A review of hypersensitivity methods to detect immune responses to SARS-CoV-2

The investigation of the immune response after SARS-CoV-2 infection has been the goal of many researchers worldwide. The study of humoral immune responses and in vitro T cell production after infection requires the obtaining of individualized blood samples to test the presence of antibodies or activated T cells specific for the virus. In vitro T cell studies are especially troublesome due to the need for more specialized resources often outside the daily routine of clinical laboratories. For this reason the development of a simple and objective method to achieve these T cell studies is needed. In this manuscript we reviewed the hypersensitivity reactions, the theoretical basis and the historical background of delayed type hypersensitivity (DTH) which uses the principles of use of this test in the clinical setting for the past century. In the second part of the review, we focus on COVID adaptive immune responses, to understand the differences and challenges offered by this new application of DTH to investigate immune responses elicited after infection. In the last part of the review a vision provided for the use of this test to investigate the immunogenicity elicited by the vaccines. In our opinion, the clinical guidelines of immune assessment of SARS-CoV-2-infected or vaccinated individuals should include this simple and low-cost test to measure T-cell immunity. Rationale and improved vaccination schemes could be obtained after its implementation in the routine assessment of immunity in this pandemic situation.