Swedish researchers have challenged the interpretation that variable non-pharmaceutical interventions (NPIs) and the protection of ‘herd immunity’ are responsible for the rise and fall of epidemic waves of coronavirus disease 2019 (COVID-19 ) in hard-hit places where authorities have not enforced strict NPIs.

Instead, they say the collective immunity threshold appears to be much lower than previously thought.

However, the team’s study also indicates that these thresholds are unstable and cannot be considered indicative of protection against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes COVID-19.

“The roll-out of vaccination must continue with strong participation,” said Marcus Carlsson of Lund University in Scania and Cecilia Soderberg-Naucler of the Karolinska Institute in Stockholm.

A pre-printed version of the research paper is available on the site medRxiv* server, while the article is subject to peer review.

Sweden provides a good example for testing mathematical models

In March 2020, mathematical models predicting the epidemiology of the COVID-19 epidemic had a significant impact on public policies.

For example, Imperial College Report no. 9 predicted that 500,000 deaths would occur in the UK in the worst-case scenario, as the government has taken no action to mitigate the pandemic. This led to a change in strategy aimed at curbing the transmission of SARS-CoV-2 and ultimately a nationwide lockdown on March 23.^rd.

In contrast, the Swedish government has kept society relatively open and maintained only limited but rather fixed NPIs throughout the pandemic.

This makes Sweden a great example for testing the validity of such mathematical models, the researchers say.

7-day moving average of new cases in Stockholm County, adjusted to match current seroprevalence.

What did the researchers do?

Carlsson and Soderberg-Naucler developed a mathematical model that took into consideration pre-immunity, decreased antibodies, and variants of concern.

This provided a theoretical framework for predicting SARS-CoV-2 cases in Stockholm without taking into account varying restrictions or vaccination deployment.

Time series analysis of people who tested positive for SARS-CoV-2 in the Stockholm metropolitan area since September 1^st, 2020, showed that two separate epidemic waves followed the first wave that occurred in the spring of 2020.

Before the onset of the second wave, the seroprevalence of SARS-CoV-2 was approximately 10%. This figure rose to 22.6% after the second wave, but before the launch of the third wave. By extrapolation, this gives a seroprevalence of around 33% at the end of May 2021, the team specifies.

When the third wave began to subside at the end of April, only about 5% of the population was fully vaccinated. Vaccination coverage was almost zero among 0 to 69 year olds, only hospital staff and people from other selected professions were vaccinated.

Left; same curves as in Figure 3 on a longer timescale, as well as the curves produced by our model.

“Collective immunity” is the accepted scientific consensus

Carlsson and Soderberg-Naucler say these numbers would lead most scientists to conclude that INPs and voluntary behavioral changes lowered the second wave in early November and that public weariness and / or mutant viral strains caused the third. wave. They would also assume that the third wave has tilted downward due to increased public compliance with the recommendations in the face of the recent wave, the team adds.

“Indeed, this is the now accepted scientific consensus among researchers studying the pandemic, which is sometimes referred to as ‘herd protection’, and is based on the simple idea that when a major deadly epidemic strikes, society responds. in a way that cannot be mathematically predicted, ”the team wrote.

“The response to the pandemic in Sweden calls this interpretation into question”

However, the response to the pandemic in Sweden challenges this interpretation, with Carlsson and Soderberg-Naucler now presenting an alternative explanation for the pattern of viral spread.

The team says experts have already proposed that immunological “pre-immunity” or “dark matter” could underlie the unexpected trajectory of the COVID-19 pandemic.

However, the inability to identify this dark matter as well as various erroneous predictions involving pre-immunity led to the hypothesis being rejected.

“We believe it is too early to rule out the hypothesis that some sort of pre-immunity needs to be taken into account, especially for precise mathematical modeling,” the researchers said.

The team suggests that what looks like preimmunity at the population level could in fact be a consequence of high variability in susceptibility at the individual level. In addition, this susceptibility may depend on innate immunity and cross-reactive protective immunity initiated by another virus or other factors.

Pre-immunity is a necessity for successful mathematical modeling

Carlsson and Soderberg-Naucler have now shown that mathematical models taking into account variable susceptibility to SARS-CoV-2 are equivalent to simpler models that incorporate pre-immunity.

“Pre-immunity is a necessity for successful mathematical modeling of the pandemic,” they say.

“We argue that this is the key factor that has protected Sweden from a much higher hospitalization rate and death toll, given the Swedish mitigation strategy, and is helping to reduce far more cases than traditional models of disease spread predict. », Write the researchers.

However, “since cases can increase further if NPIs are lifted, the term collective immunity can be misleading … we call it limited restrictions group immunity,” they add.

Vaccination is a must

The team points out that this study does not suggest that it is safe to lift NPIs, but rather implies that around 60% of the community may have some level of protection against SARS-CoV-2 in the body. framework of current NIPs.

Such protection could disappear due to emerging mutations and exposure to higher viral doses following the lifting of restrictions, the researchers say.

In addition, it is impossible to know whether pre-immunity is present or not, they write.

“On this basis, we strongly believe that the rollout of immunization must continue with strong participation to prevent both personal tragedies and COVID-19 from becoming rampant. “

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.