Authored by OrthoEvidence
More than 7 months have passed since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, was first identified. We are still trying to learn more about the virus and the disease. With the help of lab tests, involving clinical molecular diagnostic technology such as reverse transcription polymerase chain reaction (RT-PCR) (Carter et al., 2020), we are able to detect the RNAs of SARS-CoV-2 in subjects who are tested.
Notably, the clinical manifestations of COVID-19 vary greatly, from mild symptoms among those who are asymptomatic, to severe infection to death. A recent model built by the Centers for Disease Control and Prevention (CDC) estimated that every 4 in 10 individuals infected with SARS-CoV-2 are asymptomatic (CDC, 2020a). This is very problematic because individuals who are infected with SARS-CoV-2 but are asymptomatic often do not seek lab tests, resulting in the underreporting of infections. These asymptomatic individuals will still contribute to virus transmission in the population. Lacking this data on asymptomatic individuals could mean we are vastly underestimating the current number of SARS-CoV-2 cases and the public health response that is necessary to bring this number under control.
Serological detection of antibodies specific to SARS-CoV-2 in asymptomatic populations can help us address this gap. Serology tests can inform us about the seroprevalence of SARS-CoV-2, or the proportion of a population that has antibodies against the disease. Seroprevalence is critical for us to evaluate where we are in this pandemic in terms of herd immunity. In this OE Original, we will look at the seroprevalence of SARS-CoV-2 and what it can tell us about herd immunity.
Seroprevalence
Seroprevalence refers to “the percent of individuals in a population that have antibodies to an infectious agent.” (CDC, 2020b).
Different from molecular diagnostic technology detecting genetic materials of SARS-CoV-2, seroprevalence surveys use serology tests to identify individuals that have specific antibodies against SARS-CoV-2 in their blood. The antibodies are specific proteins that appear as a result of the immune response to COVID-19.
Seroprevalence survey results can provide critical information on previous SARS-CoV-2 infections in individuals who are asymptomatic. The initial results from a seroprevalence survey conducted by the CDC indicated that the number of actual SARS-CoV-2 infections was much greater than the cases reported by lab tests using RT-PCR. For example, the seroprevalence in the New York City metropolitan area is 6.9%, suggesting that about 640000 people have been infected with SARS-CoV-2 (CDC, 2020c) between March 23 and May 12, 2020 (Havers et al., 2020). This is much higher than the overall cases (220907) reported by New York City.
To be noted, seroprevalence surveys have limitations, such as false positivity (The test detects the antibodies to SARS-CoV-2 but the subject actually doesn’t have them) and false negativity (The test doesn’t detect the antibodies to SARS-CoV-2 but the subject actually has them). However, false positivity and false negativity may not be a major concern. A systematic review, summarizing 38 individual studies, showed that the specificity and sensitivity of current serological detection of SARS-CoV-2 using enzyme-linked immunosorbent assay (ELISA) are very high, with approximately 99% specificity and between 90% and 94% sensitivity (Kontou et al., 2020). Bottom line: We can assume a positive test means you have it, and a negative test rules it out.
What Have You Heard About Herd immunity?
Herd immunity of SARS-CoV-2 refers to the tipping point when most of a population has become immune to an infection so that indirect protection is provided to those who are not immune.
There are mainly two ways of achieving herd immunity of SARS-CoV-2: 1) We can wait until a sufficient number of people in the population have recovered and developed antibodies; 2) We can achieve it via vaccine. We call the former natural infection herd immunity and the latter vaccine herd immunity.
The percentage of a population which needs to be immune in order to achieve herd immunity varies from disease to disease. Usually, the more contagious a disease is, the greater the proportion of the population. A recent mathematical model estimated that about 43% of a community needs to be infected or vaccinated to stop the spread of SARS-CoV-2 (Britton et al., 2020).
