From early reports on the clinical characteristics of COVID-19, it is now apparent that not all people exposed to SARS-CoV-2 are infected and not all infected patients develop severe symptoms [18
]. Indeed, three broad presentations of SARS-CoV-2 infection can be characterised: (i) an asymptomatic incubation stage with or without detectable virus; (ii) non-severe symptomatic presentation with confirmed presence of virus; and (iii) a severe respiratory symptomatic stage with high viral load [68
]. Determining the immune status of an individual is likely to become increasingly critical as the COVID-19 pandemic progresses, because from a prevention perspective, individuals at stage I (the stealth carriers or the super spreaders), are particularly important because they may spread the virus unknowingly.
Two stages of the immune response during COVID-19 disease progression have been proposed [69
]: (1) Immune-defense-based protective phase: elimination of SARS-CoV-2 virus by an individual’s adaptive immune response; and (2) inflammation-driven phase: when the protective immune response is impaired and prolonged propagated virus load leads to an adverse inflammatory response in organs with high hACEs expression. Indeed, a likely pathogenic mechanism of SARS-CoV-2 is overactivation of T cells with an increase in CD4+ T Helper cells and enhanced cytotoxicity of CD4+ and CD8+ T cells [70
], which leads to an imbalanced pro-inflammatory and anti-inflammatory cytokine response and severe immune injury in susceptible patients [71
]. Although this concept needs to be confirmed by more clinical research, it may provide useful research directions to tackle COVID-19.
During the previous SARS outbreak, a common transmission pattern hypothesis was that SARS-CoV virus silently infected asymptomatic patients, which may have led to population immunity against infection (herd immunity) that may explain the eradication of the virus, although this is yet to be confirmed [72
]. Although a study suggests that coronavirus antibodies are highly prevalent in the general population after exposure to four non-SARS coronavirus strains [73
], there is no definitive evidence on whether permanent immunity would be generated against other CoV species, such as SARS-COV-2. Notably, after SARS-CoV infection in a murine model, the production of SARS-CoV-specific serum IgG and secretory immunoglobulin A (sIgA) were detected in saliva following intranasal immunisation [74
In relation to COVID-19, intensive care unit (ICU) patients had higher plasma levels of pro-inflammatory cytokines, including IL-2, IL-7, IL-10, GSCF, IP10, MCP-1, MIP-1A, and TNF-α, compared with non-ICU patients [48
], suggesting the emergence of a robust immune-inflammatory response in severe symptomatic COVID-19 patients. Importantly, several studies have demonstrated that COVID-19 patients developed IgG and IgM antibodies against SARS-CoV-2 in blood samples. Both IgG and IgM antibodies against the SARS-CoV-2 nucleoprotein and spike receptor-binding domain were increased in serum at day 10 after symptom onset for up to three weeks [30
]. A point-of-care lateral flow immunoassay (LFIA) test product (VivaDiag COVID-19 IgM/IgG Rapid Test) was designed to detect IgM and IgG in blood samples of COVID-19 patients in 15 min [75
]. However, the sensitivity of the VivaDiag COVID-19 IgM/IgG Rapid Test was only 18.4% in blood samples of acute COVID-19 patients from the emergency department [76
], suggesting that serological tests require more research before being deemed suitable for routine diagnosis. Additionally, the seroconversion rate for total antibodies, IgM, and IgG were shown to be 93.1%, 82.7%, and 64.7%, respectively, in hospitalised COVID-19 patients, peaking 7–14 days after symptom onset [77
]. Given the non-invasive and cost-effective nature of saliva collection, it would be important to investigate whether this immunity detection is feasible in saliva samples as a tool for facilitating the testing of COVID-19 immunity at the population-level.