Patient A
Patient A is 38-year-old Caucasian, female with a past medical history of infrequent childhood seizures, beginning at age eight, which co-occurred with vasovagal syncope between ages 25-30. She also has a history of Lyme Disease, which was diagnosed and treated with IV ozone therapy and supplements in 2018, following symptom onset two years prior. She is a never-smoker.
She contracted COVID-19 in the second week of March 2020, four days after a flight. She tested positive by PCR and subsequently showed the presence of antibodies. She initially experienced cold-like symptoms, including fever (103 F), dyspnea both at rest and exertional, rhinitis, and pharyngitis, followed by an initially productive, then dry cough, nausea, diarrhea, and visual and auditory hallucinations that lasted for approximately three weeks.
Over the next several months she experienced periods of exacerbation and remission, during which, she felt “okay” for a few weeks, followed by worsening dyspnea, chest tightness, anxiety, and panic attacks. She also experienced fatigue and post-exertional malaise, where she felt “good-to-great” during an hour-long walk or yoga class, but then experienced profound fatigue, increased dyspnea, and chest pressure over the subsequent 24-48 hours. She reported mild symptom relief with albuterol sulfate but tried to limit its use due to increased jitteriness. Medications at the time of her initial evaluation included daily hydroxychloroquine, prednisone, Topamax, and Adderall as needed, as well as multiple non-prescription anti-inflammatory supplements.
Patient B
Patient B is a 39-year-old Caucasian, female with a medical history of allergic rhinitis and allergic reaction to penicillin, amoxicillin, and tetracycline. Her psychiatric history includes three hospitalizations in 2002 for medical complications associated with anorexia nervosa, which has been in partial-to-full remission since 2004. She also has a history of persistent depressive disorder, generalized anxiety, specific phobia (in partial remission), and attention-deficit hyperactivity disorder. She was a nationally competitive swimmer, exercised frequently pre-COVID and is a never-smoker.
She contracted COVID-19 in the third week of March 2020, when she began to experience rhinitis, dry cough, and chest tightness. Those symptoms resolved completely three days later, followed by a sudden onset of anosmia, ageusia, and dysgeusia (which lasted until June). On March 23rd she developed a fever (102 F) with intermittent borderline hypothermia (95 F), return of the cough, dyspnea, both on exertion and at rest, chills, and muscle aches, at which time she was clinician diagnosed with COVID-19 as PCR testing was unavailable. She had multiple dermatologic issues including transient hives and “canker-like” sores that would come and go within hours of initial onset. She also experienced olfactory hallucinations on three occasions.
On April 11, Patient B was admitted to the ER, during which, a chest x-ray revealed “possible mild pleural effusions.” She was discharged without further testing or treatment. Her dyspnea, cough, and fatigue worsened over the next month. She also reported decreased oxygen saturation (low 80’s and high 70’s) after speaking for more than 10-15 minutes or climbing a flight of stairs, which coincided with heart rate lability (154 to 40 within 60 seconds). Other symptoms included brain fog, impaired memory, nightmares, and night sweats. She had two more ER admissions in June for oxygen desaturation upon exertion, dyspnea, persistent fever, and chest pain, at which time she was diagnosed with hypertension. Her last ER admission, in late July, was for chest pain which, at the time, was attributed to a cough-induced muscle strain. Pulmonary function tests, echocardiogram, and cardiac stress test were all normal. Holter monitor showed inappropriate sinus tachycardia. She continued to experience daily fevers (99.5-102) until early October.
Medications at the time of her initial evaluation included Zoloft, Adderall XR, and TriNessa Lo daily, as well as Singulair (for allergic rhinitis), trazadone, and albuterol as needed. After her evaluation she was diagnosed with coronary vasospasms for which daily Procardia XL was prescribed.
Patient C
Patient C is 34-year-old, Black, female who has a medical history significant for sickle-cell trait (carrier only), HSV-1, and a childhood history of Tourette's syndrome (in remission). She is a runner and never-smoker.
Patient C began experiencing dyspnea on April 17, 2020 and was clinician diagnosed with COVID-19 in the emergency department the following day, but subsequently released without treatment. Although her oxygen saturation remained ≥ 98%, she continued to experience dyspnea with suspected pneumonia in the months that followed, even as she was able to work and run 1-2 miles several times each week. An August CT scan was "mostly normal," but showed some post-viral inflammation and a vascular assessment of that same CT scan found “damage to approximately 30%of a group of smaller blood vessels in the lungs.”
In early August, Patient C experienced severe laryngeal spasms for seven days, after using albuterol and Advair. She discontinued those medications but continued to experience persistent inflammation in her throat and larynx. A January CT scan was normal with the exception of mildly dilated distal esophagus. After endoscopic evaluation was normal, her ENT suggested her symptoms might indicate irritable larynx syndrome and/or possible nerve damage.
Medications at the time of Patient C’s initial evaluation included Albuterol, Advair Naproxen, Celebrex, and non-prescription supplements.
TREATMENT
All three patients underwent pre- and post-rehabilitation exercise testing using the Bensen treadmill protocol.12 Resting heart rate and rhythm via ECG, blood pressure, and oxygen saturation were measured pre-exercise, at each stage of testing, and during recovery. Rate of Perceived Exertion (RPE) and Breathlessness13 were obtained at peak exercise. The patients walked on the treadmill at an initial speed of 1.0 MPH with a 0% incline (1.77 METs) for two minutes. Intensity was then increased by approximately 25% every two minutes, alternating between speed and incline. The test was terminated when age-adjusted (200 - age) heart rate maximum was reached, or moderate symptom burden was reported.
Patients underwent two (Patients A & C) or three (Patient B) exercise sessions per week for a total of 24 sessions. Initial treatment sessions were approximately 25% longer in duration and lower in intensity, such that 80-100% of peak exercise tolerance was achieved within three sessions. In subsequent sessions, time and intensity were increased by no more than 0.5 METS, as tolerated based upon vital signs and patient-reported symptoms since previous session and during exercise. The patients received 6 liters per minute of continuous oxygen via nasal cannula regardless of oxygen saturation 5 minutes prior to, during, and 5 minutes post-exercise.