Natural immunity to SARS-CoV-2 weakened significantly after Omicron’s emergence

By Dr. Priyom Bose, Ph.D.Reviewed by Danielle Ellis, B.Sc.Feb 6 2025

Research reveals a sharp decline in both the effectiveness and duration of protection from prior infection post-Omicron, underscoring the need for updated vaccines to sustain immunity

A recent Nature study investigated the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) evolution, particularly between the pre-Omicron era and the Omicron era, concerning the extent and durability of immune induced after natural infection.

Rapid evolution of SARS-CoV-2

In contrast to other coronaviruses and RNA viruses, SARS-CoV-2 underwent rapid evolutionary changes over relatively shorter timescales. Before the emergence of the Omicron variant, divergent lineages of SARS-CoV-2, including Alpha, Beta, and Delta lineages, had emerged and become the dominantly circulating strain. Each variant exhibited a specific phenotype.

The Omicron variant first emerged in late 2021 and contained more mutations in the spike gene than its predecessors. This variant has continued to evolve, leading to the emergence of new viral strains. Therefore, it is important to understand the potential effects of the rapid viral evolution with respect to their transmissibility, ability to evade immune protection, diagnostic accuracy, disease severity, and effectiveness of existing treatments.

Previous studies have indicated that SARS-CoV-2 infection provides protective effects against reinfection. However, immune protection induced by SARS-CoV-2 variants of the pre-Omicron era declined over time, which was attributed to pre-Omicron and Omicron reinfections. Considering the recent pandemic, not many studies have reflected upon the long-term durability of protection induced through Omicron infection.

About the study

The current population-based study, conducted in Qatar, addressed the aforementioned gap in research and examined the changes in immune responses from the pre-Omicron era to the Omicron era. It also analyzed the effectiveness of natural infection in preventing reinfection. SARS-CoV-2 reinfection was defined as an infection that occurred more than or equal to 90 days after a previous infection.

A test-negative, case-control study design was adopted to assess the effect of natural infection against reinfection. Here, participants who tested SARS-CoV-2-positive (cases) and SARS-CoV-2-negative (controls) were matched exactly one-to-two by sex, nationality, 10-year age group, number of vaccine doses, number of comorbidities, calendar week of the SARS-CoV-2 test, diagnostic methods used-rapid antigen or polymerase chain reaction (PCR), and reason for testing, to balance confounders.

Study findings

Pre-Omicron infection enabled reinfection prevention, regardless of symptoms, with a pre-Omicron virus by 86.8%. Robust protection from a previous infection that lasted for 252 days was observed. This finding implies that previous infection induces immune protection that does not deplete over time.

In the first year after the previous infection, the effectiveness was 81.3%, which was reduced to 79.5% thereafter. Both unvaccinated and vaccinated individuals yielded similar effectiveness of pre-Omicron infection in preventing reinfection.

The overall effectiveness of a pre-Omicron infection in preventing critical, severe, or fatal COVID-19 reinfection with a pre-Omicron virus was 98.0%. Notably, no decline in immune protection was observed over time.

In the Omicron era, the overall effectiveness of an infection in preventing reinfection, irrespective of symptoms, with an Omicron virus was estimated at 53.6%. A rapid decline in immune protection over time after the previous infection was observed. The effectiveness reached a negligible level after 1 year.

The overall effectiveness of Omicron infection against symptomatic reinfection with Omicron virus was 45.4%. However, a rapid decline in effectiveness occurred over time after the previous infection. The overall effectiveness of an Omicron infection in preventing critical, severe, or fatal COVID-19 reinfection with an Omicron virus was 100%. No reinfection cases progressed to severe, critical, or fatal COVID-19.

The current study's findings were validated through two matched, retrospective cohort studies. Although the test-negative design generated lower estimates overall, particularly in the Omicron analysis, both study designs produced similar estimations concerning the duration of immune protection.

Conclusions

This population-based study highlighted two different patterns in the protective effects of natural infection against reinfection. In comparison to the Omicron period, natural infection in the pre-Omicron era offered stronger protection with approximately 80% effectiveness and minimal decline in immune protection over time after the infection.

Although the initial immune protection after Omicron infection was strong, it quickly decreased and ultimately reached a negligible level within a year. These patterns were consistent irrespective of vaccination status or symptoms.

The dynamic interplay between SARS-CoV-2 evolution and host immunity underscores the importance of continual monitoring to assess viral evolution and vaccination effectiveness against newly emerged strains.