Coronavirus disease 2019 (COVID-19) which is a respiratory system disease has created inevitable pandemic. In the course of disease; the uncontrolled inflammatory response may cause tissue damage. 80-90% of patients undergo mild-to-moderate disease symptoms, the rest of the patients proceeds to critical or severe disease. Type I Interferons (IFN-I) are crucial immune mediators in order to host responses to viral infection likewise those are major components of the innate immune system moreover serve as critical antiviral molecules. IFN-I are within the first cytokines secreted during a viral infection. Until now, IFN-I response has been evaluated in patients with COVID-19 in a few publications and its contribution to the viral load control and inflammation is very little known. In those studies, the researchers have found that IFN-I deficiency which characterized by no IFN-beta and low IFN-alpha production and activity is a hallmark of severe and critical COVID-19. Until recently, measurement of circulating serum levels of IFN-alpha have been limited owing to the limits of conventional immunoassay technology. Limit of detection problems of immunoassays has started to figure out thanks to SIMOA. On the top of that, generally the platforms that use SIMOA technology is 10-100 fold more sensitive than most conventional immunoassays. We should strive to do research that includes IFN-I with using platforms that include SIMOA technology, especially in severe COVID-19.