RxCe - Treating COVID-19 Materials

TREATING COVID-19

STEVEN MALEN, PharmD, MBA

Dr. Steven Malen graduated with a dual degree: Doctor of Pharmacy (PharmD) and Master of Business Administration (MBA) from the University of Rhode Island. Over his career, he has worked as a clinical pharmacist in the retail, specialty, and compounding sectors. He specialized and taught on topics from vaccines to veterinary compounding. Dr. Malen has also written a science fiction novel and taught and co- founded the concept of Patient Empowered Blockchain (P.E.B.). Currently, Dr. Malen continues to write, teach, and consult various companies in the healthcare sector.

Topic Overview

This course provides an overview of the current understanding of COVID-19, its impact on the human body, and the available treatment options. Participants will learn that COVID-19 is not just a respiratory virus, but a systemic inflammatory virus that affects major organs in the body. The severity of the disease ranges considerably, with the elderly and those with comorbidities at a significantly higher risk of hospitalization and death. Treatment protocols for acute COVID-19 and long COVID will be discussed, but it will be emphasized that the research in this field is rapidly evolving, and clinicians must stay current on the latest studies and publications to provide the best care for their patients.

Accreditation Statement:

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is

Pharmacist 0669-0000-23-066-H01-P

Pharmacy Technician 0669-0000-23-067-H01-T

Credits: 2 hours of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 hours, including Course Test and course evaluation

RxCe.com

Release Date: May 8, 2023 Expiration Date: May 8, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From May 8, 2023, through May 8, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Identify the latest research studies and publications on COVID-19 treatment and apply them to clinical practice

Describe the systemic inflammatory response to COVID-19 and how it affects major organs in the body

Compare the effectiveness and safety profiles of different COVID-19 treatments based on the latest research studies and publications

Describe long COVID symptoms and diagnosis

Discuss treatment options for long COVID

Disclosures

The following individuals were involved in developing this activity: Steven Malen, PharmD, MBA, and Pamela Sardo, PharmD, BS. Pamela Sardo, Pharm.D., B.S., was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

Introduction

The COVID-19 pandemic has brought unprecedented challenges to the healthcare system and has affected people's lives worldwide. This course aims to provide a comprehensive overview of the virus and its impact on the human body, from the respiratory system to major organs. Participants will learn about the systemic nature of the disease, the range of severity, and the factors that influence the course of the disease. Additionally, the course will cover the available treatment options for COVID-19, including antiviral medications, immunomodulators, and supportive care. Research and changes in this field are evolving rapidly, so clinicians must stay current on the latest studies and guidelines to provide the best care for their patients. This course will equip participants with the knowledge and skills to identify, describe, and compare COVID-19 treatment options and apply the latest research to clinical practice.

History of COVID-19

The first cases of Coronavirus Disease 2019 (COVID-19) were reported in December 2019, and in just four months, the outbreak spread to over 210 countries, with 2,400,000 cases and 170,000 deaths.1 Severe Acute Respiratory Distress Syndrome 2 (SARS-CoV-2) is the virus that causes the disease COVID-19. Due to this sharp rise in cases and deaths, restrictions on travel and mask mandates were implemented worldwide. Health systems struggled to keep up with this large rise in morbidity and mortality.1

By the end of 2020, COVID-19 killed 350,831 people in the U.S., making it the number three leading cause of death.2 This statistic held strong long into 2021, with 12.2% of deaths being attributed to COVID-19 between March 2020 and October 2021.2 By 2022, COVID was reported to be the 4th leading cause of death. There were 186,702 deaths, compared to 416,893 in 2021.

There were six known human coronaviruses, including Severe Acute Respiratory Distress Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).1,4 SARS-CoV-2 was added to this list. Genome sequences indicate that SARS-CoV-2, SARS-CoV, and MERS-CoV belong to the Betacoronavirus

genus, including the Bat SARS-like coronavirus.2 These Betacoronaviruses can infect humans and animals. SARS was commonly thought to have come from bats, and MERS was theorized to come from camels.1,5 This means that these viruses are zoonotic, i.e., they may be transmissible across species, animal to human, or human to animal. It is most likely that the SARS-COV-2 virus was a zoonotic transmission from bats to humans, but it is impossible to exclude the possibility of a laboratory origin or voluntary manipulation of the SARS- COV-2 virus.6

When a virus jumps to human hosts, it can lead to disease outbreaks. There were coronavirus outbreaks from SARS in 2002 and MERS in 2012.1 Like COVID-19, they caused injuries to the lungs, and other organs, such as the liver and kidneys.1 However, SARS-CoV-2 is much less pathogenic than MERS-CoV or SARS-CoV, and SARS-CoV-2 has a much lower case fatality rate compared to MERS and SARS: SARS caused 774 deaths with a 5-10% mortality rate and MERS caused 858 deaths with a 50% ICU rate and a 75% death rate once in the ICU; COVID-19 had significantly lower mortality rates at around 2.13% per the latest date.1 The main distinction of SARS-CoV-2 was its rapid spread elevating it to a global pandemic, and its presence continues to be felt.1 In May 2023, a possible new SARS-CoV-2 variant XBB.1.16, named Arcturus, was identified.7 Arcturus may cause a summer 2023 surge in SARS- CoV-2 infections, a percentage of which will present with the concomitant disease state known as COVID-19.7 This could mean that SARS-CoV-2 is not disappearing any time soon, and healthcare professionals will need to remain ready to treat patients who become infected.

