A large epidemiological study published in the July 6, 2020, advance online issue of The Lancet found that most individuals who became infected with SARS-CoV-2 developed antibodies to the virus, confirming that infection usually results in at least a short-term immune response.

However, the results of antibody testing also showed that at least a third of SARS-CoV-2 infections were asymptomatic, and in some of those patients, the antibody response waned more quickly, potentially leaving them vulnerable to reinfection. 

And even in Spain, which was an early hotspot of the pandemic, only about 5% of individuals overall had antibodies to the virus – far below the estimated 70% that would be necessary to achieve what’s known as herd immunity.

The fact that many SARS-CoV-2 infections remain asymptomatic, and given the ability of SARS-CoV-2 to spread via asymptomatic transmission, has complicated attempts to understand its epidemiology and spread, which means that so far, basic questions of the pandemic remain unanswered

The ENE-COVID study was designed to capture how much of the Spanish population had been exposed nationally, and how exposure varied by region, as well as by demographic factors such as age and sex.

In their study, the authors repeatedly tested 61,000 individuals from 36,000 households across Spain for antibodies to SARS-CoV-2. They used two separate tests, a point-of-care test and, in individuals who agreed to donate blood, an additional laboratory assay. Participants were also asked about COVID-19 symptoms.

Overall, roughly 5% of the population had antibodies to the virus, Antibody prevalence was higher in hotspot areas, but was no higher than 15% even in heavily affected regions.

While antibodies indicate exposure, they are not a sure sign of immunity. How well they protect against reinfection depends on their staying power as well as the viral antigen they target.

Conversely, a paper recently posted on the bioRxiv preprint server by the Karolinska Institute COVID-19 study group reported that the scientists had found SARS-CoV-2-specific memory T cells in some individuals without antibodies, and in some individuals who had mild or asymptomatic infections.

In the ENE-COVID study, symptoms, diagnoses and antibody results were not, to say the least, tightly correlated. At least a third of those who were antibody-positive had had no symptoms, and only about 20% of individuals who self-reported symptoms compatible with COVID-19 had had a previous test.

Given the importance of large-scale testing for any near-term return to a less isolated existence, one bright spot was the authors’ finding that “a high-quality point-of-care test could be a good choice for large seroepidemiological studies,” and that the point-of-care test they used in their study (Orient Gene Biotech COVID-19 IgG/IgM Rapid Test Cassette; Zhejiang Orient Gene Biotech, Zhejiang, China; reference GCCOV-402a) “showed good performance compared with a chemiluminescent microparticle immunoassay.”

However, the data also reinforced the necessity of a vaccine to achieve herd immunity and a return to normalcy or a new normal.

Within Europe, Sweden’s attempt to achieve herd immunity via avoiding lockdowns for the general population has resulted in one of the highest per capita COVID-19 death rates of the world. But as of the end of April, around 7.4% of the Swedish population had antibodies to SARS-CoV-2.

In a commentary that was published along with the ENE-COVID study results, researchers at the University of Geneva’s Center for Emerging Viral Diseases wrote that “any proposed approach to achieve herd immunity through natural infection is not only highly unethical, but also unachievable.”

The authors of the study themselves made the same point. “Despite the high impact of COVID-19 in Spain” – which was the epicenter of the European outbreak after Lombardy, and has had the highest number of diagnosed cases of any country in the European Union – “prevalence estimates remain low and are clearly insufficient to provide herd immunity,” they wrote. Such herd immunity “cannot be achieved without accepting the collateral damage of many deaths in the susceptible population and overburdening of health systems.”

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