Long COVID Management By Sara Walker, MD, MS, CEDS, FAAFP, and Lisa Barkdull, FNP-BC Six years ago, we had no idea what would happen next. We wore face shields, reused masks and hoped our hospitals’ capacity would not be overwhelmed. “Zoom” became part of everyday language, and clinicians developed an elaborate mix of hand gestures and handwritten notes just to troubleshoot telehealth visits. Around that same time, we started seeing patients who had technically recovered from COVID-19 but were still exhausted, short of breath, tachycardic or cognitively foggy weeks to months later. At the time, we had few answers beyond reassurance, repeated testing and hoping symptoms would eventually improve. We now know much more about long COVID, officially called “Post-Acute Sequelae of SARS-CoV-2 infection (PASC),” but treatment options remain frustratingly limited for many patients. Some people recover gradually, while others continue to experience disabling symptoms years later. One major challenge is that long COVID probably represents several overlapping disease patterns rather than a single disease process. Some patients appear to have persistent viral reservoirs, others show evidence of endothelial dysfunction and micro-thrombotic disease, and many seem to have a mix of immune, neurologic and autonomic abnormalities. This overlapping nature is highlighted by the different treatment arm types in one of the largest ongoing studies, the NIH-funded RECOVER-AUTONOMIC trial, a multicenter randomized study evaluating three treatments for PASC-associated postural orthostatic tachycardia syndrome (POTS): coordinated nonpharmacologic care, intravenous immunoglobulin (IVIG) and ivabradine. Several broad symptom clusters are commonly seen in long COVID: respiratory/allergic symptoms, neurologic and gastrointestinal dysfunction, dysautonomia/POTS, systemic inflammation and viral persistence. Respiratory and allergic symptoms are often related to mast cell activation. Mast cells release histamine and inflammatory mediators that can contribute to dyspnea, flushing, tachycardia, fatigue and GI symptoms. Initial treatment frequently includes H1- and H2-blockers, followed by leukotriene inhibitors such as montelukast and mast cell stabilizers like oral cromolyn when needed. Oral cromolyn is generally preferred over nasal or ophthalmic formulations because many symptoms appear to be driven by mast cell activity within the GI tract itself, and cromolyn works best when in direct contact with the target cells. Many patients are skeptical that over-the-counter antihistamines could significantly help symptoms, yet some patients experience meaningful improvements in fatigue, dyspnea and overall symptom burden. Neurologic and GI symptoms may involve mitochondrial dysfunction, neuroinflammation, autonomic dysregulation and microbiome disruption. Metformin initially showed promise in reducing long COVID risk, though later studies have been mixed. Small studies have also suggested potential benefits from L-arginine and vitamin C, including improvements in fatigue, endothelial function and exercise tolerance. Urolithin A (UA) has attracted growing interest because of its apparent ability to improve mitochondrial quality control and cellular energy regulation. Produced by gut metabolism of ellagitannins found in foods such as pomegranate, berries and walnuts, UA appears to improve mitochondrial function, reduce oxidative stress and decrease inflammatory signaling. Autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), is one of the most common cardiovascular manifestations of long COVID. The 2022 American College of Cardiology (ACC) Expert Consensus recommends a 10-minute active stand test when evaluating orthostatic intolerance after COVID-19. Diagnostic criteria include a sustained heart rate increase of more than 30 beats/min in adults without orthostatic hypotension, accompanied by symptoms. Initial treatment usually focuses on nonpharmacologic strategies: • Increased sodium intake in patients with suspected hypovolemia • Fluid intake of 2-3 liters daily • Compression stockings • Avoidance of heat, dehydration, alcohol and large meals • Small, frequent meals and higher-fiber diets to reduce GI pooling and support the microbiome • Screening for ferritin, vitamin B12, thiamine and vitamin D deficiencies • Recumbent or semi-recumbent exercise with gradual progression as tolerated Pharmacologic treatment often begins with beta-blockers such as metoprolol or nadolol. Propranolol is sometimes poorly tolerated because it can worsen 22
RkJQdWJsaXNoZXIy ODQxMjUw