Clinical guideline highlights for the hospitalist: Management of COVID-19
Abstract
GUIDELINE TITLE: 2023 IDSA Guidelines on the Treatment and Management of Patients with COVID-19
RELEASE DATE: 06/26/2023
PRIOR VERSION (S): 2021
DEVELOPER: Infectious Diseases Society of America
FUNDING SOURCE: Infectious Diseases Society of America
TARGET POPULATION: Patients with COVID-19 Infection
INTRODUCTION
In March 2020, the World Health Organization designated COVID-19, induced by SARS-CoV-2, as a global pandemic, with over 770 million cases and approximately 7 million fatalities worldwide to date.1, 2 New viral strains have repeatedly stressed healthcare systems, necessitating models to predict patient needs, including prolonged hospital stays and increased oxygen and staffing requirements.3 Effective inpatient management of COVID-19 is crucial to improve patient outcomes and reduce hospital burden.4, 5 In May 2021, the Infectious Diseases Society of America (IDSA) released its initial guidelines for managing acute COVID-19 infection. With the ongoing evolution of research, these guidelines have been iteratively updated; however, the pace of change has significantly slowed since the peak of the pandemic. This slowdown marks an opportune moment for this article, which provides an up-to-date overview of the latest inpatient medication management for acute COVID-19 respiratory infections as per the IDSA's June 2023 revision.6
KEY RECOMMENDATIONS FOR THE ADULT HOSPITALIST
Recommendation 1: Categorize hospitalized patient with COVID-19 by illness severity.
The IDSA guidelines utilize patient severity to determine medication management. Below are the suggested severity categorizations for hospitalized patients.
Mild to Moderate Illness: SpO2 >94% on room air, or those not requiring oxygen.
Severe Illness: SpO2 ≤94% on room air, including those who require oxygen.
Critical Illness: Requiring ventilatory support, ECMO, including those with end organ dysfunction/ARDS—not addressed in this Clinical Guideline.
RECOMMENDATIONS FOR THE TREATMENT OF PATIENTS WITH MILD TO MODERATE COVID-19 ILLNESS
Recommendation 2: A 3-day course of Remdesivir is suggested for these patients, initiated within 7 days of symptom onset, with the decision supported by low certainty of evidence. Of note, the use of systemic glucocorticoids (as summarized in Table 1) is suggested against with low certainty of evidence.
| Mild to moderate illness | Severe illness | |
|---|---|---|
| Definition | Hospitalized, O2 saturation >94% | Hospitalized, O2 saturation ≤94% on room air, or with any supplemental oxygen use |
| Recommended treatments | ||
| Glucocorticoids | Suggested against use | Dexamethasone 6 mg IV or PO for 10 days or until dischargea |
| Antivirals | Remdesivir 200 mg on Day 1 and 100 mg on Days 2–3 for total course of 3 days or until dischargeb | Remdesivir 200 mg on Day 1 and 100 mg on Days 2–5 for total course of 5 days or until dischargeb |
| Janus kinase inhibitors | Not applicable | Baricitinib 4 mg per day or Tofacitinib 10 mg BID up to 14 days or until discharge, used with glucocorticoids or Remdesivir |
| Interleukin-6 inhibitors | Not applicable | Tocilizumab 8 mg/kg once or Sarilumabc 400 mg once, used with glucocorticoids |
- a If dexamethasone unavailable, can use equivalent glucocorticoid dosing.
- b Remdesivir dosing must be initiated within 7 days of symptom onset.
- c Sarilumab to be used if Tocilizumab unavailable in progressive severe illness.
RECOMMENDATIONS FOR THE TREATMENT OF PATIENTS WITH SEVERE COVID-19 ILLNESS
Recommendation 3: Glucocorticoids are suggested for patients with severe but noncritical illness based on moderate certainty of evidence.
Recommendation 4: A 5-day course of Remdesivir is also suggested for these patients, with the decision supported by moderate certainty of evidence. Remdesivir has not shown benefit in patients who require mechanical ventilation, and is therefore not recommended in such patients.
Recommendation 5: Janus Kinase Inhibitors, specifically Baricitinib or Tofacitinib, are suggested for use in severe illness. Baricitinib is recommended with moderate certainty of evidence when used alongside corticosteroids and with low certainty of evidence when used with Remdesivir alone. However, its benefit significantly decreases if the patient requires mechanical ventilation. For Tofacitinib, the evidence of benefit is low; it requires consideration for prophylactic anticoagulation and should not be used concurrently with interleukin (IL)-6 inhibitors.
