PlexCovid-19

SARS-CoV-2

SARS-CoV-2 is the newest member of the coronavirus group to cause a respiratory illness, and a pandemic. The viral illness is called COVID-19.

Cough and fever appear early during infection. Pneumonia, respiratory failure and death can occur in older individuals with underlying lung disease or other chronic illness. Symptomatic patients make up a smaller proportion of infected individuals. Emerging information suggests that asymptomatic infection affects many more individuals, who can spread infection just as easily as those with symptomatic infection. Social distancing and hand hygiene have been effective in containing spread of this virus.

As with other common viruses, antibodies that develop after infection can be protective. Anecdotally, the virus can reappear after the initial infection has resolved. It is unclear whether this reappearance of the virus in some individuals represents a true recurrent infection, or the persistence of viral fragments, which are non-infectious.

Because the SARS-CoV-2 virus spreads rapidly, a complete understanding of the immune response to this virus remains work in progress. The nature of cell-mediated immunity (CMI) to this virus is not known.

Rationale

Cell-mediated immunity (CMI) is one of the earliest immune responses to any virus. Some immune cells are programmed to attack any pathogen upon initial contact. Others develop long term memory, and mount a potent anti-viral response. An ongoing recruitment of other specialized immune cells, for example, the B-lymphocyte, results in production of antibodies which provide long-lived protection from the virus.

Intact cell-mediated immunity (CMI) to some common viruses may be present in many healthy individuals, who report no previous infections. One example is the Cytomegalovirus, or CMV, a common virus. CMV can infect healthy individuals without causing any symptoms, or may reawaken in transplant patients who receive drugs to suppress the immune system. In one study, CMI to CMV was present in over half of 32 children and young adults in whom there was no evidence of prior CMV infection such as CMV antibody. These individuals had a very low incidence of subsequent CMV infection in follow-up.

For many common viruses, cell-mediated immunity (CMI) to the virus is either quite low or absent during acute infection. CMI becomes detectable or is restored when the infection resolves.

Thus, CMI to SARS-CoV-2 may aid the assessment of risk for COVID-19 infection, when combined with other measurements to diagnose this infection.

Investigational Use

PlexCovid-19 is an investigational lab-developed blood test to measure the level of cellular immunity or CMI to the SARS-CoV-2 virus.

Test Description

PlexCovid-19 measures functional cell-mediated immunity to the SARS-CoV-2 virus.

• Whole blood, 3 ml from children, 5 ml from adults in sodium heparin green top tubes, is shipped at ambient temperature overnight to Plexision’s reference laboratory
• SARS-CoV-2-specific T-cells, B-cells, natural killer (NK) cells and monocytes, which express the inflammatory marker, CD154 are measured after stimulation with the SARS-CoV-2 spike antigen.
• Simultaneously, general cell-mediated immune responses are measured in the abovementioned cell types after stimulation with mitogen

Results

• Are reported within 30 hours after blood samples reach the laboratory.
• Are reported as frequencies of SARS-CoV-2-specific cells. Also provided are reference ranges for each cell type that have been established with stimulation of blood immune cells from healthy adults.
• These data reflect reference ranges for the frequency of four different immune cells that are present in blood from 20 healthy adults. These reference ranges do not reflect relationship to active disease. No reference ranges have been established in patients with known or prior history of COVID-19 infection.

References

1. US Patent 9606109

2. Ashokkumar C, Green M, Soltys K, Michaels M, Mazariegos G, Reyes-Mugica M, Higgs BW, Spishock B, Zaccagnini M, Sethi P, Rzempoluch A, Kepler A, Kachmar P, Remaley L, Winnier J, Jones K, Moir K, Fazzolare T, Jenkins K, Hartle T, Falik R, Ningappa M, Bond G, Khanna A, Ganoza A, Sun Q, Sindhi R. CD154-expressing CMV-specific T cells associate with freedom from DNAemia and may be protective in seronegative recipients after liver or intestine transplantation. Pediatr Transplant. 2019 Oct 27:e13601. doi: 10.1111/petr.13601. [Epub ahead of print] PMID: 31657119

*PlexCovid-19 is not FDA-approved. Its use must be considered investigational only.