Peer reviewed, science driven, compassion focused
Case Study Report
SARS-CoV-2 and The Case for Empirical Treatment Authors – Richard P. Bartlett, MD and Alexandria Watkins, DNP
Richard P. Bartlett, MD and Alexandria Watkins, DNP
SUMMARY
As of June 17, 2020, Google Trends reports that the topics “steroids and coronavirus”
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have increased +4,750%.
in the United States with unique cases that involve oncology and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as COVID-19. This case study aims to reveal the identification process, diagnosis, clinical course, and management of such a distinctive case – including the patient’s prodromal phase and subsequent progression of the disease in an outpatient setting utilizing telemedicine. The goal is to call attention to the success of proactive, early empirical treatment, combining a classic corticosteroid (budesonide) administered via a nebulizer and an oral macrolide antibiotic known as clarithromycin (Biaxin).
INTRODUCTION
Beast.
A beauty named budesonide and a beast named SARS-CoV-2. Budesonide, a
This is an outpatient case study that examines two patients
A classic drug and a novel case, it is a story out of a Disney playbook – Beauty and The
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drug initially patented in 1973 and on the World Health Organization’s (WHO) List of
Essential Medicines, and SARS-CoV-2 first presenting itself in the United States on
8 & 46
January 20, 2020.
treating a respiratory disease with a pinpoint focused nebulized therapy versus systemic therapy. One can go as far back as ~1554 BC and find that even the ancient Egyptians
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This is a case study that demonstrates the effectiveness of
had an appreciation for the therapeutic effects of sequestered aerosol inhalation.
aim of pinpoint focused treatment is to find specific targets and treat effectively with minimal side effects. ‘Work smarter, not harder’ is an underlying theme with early, pinpoint focused empirical treatment.
Like asthma, SARS-CoV-2 is a form of a respiratory inflammatory disease that is more severe and acts on the angiotensin-converting enzyme (ACE) receptors of the lungs. SARS-CoV-2 presents as a local vascular problem due to the activation of B1 receptors on endothelial cells within the lungs – B1 receptors increase the response to proinflammatory cytokines. This activation takes place when the angiotensin-converting enzyme 2 (ACE2) acts as a receptor, permitting the spike protein of SARS-CoV-2 to bind to host cells. When ACE2 is interrupted, and the ligands of B1 are active, the lung environment is predisposed to vascular leakage and angioedema – rapid swelling in the mucosa. The primed spike protein is also allowed viral entry and spread by the
24, 34 & 43
transmembrane protease, serine 2 (TMPRSS2).
discovery that inhaled corticosteroids (ICS) via nebulizer permit for localized down- regulation of proinflammatory cytokine synthesis and decreased expression of ACE2
15, 23, 24, 28, 34 & 49 (receptor of SARS-CoV-2) and TMPRSS2, thus reducing mortality. For
this reason, this case study postulates that focused treatment with nebulized
budesonide has clinical significance over systemic corticosteroids and does not
2, 24 & 30
increase the risk of infection with SARS-CoV-2. This case study supports early
empirical treatment in symptomatic patients.
METHODS
Study Population, Setting, and Data Collection
This case study involves two patients in the outpatient setting – treated via telemedicine, with laboratory-confirmed SARS-CoV-2 infection in the West Texas region between
Multiple studies agree with our
The
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Richard P. Bartlett, MD and Alexandria Watkins, DNP
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March 29 , 2020, and May 14 , 2020. The cases presented are confirmed SARS-CoV-
2 positive cases as defined by a positive result on a reverse-transcriptase-polymerase- chain-reaction (RT-PCR) assay of a specimen collected on a nasopharyngeal swab. The two identified adults were identified and managed through telemedicine by a primary care provider in an outpatient family medicine practice.
Informed consent for medical records release was obtained through password-protected emails, and patients were interviewed by phone.
CASE REPORT
The first patient is a 63-year-old female, non-smoker, who is diagnosed with Waldenstrom’s Macroglobulinemia (2012) and Primary Cutaneous Marginal Zone Lymphoma (2020) and currently being treated with ibrutinib (Imbruvica). The patient also has a history of hypertension and hypothyroidism; treatment for these comorbidities includes losartan potassium 50mg tab once-daily, and levothyroxine 50mcg tab once-
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daily respectively. The patient reports complete isolation until May 7 , 2020, when her
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family visited, this is the initial exposure date. On May 10 , 2020, the patient became
symptomatic with sinus cavity pressure, fever, aches, and chills. In the early morning
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hours of May 11 , the patient had multiple episodes of nausea and vomiting and, by
that evening, had fever greater than 100.4°F, constant chills, unproductive cough, decreased appetite related to change in taste and smell. The patient remand
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symptomatic and continued to self-isolate until May 15 , she received news that she
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had been exposed to a family member on May 7 , that tested positive for SARS-CoV-2.
