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Lyme borreliosis, which is caused by several species of the Borrelia burgdorferi sensu lato complex, is the most common vectorborne disease in the Northern Hemisphere. The first sign of infection [...]

Background Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. Methods The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. Results Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P <.01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. Conclusions Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis. [ABSTRACT FROM AUTHOR]

Background: COVID‐19 hospitalizations of non‐institutionalized persons during the first COVID‐19 wave in Connecticut disproportionately affected the elderly, communities of color, and individuals of low socioeconomic status (SES). Whether the magnitude of these disparities changed after the initial lockdown and before vaccine rollout is not well documented. Methods: All first‐time hospitalizations with laboratory‐confirmed COVID‐19 during July to December 2020, including patients' geocoded residential addresses, were obtained from the Connecticut Department of Public Health. Those living in congregate settings, including nursing homes, were excluded. Community‐dwelling patients were assigned census tract‐level poverty and crowding measures from the 2014–2018 American Community Survey by linking their geocoded addresses to census tracts. Age‐adjusted incidence and relative rates were calculated across demographic and SES measures and compared with those from a similar analysis of hospitalized cases during the initial wave. Results: During July to December 2020, there were 5652 COVID‐19 hospitalizations in community residents in Connecticut. Incidence was highest among those >85 years, non‐Hispanic Blacks and Hispanic/Latinx compared with non‐Hispanic Whites {relative rate (RR) 3.1 (95% confidence interval [CI] 2.83–3.32) and 5.9 (95% CI 5.58–6.28)}, and persons living in high poverty and high crowding census tracts. Although racial/ethnic and SES disparities during the study period were substantial, they were significantly decreased compared with the first wave of COVID‐19. Conclusions: The finding of persistent, if reduced, large racial/ethnic disparities in COVID‐19 hospitalizations 2–7 months after the initial lockdown was relaxed and before vaccination was widely available is of concern. These disparities cause a challenge to achieving health equity and are relevant for future pandemic planning. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis (LNB) in Europe may manifest with painful meningoradiculoneuritis (also known as Bannwarth syndrome) or lymphocytic meningitis with or without cranial neuritis (peripheral facial palsy). We assessed host immune responses and the prevalence of TLR1 (toll-like receptor 1)-1805GG polymorphism to gain insights into the pathophysiology of these conditions. Regardless of LNB manifestation, most mediators associated with innate and adaptive immune responses were concentrated in cerebrospinal fluid; serum levels were unremarkable. When stratified by specific clinical manifestation, patients with meningoradiculoneuritis had higher levels of B-cell chemoattractants CXC motif chemokine ligand (CXCL) 12 and CXCL13 and T-cell-associated mediators CXCL9, CXCL10, and interleukin 17, compared with those without radicular pain. Moreover, these patients had a higher frequency of TLR1-1805GG polymorphism and more constitutional symptoms. These findings demonstrate that meningoradiculoneuritis is a distinct clinical entity with unique immune and genetic pathophysiology, providing new considerations for the study of LNB and borrelial meningoradiculitis. [ABSTRACT FROM AUTHOR]