Pathophysiology of SARS-CoV-2 and COVID-19

Coronaviruses, or CoVs, are enveloped, positive-strand RNA viruses, with a poly-A tail that is the longest of all RNA viruses.8 The SARS-CoV-2 virus has 4 structural proteins: they have a protective helical nucleocapsid protein shell, and three fundamental proteins - the spike protein, matrix membrane, and a highly hydrophobic small envelope protein.8 The SARS-CoV-2 virus also forms non-structural proteins (nsps), when two proteases (e.g., 3C-like

protease or main protease (3CLpro) and papain-like protease (PLpro)) cleave the pp1ab (a polyprotein) making non-structural nsps.8

The way Coronaviruses cause disease is via the structural proteins and nsps. The nsps play a pivotal role in host cell infection and RNA synthesis.8 The surface glycoproteins guide the link to the receptors, which later became the target of the mRNA vaccines. The spike protein also looks like a crown which translates to “corona” in Latin and is the reason for the name of the virus.8

The virus inhibits the renin-angiotensin-aldosterone system (RAAS); however, this does not increase morbidity or mortality, as previously theorized. Along the same lines, the virus binds to the human angiotensin- converting enzyme 2 (ACE 2) receptors which are concentrated in the lungs.8 These receptors are also in the esophagus, intestines, heart, kidney, and bladder. This is why the CoV virus is considered not only a respiratory virus but also a vascular illness. The respiratory part is pneumonia which has two stages: early and late. The early stage includes viral replication causing tissue damage, while the late stage causes an autoimmune response causing the release of cytokines. Severe COVID-19 is an extreme version of the late stage, including a “cytokine storm” which causes a local and systemic inflammatory response. This results in pulmonary edema because of endotheliitis, dysregulation of the RAAS, activation of the kallikrein-bradykinin pathway, and finally, epithelial cell contraction. Outside of the lungs, COVID affects the gastrointestinal system, liver, cardiovascular system, kidneys, and the central nervous system. This damage occurs by viral toxicity and/or ischemic injury per the pathways listed above.8

The incubation period for SARS-CoV-2 is 4 to 14 days, and patients may experience symptoms thereafter.8 There is a wide range of symptoms, from asymptomatic to severe, including the need for ventilation, septic shock, organ failure, and death. The major symptoms of SARS-CoV-2 infection include cough, loss of appetite, high fever, headache, breath shortness, vomiting, dyspnea, sore throat, rhinorrhea, diarrhea, and abdominal pain.8 A patient’s laboratory blood tests will show elevated C-reactive protein levels,

elevated cardiac enzymes, lymphopenia, abnormal liver function, leukopenia, elevated D-dimer, elevated erythrocyte sedimentation rate, elevated procalcitonin, abnormal renal function, leukocytosis.8

Guidelines from the NIH separate COVID-19 into five types based on the severity of the symptoms: “asymptomatic, mild, moderate, severe, and critical.”9 The vast majority of patients infected with SARS-CoV-2 will be asymptomatic or experience mild symptoms.9,10 The NIH’s Clinical Spectrum of SARS-CoV-2 Infection is as follows:

“Asymptomatic or presymptomatic infection: Individuals who test positive for SARS-CoV-2 using a virologic test (i.e., a nucleic acid amplification test [NAAT] or an antigen test) but have no symptoms consistent with COVID-19.

Mild illness: Individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but do not have shortness of breath, dyspnea, or abnormal chest imaging.

Moderate illness: Individuals who show evidence of lower respiratory disease during clinical assessment or imaging and have an oxygen saturation measured by pulse oximetry (SpO2) ≥94% on room air at sea level.

Severe illness: Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, a respiratory rate >30 breaths/min, or lung infiltrates >50%.

Critical illness: Individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction.”11

Budinger, et al. (2021) report that although a patient is asymptomatic, the patient may still have abnormalities seen in chest imaging.9 This is important for clinicians evaluating the severity of a patient’s COVID-19.

COVID-19 Treatment Options

There are treatments for patients with COVID-19 or who are at high risk of severe illness.

Antiviral Drugs

A primary physician may recommend an antiviral, such as molnupiravir, or ritonavir with nirmatrelvir.12-14

molnupiravir (Brand name: Lagevrio)

Originally developed for influenza, alphaviruses, and horse encephalitis viruses

Meta-Analysis: Reduces hospitalization and death in mild COVID-19

Phase 3 study: Early treatment reduces hospitalization or death of unvaccinated adults with mild-moderate COVID-19

ritonavir + nirmatrelvir (Brand name: Paxlovid)13,14

Pfizer clinical trial reported that the risk of hospitalization or death is 89% lower when Paxlovid is started within three days of symptoms13

Paxlovid is contraindicated in patients with estimated glomerular filtration rate <30 mL/minute/1.73 m2, dialysis, weight <40 kg, or pregnancy13,14

Numerous drugs are contraindicated with Paxlovid, including but not limited to carbamazepine, clozapine, colchicine, dihydroergotamine, ergotamine, flecainide, lovastatin, midazolam, and phenobarbital.13 Prescribing information should be consulted for a complete list.13

remdesivir (Brand name: Veklury)15

Early trials showed faster recovery in hospitalized COVID- 19 patients

It is approved for the treatment of adults and pediatric patients (28 days of age and older and weighing at least 3 kg) with positive results of direct SARS-CoV-2 viral testing,

who are: hospitalized or not hospitalized and have mild-to- moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.15

WHO SOLIDARITY Trial, which included 405 hospitals, 40 countries, and 11,330 inpatients, showed “little or no effect on overall mortality, initiation of mechanical ventilation, and length of hospital stay.”16

87% lower hospitalization or death in at-risk non- hospitalized patients

Monoclonal Antibodies

The U.S. Food and Drug Administration (FDA) issued an emergency use authorization for tixagevimab and cilgavimab, monoclonal antibodies used for the pre-exposure prevention of COVID-19 in certain individuals.10 Antibodies are part of the human immune system and seek out antigens (foreign materials) to destroy them. Monoclonal antibodies are manufactured proteins that act like antibody proteins in the body.10 Tixagevimab and cilgavimab and other monoclonal antibodies may be appropriate for a patient seeking pre- exposure protection.

