Recurrence following invasive GAS infections in adults: Triumph of virulence or failure of immunity?

Since late 2022, an increase in <i>Streptococcus pyogenes</i> (Group A <i>Streptococcus</i>, GAS) infections, both non-invasive and invasive (iGAS), has been reported globally. This study investigates iGAS cases complicated by recurrent infection (rGAS). From January to September 2023, four adults with severe iGAS suffered from rGAS. Clinical and whole-genome sequencing data were analysed. All patients required ICU admission and surgical debridement during their initial iGAS. The median interval between the initial iGAS and rGAS was 25.5 days, with a median duration of antibiotic treatment of 25 and 17.5 days, respectively. Patients A (female, age 69) and B (male, age 46) had upper limb necrotising fasciitis complicated by a subsequent cellulitis at the exact location. GAS <i>emm</i>1.3 (M1_UK) was isolated in both patients, but patient A´s isolates carried a type-IV secretion system (T4SS), and this patient had a more severe course of infection. Patient C (male, age 66) had two episodes of bacteremia caused by GAS <i>emm</i>89.0 carrying T4SS and GAS <i>emm</i>12.37 with a frameshift in the <i>rocA</i> gene. Patient D (female, age 69) had upper limb cellulitis with bacteremia during the initial iGAS and upper limb cellulitis with septic gonitis as two concurrent manifestations of rGAS. All three isolates were identical, belonging to <i>emm</i>12.0 and carrying a 79 amino acid deletion in the SclA. Patients B and C had a reduced function of the complement lectin pathway and CD19+ lymphocyte deficiency. A combination of strain virulence factors and host immune deficiencies may predispose patients with iGAS to recurrence.