Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.

Background: Immunotherapy with immune checkpoint inhibitors (ICIs) enhances the host immune reaction against tumour cells by inhibiting intrinsic down-regulators of the T cell-mediated immune response. Although the advent of ICIs has dramatically changed oncology, ICIs may also trigger an overactivation of T cells against non-cancerous tissues, leading to off-target immune-related adverse events (irAEs). Case summary: A 64-year-old man with a history of seven courses of atezolizumab, an ICI, for small-cell lung cancer and coronavirus disease 2019 (COVID-19) was admitted to the hospital complaining of acute chest pain. Transthoracic echocardiography showed preserved ejection fraction (EF), but electrocardiography indicated precordial ST-elevations and marked increases in biomarkers for myocardial injury were observed. Emergent cardiac catheterization showed no significant coronary stenosis. On the fifth hospital day, EF decreased to 25% and pericardial effusion occurred. Endomyocardial biopsy was immediately performed, and prednisolone (60 mg/day) was administered. Troponin I level rapidly reduced, ST changed, and EF improved. Histological examinations demonstrated CD8-predominant T lymphocytic infiltration with myocardial cell injury, consistent with irAE-myocarditis. Discussion: In irAEs, myocarditis is the most common and severe cardiac manifestation with a high mortality. Even at 20 weeks after the initial ICI treatment, irAE-myocarditis occurs and the clinical presentation may mimic ST-elevation myocardial infarction. The histopathological findings suggested the high possibility of irAE-myocarditis rather than COVID-19-induced myocarditis, but COVID-19 has possibly played a role in the development of late-onset irAE-myocarditis. This educational case implies the importance of immediate recognition of irAE even after stable ICI treatment.