Monoclonal antibodies are derived from patients with COVID-19 or from mice.17

Bamlanivimab/etesevimab18

Phase 2 BLAZE-1 trial showed significant reduction in viral load

Phase 3 BLAZE-1 trial showed 70% reduction in hospitalization or death

The FDA reported on January 24, 2022, that the NIH COVID-

19 Treatment Guidelines Panel recommended against the use of bamlanivimab and etesevimab (administered together) because of markedly reduced activity against the omicron variant and because real-time testing to identify rare, non-omicron variants is not routinely available.19

Casirivimab/imdevimab20

RCT of non-hospitalized patients had reduced viral load with safety

Phase 3 trial showed 70% reduction in hospitalization/death in non-hospitalized patients

The FDA reported on January 24, 2022, that the NIH COVID- 19 Treatment Guidelines Panel recommended against using REGEN-COV (casirivimab and imdevimab) because of markedly reduced activity against the omicron variant and because real-time testing to identify rare, non-omicron variants is not routinely available.19

Sotrovimab21

RCT Phase 3 trial COMET-ICE showed 79% reduction in hospitalization/death in high-risk non-hospitalized mild- moderate COVID-19 patients22

Bebtelovimab

Bebtelovimab is a monoclonal antibody that targets the S- protein of SARS-CoV-2 as found in the BLAZE-4 study.23,24 In February 2022, bebtelovimab received emergency use authorization by the FDA for the treatment of mild-to- moderate COVID-19.23-25 However, on November 30, 2022, the FDA announced bebtelovimab is not currently authorized for emergency use in the U.S., because it is not expected to neutralize Omicron subvarianta BQ.1 and BQ.1.1.26

Tocilizumab

Tocilizumab is an interleukin receptor inhibitor used in patients with COVID-19 pneumonia.27,28

Six RCTs were included in the analysis, and the primary outcome was a composite of mechanical ventilation or 28- day mortality, while the secondary outcomes were 28-day mortality and major adverse events.28 The analysis results showed that tocilizumab was associated with a statistically significant reduction in the primary composite outcome of mechanical ventilation or 28-day mortality, but not with a statistically significant reduction in 28-day mortality or rate of serious adverse events. Overall, the article concludes that

tocilizumab may be beneficial in reducing the incidence of mechanical ventilation or death in hospitalized patients with COVID-19 pneumonia.28

Anti-inflammatory drugs:

Dexamethasone

Inflammation in severe COVID-19 causes lung injury29

RECOVERY trial showed hospitalized patients had lower one- month mortality on ventilation or oxygen support; however, there was no benefit if they were receiving any respiratory support29

Due to the trial above, dexamethasone is the standard of care in hospitalized patients29

Immunomodulators:

Baricitinib

Janus kinase (JAK) inhibitor FDA labeled for rheumatoid arthritis (RA)

Phase 3 RCT showed an equal reduction in morbidity/mortality compared to the standard of care, including dexamethasone.

An option in case of intolerance

Tofacitinib

Another JAK inhibitor for RA

Small RCT showed lower respiratory failure and death in severe COVID-19

Treatments that Require Further Study

Hydroxychloroquine and chloroquine:30

RCTs showed no improvement in morbidity or mortality in hospitalized patients with or without azithromycin

Another RCT showed superiority in addition to remdesivir compared to remdesivir alone.

Lopinavir/ritonavir:31

FDA-approved for HIV

RCT showed no benefit in hospitalized patients with severe COVID-19

Ivermectin:

RCT showed no significant improvement in symptoms.32

However, a more recent meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was

5.74 days shorter in the case of ivermectin treatment compared to the control groups. More eligible studies are needed to increase the quality of evidence for using ivermectin to treat COVID-19.33

Convalescent plasma:34

Retrospective study showed lower death in hospitalized patients

Three small RCTs showed no significant morbidity or mortality reduction

In vitro studies also mixed

Interferon-β-1a:35

Interferons initiate immune response to viral infections, and the rationale for their use was that COVID-19 suppresses them

Clinical trial data is limited and mixed; therefore, it is not recommended

Anti-Interleukin-6 receptor antibodies:36

anakinra (Brand name: Kineret)37

FDA-approved for rheumatoid arthritis

Rationale based on interleukin, a cytokine

Small case series showed a reduction in ventilation and mortality in severe COVID-19 patients

Given low-quality data it is not recommended

Sarilumab and siltuximab:38

Same issue as anakinra

Ruxolitinib:39,40

RCT trial showed no significant reduction in mortality in mechanically ventilated patients with acute respiratory distress syndrome (ARDS)

A prospective study showed significant resolution in hyperinflammatory state; however, no significant difference in morbidity and mortality.

