[ad_1]
COVID-19, therapeutics, best practices
Do the COVID-19 vaccines prevent disease and decrease hospital visits? We know that the Moderna vaccine was found to be 95 percent efficacious after phase 3 trials but had 90 percent efficacy after six months. (Yale Medicine. Dec. 10, 2021; https://bit.ly/3F34zC2.) Another study exploring the effectiveness of the vaccines among health care workers found that Moderna was 96.3 percent effective with Pfizer-BioNTech being 88.8 percent effective. (N Engl J Med. 2021;385[25]:e90; https://bit.ly/3p2ttwc.)
Pfizer-BioNTech was initially found to be 95 percent effective during phase 3 trials, and had a 91.3 percent efficacy six months after the second dose. The Centers for Disease Control and Prevention said Pfizer-BioNTech is 100 percent effective in preventing severe disease caused by COVID-19. The Johnson & Johnson vaccine has an efficacy of 72 percent, and is 86 percent effective against moderate to severe disease. (Yale Medicine. Dec. 10, 2021; https://bit.ly/3F34zC2.)
Yet another study showed that only one percent of emergency care visits related to COVID-19 were by fully vaccinated patients, and that ED visits and hospitalizations were 96 percent lower in vaccinated patients compared with unvaccinated patients. (Lancet Reg Health Am. 2021;4:100065; https://bit.ly/3EefTdv.) The CDC said adolescent patients who were fully vaccinated had a significantly lower number of ED visits for COVID-19 illness. (MMWR Morb Mortal Wkly Rep. 2021;70[36]:1249; https://bit.ly/3J5yaxc.) It also reported vaccine rates by U.S. region and found that those with lower rates of fully vaccinated people had significantly higher rates of COVID-19 ED visits and hospitalizations.
Remdesivir
Remdesivir, an antiviral that inhibits RNA-dependent RNA-polymerase in coronaviruses, has been used to treat COVID-19 infection in hospitalized patients. (Veklury Package Insert. Gilead Sciences, Inc. 2020; https://bit.ly/3dTPnLE.) Beigel, et al., showed that patients receiving remdesivir had a median recovery time of 10 days compared with 15 days with placebo. (New Engl J Med. 2020;383[19]:1813; https://bit.ly/3GSELsX.)
Remdesivir was found to have a statistical difference in efficacy in the five-day course, but this was not clinically relevant. Wang, et al., followed patients treated with remdesivir for 28 days and found that patients with mild or moderate disease had a 31 percent faster recovery time compared with placebo. (Lancet. 2020;395[10236]:1569; https://bit.ly/3s9qhR4.) No statistically significant difference was seen between remdesivir and placebo in the severe COVID-19 group.
Dexamethasone
Dexamethasone has become a cornerstone of COVID-19 treatment for moderate to severe cases in the ED. A steroid more potent than prednisone, dexamethasone aids in decreasing the inflammation of respiratory infections. Viruses such as the coronavirus are cytokine deregulators that can disrupt the immune response causing organ injury, ARDS, etc., from cytokine storm-induced damage. (Trials. 2020;21[1]:717; https://bit.ly/3F36WVs.)
The standard dosage of dexamethasone is 6 mg IV or PO daily for 10 days. The RECOVERY trial found that dexamethasone decreased mortality in patients who required oxygen compared with patients who received usual care and no dexamethasone. (New Engl J Med. 2021;384[8]:693; https://bit.ly/3scvXdm.) This study also found that more patients who received the drug were discharged from the hospital within 28 days compared with patients not receiving it.
The RECOVERY trial found no benefit in using dexamethasone in patients not requiring oxygen. (New Engl J Med. 2021;384[8]:693; https://bit.ly/3scvXdm.) A review paper reiterated these findings with the use of low-dose dexamethasone. It reported that low doses of the drug (6 mg/day) reduced 28-day mortality by 20 percent in patients receiving supplemental oxygen and 35 percent in patients who were intubated or on mechanical ventilation. (SN Compr Clin Med. 2020;2[12]:2637; https://bit.ly/3GUkwet.) A meta-analysis reported that glucocorticoids reduced mortality in patients on invasive/mechanical ventilation compared with standard treatment and also reported that hydroxychloroquine showed no benefit. (BMJ. 2020;370:m2980; https://bit.ly/3oZhOhj.)
