Recommendation 1: hydroxychloroquine/chloroquine in the context of a clinical trial. (Knowledge gap)

Recommendation 2: hydroxychloroquine/chloroquine plus azithromycin only in the context of a clinical trial. (Knowledge gap)

Recommendation 3: the combination of lopinavir/ritonavir only in the context of a clinical trial. (Knowledge gap)

Recommendation 4: COVID-19 pneumonia, the IDSA guideline panel suggests against the use of corticosteroids.

Recommendation 5: ARDS due to COVID-19, the IDSA guideline panel recommends the use of corticosteroids in the context of a clinical trial. (Knowledge gap)

Recommendation 6: tocilizumab only in the context of a clinical trial. (Knowledge gap)

Recommendation 7: COVID-19 convalescent plasma in the context of a clinical
trial. (Knowledge gap)

RESULTS OF RECOMMENDATION 1 and 2

• HCQ failed to demonstrate a beneficial effect of HCQ on clinical progression of COVID-19 or on viral clearance by PCR tests
• Addition of azithromycin to HCQ provided indirect comparisons of failure of virologic clearance to historical controls.
• HCQ+AZ experienced numerically fewer cases of virologic failure
• Relying on intermediary outcomes, such as viral clearance to determine patient-important outcomes add another layer of imprecision.
• HARM: significant QT prolongation in 10 of 95 treated patients. Hence, Baseline and follow-up ECG monitoring would be indicated.
• Conclusions and research needs for this recommendation: The guideline panel recommends that the use of HCQ or the HCQ+AZ combination only be used in the context of a clinical trial.

RESULTS OF RECOMMENDATION 3

• No effect on mortality and clinical improvement
• Side effects: (GI and skin)
• anorexia, nausea, abdominal discomfort, or diarrhoea, as well as two serious adverse episodes of acute gastritis.
• Self-limited skin eruptions
• Conclusions and research needs for this recommendation: The guideline panel recommends the use of lopinavir/ritonavir only in the context of a clinical trial.

RESULTS OF RECOMMENDATION 4 and 5

• Delayed viral clearance associated with corticosteroid use.
• One small RCT in 24 patients using lower dose methylprednisolone for two days showed possible improvement of ARDS; however, two larger trials showed little or no effect in critically ill patients with pulmonary failure.
• Small subset of patients progresses from COVID-19 pneumonia to develop ARDS.
• Based on limited data from other coronaviruses, there is no clear benefit and potential harm from corticosteroids.
• If a person is on a steroid (inhaled or systemic) for another indication (e.g., asthma), the steroid should be continued.

RESULTS OF RECOMMENDATION 6

• Tocilizumab may have reduced mortality since there were no deaths reported
• Patients receiving tocilizumab are often at an increased risk of serious infections (bacterial, viral, invasive fungal infections, and tuberculosis) and hepatitis B reactivation
• Elevated IL-6 levels seen in inflammatory states have been shown to inhibit these enzymes thereby slowing the metabolism of drugs through these pathways
• Administration of IL-6 inhibitors like tocilizumab may result in enhanced metabolism in drugs utilizing the cytochrome P450 system

RESULTS OF RECOMMENDATION 7

• This looks benefecial
• Compared with a 30% mortality rate in the historical control (3/10), no deaths were reported among patients receiving COVID-19 convalescent plasma.
• No. serious adverse reactions or safety events were recorded following COVID-19 convalescent transfusion.
• Continuation of mechanical ventilation was used as a surrogate for failure of clinical improvement
• Given the limited information provided about time of extubation, the panel recognized an additional knowledge gap with the assessment of this outcome.

SOURCE:

Last updated April 11, 2020 at 10:58 AM EDT and posted online at http://www.idsociety.org

Article name: Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 Infection.

Please check website for most updated version of these guidelines.