Recommendation 6: In patients with progressive severe COVID-19 with elevated inflammatory markers (such as C-reactive protein [CRP] >75 mg/L), the use of tocilizumab along with glucocorticoids is recommended with low certainty of evidence over glucocorticoids alone. When tocilizumab is not available, sarilumab can be utilized with very low certainty of evidence.
EVALUATE FOR AND APPROPRIATELY TREAT BACTERIAL CO-INFECTIONS
In a systemic review and meta-analysis of 49 studies from multiple countries, 26.8% of patients with COVID-19 infection had a concomitant bacterial infection, despite an estimated 74.6% being started on antibiotics during their hospitalization.7 This data showed an increasing prevalence of bacterial co-infections from 2020 to 2022 with an even higher prevalence in patients admitted in critical care settings.
The guidelines suggest limiting antibiotic use in mild to severe cases of COVID when able and utilizing a steady CRP (indicating COVID infection alone) to de-escalate antibiotics and improve antibiotic stewardship. The guidelines do not specifically address laboratory workup, but suggest CRP as a potential marker to guide antibiotic de-escalation. This recommendation stems from the pattern that CRP levels decrease with antibiotic treatment in community acquired pneumonia, whereas they remain elevated in COVID-19 without co-infection.6
SPECIAL CONSIDERATION FOR IMMUNOCOMPROMISED PATIENTS WITH COVID-19 ILLNESS
The IDSA suggests against the use of convalescent plasma for both immunocompetent and immunocompromised patients. However, they note that convalescent plasma may be considered for hospitalized, immunocompromised patients who do not qualify for other treatments, after discussion of the risks and benefits.
MEDICATIONS NO LONGER RECOMMENDED FOR ANY STAGE OF ILLNESS IN PATIENTS HOSPITALIZED WITH COVID-19
The IDSA Guidelines recommend against the use of the following treatments for any severity of illness for hospitalized patients: convalescent plasma in immunocompetent patients, ivermectin, anakinra, famotidine alone, colchicine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir.
In addition, the current guidelines recommend against the use of neutralizing antibodies due to resistance. Specifically, authorization for emergency use of bebtelovimab was withdrawn due to reduced susceptibility. Tixagevimab/cilgavimab and casirivimab/imdevimab were discontinued for being inactive against the Omicron variant. Lopinavir/ritonavir is not recommended for hospitalized patients due to moderate evidence showing a lack of benefit.
CONSIDERATIONS FOR THE PEDIATRIC HOSPITALIST
Children generally have lower rates of COVID-19 hospitalizations and often experience asymptomatic infections. However, they are still at risk for serious illness. Comorbidities including medical complexity, genetic conditions, Type 1 Diabetes Mellitus, Congenital Heart Defects, and obesity all put children at higher risk of hospitalization. While many of the aforementioned recommendations for treatment of COVID-19 infection have not been separately studied in pediatric populations, the IDSA notes the following considerations: the use of remdesivir showed low adverse rates, while corticosteroids were shown to have a similar risk benefit ratio to adults. The use of janus kinase inhibitors is suggested for use in children; however, the risk to benefit ratio of baricitinib has not been studied in children. While tofacitinib has been evaluated for use in children with Juvenile Idiopathic Arthritis, the specific benefit of use for children with COVID-19 has not been elucidated. Data remains inconclusive regarding IL-6 inhibitor use in children with COVID-19 infection.
CRITIQUE
The initial IDSA guidelines were developed through a rapid systematic review, a crucial approach given the urgent context of the pandemic. While essential for timely guidance, the nature of this rapid review meant that recommendations could quickly become outdated as new evidence emerged. Subsequent updates incorporated emerging evidence, capturing key findings and potential treatments. Later iterations applied evidence-based medicine to refine these guidelines into a dynamic, living document. The findings in the guideline were specifically chosen to be largely generalizable, although the recommendations remain difficult to extrapolate to children due to lack of evidence in this population.
AREAS IN NEED OF FUTURE STUDY
Although initially a promising therapeutic intervention, neutralizing antibodies are no longer recommended due to increased resistance of recent COVID-19 strains. Future studies in this area may provide insight as variants continue to emerge. Distinguishing COVID-19 infections alone from bacterial co-infections is an additional area of study, with some evidence showing that utilizing CRP, WBC, and Procalcitonin may help distinguish appropriate timing for de-escalation of antibiotics. Additionally, many recommendations have been extrapolated to the pediatric population rather than direct study. This remains an opportunity for future study.
OTHER RESOURCES
IDSA Guideline on COVID-19 Management: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#BacterialCo-InfectionsandAntibioticUse.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
