SARS and COVID-19 coronaviruses differ significantly in cell culture

Last Updated: 2020-04-29

By Will Boggs MD

NEW YORK (Reuters Health) - SARS-CoV-2, which causes COVID-19, and SARS-CoV, which caused the 2003 SARS epidemic, show significant differences in cell damage, replication kinetics and tropism in various cell cultures, researchers in China report.

"SARS-CoV-2 multiplies with less cell damage than 2003 SARS-CoV in the lung cell line, which makes it more virus productive and thus more infectious, whereas 2003 SARS-CoV, associated with over 20 percent diarrhea, multiplies better in intestinal cells than SARS-CoV-2, associated with less than 10 percent diarrhea in human subjects," Dr. Kwok-Yung Yuen of The University of Hong Kong-Shenzhen Hospital, in Shenzhen, told Reuters Health by email.

While the clinical features of COVID-19 are similar to those of SARS, there are important clinical differences. SARS-CoV-2, for example, expanded to a much greater extent than SARS, with the number of cases in the first two months exceeding the total number of SARS cases by nearly tenfold.

Dr. Yuen and colleagues used 25 cell lines derived from different human organ tissues and nonhuman animal species to compare cell tropism, viral replication kinetics, and virus-induced cell damage in SARS-CoV-2 and SARS-CoV.

SARS-CoV-2 replication was most robust in human pulmonary and intestinal cell lines, followed by hepatic and renal cells, with modest replication in neuronal cells, the team reports in The Lancet Microbe.

"It is surprising that neuronal cell line U251 could be infected," Dr. Yuen said. "This may be linked to some of the neurological manifestations of COVID-19, such as anosmia, meningoencephalitis, and Guillain-Barre syndrome."

SARS-CoV also showed significant viral replication in all these cell lines accept neuronal cells.

Total virus production in pulmonary cells was significantly higher with SARS-CoV-2 than with SARS-CoV, whereas total virus production in intestinal cells was significantly higher with SARS-CoV then with SARS-CoV-2.

Even when inoculated at the same concentrations, SARS-CoV-2 induced less cell death and had significantly higher numbers of viable cells, compared with SARS-CoV.

The cellular tropism of SARS-CoV-2 in nonhuman cells largely matched that of SARS-CoV, both of which were capable of infecting and replicating in nonhuman primate, cat, rabbit, and pig cells. Unlike SARS-CoV-2, SARS-CoV was able to replicate in bat kidney cells.

"SARS-CoV-2 is a sneaky virus which produces rather mild symptoms to start with, which allows it to multiply to a high level (thus highly infectious), but by the time when symptoms worsen at day 7 to 10, the cell damage is severe and widespread," Dr. Yuen said. "Thus, early testing, oximetry monitoring, and early antiviral and respiratory support are indicated."

The researchers acknowledge that "cell line tropism might not fully represent how SARS-CoV-2 replicates and affects human organs in the physiological state. Thus, our cell line susceptibility results and the clinical manifestations of patients with COVID-19 might not completely accord."

"It is essential to further characterize virus-host interactions in more physiological models, such as ex-vivo human organ tissue and human organoids from patients of different ages, sexes, and with underlying diseases," they note.

"Isolates with additional amino acid mutations, particularly involving the receptor binding domain, should be studied to identify viral factors that might affect virus entry to host cells and virus replication kinetics," they add. "Finally, the viral kinetics of SARS-CoV-2 in other human cell lines (e.g., cardiomyocytes) and animal cell lines should be assessed to investigate virus-induced damage in cardiac cells and potential animal reservoirs."

SOURCE: https://bit.ly/2yTLKnr Lancet Microbe, online April 21, 2020.