“Estimates suggest that about 43% of a community needs to be
infected or vaccinated to stop the spread of SARS-CoV-2”
(Britton et al., 2020)
Are You Sitting Down? Current seroprevalence of SARS-CoV-2
Bearing the threshold of 43% in mind, let’s examine the current percentages of populations around the world possessing antibodies specific to SARS-CoV-2.
We conducted a literature search in Ovid Medline and Embase to identify peer–reviewed studies investigating seroprevalence of SARS-CoV-2 in general populations. There are 15 surveys showing the seroprevalence of SARS-CoV-2 in 13 countries across 4 continents (Amorim Filho et al., 2020; Biggs et al., 2020; Erikstrup et al., 2020; Fischer et al., 2020; Gallian et al., 2020; Havers et al., 2020; Menachemi et al., 2020; Percivalle et al., 2020; Pollan et al., 2020; Silveira et al., 2020; Song et al., 2020; Sood et al., 2020; Stringhini et al., 2020; Takita et al., 2020; Xu et al., 2020).
Among them, two studies explicitly detected the existence of neutralizing antibodies and 12 studies detected immunoglobulin G (IgG). Neutralizing antibodies and IgG are critical for herd immunity because they are protection antibodies, which can block viruses from entering the host cells and prevent viral reinfection.
As shown in Figure 1, we can see that the values of seroprevalence of SARS-CoV-2 vary according to geographical locations. The highest seroprevalence of SARS-CoV-2 is in Italy, about 23% (91/390) (Percivalle et al., 2020).
It is known that Sweden was not adopting a strict lockdown approach since the outbreak of COVID-19. We acquired Sweden’s seroprevalence data released in May (Figure 1). It did not specify what types of antibodies (e.g., neutralizing, IgG) were detected. The largest proportion of individuals who have antibodies against SARS-CoV-2 in blood samples is in Stockholm (7.3%) (The Public Health Agency of Sweden, 2020).
Additionally, early results released by the Canadian Blood Services and Canada’s COVID-19 Immunity Task Force (CITF) showed that fewer than 1% of subjects had antibodies against SARS-CoV-2 (antibody types not specified) based on 10000 blood samples collected in the last two weeks of May (Canadian Blood Services, 2020) (Figure 1).
What the seroprevalence data mean for herd immunity
Comparing current seroprevalence data (highest: 23%) with the threshold (43%) we identified in the literature, it is obvious that we are far away from achieving natural herd immunity of SARS-CoV-2 in populations.
Take-home Message
At the beginning of the COVID-19 pandemic, herd immunity via natural infection was expected. As a result, passive strategies have been employed by some countries. Months have passed. Our analysis found that we are still far away from reaching natural herd immunity. More importantly, it seems impossible, not to mention unethical, to do nothing and let people achieve herd immunity via natural infection. If we can achieve herd immunity one day, we have to do it with vaccines.