Plasma
Convalescent plasma contains antibodies against the SARS-CoV-2 virus, and Libster, et al., found that patients given plasma within 72 hours of onset of symptoms had a 48 percent reduction in progression to severe disease. This study also looked at specific doses of IgG plasma titers with 1:3200 or higher resulting in reduced risk of severe respiratory disease. (New Engl J Med. 2021;384[7]:610; https://bit.ly/3s5QMXM.)
No significant difference in 30-day outcomes compared with placebo was seen when patients with severe disease with an IgG titer of 1:3200 were given plasma. (New Engl J Med. 2021;384[7]:619; https://bit.ly/3oXbqr4.) A study from Houston Methodist Hospital found that patients who had severe or life-threatening COVID-19 had improvement in 28-day mortality, but this was not statistically significant (P=0.13 and 0.09). (Am J Pathol. 2020;190[11]:2290; https://bit.ly/3ywORg0.) This study also reported a decrease in 28-day mortality if plasma was given within 72 hours of symptom onset. Patients who were given plasma after 72 hours of symptoms onset did not show improvement.
Bamlanivimab/Etesevimab
Bamlanivimab, a monoclonal antibody used to target the spike protein of the SARS-CoV-2 virus, essentially blocks the attachment site of the virus where it enters the body. (U.S. Food and Drug Administration. Nov. 9, 2020; https://bit.ly/3p0EFt9.) The FDA approved its use in November 2020, but removed its authorization of the bamlanivimab/etesevimab combination in COVID-19 patients because it has not been well studied and because of possible resistance. Bamlanivimab, however, has shown to decrease COVID-19 ED visits and hospitalizations within 28 days after treatment compared with placebo in high-risk patients. (U.S. Food and Drug Administration. Nov. 9, 2020; https://bit.ly/3p0EFt9.)
A study at St. Luke’s University Health Network by Corwin, et al., demonstrated the significant advantage of using bamlanivimab in the prehospital setting. The study found a decrease of more than 40 percent in admission and more than 35 percent in ED visits by high-risk patients with comorbid conditions (CHF, COPD, diabetes, obesity). (Open Forum Infect Dis. 2021;8[7]:ofab305; https://bit.ly/326ayaR.) A meta-analysis by Zuo, et al., demonstrated that bamlanivimab has decent efficacy with better hospitalization outcomes and decreased mortality. (UpToDate.com. Accessed November 10, 2021; https://bit.ly/3E58Svc.)
It requires further evaluation because the drug is new and the sample sizes were small. An academic ED found that bamlanivimab use in the ED increased length-of-stay significantly, and can be a drain on resources. (Am J Emerg Med. 2021;S0735-6757[21]00565; https://bit.ly/3E23fOn.)
Etesevimab, another monoclonal antibody that binds to an alternate spike protein of the SARS-CoV-2 virus (UpToDate.com. Accessed November 10, 2021; https://bit.ly/3E58Svc), was initially approved by the FDA on an Emergency Use Authorization in combination with bamlanivimab, but that was later revoked due to the possibility of resistance and the scarcity of research. Dougan, et al., found that patients with mild to moderate COVID-19 treated with etesevimab had a decrease in mortality compared with placebo. (New Engl J Med. 2021;385[15]:1382; https://bit.ly/3F4jhZl.) That study also found that bamlanivimab-etesevimab treatment decreased viral load in patients with COVID-19 (p<0.001). A randomized clinical trial by Gottlieb, et al., compared the efficacy of bamlanivimab with the bamlanivimab-etesevimab combination for COVID-19 patients, and that showed a decrease in viral load 11 days after combination treatment compared with bamlanivimab monotherapy. (JAMA. 2021;325[7]:632; https://bit.ly/3IUIoAl.)
