The LCCS Study (Long COVID Cutaneous Signatures): An ARPA Funded Research Project
Todd Levine1, Bailey Bellaire2, Sarrah Marcotte2, Jourdan Parent2, Manuel Duval2, Roy Freeman3, Christopher Gibbons4
1Honor Health, 2CND Life Sciences, 3Beth Israel Deaconess Hosp, 4Beth Israel Deaconess Medical Center
Objective:
Define neuropathological changes in the peripheral nervous system in patients with post-acute sequelae of SARS-CoV-19 (PASC) and compare these to a healthy and disease control population.
Background:
PASC, also known as Long COVID, has impacted global, national, and state health systems. 1 in 5 people with COVID experience prolonged symptoms, and the prevalence increases to 1 in 4 over the age of 65. Many symptoms are hypothesized to be a consequence of damage to the sensory or autonomic nervous systems. The pathophysiology of these patients is not well understood.
Design/Methods:
There are 4 cohorts in this single-center study: 1) PASC defined by NIH criteria; 2) post-COVID without persistent symptoms defined by WHO criteria; Disease controls (Covid-recovered), 3) postural orthostatic tachycardia syndrome (POTS), and 4) diabetic peripheral neuropathy (DPN). After informed consent, physical and neurological examinations are completed with skin biopsies taken from three regions, and immunostained for sensory (IENFD), sympathetic cholinergic (SGNFD), and sympathetic adrenergic (PMNFD) fibers. Phosphorylated alpha-synuclein (P-SYN) was measured. Medical history, orthostatic vital signs, and questionnaires were obtained.
Results:
In an interim analysis, 148 subjects were enrolled. A total of 42 COVID-recovered (age 47.1±16.5 years, 36% Female), 5 DPN (53.2±7.1 years, 40% Female), 80 PASC (46.3±14.0 years, 67% Female), and 21 POTS (35.1±9.5 years, 100% Female). There were no significant differences in SGNFD, PMNFD, or IENFD between the PASC and Covid-recovered groups. Individuals with DPN had significantly lower IENFD values at the distal leg (P<0.05 vs other groups). P-SYN was detected in 4% of cases, with no differences between groups.
Conclusions:
There was no evidence of peripheral unmyelinated nociceptive c-fiber or autonomic nerve fiber injury in patients with PASC compared to age-matched individuals who have recovered from COVID without long-term sequelae. Symptoms of PASC are not accompanied by evidence of peripheral nerve injury in this study.
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