INTRODUCTION

In May 2023, the United States government formally declared the end of the coronavirus disease 2019 (COVID-19) pandemic as a public health emergency. Most Americans have moved toward normalcy with increased travel and in-person events. As we as a society transition to endemic management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a seasonal illness, we must continue to evaluate optimal ways to both prevent COVID-19 disease through vaccination as well as treat confirmed cases with safe and effective therapeutic agents for both ambulatory patients with mild-to-moderate COVID-19 and those hospitalized with more severe disease.

A number of questions remain with COVID-19 vaccinations and treatment as the new school year begins and the fall season starts. This continuing education program provides updates in these areas and considers unanswered questions that will be sorted out in due time.

COVID-19 CASES ARE TRENDING UP

Common endemic viruses such as respiratory syncytial virus (RSV) and influenza virus often have predictable seasons of increased cases. As COVID-19 has become an endemic condition, SARS-CoV-2 is affecting these other viral timeframes by increasing cases and resulting in people contracting multiple viruses simultaneously, known in the lay press as “flurona.” Over the course of the pandemic, various peaks have occurred in different seasons, including the usually quiet summer months.

How do we know viral patterns are changing? Traditional testing of SARS-CoV-2 has decreased significantly in the past year and especially over the past few months for several reasons. First, the end of the public health emergency declaration has reduced testing of symptomatic patients for SARS-CoV-2 testing by eliminating free and reduced-price tests. Second, the shift of testing from health care to home settings has resulted in underreporting of positive results to regulatory bodies, making trends more difficult to monitor. In addition, the “fear” of COVID-19 has somewhat abated, due to a somewhat less virulent omicron strain that produced more mild-to-moderate cases and substantial population (“herd”) immunity from vaccinations and infections. The Centers for Disease Control and Prevention (CDC) recently detailed results from approximately 143,000 citizens aged 16 and older from July–September 2022 that showed 96% had SARS-CoV-2 antibodies. This was up from 68% in April–June 2021.

Over the course of the pandemic, one of the most reliable indicators of rising cases, outbreaks, and cases has been wastewater sampling. For example, the Covid-SURGE algorithm was developed to help communities differentiate between noise and signals in sample data in real-time so they can plan when more cases are likely based on increased viral circulation among the population.¹ A recent Australian study used 20 months of past wastewater data to develop a model that predicts weekly COVID-19 hospitalizations across 45 states. This model allows communities to have a preparation window of 1 to 4 weeks before increases in cases are seen in clinical settings.²

While overall COVID-19 rates are low compared with earlier in the pandemic, cases and hospitalizations increased during summer 2023. As of mid-July, emergency department visits and hospitalizations in SARS-CoV-2–positive patients had increased by 7% and 10%, respectively. This is not surprising based on wastewater data. For instance, positive wastewater samples in Houston tripled in only 3 weeks, resulting in a doubling of positive cases in the ensuing weeks.

Fortunately, deaths from COVID-19 remain low, likely because of population immunity and the availability of COVID-19 treatments such as dexamethasone that are proven to decrease mortality. Cases are increasing for several reasons. The extremely hot summer weather in a number of geographic areas of the United States forced patients indoors, increasing the spread of disease through air-conditioned living spaces. Increased travel, including on airplanes, may play a role as well, with people continuing to vacation to make up for lost opportunities during the pandemic. Overall, these trends will be interesting to monitor as regulatory bodies make decisions on the COVID-19 vaccine composition that will influence cases throughout the fall and winter seasons.

VARIANTS AND VACCINES: WHERE ARE WE NOW AND WHERE ARE WE GOING?

As cases continue to rise, the primary subvariant is shifting. While prediction capability is negated currently due to lack of testing and sequencing data, XBB.1.9.2 appears to be giving way to a new omicron subvariant, EG.5. Some scientists have unofficially dubbed EG.5 “Eris,” and this name is circulating in the lay press. EG.5 was the most common circulating variant in late August 2023, making up approximately 20% of cases. This subvariant, declared a variant of interest by the World Health Organization, had been found in more than 50 countries when this program was prepared. With symptoms similar to other viral illnesses, this subvariant has not demonstrated increased severity compared with other omicron subvariants.

