iarjimphIARJIMPHIARJIMPH2709-331Xhttps://doi.org/10.47310/iarjimph.2021.v02i01.003Prospective Trials are warranted to Assess if Immunosuppression Affects the Outcome of COVID-19 in Neuroimmunologic DiseaseJosefFinstererFulvioAScorzaWith interest we read the article by Kovvuru et al. about the outcome of COVID-19 patients under immune-suppressive therapy (IST), excluding steroids, for autoimmune neuromuscular disorders (aNMDs) and multiple sclerosis (MS) [1]. aNMDs included were myasthenia gravis (MG), inflammatory myositis (IMS), and chronic inflammatory neuropathies. It was found that one third of the patients with aNMDs or MS required hospitalisation because of an infection with SARS-CoV-2 [1]. IST did not have a significant impact on the risk of a SARS-CoV-2 infection but the infection increased the risk of hospitalisation in patients with aNMDs requiring IST and NMDs with additional IST [1]. We have the following comments and concerns.We do not agree with the conclusion that IST does not make patients with NMD or MS more vulnerable to SARS-CoV-2 [1]. In a recent review of 16 patients with myasthenia gravis (MG) who experienced an infection with SARS-CoV-2, half of the patients experienced exacerbation of MG during the viral infection [2]. In another study on MG patients with a SARS-CoV-2 infection, 40% of the 91 included patients experienced exacerbation of MG or an MG crisis [3]. There is also one report about a patient with chronic inflammatory demyelinating (CIDP) in whom COVID-19 precipitated exacerbation of the disease [4]. The main disadvantage of the study is that data were retrieved from the TriNetX COVID-19 Research Network [1]. Thus, only what has been recorded and classified by the network can be assessed. For MG patients, for example, it is crucial to know the current medication, particularly at the point exacerbation of MG occurs. Newly applied drugs frequently worsen MG if not given in accordance with guidelines for the choice of allowed co-medication. Thus, if a drug but not SARS-CoV-2 was responsible for exacerbation of MG or for the occurrence of a MG crisis, it would have been missed since the compounds an MG patient was taking shortly prior to admission were not included in the pathophysiological reasoning. Thus, COVID-19 may be falsely made responsible for deterioration of MG. Generally, all other factors leading to exacerbation of MG should have been excluded before attributing exacerbation of MG to SARS-CoV-2. Several studies showing that SARS-CoV-2 may even trigger the development of new MG [5,6,7] were not included in the discussion. Thus, we should know if any patient was diagnosed with MG at discharge but not on admission.  Missing is a definition of the group of chronic inflammatory neuropathies. Since some of them may be associated with malignancy (MGUS, Waldenström’s macroglobulinemia, POEMS syndrome) [8], we should be told how inflammatory neuropathies associated with malignancy were excluded. Since the authors excluded autoimmune encephalitis because of possible interfering chemotherapy [1], generally all patients receiving chemotherapy, including those with immune neuropathies, should have been excluded and exclusion criteria should have been more precisely defined. A further limitation of the study is that it is unclear how inflammatory myositis was diagnosed. We should be told how many of the included patients in the database were diagnosed solely upon clinical assessments, how many upon determination of serum antibodies, how many upon muscle MRI with contrast medium, and how many upon muscle biopsy. Since myalgia, fatigue, and exercise intolerance are frequent features of COVID-19 [9], these general clinical manifestations may be mixed up with myositis. Thus, a number of patients might have been falsely diagnosed with myositis without having it.  Another shortcoming is that “deterioration” was defined as “hospitalisation”. Since exacerbations may be also treated by ambulatory wards, or neurologists practising outside the hospitals, and since many patients with the infection are still not tested, a number of patients may have never reached the hospital and thus gone undetected. How can the authors conclude that the majority of patients with chronic autoimmuneneurological disorders likely have mild-to-moderate COVID-19 and do not require hospitalisation. They looked for patients requiring hospitalisation and not for outdoor patients. To investigate the effect of IST on the outcome of COVID-19 patients with aNMD and MS, ambulatory patients need to be included in the evaluation. Further shortcomings were that exclusion criteria were not precisely defined and that the severity of COVID-19 was not classified. To assess the effect of IST on the outcome of COVID-19, categorisation of the severity of COVID-19 is warranted. Furthermore, the outcome of COVID-19 may not only depend on the presence or absence of IST and the severity of COVID-19 but also on comorbidities, comedication, and the treatment given for the viral infection. According to a recent guideline paper by experts [10], therapy decisions for MG patients should be individualized and made collaboratively between the MG patient and his/her healthcare providers. Overall, this retrospective study has a number of limitations, which should be met before drawing conclusions as those provided. It is crucial to exclude drugs as the cause of MG exacerbation or crisis, to know how myositis was diagnosed, to know the co-morbidities, and treatment for COVID-19, the co-medication, to re-consider the definition of “deterioration” as hospitalisation, to precisely define exclusion criteria, to classify the severity of COVID-19, and to exclude patients under chemotherapy. The influence of IST on the outcome of COVID-19 should be rather assessed by studies with a prospective than a retrospective design.