Volume 35 Number 4 | August 2021
A Tale of Two Patients from Diagnosis Until Now
Pat Tille, PhD, MLS(ASCP)CM, AHI(AMT), FACSc, AMTF President-Elect
You may have read about my unexpected diagnosis of COVID-19 and the experience from a personal perspective in the October 2020 issue of ASCLS Today. Now you are going to see the rest of the story from the diagnostic to the treatment of COVID-19.
Path to Diagnosis
On August 10, 2020, I presented to acute care with congestion, postnasal drip, rhinorrhea, sinus pressure and pain, and a sore throat. I was negative for chills and fever. The primary care provider noted that I had a cough and upon physical evaluation my nasal cavities showed mucosal edema with positive erythema. There was no evidence of shortness of breath or chest discomfort. My temperature was normal (98.9°F), and my blood oxygen saturation was 94 percent. However, my blood pressure was elevated at 142/84 with a pulse of 108. The primary care provider diagnosed a sinus infection and placed me on a seven-day prescription of Augmentin and steroids.
Approximately six days later, on August 16, while traveling with family, I felt very weak and out of sorts. I was unable to sleep but had no other obvious new signs or symptoms. I asked my husband to drive me home, as we were approximately five hours away in a remote cabin in western South Dakota. Upon arriving on the east side of the state, I had my husband take me directly to the Emergency Department (ED) at the local hospital. Let me remind you, from the earlier article in ASCLS Today how the diagnosis proceeded in the ED.
In the emergency room (ER), the nurse checked my vitals and placed a nasal canula on me underneath my mask with two liters of O2. The ER physician came in and went through my signs and symptoms with me and said he wanted to do a computed tomography to check my colon, etc., and collect a stool sample for Clostridiodes difficile. In the meantime, I was given a bag of IV fluid, an injection of Zofran to reduce nausea, and a shot of morphine for discomfort.
I came back from radiology, and the provider pulled up the digital image from the CT. He said my GI looks great, but it is this in my lungs that is concerning. Well, being the healthcare professional that I am, and a microbiologist who was reading and watching the pandemic for many months, he had to say no more. In both of my lungs there were some patchy areas that were quite diffuse and clearly evidence of viral infiltrates.
The provider said it was a concern and began to question me about my breathing. After about two hours from my initial arrival in the ER, he first realized I had a nasal canula with O2. He asked when I put that on. I calmly responded that the nurse did it after my initial vitals. The provider thought I was wearing it simply because morphine can cause a drop in your saturation levels, but it returns to normal within a reasonable time. The provider said he was concerned and was thinking of admitting me to the COVID-19 acute care ward. Of course, I had no intention of going there, and asked him why. He said because your oxygen saturation is not staying above 88 percent, even on two liters.
Treatment in the COVID Ward
I was admitted to the hospital on August 16, Day 1, with what the physician noted was new peripheral and subsolid, reticular opacities within the lung bases along with acute hypoxemic respiratory failure secondary to COVID-19 pneumonia. My complete blood count (CBC), basic metabolic panel, and magnesium levels were all within normal ranges. Research has now shown that patients with severe COVID disease demonstrate a high white blood count and a decrease in lymphocytes and platelets.1 Looking back, this would indicate from my normal CBC that my prognosis was good. However, the inflammatory markers indicative of COVID-19 and potential thrombosis were elevated as noted in Table 1.
Biomarkers for inflammation, and the elevated D-dimer (a measure of fibrin degradation) is an indicator that the patient is experiencing systemic and severe COVID-19 disease, often leading to a fatal outcome.1 The level of ferritin elevation demonstrated in my initial blood sample was indicative of severe COVID-19 disease. In addition to the elevated ferritin, Interleukin-6 (IL-6) levels are extremely elevated in severe COVID-19 disease. Upon admission, my IL-6 was 33.5 pg/mL (reference range≤1.8 pg/mL). The elevation of these two biomarkers, along with an elevated CRP of 172.6 mg/L (reference range ≤ 5.0 mg/L), are considered essential diagnostics for the monitoring and prognosis for patients with severe COVID-19 with progression to systemic inflammatory response syndrome (SIRS).1 The combined effects of the viral infection and the elevation of inflammatory biomarkers often leads to SIRS resulting in systemic damage from what is referred to as a “cytokine storm.” Once IL-6 becomes elevated, additional cytokines associated with the immune system inflammatory response become elevated resulting in damage to lung, cardiac, and vascular epithelial tissue.
Once the laboratory results were received, the primary care provider immediately initiated treatment. The primary care provider asked that I commit to a five-day regime of treatment that included a daily infusion of remdesivir, along with oral dexamethasone for inflammation, vitamin D, vitamin C, and zinc. In addition, I received an injection of Lovenox (anti-coagulant) daily, in my abdomen. To combat the activation of my immune system on Day 1, I also received an infusion of the human monoclonal antibody for IL-6, tocilizumab. This drug targets IL-6 to suppress immune activity and control the immune response.
