Serology: A Precise Tool in Diagnosis and Epidemiology of COVID-19

Abstract

The coronavirus infectious disease-2019 (COVID-19), caused by a β-Coronavirus, named SARS-CoV-2, has become a global pandemic since its origin in Wuhan, China during the last week of December 2019, affecting 212 countries and territories in the World involving all the five continents. Prompt and precise diagnosis of the disease is central to its control and eradication. Real- time polymerase chain reaction (real-time PCR) using dual labelled TaqMan probe and targeting two genomic areas, usually RdRp and envelope (E) regions, of the virus is being extensively used for the diagnosis of SARS-CoV-2 in respiratory clinical specimens. As stage of the infection cannot be ascertained during collection of respiratory specimens for nucleic acid test (NAT; RT-PCR), this may lead to false negatives (error of omission) as virus load in the respiratory exudates and saliva gradually decreases with the increase in time post infection. Virus excretion would be maximum during clinical sickness that follows incubation period of usually up to ~14 days and clinical samples collected during this period are suitable for PCR diagnosis than those collected after clinical sickness. In addition, there are other variables, like quality of swabs and virus transport medium, PCR protocol and reagents, enzyme inhibitors, and proficiency of the manpower engaged in executing diagnostic techniques may affect the quality of the test result. There are three grades of clinical sickness in COVID-19, viz. asymptomatic, mild symptomatic and highly symptomatic. Available data indicate that about 50% of the people exposed to SARS-CoV-2 infection may become asymptomatic, as was observed in case of the COVID-19 affected Japan cruise ship ‘Diamond Princess’ with 3,711 people on board. In case of asymptomatic and mild symptomatic cases, due to low virus load in the clinical specimens collected, the negative result in NAT/PCR need to be cross checked using a suitable antibody assay. It is known that virus load in the body and the quantum of virus excreted in body fluids gradually decreases with the remission from sickness, whereas quantum of specific antibody against the virus increases with time till plateau. Anti-virus antibody remains in the host for longer duration and can be detected even after clearance of the infection from the body. Therefore, NAT must be complemented by antibody test to enhance quality of diagnosis and mitigate errors of omission. Further, unlike NAT/PCR, serology/antibody test is a powerful tool in tracking virus transmission, estimating actual number of cases, and epidemiological mapping of the disease in a population. Further, availability of a precise antibody test system/assay would be handy for post-pandemic surveillance of COVID-19. The current review includes the results of COVID-19 diagnosis and kinetics of antibody response reported by different authors/groups of scientists that vouch for quick development of a ‘COVID-19 antibody assay’ system for use in epidemiological studies of the disease.