COVID-19 Treatment
Clarissa Chan, PharmD
At the beginning of the pandemic, the world was desperate to find therapies that could improve outcomes in patients with COVID-19. The urgency brought repurposed drugs into the spotlight, but studies were poorly designed with many limitations and biases.
“Good patient outcomes were attributed to the investigational drug, while bad patient outcomes were attributed to the disease,” said Jefferson Cua, PharmD, BCIDP, infectious diseases and antimicrobial stewardship pharmacist at Baptist Health South Florida in Miami. “Some failed to acknowledge that good outcomes may come from supportive therapy alone or that bad outcomes could be due to drug toxicity,” Cua said.
Landmark studies such as the REMAP-CAP and RECOVERY trials have provided more insight into the novel therapeutic management and treatment of COVID-19 to guide recommendations from NIH and the Infectious Diseases Society of America (IDSA). For evidence-based guidance on management of COVID-19, Cua said he relies heavily on the NIH and IDSA guidelines to ensure that only patients who meet certain criteria receive the appropriate therapy.
“Many of the recommendations in either the IDSA or NIH guidelines are relatively ‘weak’ compared to clinical guidelines for other disease states,” said David Butler, PharmD, BCPS, AAHIVP, assistant professor at Albany College of Pharmacy and Health Sciences in New York. “The strongest recommendations are often what not to do.”
“The panel of experts behind the NIH and IDSA guidelines reconcile the available data and present a consensus recommendation,” said Cua. Likewise, Butler said that the strength of the recommendations appropriately reflects the quality of evidence available for patient benefit or potential patient harm.
Current management of COVID-19
In both NIH and IDSA guidelines, disease severity is a key determinant in the pharmacotherapeutic management of COVID-19.
“Early in the disease course, use of anti-SARS-CoV-2 monoclonal antibodies in high-risk patients may neutralize the virus before it can cause significant disease, but once a patient is sick enough to be hospitalized, the infection has progressed to the point that use is no longer anticipated to be beneficial,” said Kellie J. Goodlet, PharmD, BCPS, BCIDP, assistant professor of pharmacy practice at Midwestern University in Glendale, Arizona.
Similarly, in the early stages of mild COVID-19 illness, corticosteroid use is not advised because a patient’s own immune system response is important in the fight against the virus. However, in severe disease, dexamethasone use is one of the guidelines’ strongest recommendations and has been shown to improve survival, Goodlet said.
“COVID-19 illness is much more complicated than a simple disease caused by viral infection,” said Cua. “Later in the disease course, immune system dysregulation may play a bigger role, as immunomodulating agents such as steroids and interleukin-6 (IL-6) antagonists may improve outcomes.”
NIH and IDSA guideline differences
A notable difference relates to recommendations for remdesivir use. While both guidelines support use among inpatients requiring supplemental oxygen, NIH guidelines do not recommend for or against use in hospitalized patients who do not require supplemental oxygen or routine use in patients requiring mechanical ventilation because of a lack of data showing benefit at this advanced stage of diseases, said Goodlet.
In contrast, IDSA’s recommendations for remdesivir use would be anticipated to encompass virtually all inpatients, including any with 94% oxygen saturation on room air or lower and those receiving mechanical ventilation or extracorporeal membrane oxygenation.
“With many hospitals adopting or considering implementation of remdesivir restriction criteria, the NIH guidelines may provide increased guidance on which patients may be less likely to benefit from remdesivir therapy,” said Goodlet.
Pharmacists can help
Pharmacists should educate patients and encourage them to get vaccinated. They can also make a difference by upholding antimicrobial stewardship principles. There has been an increase in use of antibiotic therapy despite several studies suggesting that the incidence of bacterial coinfection in COVID-19 patients is low.
“Pharmacists can help provide information to providers and encourage use of lab testing such as procalcitonin and methicillin-resistant Staphylococcus aureus (MRSA) screening tests to help de-escalate antibiotics,” said Cua.
“There should not be a ‘one-size-fits-all’ approach to treating patients with COVID-19,” Cua added. Factors such as severity of illness, disease stage, and labs such as inflammatory markers should guide therapy, he said.
“Because some immunomodulating agents such as steroids and IL-6 antagonists like tocilizumab have been shown to have mortality benefits, this may be misconstrued to be routine use in all COVID-19 patients. Overuse in patients who do not meet criteria can lead to patient harm, such as increased risk for infections,” said Cua.
NIH currently recommended therapeutic management of patients with COVID-19
Nonhospitalized with mild to moderate COVID-19:
- Low risk for disease progression: supportive care and symptomatic management
- High risk for disease progression: defined by FDA emergency use authorization criteria for treatment with anti-SARS-CoV-2 monoclonoal antibodies
- Bamlanivimab and etesevimab
- Casirivimab and imdevimab
Hospitalized and no supplemental oxygen required:
- High risk for disease progression: remdesivir may be appropriate (insufficient data to recommend for or against use)
Hospitalized and supplemental oxygen required: dRemdesivir (minimal oxygen required)
- Dexamethasone and remdesivir (increasing oxygen required)
- Dexamethasone (combination therapy with remdesivir cannot be used)
Hospitalized and oxygen required through a high-flow device or noninvasive ventilation:
- Dexamethasone
- Dexamethasone and remdesivir
- Recently hospitalized, rapidly increasing oxygen needs and systemic inflammation: add tocilizumab to one of the two options above
Hospitalized and invasive mechanical ventilation or extracorporeal membrane oxygenation required:
- Dexamethasone
- Within 24 hours of admission to ICU: administer dexamethasone and tocilizumab
