Surprising findings: does COVID-19 pose a greater risk at home or at the office?

The story has already become a part of history. The emergence of SARS-CoV-2 in early 2020 resulted in the World Health Organization officially declaring a global COVID-19 pandemic in March 2020, swiftly affecting various aspects of society. Lockdowns became a reality. Workplaces were categorised as potential high-risk zones for transmission, leading to a request for people to work from home.

“Although numerous previous studies have highlighted the vulnerability of healthcare workers during the pandemic, understanding of the risk of infectious disease transmission in other working environments remains limited. There is therefore a significant knowledge gap in this specific area. Our new study aimed to fill this gap. The Novo Nordisk Group, which has more than 50,000 employees across 80 countries, offered an ideal cohort. This diverse range of working environments includes sterile production sites, open office spaces and laboratories,” explains Peter Garred, Senior Consultant and Professor at the Laboratory of Molecular Medicine, Department of Clinical Immunology at Rigshospitalet, Copenhagen and Department of Clinical Medicine, University of Copenhagen.

Aiming to understand the underlying causes

In Denmark, the first confirmed COVID-19 case was reported on 27 February 2020. In response to the outbreaks, the government implemented nationwide lockdowns and various preventive measures such as facemask mandates, physical distancing, bans on gathering and testing strategies. During the national lockdowns, most employees worked from home, and those who had to be at the workplace followed strict preventive measures.

“Because of the nature of their work, employees of the Novo Nordisk Group engage in frequent travel and meetings across multiple sites and countries. This variety in contact patterns poses a potentially high risk of infection. Our study sought to understand the factors influencing antibody levels, SARS-CoV-2 transmission and persistent COVID-19 symptoms among employees during the first and second waves of the pandemic in Denmark,” says Peter Garred.

The study aimed to investigate the overall seroprevalence and transmission of SARS-CoV-2 at a workplace in Denmark using the Novo Nordisk Group as a model and to identify potential risk factors. The study period examined two waves of infection. Testing for SARS-CoV-2 became available nationwide in May 2020, so the first sampling period was in summer 2020, the second in autumn/winter 2020/2021 and the third in summer 2021. COVID-19 vaccination was introduced in the middle of these three periods.

“Another aim was to analyse factors influencing antibody levels – including the vaccines – among employees during the COVID-19 pandemic and then finally to investigate persistent COVID-19 symptoms among employees and possibly to understand the underlying causes,” adds Peter Garred.

Surprising results

A total of 18,614 individuals accepted the invitation to participate, provided at least one blood sample and completed a questionnaire encompassing socioeconomic background, health status, previous SARS-CoV-2 infection and persistent symptoms. The results revealed that close to 4% were seropositive – meaning they had antibodies against SARS-CoV-2 at the first sampling in summer 2020.

“Interestingly, the 6-month sampling, performed before and after Christmas, revealed a sharp increase in seropositivity from 8% before Christmas to 18% after Christmas. This could be attributed to social gatherings during the holiday season. However, it could also partly result from bias in the study population, since individuals who suspected or knew that they were infected were more likely to participate in the sampling after Christmas to confirm that they had indeed been infected,” explains the first author, Cecilie Bo Hansen, a PhD student funded by the Novo Nordisk Foundation and an Assistant Lecturer in Immunology at the University of Copenhagen.

At the 12-month sampling, after the vaccine roll-out in Denmark, the seropositivity rate increased to 94%.

The researchers found that the seroprevalence in the studied population was comparable to, yet higher than the seroprevalence reported in nationwide surveys in Denmark. This might result from the study population mostly comprising individuals living or working in the Capital Region of Denmark, which had the highest seroprevalence during the pandemic. However, this could also result from sampling bias or differences in testing methods.

Quite peculiar findings

One quite peculiar finding was that the household members of employees seemed to have a higher risk of being COVID-19 positive than the employees.

“This might seem odd, but we clearly found that in both rounds, the summer of 2020 and the winter of 2020/2021, that the household members of Novo Nordisk Group employees had higher COVID-19 positivity. So, you might be tempted to say, ‘Welcome to the Novo Nordisk Group and stay protected.’ The only good explanation is that the household members of Novo Nordisk Group employees who thought they had been infected were more likely to get tested, so I assume that this is a bias in the testing set-up,” says Cecilie Bo Hansen.

The study revealed substantial waning of antibodies among the participants who had antibodies at baseline in spring 2020 and participated in the 6-month follow-up. The waning patterns were similar regardless of age, sex and initial antibody levels.

“This indicates that individuals with a low starting antibody level lost detectable antibodies after about 6 months. However, the waning of humoral immunity following infection versus vaccination is still a subject of debate. This finding emphasises the importance of ongoing surveillance and potential booster vaccinations to maintain immune protection,” explains Cecilie Bo Hansen.

The study compared antibody levels between individuals infected before vaccination and those who were vaccinated but had no previous infection. The researchers found that individuals infected before being vaccinated had higher antibody levels than vaccinated infection-naive individuals.

“This observation suggests that previous infection combined with vaccination may boost the antibody response. It confirms the findings of other studies, emphasising that individuals with previous infection may experience a more robust immune response following vaccination. This underscores the advantages of vaccinating individuals who were previously infected and supports the idea of integrating both mucosal and systemic vaccination approaches. These findings reinforce the notion that we need to re-evaluate our vaccination strategies going forward, teaching a valuable lesson,” comments Peter Garred.

Need for further research

The researchers also investigated the prevalence of persistent COVID-19 symptoms in the study population. About one third of seropositive individuals from round one in spring 2020 reported experiencing one or more persistent symptoms in the second round of sampling.

“The most pronounced symptoms reported were loss of smell and taste – and fatigue. Especially women reported these symptoms more often than men, and age appeared to affect symptoms,” says Peter Garred.

According to the researchers, the findings underscore the long-lasting impact of COVID-19 on individuals, even after antibodies have waned. Previous research has suggested that long COVID symptoms should be regarded as a multiorgan syndrome characterised by fatigue, weakness, malaise, breathlessness, impaired concentration and other less frequent symptoms.

“However, the findings also emphasise that the existing scientific evidence is limited and subject to bias. Our participants were not asked to specify the duration of symptoms or the time elapsed since suspected infection. But since almost one third of the participants report these symptoms, this emphasises the need for further research on the mechanisms and management of persistent symptoms,” adds Peter Garred.

Quite unique

The new study provides a comprehensive understanding of both SARS-CoV-2 antibody seroprevalence following infection and vaccination, the waning of antibodies over time, persistent COVID-19 symptoms and risk factors for seropositivity in large workplaces.

“The findings highlight the importance of ongoing monitoring and potential booster vaccinations, but what I find original in relation to this study is the entire translational process, starting from developing completely new measurement methods from scratch to setting up this system on a very large scale within a few weeks and achieving these results,” explains Peter Garred.

According to the researchers, this shows that if the world experiences a new crisis – a new pandemic arising – they have a system that can be used and ability to act.

“We have built up a complete repertoire that can be applied in theory to almost any infectious disease. This was based on volunteer students and the like. It could be professionalised, but I find the concept itself quite unique: that we can move and demonstrate that we can do it, from just hearing and reading about it to having a product that can be tested in a massive population,” concludes Peter Garred.