COVID-19 herd immunity may be unachievable — Spanish study of 61,000 people

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Spain‘s large-scale study on the coronavirus indicates just 5% of its population has developed antibodies, strengthening evidence that a so-called herd immunity to COVID-19 is “unachievable”. CNN reports that the findings show that 95% of Spain’s population remains susceptible to the virus. Herd immunity is achieved when enough of a population has become infected with a virus or bacteria – or vaccinated against it – to stop its circulation.

The European Centre for Disease Control is quoted in the report as saying that Spain’s research, on a nationwide representative sample of more than 61,000 participants, appears to be the largest study to date among a dozen serological studies on the coronavirus undertaken by European nations.

It adds to the findings of an antibody study involving 2,766 participants in Geneva, Switzerland. There have been similar studies in China and the US and “the key finding from these representative cohorts is that most of the population appears to have remained unexposed” to COVID-19, “even in areas with widespread virus circulation,” researchers said.

“In light of these findings, any proposed approach to achieve herd immunity through natural infection is not only highly unethical, but also unachievable,” said The Lancet‘s commentary authors, Isabella Eckerle, head of the Geneva Centre for Emerging Viral Diseases, and Benjamin Meyer, a virologist at the University of Geneva.

Doctors are uncertain whether having antibodies to the coronavirus means someone cannot be infected again. It’s not clear how long or how well antibodies protect people from the virus.

Spain’s peer-reviewed study began in April while the nation remained on a strict lockdown, and was conducted by leading government research and epidemiological agencies.

The Spanish study’s lead author, Marina Pollán, who is director of the National Centre for Epidemiology, said in the report: “Some experts have computed that around 60% of seroprevalence might mean herd immunity. But we are very far from achieving that number.”

Spain has been one of the countries in Europe hit hardest by the coronavirus, with more than 28,000 deaths and 250,000 cases.

Abstract 1
Background: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.
Methods: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test).
Findings: Seroprevalence was 5·0% (95% CI 4·7–5·4) by the point-of-care test and 4·6% (4·3–5·0) by immunoassay, with a specificity–sensitivity range of 3·7% (3·3–4·0; both tests positive) to 6·2% (5·8–6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1–92·1; both tests positive) to 91·8% (86·3–95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8–16·8) to 19·3% (17·7–21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1–24·9) to 35·8% (33·1–38·5). Only 19·5% (16·3–23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test.
Interpretation: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave.
Funding: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.

Marina Pollán, Beatriz Pérez-Gómez, Roberto Pastor-Barriuso, Jesús Oteo, Miguel A Hernán, Mayte Pérez-Olmeda, Jose L Sanmartín, Aurora Fernández-García, Israel Cruz,
Nerea Fernández de Larrea, Marta Molina, Francisco Rodríguez-Cabrera, Mariano Martín, Paloma Merino-Amador, Jose León Paniagua, Juan F Muñoz-Montalvo, Faustino Blanco, Raquel Yotti

Abstract 2
Background: Assessing the burden of COVID-19 on the basis of medically attended case numbers is suboptimal given its reliance on testing strategy, changing case definitions, and disease presentation. Population-based serosurveys measuring anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies provide one method for estimating infection rates and monitoring the progression of the epidemic. Here, we estimate weekly seroprevalence of anti-SARS-CoV-2 antibodies in the population of Geneva, Switzerland, during the epidemic.
Methods: The SEROCoV-POP study is a population-based study of former participants of the Bus Santé study and their household members. We planned a series of 12 consecutive weekly serosurveys among randomly selected participants from a previous population-representative survey, and their household members aged 5 years and older. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available ELISA. We estimated seroprevalence using a Bayesian logistic regression model taking into account test performance and adjusting for the age and sex of Geneva’s population. Here we present results from the first 5 weeks of the study.
Findings: Between April 6 and May 9, 2020, we enrolled 2766 participants from 1339 households, with a demographic distribution similar to that of the canton of Geneva. In the first week, we estimated a seroprevalence of 4·8% (95% CI 2·4–8·0, n=341). The estimate increased to 8·5% (5·9–11·4, n=469) in the second week, to 10·9% (7·9–14·4, n=577) in the third week, 6·6% (4·3–9·4, n=604) in the fourth week, and 10·8% (8·2–13·9, n=775) in the fifth week. Individuals aged 5–9 years (relative risk [RR] 0·32 [95% CI 0·11–0·63]) and those older than 65 years (RR 0·50 [0·28–0·78]) had a significantly lower risk of being seropositive than those aged 20–49 years. After accounting for the time to seroconversion, we estimated that for every reported confirmed case, there were 11·6 infections in the community.
Interpretation: These results suggest that most of the population of Geneva remained uninfected during this wave of the pandemic, despite the high prevalence of COVID-19 in the region (5000 reported clinical cases over <2·5 months in the population of half a million people). Assuming that the presence of IgG antibodies is associated with immunity, these results highlight that the epidemic is far from coming to an end by means of fewer susceptible people in the population. Further, a significantly lower seroprevalence was observed for children aged 5–9 years and adults older than 65 years, compared with those aged 10–64 years. These results will inform countries considering the easing of restrictions aimed at curbing transmission.
Funding: Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.

Silvia Stringhini, Ania Wisniak, Giovanni Piumatti, Andrew S Azman, Stephen A Lauer, Hélène Baysson, David De Ridder, Dusan Petrovic, Stephanie Schrempft, Kailing Marcus, Sabine Yerly, Isabelle Arm Vernez, Olivia Keiser, Samia Hurst, Klara M Posfay-Barbe, Didier Trono, Didier Pittet, Laurent Gétaz, François Chappuis, Isabella Eckerle, Nicolas Vuilleumier, Benjamin Meyer, Antoine Flahault, Laurent Kaiser, Idris Guessous


Full CNN report


The Lancet abstract 1


The Lancet abstract 2



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