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Pneumococcal vaccine serotypes and host factors may increase the risk of severe invasive pneumococcal disease (IPD). In France, pneumococcal vaccination in adults is recommended for at-risk groups (immunosuppression or at-risk conditions/diseases). In 2014-2017, we conducted a study of IPD in adults to identify factors/serotypes associated with disease severity. We included IPD cases, excluding meningitis, in adults from 25 acute-care sentinel hospitals in six regions. Severe cases were IPD patients either admitted to an ICU or under mechanical ventilation or with severe sepsis or shock. Infectious disease specialists collected clinical/microbiological data on all cases. We calculated adjusted risk ratios (aRR) using binomial regression. In 2014-2017, 908 cases (median age 71 (range 18-101) years) were diagnosed; 48%(431/908) were severe and 84%(764/908) were at-risk. Compared with non-risk individuals, the risk of severe disease increased from 20% (aRR 1.2; 95%CI 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aHR 1.3; 95%CI 1.0-7.0) in those with &amp;gt;2 chronic diseases. The risk of severe disease was 42% (aRR 1.4; 95%CI 1.2-1.6) higher for PCV13 serotypes compared with non-vaccine serotypes. Among cases infected with PCV13 serotypes, the risk of severe disease did not differ (aRR 0.96; 95%CI 1.2-23) between no-risk or at-risk cases. However, among cases infected with non-vaccine serotypes, the risk increased 49% (aRR 1.5; 95%CI 2.1-22) in at-risk compared with no-risk cases (homogeneity test p = 0.03). We observed a cumulative effect of concurrent comorbidities on severe IPD outcomes. The risk of severe IPD increased for vaccine serotypes regardless of risk status. However, non-vaccine serotypes increased the risk of severe outcomes only in risk groups, suggesting a different interplay between host factors and the pathogen in vulnerable groups. We recommend enhancing vaccination among risk groups and especially in those most at risk for poor IPD-related outcomes. Key messages Cumulative effect of concurrent comorbidities on severe invasive pneumococcal disease outcomes. Non-vaccine serotypes increase the risk of severe invasive pneumococcal disease outcomes only in vulnerable groups.

Severe outcomes following invasive pneumococcal disease in adults in France