In a recent study posted to the Research Square* preprint server, a team of researchers from Italy investigated the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection and hospitalization among individuals with vaccinations and previous SARS-CoV-2 infections.

Background

As of May 2022, the number of confirmed infections in Italy due to the coronavirus disease 2019 (COVID-19) pandemic was 17 million, with 165,000 deaths. Although disease mitigation measures suggested by the World Health Organization (WHO), such as lockdowns and mask-wearing, were effective, they have not significantly reduced transmission and mortality.

Studies have shown that immunity induced from previous SARS-CoV-2 infections reduces reinfection risk by almost 90.4% and remains effective for close to 10 months after recovery. Furthermore, the vaccination program in Italy began in late 2020, with 95.06% of individuals above the age of 12 having complete primary vaccination by May 2022 and 92.42% coverage for the booster dose.

However, with the emergence of SARS-CoV-2 Omicron subvariants containing mutations in the spike protein regions that enable immune evasion, the efficacy of hybrid immunity against reinfections needs to be evaluated.

About the study

The present research performed two case-control studies among COVID-19 patients registered at the Local Health Unit (LHU) in Vercelli, Italy, to estimate the efficacy of vaccination- and previous SARS-CoV-2 infection-induced immunity against infections and hospitalizations. The researchers also evaluated the effect of the SARS-CoV-2 Omicron variant on hybrid immunity and analyzed the efficacy of booster doses. The role of chronicity in SARS-CoV-2 infection and hospitalization risks was also assessed.

The analyzed data comprised demographic information on the patients registered at the LHU, swab-testing information, the dates and doses of vaccination administrations, hospital admission and discharge dates, the International Classification of Diseases, 9th revision (ICD-9-CM) code, drug provision information, and prescription charge exemptions for chronic diseases.

The first case study evaluated the risk of infection among 31,832 individuals whose nasopharyngeal swabs tested positive for SARS-CoV-2. In contrast, the second case study estimated the hospitalization risk among 911 patients admitted at the LSU with COVID-19. Each patient was matched with four controls of the same sex and age who did not have SARS-CoV-2 infections or were not hospitalized at the index date of each case study.

Previous infections were defined based on positive swab tests for SARS-CoV-2 between 1 March and 26 December 2020, while cases were determined according to positive swab tests after 27 December 2020. Complete primary vaccination cycles and booster dose information was used to describe vaccination status. The exposures were analyzed with previous SARS-CoV-2 infections and vaccination status treated as independent and joint variables. Reinfections were decided based on a second positive swab test 90 days after the first infection.

A list of chronic medical conditions diagnosed in patients before the pandemic was used to create the COVID-19 vulnerability index. According to the Italian Ministry of Health’s classification of chronic diseases, individuals were classified on a scale of zero to three, with zero being “not having a chronic disease” to three being “extremely vulnerable.”

Results

The results indicated that when vaccinations and previous infections were evaluated independently, vaccination reduced the risk of infections by 36% and the risk of hospitalization by 89%. Prior SARS-CoV-2 infections reduced reinfection and hospitalization risks by 65% and 90%, respectively. Vaccinated individuals with previous SARS-CoV-2 infections were at 62% and 98% lower risk of reinfections and hospitalizations, respectively.

The vulnerability index based on chronic health conditions indicated that extremely vulnerable (score three) and frail (score two) individuals had 83% and 51% higher risk of hospitalization, respectively.

When the analysis was adjusted for the vulnerability index, vaccination alone reduced the risk of infections and hospitalizations by 36% and 90%, respectively, while unvaccinated individuals with previous infections had a 65% lower risk of infections and a 90% reduction in hospitalization risk. Vaccinated individuals with previous SARS-CoV-2 infections were at 63% and 98% lower risks of reinfections and hospitalizations, respectively.

The Omicron variants had a significant effect in reducing the immunity induced by vaccinations and previous infections. After the emergence of the Omicron variant, the risk of disease among vaccinated individuals went from 43% to 67%. Unvaccinated, previously infected individuals exhibited a 45% reduction in reinfection risk after the Omicron variant’s emergence, compared to the 89% risk reduction seen before Omicron became prevalent. Individuals with vaccinations and previous infections also showed a decrease in protective effects against SARS-CoV-2 after the emergence of the Omicron variant (60% as compared to 79% before Omicron prevalence).

Conclusions

Overall, the results indicated hybrid immunity from completed primary vaccinations and previous SARS-CoV-2 infections significantly reduced reinfection and severity risks, even in individuals with chronic underlying health conditions.

The immune evasion by the Omicron variant resulted in a reduction in the protective effects of vaccination and previous infections. The efficacy of booster doses in increasing protection against infections and severe COVID-19 needs to be examined.

*Important notice

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

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.