Lumbrokinase for Adults With Long Covid, Post-treatment Lyme Disease Syndrome, and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This will be a pilot multi-arm clinical trial investigating the feasibility of 6 weeks of Lumbrokinase (LK) as an intervention in three clinical cohorts:

• Long Covid (LC)
• Post-treatment Lyme disease syndrome (PTLDS)
• Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

[STUDY-24-00154, PI: David Putrino, PT, PhD, IRB approved through 7/29/2025].

Inclusion Criteria:

• Any gender
• Aged 18+
• Baseline EQ-VAS ≤70; EQ-VAS before the index infection ≥80 (this information is collected as part of the baseline survey).
• Diagnosed with only one of the following conditions:
• Long Covid
• Documented clinical history of confirmed or suspected acute COVID-19 infection a minimum of 3 months prior to contact with the study team
• Formal diagnosis of Long Covid from a physician
• Post-treatment Lyme disease syndrome
• Diagnosis will be based on participants meeting either Group 1 or Group 2 criteria of the Columbia Clinical Trial Network PTLDS diagnostic criteria:

Group 1. Well-defined Lyme disease meeting CDC Surveillance Definition Erythema Migrans History of possible exposure to a high incidence county or state (or an adjacent area) Erythema migrans rash

EM 1: EM rash diagnosed by HCP previously (either in person or telemedicine)
EM 1A: MOA self-report & medical record documentation of rash > 5 cm
EM 1B: MOA: self-report and medical record documentation of EM rash but not size
EM 1C: MOA: self-report & rash misdiagnosed in medical record as cellulitis/spider bite
EM 1D: MOA: self-report and either: photo of EM or Class 1 lab test confirmation within 4 weeks of illness onset OR
Disseminated "objective" manifestation with lab test confirmation of Bb infection
Clinical history includes at least one of the following symptoms/signs, which are not better accounted for by another cause (MOA: medical records and/or self-report).
Neurologic: Lymphocytic Meningitis ; Encephalitis; Encephalomyelitis Cranial Neuritis (especially facial palsy); Radiculoneuropathy; Other Neurologic Signs (with objective measures) : Encephalopathy, Polyneuropathy
Carditis: 2nd or 3rd degree AV block; Myocarditis; Pericarditis
Lyme arthritis: Recurrent joint swelling in one or more joints
Dermatologic: Disseminated EM ("satellite") or Acrodermatitis atrophicans AND
Lab test Confirmation (requires at least one of the Class 1 lab tests) (MOA: self-report & documentation)
Group 2. Probable

2A. Chronic Multisystem Symptoms attributed to Lyme disease (insufficient to meet Group 1) and not better explained by another diagnosis and patient has evidence of positive lab results on a Class 1 lab test (or 4 of 10 bands for IgG Western blot (WB)) (MOA: self-report with lab documentation Class 1 lab test confirmation (excluding IgM WB) Highly suggestive IgG WB (4 of 10 bands) OR
2B. EM rash by history after exposure to a Lyme-endemic area but not previously diagnosed by a HCP and no photo or Class 1 lab test confirmation is available (MOA: self-report) OR
2C. Viral like illness (not better explained by other cause) with indeterminate or + enzyme immunoassay (EIA) with positive IgM WB or positive Class 1 lab test (within 4 weeks of illness onset after known exposure to a Lyme high-incidence area for standard two-tiered (STT) IgM) (MOA: medical records, lab test and self-report) (MOA: lab test and self-report) OR
2D. Viral like illness (not better explained by other cause) with indeterminate or positive EIA with positive IgM WB or positive Class 1 lab test (within 6 months of illness onset after known exposure to a Lyme high-incidence area for standard two-tiered (STT) IgM)
(MOA: medical records, lab test and self-report)
(MOA: lab test and self-report)
ME/CFS
Formal diagnosis of ME/CFS prior to 2020 from a physician
Actively symptomatic such that the 2011 International Criteria for ME/CFS is met at time of screening

Exclusion Criteria:

• Current use of antiplatelet or anticoagulation regimen
• Diagnosis of an autoimmune condition such as Chronic EBV, Multiple Sclerosis, Hashimoto's Disease, etc. which would impact the immunological profiling analysis.
• Pregnancy or lactation
• Known allergy to earthworms (Lumbrokinase is a supplement that is derived from earthworms)
• Past medical history of a bleeding or clotting disorder
  Has a scheduled surgery during, or immediately after, the study period

Conditions:
• Long Covid/Post-Acute Sequelae of COVID-19 (PASC)
• Post-treatment Lyme disease syndrome (PTLDS)
• Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)