Acalabrutinib, ibrutinib, rilzabrutinib:

Small trials show a clinical benefit, but it is too early to recommend these drugs for the treatment of COVID-1941

Treatment Based on the Severity of COVID-19

As mentioned above, the NIH has classified COVID-19 into five types based on the severity of the symptoms: asymptomatic, mild, moderate, severe, and critical.9 The disease's severity partly drives treatment options and preferences.9,11,12

Asymptomatic or Presymptomatic

It is important for asymptomatic or presymptomatic patients to isolate as they can still transmit the virus despite not having symptoms.

Mild Illness

With mild COVID-19 illness, isolation and standard respiratory viral infection care are first and foremost. A patient should drink plenty of liquids, try to sleep well, and be monitored closely for COVID-19 symptoms. Patients and caregivers should practice hand washing, and clean often-touched surfaces, such as doorknobs, light switches, electronics, and counters, daily.42 Avoid sharing personal household items, such as dishes, towels, bedding, and electronics, such as phones.43

If the patient is at high risk, such as elderly or immunocompromised, then Paxlovid or remdesivir are recommended. If these are unavailable, another antiviral, e.g., molnupiravir can be used.44 Dexamethasone and bebtelovimab are not recommended, according to the NIH.26,45

The most common adverse effects of ritonavir-boosted nirmatrelvir (Paxlovid) are dysgeusia (disturbed taste), diarrhea, hypertension, and myalgia. Anaphylaxis and other hypersensitivity reactions have also been reported.46 If a patient has renal impairment, clearing nirmatrelvir will be

reduced. Patients with suspected renal impairment should have renal function testing to establish an appropriate dose for ritonavir-boosted nirmatrelvir. The dose should be reduced to nirmatrelvir 150 mg with ritonavir 100 mg twice daily in patients with moderate renal impairment (i.e., those with an estimated glomerular filtration rate [eGFR] of ≥30 to <60 mL/min).46

Adverse effects seen with remdesivir are gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time without a change in the international normalized ratio, and hypersensitivity reactions.47 Before starting a patient on remdesivir, the FDA recommends that the patient have an estimated glomerular filtration rate (eGFR), liver function, and prothrombin time tests as clinically appropriate and repeating these tests during treatment as clinically indicated.47

Common adverse effects of molnupiravir are diarrhea, nausea, and dizziness.48

Moderate Illness

With moderate COVID-19 illness, hospitalization is recommended, and healthcare staff must wear PPE while caring for patients.45 Intravenous fluids should be initiated if the patient is volume depleted, and oxygen should be given to maintain SpO2 greater than 96%. Antibacterial therapy can be started if there is suspicion of bacterial infection. If the patient is at risk of developing clots, then prophylactic anticoagulation medication should be initiated. Remdesivir and/or dexamethasone can be started if the patient requires oxygen.45

Toroghi, et al. (2022) reported that “[h]igher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone.”49 This is important because the potential side effects from dexamethasone can be severe: “Acute Kidney Injury (AKI), gastrointestinal (nausea, vomiting, gastrointestinal upset, bleeding), musculoskeletal (weakness, myopathy),

hepatic (rise in serum aminotransferases and bilirubin), endocrine (hyperglycemia), hematologic (leukocytosis, lymphopenia, thrombocytosis or thrombocytopenia), cardiovascular (bradycardia, cardiac arrhythmia, heart failure, hypertension, myocardial infarction, tachycardia), psychiatric and neurologic (depression, emotional lability, euphoria, headache, insomnia, malaise).”49 Moreover, patients on dexamethasone should be monitored for secondary infections and drug allergies. This may involve a multidisciplinary approach where a clinical pharmacist monitors the patients daily, with specialists (e.g., heart specialists) consulting depending on the complications.49

Severe Illness

Treating severe COVID illness has the same approach as moderate illness, with additional protocols, depending on clinical presentations.45 If renal failure occurs, it is vital to initiate replacement treatment. Instead of remdesivir, a combination of either baricitinib or tocilizumab plus dexamethasone is indicated if the disease progresses.50 Mean arterial pressure should be maintained between 60-65 mmHg using norepinephrine as the preferred vasopressor.

Baricitinib or tocilizumab are equally recommended for the management of COVID-19.45,51 However, Cherian, et al. (2022) reported that clinicians should consider baricitinib’s ease of administration, shorter half-life, and lower cost of treatment. They also reported that baricitinib had “better mortality data and other comparable efficacy and safety outcomes,” thereby causing them to favor baricitinib over tocilizumab.51

Combining dexamethasone and baricitinib or tocilizumab may increase the risk of opportunistic infections or the risk of reactivating latent infections.45 There is insufficient data to recommend initiating prophylaxis against these infections.45

Although vaccination is not part of the treatment covered in this course, it is interesting to note that several agents above are being used to prevent COVID-19 in patients that cannot receive a COVID-19 vaccination. Tixagevimab with cilgavimab can be used for adults and children at least 12 years old and 40 kg with:

No active COVID-19 infection and recent exposure

Plus one of the following

Moderate or severe immunocompromised

Vaccination contraindicated

COVID-19 Test to Treat

During the pandemic, pharmacies became testing centers; however, if a patient had a positive test, the patient was referred to his or her primary physician to get appropriate treatment, if necessary. Access to timely testing and treatment remained suboptimal once Paxlovid and other oral therapies became available. Given that COVID-19 treatment is time-sensitive, making testing and treating as easy as possible is important. “Test to Treat” became a priority to allow pharmacies to not only test patients for COVID-19 but to treat COVID-19 patients with prescription-only medication bypassing the need for the patient to leave the pharmacy to see a prescriber.52,53

In March 2022, the Test to Treat initiative was launched by the federal government, and now thousands of pharmacies, health centers, LTC facilities, and community sites. Patients can be tested at these sites or bring a positive test, and then if eligible, the patient will be prescribed Paxlovid or molnupiravir (Lagevrio).

