Borreliosis, also known as Lyme disease, is a zoonosis caused by the bacterium Borrelia burgdorferi transmitted to humans by ticks. A characteristic symptom of infection is the skin rash called erythema migrans, which however occurs in only 60–80% of infected persons, with a delay of 3–30 days after the tick bite. Other typical symptoms are non-specific, including fever, mild headaches, muscular-articular pain, and fatigue. Thus, a considerable number of cases of Borrelia infection can be overlooked, while if left untreated, infection can spread to joints, the heart, and the nervous system1–3. Subjective symptoms may persist or recur for at least six months after a patient was infected, even after antimicrobial treatment3,4. So-called ‘chronic Lyme disease’, sometimes with severe manifestations, remains controversial, lacking clearly recognized or demonstrated significance for a patient’s health5.
The diagnostics of Borrelia infection is challenging, primarily due to the multitude of bacterial strains that may cause the infection. In Eurasia, Borrelia burgdorferi sensu lato includes various spirochete species: B. burgdorferi sensu stricto (s.s.), B. afzelii, B. garinii, B. bavariensis, B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B. valaisiana, B. yangtze, B. bissettii, and B. carolinensis. Within the area of this study (Central Europe), the predominant species as the causative agents of borreliosis are Borrelia afzelii and Borrelia garinii, less frequently Borrelia burgdorferi s.s.6–8. B. spielmanii has also been found in an animal reservoir, postulated as an appropriate antigenic component in diagnostic tests in Europe9.
Serological testing of patients’ sera with antigens representing pathogenic species of Borrelia is the major approach in diagnostics10, even though seropositivity alone is not sufficient for a diagnosis of active borreliosis, since antibodies may persist for long after treatment of the disease and they can be detected even in individuals after a successful treatment 4. Proper interpretation of a patient’s clinical status is difficult due to different life strategies of B. burgdorferi; these are related to their antigenic variability, which is in turn linked to adaptation to different environmental conditions, their intracellular residence, and their hiding in immunologically privileged areas11,12. Presence of antibodies targeting multiple antigens of Borrelia, however, indicates that an individual has been infected, without a clear indication of whether the infection has been eradicated or it is still active. Thus, serological testing remains the major tool available for epidemiological studies10.
The emergence of COVID-19, a new disease caused by the previously unknown SARS-CoV-2 virus, is linked to still very high uncertainty about factors that determine the clinical manifestation and course of this disease. The course of COVID-19 ranges from asymptomatic or mild to severe or fatal with fulminant development and dramatic symptoms. Some crucial conditions in COVID-19 have been revealed, including comorbidities such as diabetes, cardiovascular diseases, cancer, pulmonary disorders, and immunological disorders, but also obesity, advanced age, and others13–15. Infectious diseases, however, have been much less recognized as comorbidities in SARS-CoV-2 infection and their potential effect on the risk of severe COVID-19 is poorly understood. Particularly, the possible association between Lyme disease and COVID-19 disease has not been established, in spite of indications that flu-like symptoms reported in both Lyme disease and COVID-19 can be very similar16. One available case report by Shutikova et al. (2021) describes a patient with disseminated Borrelia infection (starting in mid-2019), after an unsuccessful first round of antibiotic treatment (early 2020), who was infected with SARS-CoV-2 (mid-2020). Anti-COVID-19 treatment included umifenovir, hydroxychloroquine, azithromycin, and ceftriaxone, and it resulted in suppression of borreliosis, as manifested by the first decrease of anti-Borrelia IgG in diagnostics. However, that report was not dedicated to possible effects of borreliosis on the course of COVID-1917. Piotrowski and Rymaszewska (2022) pointed out a reduced number of cases of Lyme disease registered during the COVID-19 pandemic in Poland, and they concluded that it may result from limited outdoor activities in the lockdown, but possibly also from poor access of patients to the overburdened health care system18.
Further studies, for instance on the potential association of borreliosis with increased risk of SARS-CoV-2 infection or with severe COVID-19, have not been reported so far. In this study we analyzed a wide range of anti-Borrelia IgG and IgM antibodies (targeting 19 antigens derived from Borrelia spp.) in patients representing three different types of clinical history: severe COVID-19 (hospitalized), asymptomatic to mild COVID-19 (home treated or not aware of being infected), and not infected with SARS-CoV-2, to identify potential association between previous exposure to Borrelia spp. and the risk of SARS-CoV-2 infection or severe COVID-19.