Microfilaremic loiasis is associated with T cell hyporesponsiveness against SARS CoV-2

Abstract

BackgroundLoiasis is a chronic filarial infection endemic to Central and West Africa. Although long considered benign, increasing evidence links loiasis to substantial morbidity and mortality. The infection is associated with immune modulation, including Th2-skewed responses and elevated regulatory cytokines. Clinically, loiasis is classified as microfilaremic (presence of circulating microfilariae) or amicrofilaremic ("occult") disease, the latter defined by a history of eyeworm migration without detectable microfilaremia. This study investigated how chronic L. loa infection influences antibody and T cell responses to SARS-CoV-2 following natural infection. MethodsBetween 2022 and 2024 this cross-sectional study was done in Lambarene and surrounding rural areas of Gabon. Study procedures included diagnostics for loiasis and immunological assays. Microfilaremia was confirmed by stained blood smear microscopy, and occult disease was identified using the Rapid Assessment Procedure for Loiasis. SARS-CoV-2-specific IgG responses to spike and nucleocapsid proteins were measured by ELISA, and IFN-{gamma} responses to spike antigen were assessed using an interferon-gamma release assay. ResultsOverall, 192 participants were categorized as microfilaremic (n=43), occult loiasis (n=59), or without evidence of active loiasis (n=90). IFN-{gamma} responses were reduced in microfilaremic individuals compared with other participants (p= 0.031), whereas IgG responses did not differ. Subsequent analysis across the three groups confirmed that IFN-{gamma} responses were lower in microfilaremic compared with occult participants (p= 0.012). ConclusionThese findings suggest that microfilaremic loiasis may impair proinflammatory T cell responses to viral antigens, highlighting the need for further research into the broader immunological effects of Loa loa infection in endemic populations. Authors summaryLoiasis is a parasitic infection caused by the worm Loa loa and is common in parts of Central and West Africa. Although long considered relatively benign, growing evidence indicates that loiasis is associated with substantial morbidity. The immunological consequences of chronic Loa loa infection remain poorly understood. A small number of studies suggest that Loa loa may influence immune regulation, but its broader impact on antiviral immunity is largely unknown. The COVID-19 pandemic provided a unique opportunity to examine immune responses to a newly emerging virus in a population where loiasis is endemic. We therefore investigated how different forms of Loa loa infection influence immune responses after natural SARS-CoV-2 infection. We compared individuals with circulating microfilariae in their blood (microfilaremic), individuals with occult loiasis (history of eye worm), and individuals without signs of active infection. We found that microfilaremic individuals had weaker virus-specific IFN-{gamma} T cell responses, while antibody levels were similar across groups. These findings suggest that active loiasis may dampen certain antiviral immune functions. Understanding the underlying mechanisms is important, as such immune modulation could affect responses to vaccines and other infectious diseases in endemic regions.