Management of Outpatient COVID-19: Best Practices in Patient Assessment and Treatment

Educational Objectives

The goal of this program is to improve the management of outpatient COVID-19. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate patients with COVID-19 who may be evaluated remotely from those who should be seen in-person.
2. Identify risk factors for increased mortality in patients with COVID-19.
3. Select medications for outpatient treatment of COVID-19.

Summary

Components of COVID-19 management: a systems approach for management of COVID-19 may lead to superior outcomes for patients; clinics should make available patient-facing educational information, initial telephone triage, and telehealth evaluation; evaluation should consist of, eg, clinical status assessment, review of tests; patients should also be able to make in-person visits for, eg, evaluation, imaging, laboratory testing, intravenous therapy

U.S. National Institute of Health (NIH) practice recommendations: patients suspected of having COVID-19 should be triaged via telehealth before an in-person evaluation, to impede the spread of infection; a greater number of patients may be evaluated through telehealth consultations; however, a capacity for in-person evaluation of patients at high-risk or with severe symptoms (eg, dyspnea, hypoxemia) should be maintained

Initial evaluation: Stokes et al (2020) found that 81% of patients with COVID-19 (prior to vaccination) had mild symptoms and absence of viral pneumonia and hypoxemia; management in outpatient settings or at home is appropriate

Diagnosis: symptoms are similar to those of the flu, eg, muscle pain, fatigue, headache, fever, cough; anosmia and ageusia distinguishes COVID-19 from the flu; however, anosmia and ageusia were rare among patients with early omicron variants; rash and conjunctivitis are rarely seen in patients with COVID-19; individual symptoms have poor specificity and poor sensitivity, excepting anosmia and ageusia, which have high specificity

Testing: rapid at-home antigen tests are less sensitive than polymerase chain reaction (PCR) tests or nucleic acid amplification tests; a negative test does not rule out COVID-19; treatment should be initiated after positive results from a rapid at-home test; PCR tests are the gold standard for testing, and patients who repeatedly test negative or have mild symptoms should submit a sample for PCR testing; repeat testing after a positive test is of limited use; the Centers for Disease Control recommends symptom-based treatment planning, as opposed to test-based planning; antibody testing is not recommended in acute settings

Symptom Assessment: clinicians are able to understand the trajectory and evolution of the illness when patients are able to report for how many days they have had symptoms; patients who report shortness of breath should be asked whether they measure oxygen saturation at home; additional symptoms that are relevant are, eg, reports of confusion by family members, dizziness, history of falling, leg swelling (bilateral or unilateral), chest pain (pleuritic or exertional), nausea, vomiting, diarrhea; social support and health literacy of patients may be relevant

Dyspnea: the most common morbid condition in patients with COVID-19; may be mild, severe, or worsening; provider should differentiate cough from dyspnea; the functional effects of dyspnea (eg, the ability to do housework, climb stairs) should be recorded; respiratory rate and effort during video or in-person conversation should be assessed; pulmonary embolism must be considered in patients with COVID-19 presenting with dyspnea and pleuritic chest pain; COVID-19 causes hypercoagulability; patients with dyspnea should also be evaluated for deep vein thrombosis; most guidelines suggest an oxygen saturation <94% indicates hypoxemia; however, pulse oximetry is not reliable for Black patients; Lipnick et al (2016) listed the most accurate pulse oximeters

Risk assessment: data generated at the beginning of the pandemic focused on age; the mortality risk increases in patients >55 yr of age, and is highest in patients >85 yr of age; data from China found that cardiovascular disease was the most significant comorbidity in predicting mortality; the risk for death from COVID-19 increases as the numbers of comorbidities increases; age is the most important risk factor for mortality

Other risk factors: Cottini et al (2021) found a hazard ratio of 5.83 in patients with body mass index (BMI) >25; patients with a high BMI are more likely to suffer adverse consequences than patients who are not obese; a recent meta-analysis found that the recommendations for pregnant patients vary; pregnant patients should have an oxygen saturation >95%; Black and Latinx patients in the U.S. have a disproportionately high rate of hospitalization, which is likely the result of the social determinants of health rather than a susceptibility to COVID-19; Yehia et al (2020) found that after controlling for social factors (eg, insurance, neighborhood deprivation, accessibility of care), there was no significant difference in risk for mortality from COVID-19 between Black and White patients

