Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice, 2025, Mig

J

Jaybee00

Senior Member (Voting Rights)
Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice

Mignolet, Margaux; Deroux, Catherine; Florkin, Thomas; Bielarz, Valery; De Swert, Kathleen; Halloin, Nicolas; Sprimont, Lindsay; Ladang, Aurelie; George, Fabienne; Gilloteaux, Jacques; Abeloos, Laurence; Van Weyenbergh, Johan; Jamoulle, Marc; Diederich, Claire; Gillet, Nicolas Albert; Bulpa, Pierre; Nicaise, Charles

Abstract
Approximately 30% of long COVID patients still experience neurological symptoms (brain fog, pain, chronic fatigue) more than 4 months after the onset of COVID-19. This condition, known as neurological long COVID, remains poorly understood and might be explained by a persisting autoimmune response against nervous-derived self-antigens. The aim of this study is to determine whether IgG autoantibodies from long COVID patients with neurological sequelae can bind to central or peripheral nervous system epitopes and triggers neuropsychiatric symptoms upon passive transfer into mice, thereby mirroring patient-reported manifestations. Long COVID patients meeting the 2021 consensus WHO definition were included following a standardized neuropsychological assessment, while excluding patients with a medical history of autoimmune and neurological disorders. Age- and sex-matched asymptomatic individuals were used as healthy controls. Total IgGs were isolated using protein G purification and injected intraperitoneally into C57Bl6/J mice for four consecutive days. During the two weeks post-injections, behavioral tests assessed mechanical allodynia, thermal hyperalgesia, spatial working memory, depression, and anxiety. Mice injected with IgG from long COVID patients showed no difference with the control group in terms of anxiety or depression behaviors, as well as no impairment of short- or long-term spatial memories and thermal hyperalgesia. However, they displayed a transient decrease of paw withdrawal threshold during the first week. This effect was abolished when IgG-depleted serum or papain-digested IgGs were transferred. IgG from long COVID patients accumulated in the lumbar dorsal root ganglia of injected mice and colocalized with proprioceptive and nociceptive sensory neurons, without inducing local neuroinflammation or astrogliosis. These data demonstrate that IgGs from long COVID patients bind to peripheral sensory neurons and induce pain-related symptoms in mice. Our findings also support the hypothesis that autoantibodies mediate pain-related pathophysiology in the spectrum of long COVID symptoms.

Web | DOI | bioRxiv
 
I am always slightly fascinated by these inject-a-mouse-with-blood, see-what-happens studies. Feels vaguely occult. But also pretty validating, assuming/hoping the results hold up.

Says they had 13 patients and 10 covid-recovered controls. The selection criteria seems relatively light? 2 months of (cognitive impairment, pain, fatigue) symptoms.

If I'm understanding correctly they purified out the IgG from the patient/control blood, and that purified IgG was injected into the mice (for 4 days). Every patient/control had 10 corresponding mice.

In addition to using IgG from covid-recovered individuals as the control, they added two extra types of control mouse as well: (1) LC patient serum that had been IgG-depleted, and (2) IgG from patients that had been papain-digested (which I am now learning is a way to destroy human IgG).

They ran a number of behavioural tests on the mice, most of which showed no difference:
- The LC mice did not seem more bothered by hot plates than the control mice (they did not withdraw their paws any faster).
- Both groups were equally into building nests, which is apparently a sign of general well-being.
- The LC mice did just as well at the two maze cognitive tests.
- The LC mice did not display more anxiety (according to the Elevated-plus maze test and the Light/Dark box tests, which I didn't look into)
- The LC mice did not display more depression according to the tail suspension test (where they hold the mouse up by its tail and it counts as depressed if it doesn't struggle much, I always wonder about that one.)

The two differences they did find were:
- The LC mice were more sensitive about having their paws poked with long wires.
- The LC mice grimaced more (apparently there is a standardized way of assessing mice facial expressions for pain and I guess some poor experimenter watched like hours and hours of mouse footage?)

They then looked at where the human IgG antibodies actually accumulated in the mouse tissue, but I am getting too foggy (and know too little neurology) to follow what they're saying right now.
 
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