Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism, Turkey.
Mol Genet Metab. 2023 Jun;139(2):107607. doi: 10.1016/j.ymgme.2023.107607. Epub 2023 May 11.
Old age, obesity, and certain chronic conditions are among the risk factors for severe COVID-19. More information is needed on whether inherited metabolic disorders (IMD) confer risk of more severe COVID-19. We aimed to establish COVID-19 severity and associated risk factors in patients with IMD currently followed at a single metabolic center.
Among all IMD patients followed at a single metabolic referral center who had at least one clinic visit since 2018, those with accessible medical records were reviewed for SARS-CoV-2 tests. COVID-19 severity was classified according to the WHO recommendations, and IMD as per the international classification of IMD.
Among the 1841 patients with IMD, 248 (13.5%) had tested positive for COVID-19, 223 of whom gave consent for inclusion in the study (131 children and 92 adults). Phenylalanine hydroxylase (48.4%) and biotinidase (12.1%) deficiencies were the most common diagnoses, followed by mucopolysaccharidoses (7.2%). 38.1% had comorbidities, such as neurologic disabilities (22%) or obesity (9.4%). The majority of COVID-19 episodes were asymptomatic (16.1%) or mild (77.6%), but 6 patients (2.7%) each had moderate and severe COVID-19, and two (0.9%) had critical COVID-19, both of whom died. 3 patients had an acute metabolic decompensation during the infection. Two children developed multisystem inflammatory syndrome (MIS-C). Long COVID symptoms were present in 25.2%. Presence of comorbidities was significantly associated with more severe COVID-19 in adults with IMD (p < 0.01), but not in children (p = 0.45). Compared to other categories of IMD, complex molecule degradation disorders were significantly associated with more severe COVID-19 in children (p < 0.01); such a significant IMD category distinction was not found in adults.
This is the largest study on COVID-19 in IMD patients relying on real-word data and objective definitions, and not on merely expert opinions or physician surveys. COVID-19 severity and long COVID incidence in IMD are probably similar to the general population, and the risk of acute metabolic decompensation is not likely to be greater than that in other acute infections. Disease category (complex molecule degradation) in children, and comorbidities in adults may be associated with COVID-19 severity in IMD. Additionally, the first documented accounts of COVID-19 in 27 different IMD are recorded. The high occurrence of MIS-C may be coincidental, but warrants further study.
年龄、肥胖和某些慢性疾病是 COVID-19 重症的危险因素之一。关于遗传性代谢紊乱（IMD）是否会增加 COVID-19 重症的风险，需要更多信息。我们旨在确定在一家代谢中心接受治疗的 IMD 患者中 COVID-19 的严重程度和相关危险因素。
在所有自 2018 年以来至少有一次就诊记录的接受单代谢转诊中心治疗的 IMD 患者中，对可获得病历的患者进行了 SARS-CoV-2 检测。根据世界卫生组织的建议对 COVID-19 的严重程度进行了分类，根据国际 IMD 分类对 IMD 进行了分类。
在 1841 名 IMD 患者中，有 248 名（13.5%） COVID-19 检测呈阳性，其中 223 名同意纳入研究（131 名儿童和 92 名成人）。苯丙氨酸羟化酶（48.4%）和生物素酶（12.1%）缺乏症是最常见的诊断，其次是黏多糖贮积症（7.2%）。38.1%的患者有合并症，如神经残疾（22%）或肥胖（9.4%）。大多数 COVID-19 病例为无症状（16.1%）或轻症（77.6%），但有 6 名患者（2.7%）分别为中重度 COVID-19，2 名（0.9%）为危重症 COVID-19，均死亡。3 名患者在感染期间发生急性代谢失代偿。2 名儿童出现多系统炎症综合征（MIS-C）。25.2%的患者有长期 COVID 症状。合并症与 IMD 成人的更严重 COVID-19显著相关（p<0.01），但与儿童无关（p=0.45）。与其他 IMD 类别相比，复杂分子降解障碍与儿童的更严重 COVID-19显著相关（p<0.01）；在成人中没有发现这种显著的 IMD 类别差异。
这是一项基于真实数据和客观定义的最大规模的 IMD 患者 COVID-19 研究，而不是仅仅依靠专家意见或医生调查。IMD 患者的 COVID-19 严重程度和长期 COVID 发生率可能与一般人群相似，急性代谢失代偿的风险不太可能大于其他急性感染。儿童的疾病类别（复杂分子降解）和成人的合并症可能与 IMD 中的 COVID-19 严重程度相关。此外，还记录了 27 种不同 IMD 中的首例 COVID-19 病例。MIS-C 的高发可能是偶然的，但值得进一步研究。