REGEN
REGEN-COV is a combination of the monoclonal antibodies casirivimab and imdevimab, and the FDA approved it in February 2021. (U.S. Food and Drug Administration. Accessed November 19, 2021; https://bit.ly/30CCOBq.) O’Brien, et al., found that 1200 mg of subcutaneous REGEN-COV significantly reduced the progression of COVID-19 infection (from asymptomatic to symptomatic). (medRxiv. 2021; https://bit.ly/3saPjzf.) They also found it decreased viral load (P=0.001) and decreased length of time of symptoms as compared with placebo.
The REGEN-COV group had a reduction of 45.3 percent in length of time of symptoms to an average of 5.6 days per subject. (medRxiv. 2021; https://bit.ly/3saPjzf.) The reduction in symptoms is important because less symptomatic patients will lead to a decrease in ED crowding.
Weinreich, et al., also found that REGEN-COV “resolved symptoms and reduced SARS-CoV-2 viral load more rapidly than placebo.” (New Engl J Med. 2021;385[23]:e81; https://bit.ly/3q5p36X.) The clinical trial also found that REGEN reduced risk of COVID-19 hospitalizations. Questions still remain about the practicality of treatment. A study by Ash, et al., in a community hospital ED found that length of stay in the ED increased with the use of REGEN-COV. Few patients under age 65 who received REGEN-COV returned to the ED at seven days and 14 days, but a large group of REGEN-COV patients over 65 returned to the ED. (Am J Emerg Med. 2021;50:129; https://bit.ly/3yvEDfM.)
Baricitinib
Baricitinib is a Janus kinase inhibitor previously used to treat rheumatoid arthritis. It has been hypothesized to have anti-inflammatory and antiviral effects against SARS-CoV-2. (New Engl J Med. 2021;385[23]:e81; https://bit.ly/3q5p36X.) It is also believed to limit the cytokine release syndrome caused by COVID-19. (Clin Infect Dis. 2021;72[7]:1247.) Baricitinib in combination with remdesevir was initially given emergency use authorization by the FDA in November 2020.
The ACCT-2 trial, a double-blind, randomized, placebo-controlled trial, studied the effect of remdesivir in combination with baricitinib v. placebo on mortality in patients with COVID-19. The study suggested an improvement in 28-day mortality from 7.8 percent in the control group to 5.1 percent in the combination group. (New Engl J Med. 2021 384[9]:795; https://bit.ly/3s8x8Kz.) Baricitinib was also studied in the COV-BARRIER trial, a randomized, double-blind, parallel-group, placebo-controlled trial of 1525 hospitalized participants.
Data from this study revealed “no significant reduction in the frequency of disease progression overall,” but again revealed an improvement in mortality. The 60-day all-cause mortality was 10 percent for the baricitinib group and 15 percent for the placebo group. (LancetRespir Med. 2021;9[12]:1407.) The FDA later revised its authorization to allow the drug to be given independently in “hospitalized patients and pediatric patients two years or older requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.” (FDA News. Aug. 2, 2021; https://bit.ly/31V2IkB.)
Hydroxychloroquine
Hydroxychloroquine was proposed long ago to have antiviral effects, which resulted in the exploration of its use to treat many different viruses over the past 50 years. (J Antimicrob Chemother. 2020 Oct 8:dkaa403.) Antiviral mechanisms have been proposed due to the medication’s capability of increasing intracellular pH, which ultimately affects the function of the endosome and interrupts the viral life cycle. (FDA News. Aug. 2, 2021; https://bit.ly/31V2IkB.) A meta-analysis performed by Kashour, et al., which included seven randomized clinical trials and 14 cohort studies, a total of 20,979 patients of varying COVID-19 disease severity, found that “hydroxychloroquine monotherapy did not reduce short-term mortality among COVID-19 patients.” In fact, mortality was increased when used in combination with azithromycin. (J Antimicrob Chemother. 2020 Oct 8:dkaa403.) Hydroxychloroquine has fallen out of favor for wide use as a viable COVID-19 treatment.
