Monday, June 5, 2023
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Health Sciences Clinical Professor of Family Medicine
University of California, Irvine School of Medicine
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Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 0.25 ABIM MOC points
Nurses - 0.25 ANCC Contact Hour(s) (0.25 contact hours are in the area of pharmacology)
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This activity is intended for primary care physicians, infectious disease specialists, nurses, pharmacists, physician assistants, and other clinicians who care for adults with COVID-19 infection.
The goal of this activity is for learners to be better able to evaluate the risk for viral rebound of SARS-CoV-2 after treatment with oral antiviral therapy vs no antiviral therapy.
Upon completion of this activity, participants will:
Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.
Health Sciences Clinical Professor of Family Medicine
University of California, Irvine School of Medicine
This activity has been peer reviewed and the reviewer has no relevant financial relationships.
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CME / ABIM MOC / CE Released: 3/24/2023
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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to the approved COVID-19 vaccines are provided in this activity in an effort to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.
Individuals infected with the SARS-CoV-2 virus may experience bothersome symptoms lasting a few to several days. With antiviral medications, the severity of these symptoms may be lessened, and the duration may be shortened. Approved antivirals for the treatment of SARS-CoV-2 may be administered through intravenous infusion or given orally.
Nirmatrelvir-ritonavir and molnupravir are the two approved oral antiviral agents for SARS-CoV-2. Both inhibit viral replication through different viral targets. Nirmatrelvir-ritonivir targets the main protease of SARS-CoV-2, while molnupiravir targets the viral RNA-dependent RNA polymerase. While current guidelines recommend the use of these agents within 5 days of symptom onset for adult patients with mild to moderate COVID-19 who are at high risk of disease progression, nirmatrelvir-ritonavir is recommended over molnupravir unless it is not available, feasible to use, or clinically appropriate.
Utilizing antiviral therapy can be beneficial for patients infected with SARS-CoV-2, but it does not come without limitations. One such limitation is the possibility of rebound infection, as defined by a viral load that increases after an initial reduction. A recent study examines this issue.
Antivirals in the Omicron Era
A recent study by Aggarwal and colleagues examined the efficacy of nirmatrelvir-ritonavir against subvariants of the Omicron variant, using a retrospective analysis of outpatients with COVID-19 diagnosed in Colorado between March and August 2022. This study period included infections with the BA.4 and BA.5 variants of SARS-CoV-2. The results of their study were published February 10, 2023, in the Lancet Infectious Diseases.[1]
A total of 9881 patients treated with nirmatrelvir-ritonavir were compared with 11,612 patients who were untreated. The adjusted odds ratio (OR) for hospitalization within 28 days of a positive COVID-19 test was 0.45 (95% CI, 0.33-0.62) in comparing the nirmatrelvir-ritonavir vs placebo groups. Nirmatrelvir-ritonavir was also associated with a lower risk for mortality at 28 days (OR, 0.15; 95% CI, 0.03-0.50), as well as a slight reduction in subsequent visits to the emergency department.
As of the date of publication of this article, a similar study with molnupravir has not been published.
People who received the antivirals nirmatrelvir-ritonavir or molnupiravir to treat COVID-19 infections were not more likely to get back-to-back bouts of the virus, a new study shows.
The findings offer clarity amid concerns that the use of antivirals, which work by stopping the spread of the virus in the body, increased the risk for COVID-19 rebound.
“Rebound is a re-emergence of symptoms and an uptick in viral load after a period of recovery,” the Center for Infectious Disease Research and Policy explained in a summary of the study.
The researchers found that patients who received nirmatrelvir-ritonavir, another antiviral called molnupiravir, or no antiviral medication had rebounds at similar rates, ranging from 4.5% to 6.6%.
The study was published February 13 in the Lancet Infectious Diseases and included 4592 people in Hong Kong who were hospitalized within 3 days of a COVID diagnosis.[2] The study period was from February 26, 2022, to July 3, 2022, which is the time that the Omicron subvariant BA.2.2 was predominant.
The study further found that the risk for rebound was tied to being 18 to 65 years old (compared with older patients), having chronic medical conditions, and receiving steroid treatment. Another finding, which the authors noted was important, was that it appeared that the use of antivirals did not make rebounds more severe. People who received antivirals and had a rebound infection were not more likely to be admitted to the intensive care unit, need a ventilator to help them breathe, or die.
In a commentary published alongside the study, infectious disease expert Nicola Petrosillo, MD, noted that an unexpected finding was the relationship between vaccination status and rebound.[3]
“Surprisingly, the odds of viral burden rebound in patients receiving nirmatrelvir-ritonavir were significantly reduced in individuals who were not fully vaccinated,” he noted.
Dr Petrosillo, who treated some of the earliest COVID cases in Rome, said that the takeaway from the study is the importance of continuing to offer antivirals to people at high risk of developing severe COVID.
Lancet Infect Dis. Published online February 13, 2023.