Test-and-treat is evolving and has been tried for other conditions. One trial aimed to determine the effect of a test-and-treat to correct suboptimal vitamin D status. The trial evaluated the risk of all-cause acute respiratory tract infection and COVID-19. The trial included 6200 participants who were not taking vitamin D supplements at baseline. The participants were offered a finger prick test to reveal blood 25-hydroxyvitamin D (25(OH)D)

concentration. Participants were provided with vitamin D if their blood 25(OH)D concentration was low, while others received no testing or supplementation. The primary outcome was the proportion of participants with at least one acute respiratory tract infection of any cause and a secondary outcome was the proportion of participants with swab test confirmed COVID-

19. The results showed that the test-and-treat approach to vitamin D supplementation was not successfully associated with a reduction in the risk of all-cause, acute respiratory tract infection or COVID-19.54

Long COVID-19 Treatment

After acute COVID, COVID-related health issues may linger for years, even in asymptomatic patients.55 Health issues may be physiological and consist of multi-organ impairment. The lingering symptoms are called “long COVID,” “post-acute COVID syndrome,” “post-COVID-19 condition,” and “long-haul COVID-19.”55

There is no consensus on a definition for long COVID, but the WHO has stated that “Post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.”56 The National Institute for Health and Care Excellence (NICE) defined post-COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis.”57 As such, symptoms lingering during a four-to-twelve-week, post- COVID-19-onset period - that cannot be explained by an alternate diagnosis- are regarded as ongoing symptomatic, long COVID-19.55

Long COVID-19 symptoms include the following conditions:55

Lung impairment

36% experience shortness of breath

26% experience impairment such (as reduced lung capacity)

Myocarditis

68% palpitations

53% chest pain

31% POTS (Post Tachycardia Syndrome)

Gut microbial imbalance

Brain

1 in 3 patients report neuro-psych symptoms 6 months after infection

Metabolic issues

Kidney issues

35% reduced kidney function

Anywhere from 31% to 69% of COVID-19 patients experience long COVID, including the following symptoms:

29% fatigue

28% muscle pain, palpitations, cognitive impairment

27% anxiety

21% dyspnea

18% chest pain and arthralgia

Cognitive symptoms usually occur in long COVID. Also, long COVID can occur in hospitalized and non-hospitalized patients. A startling statistic is that less than 1% of COVID survivors get to complete recovery by 80 days after infection.55 The good news is in children, the long COVID statistics are less startling at 25.24% compared to up to 69% in the overall population. Also, the rates of various symptoms are lower and the biggest one is mood symptoms which is not clear whether it is from the virus or the restrictions during COVID.58

According to the NICE guideline, it is recommended to investigate long COVID at 4 weeks after symptoms.59 The following tests are recommended during this screening:55

Full blood count

Renal function test

C-reactive protein

Liver function test

Thyroid function

Hemoglobin A2C

Vitamin D

Magnesium

B12, folate, and ferritin levels

If the patient has cardiac symptoms, the following tests should be ordered:

Chest imaging

Electrocardiography

Pulmonary function tests

If a patient has trouble breathing or any pulmonary issues, the following treatments are recommended:55

Oxygen supplementation

Corticosteroids (if pneumonia is present)

It has been found that some patients have MCAS, mast cell activation syndrome, which warrants treatment with antihistamines. Since antihistamines are available over the counter, reports include misuse and elderly patients who have suffered from dementia due to antihistamines contributing to abnormal dopamine levels.55

Dietary supplements have been shown to be effective for long COVID, including the following:

Multivitamins improve symptoms55

Ginseng improves fatigue55

Coenzyme Q10 reduces fatigue and oxidative stress60

Dietary supplements under investigation:55

Vitamin B3 is being investigated for cognitive dysfunction/chronic fatigue

Omega 3 is also being investigated as an anti-inflammatory

Luteolin and quercetin under investigation. Luteolin is a flavinoid and is being researched for renal protection in individuals with COVID-19, and quercetin is an antiinflammatory flavinoid.61

Pre- and probiotics for GI issues

Medications that are being used to treat COVID-19 are also being investigated for long COVID since the immune system in long COVID is compromised, allowing for opportunistic infections. Azithromycin, remdesivir, and favipiravir are being investigated to control long COVID. Additionally, due to the inflammatory state, the following medications are being investigated for long COVID:55

Infliximab

Tocilizumab

Siltuximab

Anakinra

Leronlimab

Finally, antidepressants are being investigated to restore immune function by lessening peripheral inflammation. SSRIs like vortioxetine are being examined.55

Vaccination and male gender protect against long COVID.55 Females under 50 are five times more likely to develop long COVID.55 Meanwhile, comorbidities, such as diabetes and advanced age, increase the chance of long COVID.

