Serological approach for diagnosis of SARS-COV 2 virus

Laboratory evidence of clinical patients showed that a specific T cell humoral response against SARS-COV is important for killing of infected cell, particularly in the lungs of infected individual.

This infection induces generation of IgG that are normally targeting the N protein and can be detected by serum, as early as day 4 after the onset of disease and with the most patients serocon version by day 14.

In the late incubation period and early stages, only the viral RNA, and to lesser extent the viral antigen, may be detected by molecular or serological techniques.

While RNA detection remains the mainstay for the diagnosis of SARS-COV 2, RNA level drops quickly and after few weeks RNA or antigen are usually not detectable any more. Therefore in those instances, the laboratory support to the diagnosis may be provided by the antibody test.

Rationale for separate IgG, IgM vs total IgG
Serology will give the treating physician an insight about the disease progression and hence timely action, greater understanding of the disease. Using a total IgG could confuse the picture of patient status.

PCR positive, IgM negative, and IgG negative individual may be in early stages of infection and should be quarantined and insure healthcare workers in contact with the person have appropriate personal protective equipment.

A PCR negative but IgM positive may indicate a missed (false negative PCR) this may call for a retest on PCR or management as if in early stage of infection; A PCR negative, IgM negative and IgG positive is indicative of a past infection; IgM presence alerts the physician that there is likely an acute infection, suggesting that clinical action should be taken (treatment, patient isolation/quarantine, or return visit) and may also be used at locations where PCR is not readily available.

The continuum of data from infection to recovery helps enable better patient assessment and management. Understanding the magnitude of IgM vs IgG in a patient at different infection stages may help inform a patient’s progress towards clearing the virus. Appearance of IgM and IgM titer magnitude may also provide an indication of the cytokine storm initiation. Finally, having an IgM vs. an IgG assay targeting different viral proteins can lend itself to confirmatory algorithms.

Recency of infection to help enable more accurate epidemiological studies.

An assay targeting the whole antibody response by all Ig classes cannot reliably differentiate recent infections from more distant ones and may generate confusion on potential active infections vs. past infections, engendering the need for further testing steps on positives.

Epidemiologists and healthcare workers will need to further elucidate the type of immune reaction that is occurring when a positive signal for a total antibodies assay has been detected.

In addition, total antibody results may lead to the misclassification of individuals in terms of time of infection. As further data develops, it is IgG which will eventually be used to predict immunity and protection, if longer term immunity is found to occur for SARS-COV 2.

In our set up we therefore are planning to buy architect SARS-COV 2 IgG kit, which is capable of 200 tests per hour with sensitivity of 99 percent and specificity of 99.63 percent, which is also USFDA approved.

Outlook
Serological testing helps to enable accurate diagnosis of SARS-COV 2 infection in both symatomatic and asympatomatic patients. Since IgG testing is long lasting, the evaluation of antibody screening is well suited for the purpose of population screening to assess the burden of infections and possible to evaluate the incidence and efficacy of preventive measures.