The timing of these mutations is interesting with regard to fall vaccine planning. In June 2023, following a unanimous vote of its vaccine advisory committee, the FDA recommended that manufacturers develop a monovalent vaccine booster with an XBB lineage, specifically XBB.1.5. This is in contrast to the previously recommended bivalent booster that targeted the parent strain as well as the omicron BA.4.5 strain. At the time of these recommendations, 95% of the circulating virus variants were from XBB sublineages, and XBB 1.16 and XBB.2.3 were predicted to rise. These variants have similar spike proteins to XBB.1.5, with few amino acid differences, and therefore the proposed vaccines should provide immunity protection. However, with EG.5 beginning to dominate the subvariant landscape, the big question is whether or not the proposed composition focusing on XBB.1.5 will provide adequate coverage against the Eris strain. It takes at least 3 months for the manufacturers to produce mRNA vaccine doses, and major changes to what has been proposed are considered unlikely.

One important agency has yet to weigh in on these recommendations: the CDC and specifically the Advisory Committee on Immunization Practices (ACIP). FDA approval of the mRNA vaccines is expected by the end of August 2023, and ACIP will then meet to decide on its recommendation. This will be critical for both insurance coverage to ensure broad acceptance in an already challenging environment with regard to booster uptake by patients. With all of these factors and contingencies in play, it is possible that the newly updated COVID-19 booster vaccines will not be available until October 2023.

The updated protein-based, adjuvanted Novavax product would follow after FDA receives and acts on an application for marketing. The company said in June 2023 that it was “manufacturing at commercial scale” in anticipation of being available during the fall vaccination campaign.

In addition, the RSV vaccines will be available this fall, along with the annual influenza vaccine. There are limited data documenting the immunogenicity and tolerability of coadministered RSV and annual influenza vaccines, with several combinations demonstrating lower antibody titers, but the clinical significance of this finding is unknown. The CDC recommends that when administering more than one vaccine at the same clinical visit, providers should separate injection sites by at least 1 inch if possible and consider administering vaccines that are associated with an enhanced local reaction in separate limbs. Pharmacists will have to stay tuned frequently to news on all of these vaccines as the final composition is approved and logistics of administration are determined.

DO GENETICS PLAY A ROLE IN COVID-19?

A number of studies have demonstrated that certain adult patients documented with SARS-CoV-2 do not develop symptoms. As many as 75% of children infected with SARS-CoV-2 have remained asymptomatic, serving as an important mode of viral transmission.³ This occurs in a significant number of individuals based on a number of studies, but determining specific risk factors in adults has been difficult. Genetic research has been ongoing throughout the pandemic, with some recent studies beginning to find some potential etiologic causes for asymptomatic COVID-19.

An allele is 1 of 2 or more versions of a DNA sequence at a specific genome location. The presence of certain alleles has been associated with a higher risk of experiencing a drug-related hypersensitivity reaction. A few examples of this include the following⁴:

1. Allopurinol: Presence of the HLA-B*58:01 allele is strongly predictive of a severe cutaneous adverse reaction
2. Abacavir: Presence of the HLA-B*57:01 allele is associated with a much greater incidence of a potentially fatal hypersensitivity reaction. Abacavir is a component of Triumeq, a first-line human immunodeficiency virus treatment.
3. Carbamazepine: The HLA-B*1502 allele is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis.

A recent study in Nature demonstrated a robust association with HLA-B*15:01 and asymptomatic COVID-19 infection due to documented SARS-CoV-2 in unvaccinated individuals. This variant was found in 20% of asymptomatic patients but in only 9% of those who displayed symptoms.⁵ Those with 2 copies of the allele (from both parents) were nearly 10 times as likely to not show symptoms compared to those with no copies. These individuals are suggested to have preceding T-cell immunity, with most of the reactive cells showing a memory phenotype. They also displayed cross-reactivity to various seasonal coronaviruses. Analysis of T cells showed that patients with the HLA-B*15:01 allele had killer T cells that could effectively neutralize SARS-CoV-2 before the pandemic had begun.⁶

Genetics can also predict the severity of COVID-19, including complications such as thromboembolic events (e.g., venous thromboembolism). While age, sex, and obesity are known risk factors for severe disease, this has not been correlated with specific genetic risk factors. A recent study published in Nature Communications identified genetic risks that may increase the risk of severe disease. A cohort of about 100,000 participants within the U.K. Biobank with confirmed SARS-CoV-2 infection were evaluated. The U.K. Biobank is a large-scale biomedical database of adults ages 40–69 years and research resource that contains in-depth genetic and health information for more than 500,000 participants in the United Kingdom.⁷

Polygenic risk scores (PRS), a composite of genetic risk for a particular trait, were evaluated using data from the UK Biobank to identify any increased risk of cardiovascular and thromboembolic complications secondary to COVID-19. Standard and enhanced scores were calculated based on medical conditions found in primary care, secondary care, disease, and mortality directories. A healthy lifestyle score was generated, evaluating 9 components, such as smoking status and physical activity. Patients were grouped into 3 categories —unfavorable, moderate, and favorable — with higher scores indicating more optimal lifestyles.⁷

