Overlapping Post-COVID Conditions: A Case of Myalgic Encephalomyelitis and Postural Orthostatic Tachycardia Syndrome Triggered by Sequential Epstein-Barr Virus (EBV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections

The rise in post-infectious syndromes following COVID-19, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Postural Orthostatic Tachycardia Syndrome (POTS), has become increasingly common in clinical practice, representing an emerging clinical challenge.This case highlights a possible clinical scenario involving the interaction between sequential viral infections -such as the Epstein-Barr virus (EBV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -in triggering overlapping chronic conditions.This report presents the case of a patient who developed ME/CFS and POTS following SARS-CoV-2 infection, with a prior history of EBV mononucleosis, and discusses the diagnostic, therapeutic, and pathophysiological implications.A 48-year-old woman with a history of mononucleosis in childhood developed persistent and disabling symptoms after COVID-19 in January 2022.She presented with extreme fatigue, orthostatic intolerance, paresthesia, cognitive dysfunction, and multisystem symptoms.After extensive investigation, she was diagnosed with ME/CFS (early 2023) and POTS (later that year).Mast Cell Activation Syndrome (MCAS) was considered as a hypothesis during follow-up, but objective testing was not confirmatory.Management included pharmacological therapy (including low-dose naltrexone, duloxetine, and palmitoylethanolamide (PEA)), activity adjustments (pacing), and a multidisciplinary approach, with partial and fluctuating responses.This case illustrates how viral infections such as EBV and SARS-CoV-2 may act as sequential triggers in an individual clinical trajectory compatible with the development of ME/CFS and POTS.The symptomatic overlap, the lack of readily available objective biomarkers in this patient, and the need for a predominantly clinical and functional diagnostic approach in her evaluation highlight the complexity of these conditions.This experience also underscores the importance of continued efforts in research, clinical training, and integrated care models to improve the management of patients presenting with post-COVID conditions (PCC).