Azithromycin
Azithromycin was hypothesized as a potential treatment for COVID-19 due to past findings of antiviral properties. These properties have been revealed in previous in vitro and in vivo studies on Ebola, Zika, respiratory syncytial virus, influenza H1N1, enterovirus, and rhinovirus. The antiviral mechanism is hypothesized to be secondary to decreased viral entry into cells and enhancement of the immune response. This proposed benefit has yet to be seen in randomized clinical trials. The PRINCIPLE trial, a randomized, controlled, open-label, adaptive platform trial that studied the effect of adding azithromycin to standard care with 2265 participants, recommended against its use without additional indications. (Lancet. 2021;397[10279]:1063.)
Ivermectin
Ivermectin, an antiparasitic drug, has also been proposed for prophylaxis and as a treatment for COVID-19 due to its anti-inflammatory and antiviral properties. It is hypothesized to block the nuclear import of viral proteins and interrupt the immune response. A meta-analysis performed by Bryant, et al., which included 15 trials and 2438 participants, suggested a survival benefit in patients treated with ivermectin. (Am J Ther. 2021;28[4]:e434; https://bit.ly/3m9PmI0.)
The same study claims that ivermectin reduced the risk of death by an average of 62 percent compared with no ivermectin treatment. A study performed by Lopez-Medina, et al., involving 476 participants compared the duration of symptoms in patients with COVID-19 receiving a five-day course of ivermectin v. placebo and found no clinically significant benefit with administration of ivermectin. (JAMA. 2021;325[14]:1426; https://bit.ly/3sbmTp5.) At this time, the FDA recommends against ivermectin for COVID-19 largely due to its lack of proven efficacy, negative interactions with blood thinners, and risk of adverse effects of nausea, vomiting, diarrhea, hypotension, allergic reactions, dizziness, ataxia, seizures, coma, and even death at large doses. (U.S. Food and Drug Administration. Dec. 10, 2021; https://bit.ly/3p0lNdF.)
Oseltamivir
Oseltamivir (also known as Tamiflu) is an antiviral medication often used to treat influenza A and B. Oseltamivir is a neuraminidase inhibitor that targets the neuraminidase on the influenza virus, resulting in inhibiting spread of the virus. A study performed by Zhang, et al., revealed a structural similarity between the SARS-CoV S1 protein and the influenza virus neuraminidase, suggesting a possible role in treating COVID-19 with oseltamivir. (Theochem. 2004;681[1]:137.) A later study in Wuhan did not reveal improved outcomes with utilization of this medication. (JAMA. 2020;323[11]:1061.) Studies are ongoing, but oseltamivir has not been found at this time to be beneficial for treating COVID-19.
Paxlovid
Paxlovid (a combination of nirmatrelvir plus ritonavir) is an oral antiviral drug developed by Pfizer to combat COVID-19. (Pfizer. “EPIC-HR: Study of Oral PF-07321332/Ritonavir Compared with Placebo in Nonhospitalized High-Risk Adults with COVID-19.” ClinicalTrials.Gov, 2 Dec. 2021.) It was approved by the FDA for use on Dec. 22. The nirmatrelvir inhibits the SARS-CoV-2 protein to stop the virus from replicating, and the ritonavir slows nirmatrelvir’s breakdown.
Paxlovid is adminstered as three tablets (two of nirmatrelvir and one of ritonavir) taken orally twice daily for five days. Pfizer reported in the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR), a randomized, double-blind trial of nonhospitalized adult patients with COVID-19 who are at risk of progressing to severe illness, that there was an 89 percent reduction in the risk of COVID-19-related hospitalization or death from any cause compared with placebo in patients treated within three days of symptom onset.
The study also reported that 0.8 percent of patients who received Paxlovid were hospitalized through day 28 compared with seven percent of patients who received placebo (p<0.0001). The results of this study are promising, but newer strains such as Omicron will warrant more studies to verify efficacy in evolving strains.
Dr. Erbyis a second-year emergency medicine resident at Piedmont Macon Medical Center in Macon, GA. Dr. Attais a third-year emergency medicine resident at Mercer University in Macon, GA. Dr. Kamranis the associate medical director at Piedmont Macon Medical Center and a clinical instructor in emergency medicine at Mercer University School of Medicine.
[ad_2]
Source link
