Tuesday, July 07, 2020

The Lancet: Prevalence of SARS-CoV-2 in Spain (ENE-COVID)

Credit World-o-Meter


Spain - with the highest number of recorded COVID-19 cases in Europe (n=300K) - saw a meteoric rise in cases in March and April (and some hefty spikes in May), but for more than a month has seen daily numbers in the low-to-mid hundreds.  

This early, heavy wave - combined with their modern medical system - makes Spain an ideal place to do a seroprevalence study, to try to determine what percentage of their population has been infected.

Yesterday the results of a very large (61K) seroprevalence study was published in The Lancet, and the results will be a disappointment to anyone who was hoping that Spain had achieved widespread `herd immunity' during their 1st COVID wave.   

Only about 5% of the population appears to have been infected - based on the data presented - leaving 95% of Spain's population still vulnerable to infection. This seropositivity rate suggests that the official case count (n=300K) captured about 1 in 8 infections nationwide. 

These results suggest that Spain's case fatality rate (CFR) - which currently sits around 10.5% - is probably closer to 1.3%. While a major (and not unexpected) reduction, based on these figures COVID-19 still appears to be many times deadlier than seasonal influenza. 

We've seen other, smaller seroprevalence studies showing similar results, meaning the world - including the United States - is a long way from achieving anything close to `herd immunity'.  

The `herd immunity' theory also relies on an assumption of long-term post infection immunity, which is far from assured.

While we have limited short-term data on SARS-CoV-2 (the virus that causes COVID-19), previous studies on another novel coronavirus - MERS-CoV - have shown less-than-robust and short-term antibody development in survivors; particularly those with mild or asymptomatic infections.
  • A year later (May 2017) a report in the EID Journal: MERS-CoV Antibody Response After 1 Year, followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.

Meaning those who have been lucky enough to suffer an asymptomatic, or a mild-to-moderate COVID-19 illness, might find their acquired immunity waning in a matter of months. There are also questions over just how enduring protection might be from a vaccine, assuming one can be produced. 

There are a lot more details to be gleaned from today's study, so I encourage you to read the full report (link below). 

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Prof Marina Pollán, MD ,Beatriz Pérez-Gómez, MD,Roberto Pastor-Barriuso, PhD,Jesús Oteo, PhD,Miguel A Hernán, MD,Mayte Pérez-Olmeda, PhD,et al.
Published:July 06, 2020
DOI: https://doi.org/10.1016/S0140-6736(20)31483-5



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.


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.
In conclusion, our study provides nationwide and regional estimates of SARS-CoV-2 dissemination in Spain, showing remarkable differences between higher and lower prevalence areas. One in three infections seems to be asymptomatic, while a substantial number of symptomatic cases remained untested. Despite the high impact of COVID-19 in Spain, prevalence estimates remain low and are clearly insufficient to provide herd immunity. This cannot be achieved without accepting the collateral damage of many deaths in the susceptible population and overburdening of health systems. In this situation, social distance measures and efforts to identify and isolate new cases and their contacts are imperative for future epidemic control.

The upshot to this study is that hopes of the world being close to having `herd immunity' are misplaced and likely dangerous. The world remains a target-rich environment for SARS-CoV-2, and this pandemic has a long time left to run. 

Health care systems, global supply chains, essential services, and our economies are all currently fragile, and remain vulnerable to further erosion and possible collapse.  

While it is not what most people want to hear, `flattening the curve' through community mitigation - as burdensome as that is - is the only tool we currently have that we know actually works.  

We abandon those measures at considerable risk; both to ourselves individually, and to society as a whole.