SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID, 2025, Sano et al.

[SNT Gatchaman]

SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID

Spoiler: Authors

Kaori Sano; Yayoi Kimura; Koichi Hirahata; Hideaki Kato; Hideki Hasegawa; Hidenori Akutsu; Akihide Ryo; Atsushi Goto; Kei Miyakawa

Letter to the Editor

HIGHLIGHTS
• S-IgG4 class switching predicts symptom improvement in Long COVID patients.

• Low S-IgG1% and high S-IgG4% linked to higher recovery rates.

• S-IgG4 class switching is an independent predictor of clinical improvement.

Web | PDF | Journal of Infection | Open Access

 

[SNT Gatchaman]

We prospectively enrolled 105 Long COVID patients at a specialized post-COVID clinic in Tokyo, Japan, between November 2022 and January 2023. All patients met the World Health Organization (WHO) criteria for the post COVID-19 condition, had paired serum samples at baseline and 6-week follow-up, and no reinfection or vaccination during observation.

Of 105 patients, 48 (45.7%) showed clinical improvement during the observation period, achieving median scores of 14 (IQR 7-28) with a median reduction of 10 points (IQR 5.8-13.8), while non-improvers showed no change (p<0.001). Improved patients demonstrated significantly lower S-IgG1% (p=0.025), higher S-IgG2% (p=0.029) and higher S-IgG4% (p=0.012) compared to non-improvers. Analysis of quartile combinations revealed that patients with low S-IgG1% combined with high S-IgG4%—indicative of enhanced S-IgG4 class switching—achieved 66.7% improvement versus 40.5% in other patterns (p=0.031).

Although improved patients had higher baseline symptom scores than non-improvers, baseline severity did not independently predict improvement.

vaccination status and timing were not independent predictors of improvement. These results suggest that the resulting immune phenotype, rather than vaccination itself, contributes to outcomes, likely reflecting individual variation in class switching capacity.

 

[Stuart79]

This is curious. I wonder if LC could turn out to be a disease of immunological indecision. Like a purgatory between sufficient antigen clearance and sufficient antigen tolerance.