The emergence of COVID-19, caused by the SARS-CoV-2 virus, complicated the diagnosis of infectious diseases, particularly those with similar non-specific, flu-like symptoms. Lyme disease, a bacterial infection transmitted by infected ticks, has long been a diagnostic challenge, often peaking seasonally alongside other respiratory illnesses. The overlap in initial presentation between this vector-borne illness and the highly contagious viral disease creates potential diagnostic confusion for patients and healthcare providers. Understanding the distinctions and connections between these two conditions is important for accurate medical management.
Symptom Overlap and Diagnostic Confusion
Acute Lyme disease and acute COVID-19 infection share non-specific symptoms that make initial differentiation difficult. Both conditions frequently present with generalized fatigue, fever, chills, body aches, and headaches. This cluster of symptoms often mimics a common viral illness, leading to potential misdiagnosis, especially if a patient does not recall a tick bite or lives outside a highly endemic area.
The hallmark sign of Lyme disease, the expanding red rash known as Erythema Migrans (EM), is not always present and cannot be solely relied upon for diagnosis. Approximately 20 to 30% of infected people do not develop the rash, and when it appears, it often lacks the classic “bullseye” appearance. While respiratory symptoms are strongly associated with COVID-19, Lyme disease can cause shortness of breath or heart palpitations if the infection spreads to the heart (Lyme carditis). This symptom overlap, combined with the pressure to rule out COVID-19, has led to documented cases where a Lyme diagnosis was delayed.
Understanding Co-Infection
Co-infection refers to being infected with both Borrelia burgdorferi (the bacterium that causes Lyme disease) and SARS-CoV-2 simultaneously. While there is no evidence that one infection directly causes the other, having both is possible, particularly in regions where Lyme disease is common. The immune system is strained when responding to two biologically distinct pathogens at the same time.
A prior or current Lyme infection may complicate the body’s response to the SARS-CoV-2 virus. Research suggests that increased levels of antibodies specific to Borrelia may correlate with a greater risk of severe COVID-19 and hospitalization. This association points toward potential immune dysregulation caused by the Lyme bacterium, which could make the host more vulnerable to a severe outcome from the viral infection. The simultaneous presence of both a bacterial and a viral infection may lead to an exaggerated inflammatory response.
Comparing Post-Infection Syndromes
Both Lyme disease and COVID-19 are associated with long-term, persistent symptom complexes that can be debilitating. Post-Treatment Lyme Disease Syndrome (PTLDS) and Long COVID share many symptoms, including chronic fatigue not alleviated by rest, neurocognitive deficits described as “brain fog,” and widespread musculoskeletal pain. Both syndromes can also involve dysautonomia, a malfunction of the autonomic nervous system leading to issues like heart rate irregularities and dizziness.
The underlying mechanisms driving these persistent syndromes are still under investigation. PTLDS is theorized to be caused by ongoing inflammation or an autoimmune response triggered by the initial bacterial infection, with some studies identifying elevated inflammatory markers. Long COVID is linked to several possible causes, including viral persistence in some tissues, microclot formation affecting oxygen exchange, and a sustained, dysfunctional immune response. The clinical parallels between these post-infectious syndromes highlight a common pathway where a resolved infection can leave a lasting imprint of chronic illness.
Clinical Considerations for Testing and Treatment
Given the high degree of symptom overlap and the possibility of co-infection, clinical evaluation must prioritize differential testing. When a patient presents with non-specific flu-like symptoms, especially during peak tick season, testing for both SARS-CoV-2 and Borrelia burgdorferi may be necessary. A detailed patient history, including potential tick exposure, travel to endemic areas, and a precise timeline of symptom onset, remains an important diagnostic tool.
Treatment protocols must account for the pharmacological differences between the two infections. Lyme disease is treated with antibiotics, such as doxycycline, while acute COVID-19 may be managed with antivirals like nirmatrelvir/ritonavir (Paxlovid). Doxycycline does not appear to have significant drug-drug interactions with the ritonavir component of the COVID-19 antiviral. However, other antibiotics sometimes used for Lyme, such as certain macrolides, may require cautious use due to potential interactions. Clinicians must carefully review all medications to prevent adverse effects when treating two distinct infections simultaneously.