As noted, on Day 2, my ferritin continued to climb but my CRP, D-Dimer, and lactate dehydrogenase (LDH) (an indicator of tissue damage) began to drop slightly. On the second day of admission, I received an infusion of O negative convalescent plasma.
On Day 3, all inflammatory markers and the LDH dropped significantly. Following the infusion of convalescent plasma and continued treatment with the prescribed medications, the inflammatory markers consistently declined over the next few days. In addition, my physical evaluation slowly began to improve. (See Table 2 on page 14.)
On Day 5, the primary care provider discharged me, indicating that there was nothing more they could do at this point, and it was now up to my immune system to continue the battle with the virus in hopes of recovery. My blood oxygen levels had become manageable at 93 percent on 1 L/min of oxygen. I was sent home on oral dexamethasone and anticoagulants (Eliquis) for 30 days along with oxygen for sleeping and use during the day as needed.
Recovery at Home
Upon release from the hospital, I was required to log my blood oxygen levels and any other notable symptoms twice a day with the primary care provider monitoring system. At approximately three weeks, post admission, I was able to discontinue oxygen therapy based on my saturation staying above 94 percent on room air as approved by a follow-up visit with my primary care physician.
Throughout my recovery period, and as it continues today, it is notable that several weeks post admission, my blood pressure and heart rate remained elevated, as well as having continued shortness of breath. (Table 2) Overtime, things began to normalize, and my oxygen saturation has improved.
Because approximately 25 percent of COVID-19 patients develop cardiomyopathy and damage to other tissues, I was referred to cardiology for a complete work-up. This consisted of a medication induced stress test, and nuclear imaging studies. I was very relieved to note, that there was no cardiac inflammation or damage noted by the cardiologist.
Table 1: Inflammatory Markers and Coagulation Results
| Ferritin (5-204 ng/mL) | CRP ≤ 5.0 mg/L | APTT 23.5-36.5 Seconds | PT 11.5-14.5 Seconds | INR 0.86-1.15 | LDH 125-220 U/L | D-Dimer ≤0.50 ug/mL | |
| Day 1 | 987 | 172.6 | 31.3 | 13.6 | 1.06 | 382 | 1.09 |
| Day 2 | 1024 | 111.4 | 31.5 | 12.6 | 0.96 | 368 | 0.98 |
| Day 3 | 788 | 58.3 | 29.4 | 13.6 | 1.06 | 347 | 0.77 |
| Day 4 | 663 | 34.9 | 28.4 | 14.3 | 1.13 | 371 | 1.02 |
| Day 5 | 592 | 22.1 | 27.5 | 13.2 | 1.02 | 345 | 0.79 |
Abbreviations: CRP (C-reactive protein), APTT (activated partial thromboplastin time), PT (Protime), INR (international normalized ratio), LDH (lactate dehydrogenase)
Table 2: Physical Parameters of Recovery
| Temp | BP | Pulse | Resp | O2 | O2 Flow | |
| Day 1 | 97.6 | 150/90 | 108 | 22 | 88% | 3 L/min |
| Day 2 | 97.5 | 148/80 | 80 | 20 | 89% | 2 L/min |
| Day 3 | 98 | 148/80 | 75 | 20 | 90% | 1 L/min |
| Day 4 | 97.4 | 148/89 | 72 | 20 | 91% | 1 L/min |
| Day 5 | 97.5 | 142/80 | 59 | 22 | 93% | 1 L/min |
| 3 weeks | 97.8 | 132/82 | 98 | 22 | 95% | RA |
| 6 weeks | 98.8 | 148/84 | 110 | 18 | 94% | RA |
| 18 weeks | 98.6 | 137/74 | 90 | 16 | 97% | RA |
| 22 weeks | 97.8 | 130/70 | 72 | 16 | 98% | RA |
I am over 60 years of age. My only associated additional health concerns include hypothyroidism, which I have had for more than 30 years resulting in a continued battle with weight control. My case with COVID-19 could have been much more serious, and the lingering effects remain with continued high blood pressure and shortness of breath. Improvement continues but there is no way to know how long or if a full recovery to a pre-COVID-19 infection state will result. But what about others? Who is the second patient in this story?
Patient 2
Three days after I was released from the hospital, our 34-year-old daughter was admitted to the hospital, and her story is much more critical. Following a 10-day battle with COVID-19, including a high fever of over 103°C and chills, she went to acute care. Additional physical findings included BP 104/78, Pulse 114 beats per minute, and respiration of 20 times/minute. The primary care provider noted that clinically she appeared unwell and pale. Her oxygen saturation was 78 percent on room air.