COVID-19 Vaccine Update

Since vaccination is recommended to help people develop immunity as a preventative measure for COVID or long COVID, it is important to know that on April 18, 2023, the FDA updated its EUA for Moderna and Pfizer-BioNTech COVID-19 bivalent mRNA vaccines.62 Moderna and Pfizer-BioNTech COVID-19 bivalent mRNA vaccines are now authorized for individuals 6 months and older, including an additional dose or doses for certain populations, while the monovalent Moderna and Pfizer-BioNTech COVID-19 vaccines are no longer authorized for use in the United States.62 Most individuals who have not yet received a dose of a bivalent vaccine may receive a single dose, while most individuals who have already received a single dose of the bivalent vaccine are not eligible for another dose.62 Children between the ages of 6 months and 5 years may receive a two-dose series of the Moderna bivalent vaccine or a three-dose series of the Pfizer-BioNTech bivalent vaccine.62 The FDA will hold a meeting in June 2023 to discuss the strain composition of COVID-19 vaccines for fall 2023.62

Summary

COVID-19, unfortunately, is here to stay based on the epidemiological data over the past few years. It is important to understand that COVID-19 is not just a respiratory virus but an inflammatory virus that affects major organs in the body, including the brain, heart, kidney, and gut. Due to the systemic nature of this disease and the large range of severity, the treatment options also range considerably. This virus in young and healthy patients generally results in a flu-like illness. However, in the elderly with comorbidities, this virus has a significantly higher chance of hospitalization and death. This course outlined treatment protocols for COVID and for long COVID; however, the research in this field is changing every week. Therefore, clinicians must review the latest studies and publications and update themselves on the current guidance.

Course Test

Severe Acute Respiratory Distress Syndrome 2 (SARS-CoV-2) is a virus that

proved to be more deadly than Severe Acute Respiratory Distress Syndrome (SARS) in 2002.

proved to be more deadly than Middle East Respiratory Syndrome (MERS) in 2012.

can infect humans and animals.

has proven to be less transmissible than SARS or MERS.

The early stage of pneumonia associated with COVID-19 is marked by

viral replication causing tissue damage.

autoimmune response causing the release of cytokines.

liver damage.

renal failure.

COVID-19 can cause symptoms such as

fever and cough.

shortness of breath.

muscle pain

All of the above

A COVID-19 patient’s laboratory blood tests will show

decreased cardiac enzyme levels.

decreased D-dimer.

elevated C-reactive protein levels.

normal liver function.

Ritonavir/nirmatrelivir (Paxlovid) may decrease the risk of hospitalization or death by 89% if the drug is administered

any time before hospitalization.

within 3 days of COVID-19 symptoms.

within 10 days of COVID-19 symptoms.

within 7 days of COVID-19 symptoms.

The WHO SOLIDARITY Trial reported that remdesivir

substantially decreased mortality in hospitalized patients.

substantially decreased mechanical ventilation in hospitalized patients.

substantially decreased length of hospital stay.

had little or no effect on overall mortality, initiation of mechanical ventilation, and length of hospital stay.

True or False: Dexamethasone is the standard of care for treating inflammation in hospitalized COVID-19 patients.

True

False

Hospitalization is recommended for patients with

asymptomatic COVID-19.

mild COVID-19 illness.

moderate or greater COVID-19 illness.

a COVID-19 reinfection.

The Test to Treat program allows pharmacies to treat COVID-19 patients with prescription-only medication

so long as the prescribing physician provides an electronic prescription within 48 hours.

bypassing the need for the patient to leave the pharmacy to see a prescriber.

for hospitalized patients only.

for severe COVID-19 patients only.

Which of the following statements best describes a patient with long COVID?

A patient has long COVID if the patient had to be hospitalized.

A patient has long COVID if the patient is reinfected with SARS- CoV-2.

A patient has long COVID if the patient’s symptoms linger during a four-to-twelve-week, post-COVID-19-onset period and the symptoms cannot be explained by an alternate diagnosis.

A patient has long COVID if the patient’s symptoms move from asymptomatic to a moderate illness.

References

Pustake M, Tambolkar I, Giri P, Gandhi C. SARS, MERS and CoVID-19: An overview and comparison of clinical, laboratory and radiological features. J Family Med Prim Care. 2022;11(1):10-17. doi:10.4103/jfmpc.jfmpc_839_21

Shiels MS, Haque AT, Berrington de González A, Freedman ND. Leading Causes of Death in the US During the COVID-19 Pandemic, March 2020 to October 2021. JAMA Intern Med. 2022;182(8):883-886. doi:10.1001/jamainternmed.2022.2476

Centers for Disease Control and Prevention. National Center for Health Statistics Leading Causes of Death. CDC. 2023. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm. Accessed May 4, 2023.

Centers for Disease Control and Prevention. COVID-19. CDC. 2023. https://www.cdc.gov/coronavirus/types.html. Accessed May 4, 2023.

Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related?. Clin Microbiol Infect. 2020;26(6):729-734. doi:10.1016/j.cmi.2020.03.026

Valencak TG, Csiszar A, Szalai G, et al. Animal reservoirs of SARS-CoV- 2: calculable COVID-19 risk for older adults from animal to human transmission. Geroscience. 2021;43(5):2305-2320. doi:10.1007/s11357-021-00444-9

Nania R. What to Know About Arcturus, the Latest COVID Variant.

AARP. 2023. https://www.aarp.org/health/conditions-treatments/info-

2023/arcturus-new-covid-variant.html. Accessed May 4, 2023.

Murugan C, Ramamoorthy S, Kuppuswamy G, Murugan RK, Sivalingam Y, Sundaramurthy A. COVID-19: A review of newly formed viral clades, pathophysiology, therapeutic strategies and current vaccination tasks. Int J Biol Macromol. 2021;193(Pt B):1165-1200. doi:10.1016/j.ijbiomac.2021.10.144

Budinger GRS, Misharin AV, Ridge KM, Singer BD, Wunderink RG. Distinctive features of severe SARS-CoV-2 pneumonia. J Clin Invest. 2021;131(14):e149412. doi:10.1172/JCI149412

Wauters E, Van Mol P, Garg AD, et al. Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages. Cell Res. 2021;31(3):272-290. doi:10.1038/s41422-020-00455-9

National Institutes of Health. COVID-19 Treatment Guidelines. Clinical Spectrum of SARS-CoV-2 Infection. NIH. 2023. https://www.covid19treatmentguidelines.nih.gov/overview/clinical- spectrum/. Accessed May 4, 2023.

