However, these IgG subclasses will not lead to AuNP aggregate formation, hence, no color change of the assay solution. Open in a separate window Figure 1 Illustration of the principle of D2Dx immunity test. Acute Respiratory Distress Syndrome Virus-2 (SARS-CoV-2) virus infection, has become a global pandemic following an initial outbreak in the Peoples Republic of China at WJ460 the end of 2019 and beginning of 2020. Until October 2021, 242 million people around the world have been infected with the virus and 4.9 million people have died of COVID-191,2. Upon infection, while most people will show no or mild symptoms, a significant portion of the population will develop moderate to severe symptoms that require hospitalization, aggressive treatments such as mechanical ventilation, intensive care, and some eventually succumb to death3C5. The mortality rate based on the number of confirmed positive cases varies from on average 2C3% to as high as?~?10% in some countries1. Extensive studies have found that the immune response in COVID-19 patients is rather complicated, varies significantly from person to person, and patients immune response dynamics have a direct association with their clinical outcome6C14. Of particular interest, patients who developed severe symptoms or died of COVID-19 have reduced number of T cells and their immune responses are skewed towards type 2, antibody-mediated immunity15C21. These patients are more likely to experience cytokine storm that can lead to uncontrolled inflammation of the body, tissue damage, and eventually organ failure. WJ460 In contrast, asymptomatic patients or patients with mild symptoms appear to have stronger type 1, cell-mediated immunity than patients with more severe symptoms22. In the fight against infectious pathogens, especially intracellular pathogens such as viruses, type 1 immune response is the frontline defense against the pathogen from the immune system. If type 1 immune response fails to stop the infection, type 2 immune response is initiated, clearing the virus by producing virus-specific antibodies23. These antibodies include binding antibodies and neutralizing antibodies. While binding antibodies can only bind to virus or virus antigens, neutralizing antibodies bind with the virus in a specific way that render the virus particle no longer infectious or pathogenic24. The level of binding antibodies is determined by using immunoassays such as ELISA and quantitated as antibody titer. The level of neutralizing antibodies is analyzed by evaluating the viability of live virus using techniques such as plaque reduction assay. Higher anti-virus antibody titers were found in patients with more severe symptoms compared to those with only mild WJ460 symptoms17,18. On the other hand, neutralizing antibodies with strong potency in the COVID-19 patients is a predictor of survival25,26. While type 1 immunity is dominated with cell-mediated immune responses WJ460 and type 2 immunity leads primarily to antibody-mediated immune responses, both types are inter-connected through the humoral immune system, particularly, the immunoglobin G (IgG) subclasses. In humans, IgG1 and IgG3 are associated with type 1 immune response, and IgG4 is linked to type 2 immune response27,28. In bovine, IgG2 is associated with type 1 and IgG1 is associated with type 2 immunity29. In murine models, IgG2a is a specific indicator of type 1 immunity and mouse IgG1 is a Rabbit Polyclonal to RPS19BP1 marker of type 2 immunity30. Under typical, healthy conditions, there is a balance between type 1 and type 2 immunity-associated IgG subclasses. Upon infection or other changes of physiological conditions such as pregnancy or parturition, such balance may be disturbed29,31. The ratio of IgG subclasses in blood serum or plasma is often used as a marker to evaluate the relative balance of type 1 and type 2 immune responses in humans and animals32C34. We previously developed a rapid blood test, D2Dx immunity test, that can detect and monitor the humoral immune status and responses in laboratory and farm animals35C39. The test uses a gold nanoparticle (AuNP) as a pseudo virus pathogen to probe the humoral immunity in a blood plasma or serum sample. The.