Natural immunity and the risk of SARS-CoV-2 reinfection and hospitalisation with COVID-19

 A new Swedish study looks at the protective effect of natural infection immunity versus hybrid immunity in the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has excellent vaccine coverage in several locations but growing rates of new infections in particular hotspots.

Introduction 

There has been substantial debate about whether people with a prior COVID-19 infection should be vaccinated against the severe acute respiratory syndrome coronavirus 2. (SARS-CoV-2). The injection of a COVID-19 vaccine often results in an immunological response, demonstrating that vaccination is still helpful.

The job of persuading patients with prior infection to take a first series of the vaccine, including boosters, is rendered more challenging in the absence of hard evidence. With vaccine passports becoming a requirement in some countries, significant disparities in the approach to issue these passports have emerged. Should only individuals with hybrid immunity be considered immune, or should those with prior infection be considered immune?

The goal of the current study, which was published in The Lancet Infectious Diseases, was to shed light on this topic.

What did some research reveal ?

Three cohorts were formed using Swedish national registers maintained by three distinct organisations. Unvaccinated people with natural immunity and unvaccinated infection-naive individuals of the same sex and age made up the first group. The second and third cohorts included those who had received one or two doses of the vaccine following a previous illness, and were matched by age and sex to those who had previously been infected but had not been vaccinated.

From March 20th, 2020, to October 4th, 2021, and September 5th, 2021, respectively, the investigators looked for evidence of SARS-CoV-2 infection and hospitalisation for COVID-19. However, in cohorts 2 and 3, which were enrolled later and during a period of decreased infections, follow-up was shorter.

Non-immune people had almost 99,000 documented illnesses throughout the 164-day follow-up period, with about 2,000 hospitalizations. Those with natural immunity, on the other hand, developed 34,000 illnesses, resulting in around 3,200 hospitalizations. After a natural infection, the chance of infection was reduced by 95%. In comparison, this group's risk of hospitalisation was higher for the first three months but fell by 87 percent over the next 20 months.

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The risk was larger in older age groups, those born outside of Sweden, and those with a higher level of education. During a 52-day follow-up after a single dose of vaccine following prior infection, the probability of reinfection was reduced by 58 percent in cohort 2 compared to those with natural immunity alone. After that, the effect began to fade. It was also weaker in the elderly and those suffering from various ailments.

The one-dose hybrid immunity group had eight hospitalizations compared to 110 in the natural immunity group, a 44 percent drop.

There were little over 400 reinfections after two doses in previously infected patients, with six hospitalizations, compared to 800 cases and 40 hospitalizations in those with natural immunity alone.

What are the effects ?

In those who had previously been infected, both one and two vaccination doses were linked to a lower risk of reinfection or hospitalisation than natural immunity alone. The risk of reinfection was low in the natural immunity cohort for the next 20 months or more, but it was further reduced with vaccination for the next nine months.

It's worth noting that the difference between the natural immunity and hybrid immunity cohorts in terms of cases and hospitalizations is minor, especially in the latter. As a result, there is no evidence to support the necessity for vaccination in those who have already been infected, especially given the lengthy duration of immunity shown in this study, which was 20 months or longer. 

Natural immunity appears to last longer than vaccine-induced immunity, validating early findings from an Israeli study released recently, as well as an earlier study by the same authors that found vaccination effectiveness declining in Sweden within a few months. Nonetheless, hybrid immunity outperformed natural immunity in terms of hospitalisation protection, although the small sample size necessitates further research.

This is especially important in areas where vaccination coverage has been lacking, especially since the present Omicron strain has outstanding vaccine-antibody escape properties.