== Correlation matrix. a worldwide pandemic causing millions of infected people and a significant number of deaths [1,2,3]. In Spain, the Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 started at the beginning of 2020, with Madrid (Spain) being one of the areas with a higher number of cases. SARS-CoV-2 is a single-stranded RNA-enveloped virus whose genes S, E, M, and N encode structural proteins. Unlike other functional proteins of SARS-CoV-2, the S protein on the viral surface is responsible for virus entry into the host cells, is able to induce the host immune response, and is the main antigen of the virus to elicit neutralizing antibodies [1,4,5]. However, it must be considered that studies carried out in Singapore populations and by the Wuhan Union Hospital indicate that a percentage of 0.6 to 12% of patients MGC3199 with COVID-19 do not produce specific antibodies against SARS-CoV-2 [6,7], and a percentage of children are not affected by the virus, as reported in several works; for example, a study across 25 European countries showed 16% of asymptomatic cases to be in children [8,9,10]. In the study carried out at the University Hospital of La Paz (Madrid, Spain), the severity of the COVID-19 disease was evaluated on a sample of more than 2226 patients (this cohort of patients included patients hospitalized from 25 February to 19 April 2020), with a higher incidence in the elderly (the median age reported in the article was 61 years old). Global mortality was over 20% (460 of the 2226 patients died), with a higher percentage in men. The mortality rate surpassed 40% in men over 70 y/o and in women over 80 y/o. For elders older than 80 y/o, this mortality rate increased to above 50% on average [11]. The Polymerase Chain Reaction technique (PCR) is the accepted gold-standard diagnostic method for molecular detection of SARS-CoV-2 to control the pandemic crisis [5]. However, a great need remains for assays that measure immunity antibody responses, determine seroconversion, measure other related biomarkers of COVID-19, and study the immune response to FLT3-IN-4 SARS-CoV-2 [3,5,12]. Relevant technologies have been published regarding the detection of specific antibodies associated with the immune response of the COVID-19 infection, such as those based on enzyme-linked immunosorbent assay (ELISA), chemiluminescence (CLIA), or lateral flow (LF), among other alternatives. In addition, tests based on non-invasive samples such as saliva also facilitate the population-based mass screening of COVID-19, in an attempt to overcome the current pandemic situation [3,12,13]. Even though the viral load has been revealed to be a significant factor for the prognosis and monitoring of the disease, relevant studies suggest that the death FLT3-IN-4 of patients is caused by a defensive uncontrolled reaction of our immune system, a cytokine storm, and not by the virus itself. In this sense, it should be noted that high levels of interleukins such as IL-6 or TNFa have been reported in peripheral blood samples and have allowed medical practitioners to apply promising therapies to block their effect, inhibiting proinflammatory pathways with different drugs like Tocilizumab or Fedratinib [14,15,16]. Although PCR is a technique with high specificity, it is also a laborious FLT3-IN-4 technique, with long waiting times and the requirement of difficult sample processing to extract the genetic material in order to amplify it. On the other hand, simpler diagnostic tests such as those based on LF have less sensitivity for low concentrations of the target biomarker. This makes necessary the implementation of new diagnostic systems that allow high sensitivity and specificity but with simpler handling, low-cost equipment, and faster analysis. For this reason, a wide variety of biosensors have been developed, including field-effect transistor (FET)-based biosensors [17], electrochemical biosensors [18,19], and surface plasmon resonance (SPR)-based biosensors [20]. In a recent previous work, we reported an immunosensor for measuring specific immunoglobulins in sera and saliva [21]. In the present work,.
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