a while, and SARS-CoV-2 also lingers in the bodies of the people with COVID-19. A major study shows that traces of the virus can be detected for weeks in the upper respiratory tract and a whole week longer in the lower respiratory tract and in faeces. This is crucial knowledge, both for developing new drugs and for the researchers behind the study, who are soon starting patient trials of a drug against SARS-CoV-2, which they expect to be 40 times more effective than remdesivir.
Do I have COVID-19, will I infect other people or am I healthy? COVID-19 often leaves more questions than answers, and the battle to understand SARS-CoV-2 has often left researchers and health authorities astonished. To understand how the virus travels through the human body, a research group has systematically screened the titles of 7,226 studies and pooled the data from 22 that could paint a credible picture of where and for how long one can find traces of SARS-CoV-2 in the body after the first symptoms occur.
“The study shows that SARS-CoV-2 can be detected in both the upper and lower respiratory tracts and in faeces, regardless of how ill a person with COVID-19 becomes. SARS-CoV-2 can be detected 1 week longer in the upper respiratory tract of people who are severely ill, but in general we can detect it in the upper respiratory tract for 2 weeks and for about 1 week longer in the lower respiratory tract and faeces. We hope that this knowledge can help the many researchers who are currently trying to develop treatment, and it has been crucial for us in attempting to develop a new treatment using inhaled niclosamide,” explains Morten Sommer, Professor and Scientific Director, Novo Nordisk Foundation Center for Biosustainability at the Technical University of Denmark, Kongens Lyngby and co-founder of UNION therapeutics A/S, Hellerup, Denmark.
Surprising and somewhat worrying
The background for the study was to improve the balance between the massive activity in developing drugs and the limited knowledge about how SARS-CoV-2 spreads in the body. Researchers quickly understood how the virus infects individual cells. However, during the early stages of the pandemic there were very few studies and only a handful of small clinical trials on how SARS-CoV-2 spreads through the body over time.
“This knowledge is crucial for developing models for how SARS-CoV-2 copies itself, since a mathematical model must be tested with as much real-world data as possible. However, this knowledge is also absolutely essential in planning clinical trials evaluating the effectiveness of various treatments aimed at reducing the viral load of people with COVID-19. Knowing how long a normal infection lasts is required to assess the effectiveness of a specific drug,” explains the main author, Anne Weiss, Scientific Research Associate, UNION therapeutics.
The researchers therefore systematically reviewed small studies of how the virus spread among people with COVID-19, including determining whether the duration of viral detection differed between people with mild and moderate to severe COVID-19.
“Our review showed that SARS-CoV-2 can be detected in the upper respiratory tract, lower respiratory tract and faeces, regardless of the clinical severity of COVID-19. It also showed that the lower respiratory tract has traces of virus for 5.7 days longer for people with mild symptoms and 5.9 days longer for those with moderate to severe symptoms,” says Anne Weiss.
The review also showed that SARS-CoV-2 is present longer among patients with moderately severe COVID-19, both in the upper respiratory tract and in faeces. Conversely, the various areas of the lower respiratory tract did not differ in how long the virus was present between moderate or severe versus mild COVID-19. This last result was especially surprising and somewhat worrying because the testing normally uses samples from the upper respiratory tract.
“We can detect the virus for up to 3 weeks in the lower respiratory tract, but this does not indicate whether this person can be infectious for 3 weeks. However, we can detect peak levels of SARS-CoV-2 in the upper respiratory tract within the first week of infection, whereas the viral load in the lower respiratory tract and faeces peaks within the second week of infection. Unfortunately, we do not have enough data from other places in the body, but there is no consistent indication that the virus is present in the eyes or in urine,” adds Anne Weiss.
Completely free of SARS-CoV-2
This new knowledge has been essential for the researchers behind the study in their upcoming clinical trials of inhaled niclosamide for people with COVID-19. UNION therapeutics has been working with niclosamide for 5 years and was conducting a Phase 2 study of the drug involving people with atopic dermatitis. In recent years, however, UNION therapeutics has also envisioned the possibility of treating people with inflammatory and infectious diseases.
“When the COVID-19 pandemic emerged, we learned that niclosamide was a very effective inhibitor of SARS-CoV-2 with potency 30–40 times better than remdesivir,” explains Morten Sommer.
Niclosamide effectively blocks SARS-CoV-2 from making new copies of itself. The extensive experience and data that UNION therapeutics has already generated with the drug enabled the company to develop an novel inhaled formulation of niclosamide for treatment of COVID-19. This product has now been advanced through a battery of animal tests and a Phase 1 study in healthy volunteers with great results.
“The new systematic review has been essential knowledge for the clinical trials of the new therapy, so that the patients are examined for a long enough time, and so that, for example, they are tested to determine whether SARS-CoV-2 is no longer present in the lower respiratory tract, where the review showed that the viral load peaks later. This will ensure that the body is completely free of the virus before stopping treatment,” concludes Morten Sommer.
“Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: a systematic review and meta-analysis” has been published in EBioMedicine. Innovation Fund Denmark awarded a grant to the researchers for their study of niclosamide. In 2018, the Novo Nordisk Foundation awarded a Challenge Programme grant to Morten Sommer, Professor, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, for the project Design and Engineering of Biological Molecules and Systems.