Long COVID, a Syndrome with Many Faces

Now that the new website is ready, there is again time to continue with the presentation of case histories. Today, the story of two women who recently presented with symptoms of Long COVID. These two examples show that Long COVID, and all post-infection syndromes, require a personalized treatment approach following thorough investigation. The data have been meticulously processed and anonymized to ensure the privacy and anonymity of the patients at all times.

Patient 4 is a French woman, almost 60 years old, who experienced two infections with Sars-COV-2. She recovered from the first, but after the second, she remained tired, with complaints of limited sense of smell and brain fog. After four months, she sought advice from an internist at a university in her city. After extensive examination, including comprehensive laboratory tests, X-rays of the chest and abdomen, and an ECG, the internist diagnosed her with Post COVID Syndrome. The advice was to undergo physiotherapy and psychotherapy. Both treatments were completed six months later, and the patient remained unchanged. Treatment with amitriptyline and beta-blockers worsened her symptoms.

Patient 5 is a 28-year-old German woman who fell ill several times during the corona period. The first time, a test was not yet available. During the last two periods of illness, Sars-COV-2 infection was confirmed. The patient underwent extensive examinations by an internist, a cardiologist, a neurologist, and a rheumatologist. Based on the medical history, negative findings, and symptoms, the decision was made to diagnose Long COVID. The patient was advised to recover with physiotherapy and occupational therapy. The physiotherapy was terminated after a few sessions because the exercises were too strenuous. The occupational therapy continued because the patient felt the advice helped her deal with severe limitations. The patient attended courses in Germany and Spain but without improvement. Treatment with vitamin B12 twice weekly was discontinued after three months due to a lack of improvement.

Both patients contacted us shortly after each other via our website. When taking the medical history of patient 4, it became clear that her primary complaints were fatigue and headache, but that headaches and migraines had been present throughout her life. Migraines often occurred after exertion, such as in sports. With exertion, her heart rate increased quickly. Attempts to treat this always led to an increase in symptoms. Besides the headache, brain fog was the main complaint at the time of registration. The physical condition was not a reason for the consultation.

During the reading speed measurement, we found normal values. The hand dynamometer measurements showed values above the 50th percentile of the reference ranges. We repeated the measurements 30 times to get an impression of the energy production. After 2.5 mg of beta-hydroxybutyrate (BHB), the strength did not increase. BHB is a ketone. With the blockade of the anaerobic glycolysis due to reduced enzyme activity, we see a substantial increase in energy production if no other blockades are present. This matched the medical history in which the patient reported not experiencing any physical limitations.

Evident abnormalities were found in the NASA 10-minute lean test. In this test, the patient lies down for ten minutes and then stands leaning for ten minutes. Blood pressure and heart rate are measured every minute throughout the test. Patient 4’s heart rate increased over the threshold value of thirty beats per minute. In addition, the diastolic blood pressure increased more than the systolic blood pressure when standing. The pulse pressure index, pulse pressure divided by the systolic blood pressure expressed in percentages, dropped to 16%. This is clearly below the threshold value of 25%, indicating a too-strong reduction of the stroke volume due to increased resistance in the body’s vessels. After the test, the patient complained of the well-known headache. On her own initiative, the patient repeated the test, always with the same result.

In patient 5, we found matching values. The reading test was optimal; the hand dynamometer values were on the 35th percentile, and after BHB, there was a minimal increase within the measurement error. In the NASA lean test, the heart rate increased by 47 beats per minute, and the diastolic blood pressure more than the systolic blood pressure, with a drop in the pulse pressure index to well below 25%.

The drop in the pulse pressure index is an overshooting response to the changed pressure ratios when standing or sitting. This drop has been described in Long COVID by Vernon et al.[1] A congenital form with insufficient activity of the norepinephrine transporter has also been described [2].

Patient 4 has had characteristics of a poorly functioning system all her life. In patient 5, the problem began after COVID-19. We advise patient 4 to seek examination by a specialized center in an academic hospital. For patient 5, this does not seem necessary for the time being.

Long COVID is a syndrome with many faces. Only good diagnostics and tailor-made treatment offer chances for help for these patients.

1. 1. Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL: Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne) 2022, 9:917019.
2. 2. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med 2000, 342(8):541-549.