What are Seroprevalence Surveys and What Do They Tell Us About COVID-19?

The outbreak of COVID-19, caused by the novel infectious disease agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019-nCoV, began around December 2019 in Wuhan Hubei Province China^1,2. As of September 2020, there were over 30 million confirmed COVID-19 cases reported worldwide, a number which will likely continue to increase in certain populations³. Since the start of this pandemic scientists have learned that the range of disease manifestations and immune responses, which occur after infection with SARS-CoV-2, vary significantly. We now know that many individuals present with either asymptomatic or mild disease^4-11, and that the number of laboratory confirmed cases provides an inaccurate measure of true disease prevalence as many of these cases have not yet been captured by conventional diagnostic testing methods. Antibody or serologic testing has played an important role in our understanding of disease prevalence thus far and may continue to be crucial in addressing these concerns. 

Serologic tests, which detect the presence of antibodies produced against a pathogen within an individual’s blood, indicate whether an individual has previously been infected by the SARS-CoV-2 virus. Serological data has been collected for the SARS-CoV-2 virus using several different types of assay technologies including enzyme-linked immunosorbent assays (ELISA)^12-16,  chemiluminescent immunoassays^17-21, immunofluorescence assays²², lateral flow assays²³, and bioluminescent immunoassays (BLIA)^24-26. These types of tests, provided they have been well validated and have high clinical performance, are essential to understanding the impact of disease around the world.

Seroprevalence is the proportion of individuals within a population affected by disease at a specific time point, based on positive testing for serum antibodies.

COVID-19 Seroprevalence Surveys and Zoonotic Transmission

Globally researchers and public health organizations are exploring strategies to better understand the spread of COVID-19 disease, using seroprevalence as a critical measure. Seroprevalence is the proportion of individuals within a population affected by disease at a specific time point, based on positive testing for serum antibodies²⁷. Due to resource and time constraints, it is challenging if not impossible to test every individual within a population. To estimate the percentage of infected individuals within a population (e.g., country, state, community, etc.) seroprevalence survey studies or “serosurveys” are being developed. A serosurvey can be performed by sampling small numbers of participants within a populace, which represent the general population. When using a serologic test with high sensitivity and specificity, serosurveys provide essential information about true disease prevalence. These types of surveys are already being performed on a large scale by the United States Centers for Disease Control and Prevention²⁸, the Spanish Ministry of Health²⁹, and many other government bodies³⁰. Serosurveys also allow us to measure disease prevalence in specific communities or populations such as schools^31,32, hospital workers^33-35, military officials³⁶, nursing homes³⁷ or prisons³⁸. For example, the UK government recently launched a serosurvey to assess and monitor the prevalence of COVID-19 among pre-school, primary and secondary school pupils and teachers³². 

Evaluating the true magnitude of an outbreak is vital to establishing public health measures and control strategies. Seroprevalence surveys allow public health officials and policymakers to identify hot spots and areas where transmission has been reduced so that they may respond accordingly. Serologic data may also provide guidance to governing bodies for instituting public health strategies including vaccine procurement/prioritization, allocation of resources (PPE, financial support, etc.), and establishment of mitigation tactics.  

In addition to monitoring disease spread in humans, serosurveys are used to monitor seropositivity of animal reservoirs, which are populations of organisms in which an infectious disease agent survives and replicates. These animal reservoirs are important, as they may be able to transmit virus directly to humans. For example, the 2003 outbreak of SARS-CoV was thought to have originated from the palm civet animal reservoir, as 99.6% of the viral genome isolated from civets was homologous to the SARS-CoV viral genome extracted from humans. In this case the government instituted strict policies, leading to the elimination/quarantine of all domesticated civets for human consumption, after which there were no new community acquired cases reported in China³⁹. Studies are ongoing to determine if there are important animal reservoirs that may have facilitated zoonotic transmission of SARS-CoV-2⁴⁰. However recent studies have reported that pet animals, including cats and dogs, have been testing positive for SARS-CoV-2 antibodies⁴¹.  Only a few of the human serological assays developed so far can be used in animals. For example, assays utilizing NanoBiT® technology, in which viral antigens coupled with bioluminescent enzyme fragments are used to detect anti-SARS-CoV-2 antibodies, can be performed irrespective of species origin^25,26.

As government officials, healthcare organizations, and other institutions face an unprecedented global health crisis, determining seroprevalence for COVID-19 in both humans and animals will be an essential and necessary tool in facing the multitude of challenges ahead.