Acute Symptoms of SARS-CoV-2 Infection by Variant, Vaccination Status, Sex and Age: A Questionnaire Study in Denmark

Abstract

Background: It is not well-described how the acute symptoms of infection with SARS-CoV-2 differ by virus variants and vaccination. In the current study, we describe symptoms by variant and vaccination status in Denmark

Methods: A nationwide questionnaire study including 148,874 SARS-CoV-2 first time reverse transcription polymerase chain reaction (RT-PCR) test-positive individuals and corresponding date-matched symptomatic test-negative controls were conducted. Major variants (Index, Alpha, Delta and Omicron) were defined using periods of predominance. Information on vaccination and comorbidities was obtained from national health registers. Risk differences (RDs) were estimated for each of 21 predefined acute symptoms comparing: 1) test-positives and –negatives, by variant period, 2) fully vaccinated and unvaccinated test-positives, by variant period, 3) individuals tested positive during the Omicron and Delta periods, respectively, by vaccination status (unvaccinated, two doses or three doses), and 4) fully-vaccinated test-positive and -negative individuals during the Omicron period, by age and sex.

Findings: Compared to in previous variants periods, during the Omicron period RDs between test-positives and test–negatives were lower for most symptoms, especially for dysgeusia and dysosmia. RDs for dysgeusia and dysosmia were highest in the Delta period (RD=50.8 (49.4 - 52.0) and RD=54.7 (53.4 - 56.0), respectively) and lowest in the Omicron period (RD=12.8 (12.1 - 13.5) and RD=11.8 (11.1 - 12.4)). Across variants, vaccinated individuals reported fewer symptoms than unvaccinated. During the Omicron period, females and 30-59 year-olds reported more symptoms.

Interpretation: Omicron infection less often caused dysgeusia and dysosmia. Vaccination reduced the number of symptoms.

Funding. No specific funding was received for this work. The study was conducted as part of the governmental institution Statens Serum Institut’s advisory tasks for the Danish Ministry of Health.

Declaration of Interest: All authors declare no support from any organization for the submitted work. The work was conducted as part of the governmental institution Statens Serum Institut’s advisory tasks for the Danish Ministry of Health.

Within the past three years, AH reports having received grants from Novo Nordisk Foundation, Danish Medical Research Council, European Medicines Agency, The Lundbeck Foundation, and Global Vaccine Data Network, all unrelated to the present manuscript. NMN reports receiving grants from A. P. Møller’s Foundation of Medical Research, Lilly & Herbert Hansen’s Foundation and the Greenland Research Council within the past three years, all unrelated to the present manuscript. AH is scientific board member of VAC4EU and AK is president of the Danish Greenlandic Society for Circumpolar Health as well as former president of International Union for Circumpolar Health (IUCH), all unrelated to the present manuscript. The authors report no other relationships or activities that could appear to have influenced the submitted work.

Ethics Approval: This article has been prepared on the basis of a study carried out as part of a task imposed on the Statens Serum Institut according to national legislation. Therefore, no approval requirements from the ethics committees is obliged. The publication only contains aggregated results and no personal data. The publication is therefore not covered by the European General Data Protection Regulation. It was approved by the Danish Governmental law firm and SSI’s Compliance Department that the study is fully compliant with all legal, ethical and IT-security requirements and there are no further approval procedures regarding such studies. Participation in the study was voluntary. The invitation letter to participants contained information about their rights under the Danish General Data Protection Regulation (rights to access data, rectification, deletion, restriction of processing and objection). Accessing and filling in the questionnaire after receiving the above information was considered informed consent from the participant’s side.

Keywords: SARS-CoV-2, omicron, acute symptomatology, vaccination