Hospitalization: the NIH states that patients with COVID-19 should be hospitalized if their oxygen saturation <94%, respiratory rate is elevated, or lung infiltrates are >50%; patients who are dehydrated from vomiting or diarrhea, those with acute mental status changes, or hypotensive are recommended to go to the emergency department; the CURB-65 score for pneumonia severity may be used to determine the need for hospitalization; patients with, eg, dyspnea, multiple risk factors, concerning symptoms that do not indicate COVID-19, needing laboratory testing, should be seen in-person

Medications to stop: angiotensin-converting enzyme inhibitors, statins, non-steroidal anti-inflammatory drugs, and corticosteroids (oral, inhaled, or intranasal) may be continued; patients with HIV do not need to alter their antiretroviral regimen; patients should avoid the use of nebulized medications in the presence of others

Medications to start: systemic steroids should not be used in cases of COVID-19; may be used for patients in the hospital who are hypoxemic; anticoagulants and antiplatelet therapy should not be prescribed in the outpatient setting; do not use chloroquine or hydroxychloroquine with or without azithromycin; the NIH recommends against the use of colchicine for the treatment of patients who are not hospitalized; use of antibiotics is seldom necessary, as cases of bacterial superinfection are rare; antibiotics for pneumonia may be considered in cases of ‘double sickening’ or if there is a new infiltrate on chest x-ray after resolution of initial viral symptoms; the NIH treatment panel recommends against the use of ivermectin for treatment of COVID-19

Outpatient therapeutics: appropriate for patients who, eg, are <50 yr of age, belong to ethnic minorities, have a BMI >25, are diagnosed for depression, use tobacco; the available drugs are nirmatrelvir-ritonavir (Paxlovid), molnupiravir, remdesivir, bebtelovimab, high-titer convalescent plasma

Nirmatrelvir-ritonavir: first-line outpatient treatment for COVID-19; a combination of oral protease inhibitors; treatment should be initiated ≤5 days of onset of symptom; patients with reduced renal function may request a renal dose from the pharmacy; not recommended for patients who are renally insufficient (glomerular filtration rate <30 mL/min), or their hepatic impairment is categorized as Child-Pugh class C; Hammond et al (2022) found that nirmatrelvir-ritonavir reduced hospitalizations by 89% in patients who were not vaccinated, with one risk factor for COVID-19, compared with placebo (0.7% vs 6.5% rate of hospitalization); the Child-Pugh score is an efficient tool for assessing the prognosis of liver disease; nirmatrelvir-ritonavir has a high number of drug interactions; use of the University of Liverpool Drug Interaction Checker is recommended; nirmatrelvir-ritonavir is a CYP3A enzyme inhibitor and a CYP3A substrate; the efficacy of hormonal contraception is reduced by nirmatrelvir-ritonavir and adverse effects (eg, temporary dysgeusia, diarrhea, hypertension, nausea) are possible; the safety for pregnant or lactating women has not been established

COVID-19 ‘rebound’: the recurrence of symptoms after a negative COVID-19 test (in a patient who formerly tested positive); patients should isolate for 5 days; the disease often resolves on its own; medications or hospitalization is not likely to be required

Molnupiravir: second-line treatment; Bernal et al (2022) found molnupiravir reduced the risk for hospitalization or death in patients with COVID-19 by 31%; dose adjustment for patients with hepatic or kidney disease is not required; no known drug interactions; contraindicated in patients <18 yr of age and pregnant women (because of fetotoxicity); distribution of COVID-19 drugs is irregular; prescription rates are lower in ZIP codes with high rates of social vulnerability, compared with areas of low social vulnerability

Remdesevir: Gottlieb et al (2022) found remdesevir reduces hospitalization rates by 87%; 3 intravenous (IV) treatments, which last 3 hr, are required; may be administered ≤7 days after onset of symptoms; associated with minimal direct adverse effects; nausea is rarely reported; may be given to patients who are pregnant

