Coronavirus disease 2019 (COVID-19) was first discovered in a group of patients with severe respiratory symptoms in Hubei province, China, in December 2019. Early nucleic acid analysis of panels of known pathogens yielded results. negative, suggesting that the causative agent was of unknown origin.

In early January 2020, analysis of bronchoalveolar lavage fluid (BAL) from infected patients revealed a pathogen, later named SARS-CoV-2, with a 50%, 80%, and 96% genetic sequence overlap to the genome. Middle East respiratory syndrome virus (MERS-CoV), severe acute respiratory syndrome virus (SARS-CoV), and bat coronavirus RaTG13, respectively. Like SARS-CoV and MERS-CoV, SARS-CoV-2 is a single-stranded RNA virus that belongs to the beta Coronavirus genus of the Coronaviridae family.

Since SARS-CoV-2 can be transmitted from person to person, the disease has spread rapidly to more than 200 countries, infecting nearly 6 million people and causing at least 350,000 deaths worldwide (as of May 27, 2020).

An unprecedented and rapidly growing global effort is underway to develop COVID-19 vaccines and therapies, but at the time of this review, there are no vaccines, and only one antiviral drug (redeliver) with modest clinical benefit has been approved by the US Department of Food and Drug Administration (FDA) Emergency Use Authorization (US) [5,6]. In these circumstances, countries were forced to implement physical distancing measures to control the outbreak and, in the process, place an estimated 3 billion people under lock and key.

2. COVID-19 diagnostic tests

In any infectious disease outbreak, accurate and accessible diagnostic tests should be one of the pillars of control measures policies to understand and minimize the spread of the disease. Epidemiological studies of the outbreak in China estimated that the proportion of undetected COVID-19 cases reached 86% [7]. Since asymptomatic or mild cases may play an important role in the transmission and spread of the SARS-CoV-2 virus [7,8], symptoms alone are not reliable diagnostic markers. There are two main types of diagnostic technologies available to address this: molecular and serological tests.

Currently, much of the attention is focused on the SARS-CoV-2 molecular test, which can detect, with high precision, virus-specific RNA molecules circulating in the host body. The gold standard molecular test is based on reverse transcriptase-polymerase chain reaction (RT-PCR) technology.

However, the PCR test is not useful in distinguishing between highly infectious viruses and viruses that have been neutralized by the host, and cannot assess the status of immunity against SARS-CoV-2 [9]. Serologically-based antibody tests can complement molecular-based tests by providing a more accurate estimate of the incidence of SARS-CoV-2 and by potentially detecting individuals with immunity to the disease, as these tests detect markers of the immune response.

3. Humoral immune response to SARS-COV-2

In the humoral immune response to infection, pathogen-specific antibodies, produced by B cells, neutralize and prevent the further spread of the disease. Activation and differentiation of B cells into antibody-secreting plasma B cells is triggered by a cascade of events involving digestion of the virus by antigen-presenting cells (eg, dendritic cells, macrophages) and antigen presentation virus-specific to helper T cells (Figure 1).

Antibodies protect the host by binding to specific antigens (proteins) of the virus to neutralize its fusion and entry into the host cell and facilitate recognition and death by phagocytic immune cells [10]. In humans, three types of antibodies or immunoglobulins have been the target of COVID-19 serological tests: IgM, IgG, and IgA. Although the dynamics of the immune response in COVID-19 are not fully understood, typically IgM antibodies are produced by host immune cells during the early stages of a viral infection.

IgG is often the most abundant antibody in the blood and plays a more prominent role in the later stages of infection and in establishing long-term immune memory [11]. Although IgM and IgG antibodies have been the main candidates in the development of the COVID-19 serological test, recent studies show that IgA, predominantly present in mucosal tissue, can also