National Institutes of Health. COVID-19 Treatment. NIH. 2023. https://covid19.nih.gov/covid-19-treatments. Accessed May 4, 2023.

Mahase E. Covid-19: Pfizer's paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ. 2021;375:n2713. Published 2021 Nov 8. doi:10.1136/bmj.n2713

Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients [published correction appears in Clin Infect Dis. 2023 Mar 21;76(6):1158-1159]. Clin Infect Dis. 2023;76(3):e342-e349.

doi:10.1093/cid/ciac443

Gottlieb RL, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022;386(4):305-315. doi:10.1056/NEJMoa2116846

WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2021;384(6):497-511. doi:10.1056/NEJMoa2023184

Taylor PC, Adams AC, Hufford MM, de la Torre I, Winthrop K, Gottlieb RL. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol. 2021;21(6):382-393. doi:10.1038/s41577-021-00542-x

Nathan R, Shawa I, De La Torre I, et al. A Narrative Review of the Clinical Practicalities of Bamlanivimab and Etesevimab Antibody Therapies for SARS-CoV-2. Infect Dis Ther. 2021;10(4):1933-1947. doi:10.1007/s40121-021-00515-6

Coronavirus (COVID-19) Update: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant. January 20, 2022. https://www.fda.gov/news-events/press- announcements/coronavirus-covid-19-update-fda-limits-use-certain- monoclonal-antibodies-treat-covid-19-due-omicron. Accessed May 6, 2023.

Razonable RR, Pawlowski C, O'Horo JC, et al. Casirivimab-Imdevimab treatment is associated with reduced rates of hospitalization among high-risk patients with mild to moderate coronavirus disease-19. EClinicalMedicine. 2021;40:101102. doi:10.1016/j.eclinm.2021.101102

Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022;327(13):1236-1246. doi:10.1001/jama.2022.2832

Lokhandwala T, Acharya M, Farrelly E, Coutinho AD, Bell CF, Svedsater

H. Within-trial economic analysis of resource use from COMET-ICE: A phase 3 clinical trial evaluating sotrovimab for the treatment of patients with COVID-19 at high risk of progression. J Manag Care Spec Pharm. 2022;28(11):1261-1271. doi:10.18553/jmcp.2022.28.11.1261

Shertel T, Lange NW, Salerno DM, et al. Bebtelovimab for Treatment of COVID-19 in Ambulatory Solid Organ Transplant Recipients. Transplantation. 2022;106(10):e463-e464. doi:10.1097/TP.0000000000004278

Westendorf K, Žentelis S, Wang L, et al. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Rep. 2022;39(7):110812. doi:10.1016/j.celrep.2022.110812

U.S. Food and Drug Administration. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR BEBTELOVIMAB.

FDA. 2022. https://www.fda.gov/media/156152/download. Accessed May 4, 2023.

U.S. Food and Drug Administration. FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region. FDA. November 30, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces- bebtelovimab-not-currently-authorized-any-us-region. Accessed May 6, 2023.

Gupta S, Padappayil RP, Bansal A, Daouk S, Brown B. Tocilizumab in patients hospitalized with COVID-19 pneumonia: systematic review and meta-analysis of randomized controlled trials. J Investig Med. 2022;70(1):55-60. doi:10.1136/jim-2021-002001

Li G, Hilgenfeld R, Whitley R, De Clercq E. Therapeutic strategies for COVID-19: progress and lessons learned [published online ahead of print, 2023 Apr 19]. Nat Rev Drug Discov. 2023;1-27. doi:10.1038/s41573-023-00672-y

RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436

Kashour Z, Riaz M, Garbati MA, et al. Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis. J Antimicrob Chemother. 2021;76(1):30-42. doi:10.1093/jac/dkaa403

Amani B, Khanijahani A, Amani B, Hashemi P. Lopinavir/Ritonavir for COVID-19: a Systematic Review and Meta-Analysis. J Pharm Pharm Sci. 2021;24:246-257. doi:10.18433/jpps31668

Popp M, Stegemann M, Metzendorf MI, et al. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2021;7(7):CD015017. Published 2021 Jul 28. doi:10.1002/14651858.CD015017.pub2

Ragó Z, Tóth B, Szalenko-Tőkés Á, et al. Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection [published online ahead of print, 2023 Mar 7]. Geroscience. 2023;1-15. doi:10.1007/s11357-023-00756-y

Estcourt L, Callum J. Convalescent Plasma for Covid-19 - Making Sense of the Inconsistencies. N Engl J Med. 2022;386(18):1753-1754. doi:10.1056/NEJMe2204332

Davoudi-Monfared E, Rahmani H, Khalili H, et al. A Randomized Clinical Trial of the Efficacy and Safety of Interferon β-1a in Treatment of

Severe COVID-19. Antimicrob Agents Chemother. 2020;64(9):e01061-

20. Published 2020 Aug 20. doi:10.1128/AAC.01061-20

National Institutes of Health. COVID-19 Treatment Guidelines. Interleukin-6 Inhibitors. NIH. 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/immunomo dulators/interleukin-6-inhibitors/. Accessed May 4, 2023.