Bebtelovimab: monoclonal antibody therapy; IV-administered in a single dose; clinical data supporting the efficacy bebtelovimab is not available; sotrovimab, casirivimab-imdevimab, bamlanivimab-etesevimab are not effective against the Omicron variants BA.1 and BA.2; bebtelovimab is generally well tolerated, but patients may experience brief shivers on infusion

Other COVID therapeutics: clinical data supporting the efficacy of vitamin C, vitamin D, or zinc is not available; vitamin C should not be taken in excessive doses; insufficient data is available on the efficacy of fluvoxamine; Ramakrishnan et al (2021) found inhaled budesonide reduced hospitalization in patients with mild COVID-19; currently not recommended by the Infectious Disease Society of America and the NIH inhaled; the Food and Drug Administration has approved pharmacists to prescribe oral antiviral drugs; COVID-19 drugs are now widely available in urban areas

Readings

Abd-Elsayed A, D’Souza R. The burden of coronavirus disease 2019–related cases, hospitalizations, and mortality based on vaccination status and mandated mask use: statewide data from Wisconsin and narrative review of the literature. Anesthesia & Analgesia. 2022; 134 (3): 524-531. doi: 10.1213/ANE.0000000000005858. View Article; Douillet, Delphine, Penaloza, Andrea, MD, PhD, et al. Outpatient management of patients with COVID-19: multicenter prospective validation of the hospitalization or outpatient management of patients with SARS-CoV-2 infection rule to discharge patients safely. Chest. 2021;160(4):1222-1231. doi:10.1016/j.chest.2021.05.008. View Article; Mak PQ, Chung KS, Wong JS, Shek CC, Kwan MY. Anosmia and ageusia: not an uncommon presentation of COVID-19 infection in children and adolescents. Pediatr Infect Dis J. 2020;39(8):e199-e200. doi:10.1097/INF.0000000000002718. View Article; Marzolini, Catia, Kuritzkes, Daniel, Marra, Fiona, et al. Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid) and comedications. Clin Pharmacol Ther. 2022; doi:10.1002/cpt.2646. View Article; Molnupiravir in unvaccinated patients with COVID-19.Drug and Therapeutics Bulletin. 2022; 60 (3): 35. doi: 10.1136/dtb.2022.000002. https://www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-conditions-use-conditions_en.pdf View Article; 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. View Article; Sharafeldin N, Bates B, Song Q, et al. Outcomes of COVID-19 in patients with cancer: report from the national COVID cohort collaborative (N3C). Journal of Clinical Oncology. 2021; 39 (20): 2232-2246. doi: 10.1200/JCO.21.01074. View Article; Samim M, Dhar D, Singh V, et al. CoRe study: COVID-19 and remdesivir: an insight into the current health planning and policy. Journal of Family Medicine and Primary Care. 2022; 11 (8): 4671-4687. doi: 10.4103/jfmpc.jfmpc_2368_21. View Article; Wienhold J, Mösch L, Rossaint R, et al. Teleconsultation for preoperative evaluation during the coronavirus disease 2019 pandemic. European Journal of Anaesthesiology. 2021; 38 (12): 1284-1292. doi:10.1097/EJA.0000000000001616. View Article; Yehia BR, Winegar A, Fogel R, et al. Association of race with mortality among patients hospitalized with coronavirus disease 2019 (COVID-19) at 92 US hospitals. JAMA Netw Open. 2020;3(8):e2018039. Published 2020 Aug 3. doi:10.1001/jamanetworkopen.2020.18039. View Article; Yilmaz S, Sapci I, Jia X, et al. Risk factors associated with postoperative mortality among COVID-19 positive patients: results of 3,027 operations and procedures. Annals of Surgery. 9900; Publish Ahead of Print doi: 10.1097/SLA.0000000000005722. View Article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Nadler was recorded at UCSF CME Essentials of Primary Care: A Core Curriculum for Ambulatory Practice 2022, held July 31 to August 5, 2022, and presented by the University of California, San Francisco School of Medicine. For information about upcoming CME activities from the University of California, San Francisco School of Medicine, visit meded.ucsf.edu/continuing-education. Audio Digest thanks the speakers and the presenters for their cooperation in the production of this program.

CME/CE INFO

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Lecture ID:

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