‘Blue Legs’ Yet Another Long COVID Symptom?

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This week, media attention turned to a case report in The Lancet detailing how a man’s legs would turn blue after standing for about 10 minutes, which researchers said is likely related to his long COVID.

The 33-year-old man told doctors that for the past 6 months, his legs would feel progressively heavy, tingly, and itchy, and then would become “dusky” in color, according to medical student Nafi Iftekhar and Manoj Sivan, MD, of the Leeds Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds in England.

In addition, a petechial rash would occasionally appear on his feet, they reported. His legs would return to a normal color and the symptoms would go away when he would lay down.

Iftekhar and Sivan diagnosed the patient with “dysautonomia secondary to SARS-CoV-2 infection and associated with long COVID.”

They explained the leg discoloration was acrocyanosis, or venous pooling and cutaneous ischemia, and suggested he increase his fluid and salt intake, and do muscle strengthening exercises.

“[C]linicians may not be aware of the link between acrocyanosis and long COVID,” Sivan said in a statement. “We need to ensure that there is more awareness of dysautonomia in long COVID so that clinicians have the tools they need to manage patients appropriately.”

Bruce Hirsch, MD, an infectious disease physician at Northwell Health in Manhasset, New York, noted that the symptom of blue legs “doesn’t seem that different from what we’ve been hearing over the last couple of years, like COVID toes … and we know that the circulation is impacted in many people with the complications of long COVID.”

“As part of long COVID, many people will have a disrupted autonomic nervous system,” Hirsch told MedPage Today. “The autonomic nervous system controls blood pressure, heart rate; it’s constantly adjusting the tone in our blood vessels. And for reasons that we do not know, some people with long COVID, their autonomic nervous system is completely disrupted and they’re unable to maintain the tone in their blood vessels.”

While COVID also has been linked with hypercoagulability of the blood, that doesn’t seem to be the case here, he noted.

“This is the muscle tone in the blood vessels that is finely regulated by the autonomic nervous system,” he said. “Human biology is exquisite. Our nervous system, our circulatory system, is making adjustments second-by-second depending on our level of exertion, on the position of our body. We take that for granted. And then we’re hit in the face by the example of POTS [postural orthostatic tachycardia syndrome] and just how disabling it is.”

Hirsch added that while data have shown the frequency of long COVID is declining over time, “that does not mean there aren’t still a significant number of individuals who are suffering, who have had their ability to function normally in their life completely altered. It’s very, very concerning.”

Amesh Adalja, MD, an infectious disease physician with the Johns Hopkins Center for Health Security in Baltimore, who was not involved in the research, said it’s an “isolated case report that illustrates that POTS is part of the milieu of post-COVID syndromes.”

“The significance is to raise awareness of POTS — which is one of the only well-defined post-COVID syndrome[s] — rather than the rare POTS manifestation of acrocyanosis,” he added. “Long COVID is a nebulous term and likely lumps together several disparate conditions under this label.”

The patient had two COVID infections in his lifetime: one 18 months prior to his visit that was confirmed on PCR, and another suspected infection 6 months after that.

He’d been diagnosed with long COVID 3 months before his visit after a year-long history of post-exertional exhaustion, muscular pain, sleep disturbances, visual difficulties, sexual dysfunction, and brain fog. He also subsequently received a diagnosis of POTS from a cardiologist.

The patient had other long-standing health issues prior to his COVID infection, including irritable bowel syndrome, adult-onset attention deficit-hyperactivity disorder, joint hypermobility, and pelvic pain. He was taking sertraline (Zoloft) and oral solution amitriptyline.

On examination, the patient’s pulse was 68 bpm and his blood pressure was 138/85 mm Hg when he was laying down. When he stood for 8 minutes, his pulse rose to a maximum of 127 bpm, but his blood pressure was stable at 125/97 mm Hg, Iftekhar and Sivan said.

He described the accompanying symptoms as feeling foggy and shaky, in addition to the tingling, itchiness, and heaviness in his legs.

As for his labs, he had normal levels of immunoglobulin, C-reactive protein, and erythrocyte sedimentation rate, and was negative for antinuclear antibodies, anti-neutrophil cytoplasm autoantibody, and anti-cyclic citrullinated peptide antibodies, the researchers reported.

They noted that the evidence is growing for a link between long COVID and POTS dysautonomia. While dysautonomia is a diverse group of disorders affecting the central or peripheral nervous system or both, POTS is a dysautonomia syndrome in which patients have orthostatic intolerance with a large rise in heart rate and symptoms of light-headedness, dizziness, and palpitations when standing, though they maintain their blood pressure. They may also have low energy, headache, cognitive impairment, muscle fatigue, chest pain, weakness, or gastrointestinal symptoms.

Its onset may be precipitated by viral infection, physical trauma, menarche, pregnancy, or surgery and may co-occur with other conditions including migraine, hypermobile Ehlers-Danlos syndrome, or chronic fatigue syndrome.

“We need more awareness about dysautonomia in long-term conditions; more effective assessment and management approaches, and further research into the syndrome,” Sivan said in the statement. “This will enable both patients and clinicians to better manage these conditions.”