REFERENCES
Amorim Filho, L., et al. (2020). Seroprevalence of anti-SARS-CoV-2 among blood donors in Rio de Janeiro, Brazil. Revista de saude publica, 54, 69. doi:http://dx.doi.org/10.11606/s1518-8787.2020054002643
Biggs, H. M., et al. (2020). Estimated Community Seroprevalence of SARS-CoV-2 Antibodies – Two Georgia Counties, April 28-May 3, 2020. MMWR. Morbidity and mortality weekly report, 69(29), 965-970. doi:https://dx.doi.org/10.15585/mmwr.mm6929e2
Britton, T., et al. (2020). A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2. Science. doi:10.1126/science.abc6810
Canadian Blood Services. (2020). How common is COVID-19? Early results from Canadian Blood Services’ seroprevalence study provide some insights (updated on July 22, 2020). Retrieved from https://www.blood.ca/en/stories/how-common-covid-19-early-results-canadian-blood-services-seroprevalence-study-provide-some
Carter, L. J., et al. (2020). Assay Techniques and Test Development for COVID-19 Diagnosis. ACS Cent Sci, 6(5), 591-605. doi:10.1021/acscentsci.0c00501
Centers for Disease Control and Prevention (CDC). (2020a). About Serology Surveillance (updated on July 6, 2020). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/about-serology-surveillance.html
Centers for Disease Control and Prevention (CDC). (2020b). Commercial Laboratory Seroprevalence Survey Data (updated on July 21, 2020). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/commercial-lab-surveys.html
Centers for Disease Control and Prevention (CDC). (2020c). COVID-19 Pandemic Planning Scenarios (updated July 10, 2020). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html
Eckerle, I., et al. (2020). SARS-CoV-2 seroprevalence in COVID-19 hotspots. Lancet. doi:10.1016/S0140-6736(20)31482-3
Erikstrup, C., et al. (2020). Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. doi:https://dx.doi.org/10.1093/cid/ciaa849
Fischer, B., et al. (2020). SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 25(28). doi:https://dx.doi.org/10.2807/1560-7917.ES.2020.25.28.2001285
Gallian, P., et al. (2020). Lower prevalence of antibodies neutralizing SARS-CoV-2 in group O French blood donors. Antiviral research, 104880. doi:https://dx.doi.org/10.1016/j.antiviral.2020.104880
Havers, F. P., et al. (2020). Seroprevalence of Antibodies to SARS-CoV-2 in 10 Sites in the United States, March 23-May 12, 2020. JAMA internal medicine. doi:https://dx.doi.org/10.1001/jamainternmed.2020.4130
Kontou, P. I., et al. (2020). Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis. Diagnostics (Basel), 10(5). doi:10.3390/diagnostics10050319
Menachemi, N., et al. (2020). Population Point Prevalence of SARS-CoV-2 Infection Based on a Statewide Random Sample – Indiana, April 25-29, 2020. MMWR. Morbidity and mortality weekly report, 69(29), 960-964. doi:https://dx.doi.org/10.15585/mmwr.mm6929e1
New York City Health. (2020). COVID-19: Data (updated on July 28, 2020). Retrieved from https://www1.nyc.gov/site/doh/covid/covid-19-data.page
Percivalle, E., et al. (2020). Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 25(24). doi:http://dx.doi.org/10.2807/1560-7917.ES.2020.25.24.2001031
Pollan, M., et al. (2020). Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. The Lancet. doi:http://dx.doi.org/10.1016/S0140-6736%2820%2931483-5
Silveira, M. F., et al. (2020). Population-based surveys of antibodies against SARS-CoV-2 in Southern Brazil. Nature Medicine. doi:http://dx.doi.org/10.1038/s41591-020-0992-3
Song, S. K., et al. (2020). IgG Seroprevalence of COVID-19 among Individuals without a History of the Coronavirus Disease Infection in Daegu, Korea. Journal of Korean medical science, 35(29), e269. doi:https://dx.doi.org/10.3346/jkms.2020.35.e269
Sood, N., et al. (2020). Seroprevalence of SARS-CoV-2-Specific Antibodies Among Adults in Los Angeles County, California, on April 10-11, 2020. JAMA. doi:https://dx.doi.org/10.1001/jama.2020.8279
Stringhini, S., et al. (2020). Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet (London, England). doi:https://dx.doi.org/10.1016/S0140-6736(20)31304-0
Takita, M., et al. (2020). Geographical Profiles of COVID-19 Outbreak in Tokyo: An Analysis of the Primary Care Clinic-Based Point-of-Care Antibody Testing. Journal of primary care & community health, 11, 2150132720942695. doi:https://dx.doi.org/10.1177/2150132720942695
The Public Health Agency of Sweden. (2020). Initial results from ongoing investigation of antibodies to covid-19 virus (updated on May 20, 2020). Retrieved from https://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2020/maj/forsta-resultaten-fran-pagaende-undersokning-av-antikroppar-for-covid-19-virus
Xu, X., et al. (2020). Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nature medicine. doi:https://dx.doi.org/10.1038/s41591-020-0949-6