Pasin L, Cavalli G, Navalesi P, et al. Anakinra for patients with COVID- 19: a meta-analysis of non-randomized cohort studies. Eur J Intern Med. 2021;86:34-40. doi:10.1016/j.ejim.2021.01.016

Khan FA, Stewart I, Fabbri L, et al. Systematic review and meta- analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-

19. Thorax. 2021;76(9):907-919. doi:10.1136/thoraxjnl-2020-215266

Sarmiento M, Rojas P, Jerez J, et al. Ruxolitinib for Severe COVID-19- Related Hyperinflammation in Nonresponders to Steroids. Acta Haematol. 2021;144(6):620-626. doi:10.1159/000516464

Rein L, Calero K, Shah R, et al. Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome. Crit Care Med. 2022;50(12):1701-1713. doi:10.1097/CCM.0000000000005682

Kifle ZD. Bruton tyrosine kinase inhibitors as potential therapeutic agents for COVID-19: A review. Metabol Open. 2021;11:100116. doi:10.1016/j.metop.2021.100116

Ying Liu X, Zhang Y, Tu HX, Leck A. Cleaning and disinfection in health care settings during the COVID-19 outbreak. Community Eye Health. 2020;33(109):36-37.

Centers for Disease Control and Prevention. COVID-19. If You Are Sick or Caring for Someone. CDC. 2022. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are- sick/index.htmlAccessed May 6, 2023.

Vangeel L, Chiu W, De Jonghe S, et al. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res. 2022;198:105252. doi:10.1016/j.antiviral.2022.105252

National Institutes of Health. COVID-19 Treatment Guidelines. Therapeutic Management of Hospitalized Adults With COVID-19. NIH. 2023.

https://www.covid19treatmentguidelines.nih.gov/management/clinical- management-of-adults/hospitalized-adults--therapeutic-management/. Accessed May 6, 2023.

National Institutes of Health. COVID-19 Treatment Guidelines. Ritonavir-Boosted Nirmatrelvir (Paxlovid). NIH. 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals- including-antibody-products/ritonavir-boosted-nirmatrelvir--paxlovid-/. Accessed May 6, 2023.

National Institutes of Health. COVID-19 Treatment Guidelines. Remdesivir. NIH. 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals- including-antibody-products/remdesivir/. Accessed May 6, 2023.

National Institutes of Health. COVID-19 Treatment Guidelines. Molnupiravir. NIH. 2023. https://www.covid19treatmentguidelines.nih.gov/therapies/antivirals- including-antibody-products/molnupiravir/. Accessed May 6, 2023.

Toroghi N, Abbasian L, Nourian A, et al. Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial. Pharmacol Rep. 2022;74(1):229-

240. doi:10.1007/s43440-021-00341-0

Wong CKH, Lau KTK, Au ICH, et al. Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone. Front Pharmacol. 2022;13:866441. Published 2022 May 30. doi:10.3389/fphar.2022.866441

Cherian JJ, Eerike M, Bagepally BS, Das S, Panda S. Efficacy and safety of baricitinib and tocilizumab in hospitalized patients with COVID-19: A comparison using systematic review and meta-analysis. Front Pharmacol. 2022;13:1004308. Published 2022 Oct 14. doi:10.3389/fphar.2022.1004308

Wroe EB, Seung KJ, Baker BK, Farmer PE. Test and treat: a missing link in the global fight against COVID-19. Lancet Glob Health. 2022;10(2):e181-e182. doi:10.1016/S2214-109X(21)00568-4

U.S. Health and Human Services, Administration for Strategic Preparedness and Response. Test to treat. ASPR-HHS. 2022. https://aspr.hhs.gov/TestToTreat/Pages/default.aspx. Accessed May 4, 2023.

Jolliffe DA, Holt H, Greenig M, et al. Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT). BMJ. 2022;378:e071230. Published 2022 Sep 7. doi:10.1136/bmj-2022-071230

Koc HC, Xiao J, Liu W, Li Y, Chen G. Long COVID and its Management. Int J Biol Sci. 2022;18(12):4768-4780. Published 2022 Jul 11. doi:10.7150/ijbs.75056

Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV; WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102-e107. doi:10.1016/S1473- 3099(21)00703-9

NICE. COVID-19 rapid guideline: managing the long-term effects of COVID-19. Manchester: National Institute for Health and Care Excellence. 2020.

Lopez-Leon S, Wegman-Ostrosky T, Ayuzo Del Valle NC, et al. Long- COVID in children and adolescents: a systematic review and meta- analyses. Sci Rep. 2022;12(1):9950. Published 2022 Jun 23. doi:10.1038/s41598-022-13495-5

COVID-19 rapid guideline: managing the long-term effects of COVID-

19. London: National Institute for Health and Care Excellence (NICE); December 18, 2020.

Barletta MA, Marino G, Spagnolo B, et al. Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome [published online ahead of print, 2022 Aug 22]. Clin Exp Med. 2022;1-12. doi:10.1007/s10238-022-00871-8

Diniz LRL, Elshabrawy HA, Souza MTS, Duarte ABS, Madhav N, de Sousa DP. Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries. Biomolecules. 2022;12(11):1544. Published 2022 Oct 23. doi:10.3390/biom12111544

U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Changes to Simplify Use of Bivalent mRNA COVID-19 Vaccines. 2023. https://www.fda.gov/news-events/press- announcements/coronavirus-covid-19-update-fda-authorizes-changes- simplify-use-bivalent-mrna-covid-19-vaccines. Accessed May 4, 2023.

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses are constantly changing, and any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course, or course material.

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