ENOrphanet Journal of Rare Diseases | Impact of COVID-19 on Patients with Inherited Metabolic Diseases: A French Multicenter Study
Date: February 23, 2026
Classification: Frontiers
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This study systematically evaluated the clinical course of 317 patients with inherited metabolic diseases (IMDs) following SARS-CoV-2 infection, revealing that pediatric patients are more prone to metabolic decompensation and ICU admission, although most cases were mild to moderate in severity, and treatment interruptions were rare.
Literature Overview
The article titled 'Impact of COVID-19 infection in patients with inherited metabolic diseases: a National Multicenter Study from the French IMDs Healthcare Network for Rare Diseases,' published in the Orphanet Journal of Rare Diseases, reviews and summarizes a national multicenter observational cohort study conducted within the French rare disease healthcare network on patients with inherited metabolic diseases (IMDs) infected with SARS-CoV-2. The study included 317 IMD patients diagnosed with SARS-CoV-2 infection between 2020 and 2023, analyzing their clinical manifestations, risk of metabolic decompensation, treatment interruptions, and long-term outcomes. The study found that although most cases were mild to moderate, pediatric patients were more likely than adults to experience metabolic imbalance and require intensive care. It also emphasized the importance of disease-specific management during the pandemic. The text is coherent and logical, ending with a Chinese period.Background Knowledge
Inherited metabolic diseases (IMDs) are a group of rare disorders caused by gene mutations that disrupt metabolic pathways, including amino acid metabolism, organic acid metabolism, fatty acid oxidation, mitochondrial dysfunction, and lysosomal storage disorders. Patients typically rely on strict dietary control, enzyme replacement therapy, or pharmacological interventions to maintain metabolic homeostasis. Due to limited metabolic reserves, any stressor (e.g., infection) may trigger acute decompensation, leading to encephalopathy, liver failure, or multi-organ injury. At the onset of the SARS-CoV-2 pandemic, IMD patients were considered high-risk due to potential immune dysfunction and organ vulnerability. However, early data were limited and mostly derived from small case series or surveys, lacking systematic clinical evidence. Furthermore, healthcare disruptions during the pandemic (e.g., delayed treatments, reduced monitoring) further threatened the stability of IMD patients. This study fills that gap by providing the largest multicenter observational dataset to date on IMD patients infected with SARS-CoV-2, offering crucial evidence for clinical management. The study particularly examines differences across age groups, highlighting the metabolic vulnerability of children, and explores clinical features and outcomes associated with specific diseases (e.g., Wilson’s disease, lysosomal disorders). These findings help optimize individualized intervention strategies during future pandemics or public health crises.
Study Methods and Experiments
This was a multicenter, bidirectional observational cohort study (COVID-MHM), led by the French rare disease inherited metabolic disorders healthcare network (Filière G2m), involving 20 expert centers. The study enrolled IMD patients with PCR-, antigen-, or serology-confirmed SARS-CoV-2 infection between January 2020 and January 2023, including both children (<18 years) and adults (≥18 years). Data were collected via standardized electronic case report forms, covering demographics, IMD diagnosis classification, COVID-19 symptoms and severity, metabolic decompensation events, treatment interruptions, long-term outcomes, and comorbidities. The primary endpoint was to assess the impact of SARS-CoV-2 infection on the clinical course of IMDs, including metabolic imbalance, symptom worsening, treatment interruption, and infection-related outcomes. Categorical variables were compared using chi-square or Fisher’s exact tests, and continuous variables were analyzed using t-tests or Mann-Whitney U tests, with p < 0.05 considered significant. Data analysis was performed using GraphPad Prism 10.5.0.Key Findings and Insights
Implications and Future Directions
The study provides high-quality real-world evidence on clinical outcomes of IMD patients infected with SARS-CoV-2. Results indicate that despite generally favorable prognosis, pediatric patients face higher risks of metabolic decompensation and ICU admission, underscoring the need for enhanced monitoring and early intervention in this group. The study highlights the importance of maintaining IMD-specific therapies, minimizing treatment interruptions even during infection. Additionally, heterogeneous responses across IMD subtypes were observed—for example, lysosomal storage disorder patients may be more susceptible to severe pneumonia, while certain metabolic states might restrict viral spread, offering directions for future research.
The study also reveals the healthcare system's adaptability during crises. Despite early disruptions, the low treatment interruption rate in this cohort may reflect the successful implementation of alternative models such as telemedicine and home infusions. However, limitations exist, including potential selection bias due to voluntary reporting and lack of systematic assessment of long-term metabolic control. Future studies should incorporate comprehensive biomarker monitoring to explore the long-term impact of SARS-CoV-2 infection on metabolic homeostasis in IMD patients and evaluate the protective efficacy of vaccination in this population.
Conclusion
This multicenter analysis of 317 IMD patients infected with SARS-CoV-2 systematically characterizes the clinical features and outcomes of this rare disease population during the pandemic. The study finds that the vast majority of patients experienced mild to moderate infections, without widespread metabolic decompensation or high mortality, indicating that IMD patients can manage SARS-CoV-2 infection well under proper care. However, pediatric patients are more susceptible to metabolic imbalance and ICU admission than adults, highlighting their vulnerability under infectious stress. Notably, ICU admission reasons differ by age: children are more likely admitted due to acute decompensation from energy metabolism disorders, while adults are primarily admitted due to respiratory severity caused by the virus, especially among those with lysosomal storage disorders. Treatment interruptions were extremely rare, reflecting the healthcare system's ability to maintain continuity of care during the crisis. Only one death occurred, in an elderly male with Fabry disease and multiple comorbidities. These results provide important guidance for clinical practice, emphasizing enhanced monitoring of pediatric patients, optimized metabolic support during infection, and continued promotion of protective strategies such as vaccination and telemedicine. Overall, the study alleviates early concerns about high risk in IMD patients while identifying management priorities for specific subgroups, providing evidence for future public health emergency preparedness. Future research could further explore immune-metabolic interactions across IMD subtypes to enable more precise risk stratification and intervention.
