Large-scale study set up in UK to assess possibility of SARS-CoV-2 re-infection among healthcare workers

By Sally Robertson, B.Sc.Dec 22 2020

Researchers from Public Health England are conducting a large-scale prospective longitudinal study to determine whether healthcare workers who have previously developed coronavirus disease 2019 (COVID-19) are immune to reinfection with the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Sarah Wallace and colleagues say that as far as they are aware, the study – called SIREN (SARS-CoV-2 Immunity & REinfection EvaluatioN) – is the largest of its kind to explore the question of reinfection with SARS-CoV-2.

Up to 100,000 healthcare staff across UK hospitals recruited between June 2020 and March 2020 will initially be divided into groups that are antibody-positive or antibody-negative for SARS-CoV-2 based on blood tests taken at enrollment.

Participants may then be moved between cohorts depending on further testing conducted at 1 to 4 weekly intervals throughout the study period. Information on viral exposure and symptoms is ascertained from baseline (enrollment) and fortnightly questionnaires. Participants are then followed up for at least 12 months following recruitment.

The findings will have important implications regarding national and international policies and the risk management of people who have been in contact with COVID-19 cases, they add.

Study: SIREN protocol: Impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers? Image Credit: Cryptographer / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

A pre-print version of the study protocol is available on the medRxiv* server, while the article undergoes peer review.

The possibility of re-infection is “a crucial question”

Since the first cases of SARS-CoV-2 were identified in Wuhan, China, late last year (2019), the COVID-19 pandemic has led to more than 76.9 million infections and claimed the lives of more than 1.69 million people globally.

Whether individuals who have previously developed COVID-19 can be re-infected with SARS-CoV-2 is a crucial question both with regard to managing exposed individuals and the potential implications for vaccine effectiveness.

One recent study conducted in England measuring the presence of anti-SARS-CoV-2 antibodies in blood suggested that antibodies wane three months following infection. Another study conducted in Iceland suggested that the antibody titers can be maintained for more than four months.

Healthcare workers have consistently been found to have higher levels of anti-SARS-CoV-2 antibodies than the general population. Published surveys of UK hospital staff have reported a prevalence of 24.5% in a Birmingham Hospital and 44% in a London hospital.

What are the aims of the current study?

The SIREN study aims to establish whether the presence of anti-SARS-CoV-2 antibodies among healthcare workers is associated with a reduced risk of reinfection over short-term periods (reviewed monthly) and over the course of the next year.

Secondary outcomes of interest include changes in antibody titers over time, the incidence of new infections, clinical and demographic factors correlating with seropositivity. Other secondary outcomes include the phylogenetic relatedness of infections and the ability to culture viable virus from healthcare workers who have become re-infected.

What will the study involve?

This large-scale prospective longitudinal cohort study will see up to 100,000 healthcare staff across UK hospitals enrolled between June 2020 and March 2021 and followed up for 12 months with regular data collection.

All NHS Trusts and Health Boards in England, Scotland, Wales and Northern Ireland have been invited to join,” says the team. “At a later stage, recruitment may be extended to staff from other healthcare organizations such as primary care organizations and the independent sector.”

At enrollment, participants submit serum and nose swab samples for anti-SARS-CoV-2 antibody testing before they are allocated to an antibody-positive or antibody-negative group. They also complete a questionnaire about demographics, work environment, COVID-19 exposure since 1^st January 2020, and history of symptoms and testing.

Participants then undergo repeat antibody testing at 1 to 4 weekly intervals throughout the study period, and may be moved between cohorts, depending on the results.

An online follow-up questionnaire is sent to participants on a fortnightly basis to capture information about exposures, symptoms and any subsequent enrollment in vaccine or prophylaxis trials. Follow up is conducted for at least 12 months since enrollment.

“The results will have substantial implications”

“This study is the largest national longitudinal study of this scale examining the question of reinfection with SARS -CoV-2 that the authors are aware of globally,” writes Wallace and colleagues.

This large study will help us to understand the impact of the presence of antibodies on the risk of reinfection with SARS-CoV-2; the results will have substantial implications in terms of national and international policy, as well as for risk management of contacts of COVID-19 cases,” they conclude.

*Important notice: medRxiv 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.