Upon hearing the report, the patient reached out via telemedicine to an outpatient family
medicine doctor. The patient was tested for SARS-CoV-2 via nasopharyngeal swab
using a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay. At this time
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(May 15 , 2020), the patient was empirically started on budesonide 0.5mg nebulizer
twice daily, clarithromycin (Biaxin) 500mg tab twice daily for ten days, Zinc 50mg tab twice daily, and aspirin 81mg tab daily. The patient reported for the next two-days, symptoms improved once nebulized budesonide had been administered. By May 19 ,
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the patient developed a productive cough, pleuritic pain, and diarrhea. On May 20 , the
patient’s RT-PCR assay for SARS-CoV-2 was confirmed positive, ten days after initial symptoms. A telemedicine consult was performed the same day (May 20th), and budesonide administration was increased from twice daily to three times daily. The
th th patient reports that on May 24 , symptoms started to improve, and on May 25 , the
patient completed the clarithromycin (Biaxin) prescription and notes that this was the
first day of no fevers. As the patient continued to remain symptom-free, a second RT-
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PCR assay was ordered via telemedicine on May 29 , and on June 2 , the patient was
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still positive for SARS-CoV-2; this is 24-days from initial symptoms. On June 8 , the
patient had been symptom-free for 14-days, a third RT-PCR assay was ordered via
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telemedicine, and on June 10 , the patient received their first negative result for SARS-
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CoV-2. A fourth RT-PCR assay was ordered on June 11 , via telemedicine, and on
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June 17 , the patient received a second negative result. The patient has remained
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symptom-free, and as of June 11 , has no longer needed nebulized budesonide
therapy.
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Richard P. Bartlett, MD and Alexandria Watkins, DNP
Assumed Initial Exposure Date:
May 7, 2020
Empirical Treatment Start Date:
May 15, 2020
Test Date:
May 15, 2020 May 29, 2020 June 8, 2020 June 11, 2020
Result and Date Received:
Positive – May 20, 2020 Positive – June 2, 2020 Negative – June 10, 2020 Negative – June 17, 2020
The second patient is a 38-year-old male, non-smoker, who has the following comorbidities: Type II Diabetes Mellitus (DM), hypertension, and gout. The patient takes Metformin 1,000mg tab, twice daily and Pioglitazone 15mg tab, daily for Type II DM, Lisinopril 2.5mg tab, daily for hypertension, and Probenecid 500mg tab, daily for gout.
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The patient believes initial exposure was in Frisco, TX, on March 7 , 2020, while
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shopping at a shopping center. On March 29 , 2020, the patient became symptomatic
with cough, sore throat, loss of smell and taste, fever (>100.4°F), aches, and chills. th
March 29 , the patient was tested for Influenza using the rapid influenza diagnostic test
(RIDT), the test was negative, and the patient was discharged home. At this time, the
patient accessed his primary care doctor via telemedicine, he was treated empirically
and started on budesonide 0.5mg nebulizer twice daily, clarithromycin (Biaxin) 500mg
tab twice daily for 10 days, Zinc 50mg tab twice daily, and aspirin 81mg tab daily. April
st
1 , 2020 (three days after onset of symptoms), the patient was able to undergo SARS-
CoV-2 testing, he was tested by nasopharyngeal swab using an RT-PCR assay. On
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April 3 , the patient was informed that he had tested positive for SARS-CoV-2, six days
after initial symptoms had ensued. The patient reports that he was symptom-free April
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4 , and completed his full round of clarithromycin (Biaxin) on April 7 . The patient
continued budesonide 0.5mg nebulizer twice daily, Zinc 50mg tab twice daily, and aspirin 81mg tab daily. As the patient continued to remain symptom-free, a second RT- PCR assay via nasopharyngeal swab was ordered via telemedicine on April 15th ending with a positive result for SARS-CoV-2. At this time azithromycin 500mg tab on day one,
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then 250mg tab, daily for four-days was started. On April 27 , the patient was re-tested
via RT-PCR assay and again tested positive. It was not until May 1st that the patient
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tested negative per the nasopharyngeal swab RT-PCR assay. On May 7 , the patient
was tested with another RT-PCR assay by nasopharyngeal swab to confirm the
negative test result but tested positive for SARS-CoV-2. The patient had no new
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exposure and been self-quarantined since April 1 . The patient was re-screened again
by nasopharyngeal swab using RT-PCR May 11th and tested negative for SARS-CoV-2.
The patient completed a total of four rounds of Azithromycin 500mg tab on day one,
then 250mg tab, daily for four-days, and stopped budesonide 0.5mg nebulizer twice
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daily, May 13 . He continued Zinc 50mg tab twice daily, and the aspirin 81mg tab daily,
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until a second consecutive negative was obtained. On May 14 , the last test that was
performed on the patient was the nasopharyngeal swab using an RT-PCR assay and again confirmed a negative result.
Assumed Initial Exposure Date:
March 7, 2020
Empirical Treatment Start Date:
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Richard P. Bartlett, MD and Alexandria Watkins, DNP
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