New COVID-19 Testing Approach That Measures Immune Response Can Be Combined with Standard PCR Tests for Accurate Diagnosis

The new testing approach analyzes completely different molecules - from the person infected, rather than from the virus that infects the person – although it can be implemented using the same PCR technology on the same nasal swab samples. It could be used as a standalone test, or even combined into the same testing panels used in standard PCR tests to detect the virus. Combining the technologies could lessen the chances of false negative or false positive results, according to the researchers.

The UCSF scientists created three proof-of-concept versions of the new test - one based on readouts of gene activity from three key genes, one based on readouts from 10 genes, and one based on 27 genes. The tests independently detected COVID-19 infection in clinically confirmed cases, increasing in sensitivity with the number of genes included. The researchers aim to use one of these measures of gene activation both to flag false negative viral PCR tests, in which direct viral detection fails, and to rule out false positive results, which may arise from cross-contamination between samples in testing labs.

To determine which changes in gene activity were distinctive to SARS-CoV-2 infection the researchers first surveyed all the genetic material in swab samples from the upper respiratory tract, so that they could identify the most important and predictive indicators. The researchers examined samples from patients with respiratory symptoms who were tested for COVID-19 as a possible explanation of their illness. The tests showed many of the patients did have COVID-19, but some of them turned out to be infected with more common respiratory viruses (like the flu) or to be suffering from nonviral conditions.

With computer algorithms and a great deal of number crunching, the UCSF scientists were able to identify a distinct pattern of gene expression associated with a tamping down of specific immune responses that occurs early during SARS-CoV-2 infection. The changes differed from those seen in other viral respiratory infections or non-viral respiratory illnesses, allowing for a specific diagnosis of COVID-19. The pattern of immunosuppressive gene expression the researchers identified in COVID-19 may explain the stealthy nature of this highly transmissible virus, according to the researchers.

"Without even having to detect the virus itself, these tests to measure changes in the expression of immune-related genes can determine whether or not someone has COVID-19," said co-senior study author Chaz Langelier, MD, PhD, assistant professor in the Division of Infectious Diseases in the UCSF Department of Medicine.

"We have concluded from our work that there is an immunosuppressive effect taking place that prevents symptoms from developing early during infection despite high levels of viral replication. It's a brilliant strategy, if you're a virus," added Langelier. "Our findings of a diminished inflammatory response by the innate immune system suggest that treatments that suppress the immune system early during COVID-19 infection are unlikely to be beneficial."

Related Links:
University of California, San Francisco
Chan Zuckerberg Biohub