Her breathing was slightly labored, and she was slightly tachycardic. She had bilateral pneumonia. In acute care she was given 1000mL 0.9 percent normal saline bolus. She remained tachycardic with two L/min O2 applied, and her oxygen saturation increased to 92-94 percent. She appeared slightly better after interventions. She was sent to the emergency department for additional evaluation.
Upon arrival at the emergency department, she was admitted and was evaluated with additional blood tests. Her IL-6 was elevated at 18.9 pg/mL, ferritin 1288 ng/mL, D-Dimer 0.82 ug/mL, LDH 516 U/L, and CRP 160.7 mg/L. Here complete blood count and metabolic panel were all normal. Her IL-6, CRP and D-dimer were lower than mine, however, her ferritin was higher and her LDH was significantly higher indicating more severe tissue damage. Within the first 24 hours, her oxygen saturation was continuing to fall, and she was placed in a prone position to try and improve her saturation.
The first 24 hours were critical to avoid being transferred to the intensive care COVID-19 unit, and in fact, the physician on duty told her this was “like a diagnosis of cancer, with no cure and a potentially fatal outcome.” She was given the same therapeutic treatment for COVID-19 that I had received, however, without convalescent plasma or tocilizumab. Within three days, she was able to maintain her oxygen saturation at 93 percent on 3 L/min and was discharged.
“What recovery from COVID-19 infection means is clearly different and variable for each individual and it is clear from this tale of two patients—genetically similar, with significant age differences—that the response of the immune system and so many other factors can alter the clinical outcome.”
As everyone knows from watching all the media and reports on COVID-19, there is no clear pattern on the pathology of the virus. While our daughter was in a more serious state of disease, she seemingly recovered more quickly with less intensive treatment. However, unlike myself, she remained on oxygen for nearly seven months post admission. She experienced severe hair loss and developed numbness and tingling in her extremities and face. Her left side is significantly weaker than her right. She also complained of severe “brain fog.” Tasks that were second nature to her, now took three to four times longer. She would be working on something or trying to communicate and could not find the words.
Eventually, after arguing with physicians who refused to see her or follow-up on her symptoms, she was diagnosed with Guillain-Barre’ Syndrome (GBS) post-COVID-19. She also completed extensive cardiovascular and pulmonary assessments. The providers indicated she has no apparent cardiac involvement or damage present, however, there is evidence of some “minor” lung damage that appears to be healing. Her brain fog is improving, along with her shortness of breath, but she continues to battle the neurological effects of GBS. The GBS seems to have not progressed with continued treatment with Gabapentin.
There is no magic formula for the diagnosis and persistence of pathology from COVID-19 infection and what is referred to as long-hauler syndrome (LHS). Reports indicate variations in 3-10 percent of patients may experience LHS.2 Our daughter is considered a long-hauler and is participating in continued research studies for COVID-19 syndromes. Because the recovery from the virus can vary, deconditioning of patients and continued physical challenges also remain for COVID-19 patients. In addition to the physical manifestations of COVID-19, there is significant psychological concerns that are evident in patients who experienced isolation and medical care in a less than ideal setting that ranges from depression to post traumatic stress disorder.2 It was evident to myself and our daughter that not only were the patients subjected to what you might call, sub optimal care and isolation, the primary care providers in the COVID-19 wing were stressed and distraught from the inability to care for patients properly and unable to provide any clear prognostic information and support to patients and their families.
SARS-CoV-2 remains a mysterious and complicated virus. Continued research and diligence is required to prevent transmission and infection. Both myself and our daughter have been vaccinated, although there was some concern that she would not be able to be vaccinated due to GBS. We both continue to physically improve, however, the experience of our hospitalizations and the uncertainty of the future as well as the development of highly transmissible and potentially more deadly variants continues to haunt our memories and our concerns.
What recovery from COVID-19 infection means is clearly different and variable for each individual and it is clear from this tale of two patients—genetically similar, with significant age differences—that the response of the immune system and so many other factors can alter the clinical outcome. Undoubtedly the medical community will continue to learn, develop new treatments, and update vaccinations. But for those affected by COVID-19, only time will tell.
References
- Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020 Jun 25;58(7):1021-1028. doi: 10.1515/cclm-2020-0369. PMID: 32286245.
- Mendelson M, Nel J, Blumberg L, Madhi SA, Dryden M, Stevens W, Venter FWD. Long-COVID: An evolving problem with an extensive impact. S Afr Med J. 2020 Nov 23;111(1):10-12. doi: 10.7196/SAMJ.2020.v111i11.15433. PMID: 33403997.
Pat Tille is the Graduate Medical Laboratory Science Program Director for the University of Cincinnati, in Cincinnati, Ohio.