Across all patients, the highest incidence of cardiovascular and thromboembolic events occurred within 30 days of SARS-CoV-2 identification. The PRS was positively correlated linearly across various subgroups of interest, despite differences in baseline risk (e.g., sex, age, obesity). Patients with COVID-19 who had the top 20% of PRS scores had an excess risk of 3.5-fold for atrial fibrillation, 3.3-fold for coronary artery disease, 2.1-fold for venous thromboembolism, and 2.6-fold for ischemic stroke. Participants with healthier lifestyles also had lower risks of these events compared to those with unfavorable lifestyle scores. This benefit was primarily seen in the pre-omicron period of the study; the effect was attenuated during the period of omicron dominance.⁷

THERAPEUTIC TRIALS ON THE PREVENTION OF LONG COVID-19

Innovation has been key to decreases in morbidity and mortality during the pandemic. The novel mRNA vaccines provided broad-based immunity. A number of therapeutic agents, including antiviral agents and monoclonal antibodies, were important for decreasing the risk of hospitalization and death in ambulatory patients with mild-to-moderate COVID-19 as well as for treating patients requiring hospitalization.

Like other coronaviruses, SARS-CoV-2 has become endemic, and the focus has shifted to the management of patients with remaining symptoms after the virus has been cleared. Long COVID is a constellation of more than 200 symptoms the reflect the detrimental effects of this virus on various organs and tissues. Long COVID symptoms include cognitive impairment (e.g., brain fog), fatigue, headaches, and dyspnea. Symptoms can persist for many months or more than a year after the initial infection.

The National Institutes of Health (NIH) in July 2023 opened enrollment for phase 2 clinical trials of interventions for the prevention of long COVID-19. These trials will assess 4 options initially and possibly expand to 7 modalities, including medications, biologic agents, and other therapies. The trials are designed to rapidly identify effective therapies by evaluating multiple interventions simultaneously. These studies, known as the Researching COVID to Enhance Recovery (RECOVER) Initiative, are based on other RECOVER research studies over the past 24 months; those now being initiated are focusing on the most bothersome and persistent known symptoms of long COVID.

Another trial worth watching is the RECOVER-VITAL study, which is evaluating the persistence of SARS-CoV-2 in body tissues. Ritonavir-boosted nirmatrelvir is approved by the FDA for the treatment of mild-to-moderate COVID-19 in a 5-day treatment course. RECOVER-VITAL considers longer treatment courses of Paxlovid, either 15 or 25 days, to see if this decreases the incidence of long COVID symptoms compared with ritonavir as a control. While overall ritonavir-boosted nirmatrelvir tolerability has been excellent, longer treatment courses will have to be monitored closely for drug interactions, as ritonavir has potent cytochrome P450 enzyme inhibition potential. In the COVID-19 treatment guidelines, the NIH has published detailed recommendations on handling these interactions during the standard 5-day treatment course.

Another trial set to begin in the coming months will evaluate therapies for various sleep pattern disturbances, such as hypersomnia. The RECOVER-SLEEP study will study 2 wakefulness-assisting medications. Details have yet to be released on the specific agents to be studied and their doses, frequencies, and duration of therapy. Other studies are planned to evaluate interventions to improve sleep quality, such as trouble falling or remaining asleep.

METFORMIN TO PREVENT LONG COVID-19?

The long-awaited follow-up prespecified outcome from the COVID-OUT trial — evaluating metformin, ivermectin, or fluvoxamine for acute COVID-19 — has been published in Lancet Infectious Diseases. This randomized, placebo-controlled study evaluated participants for approximately 300 days after the initial COVID-19 infection to determine the risk of long COVID-19 symptoms. Of the 1,431 patients who were initially enrolled, 1,126 remained in the study and completed 1 or more surveys for assessment of long COVID 6 months after initial infection. Approximately 95% of these patients also completed 9 months of total follow-up. Most participants were female (56%, 7% of whom were pregnant), and the median age was 45 years.⁸

By day 300, 8.3% of participants reported a long COVID diagnosis. While ivermectin and fluvoxamine showed no impact on long COVID symptoms compared with placebo, the metformin group had a 41% decreased risk of long COVID symptoms by day 300 (6.3% vs. 10.4%). Of note, metformin was most effective when started within 72 hours of symptom onset, with a reduction in risk of 63%.⁸

The results of this trial yielded several instructive points regarding metformin. First, the initial titration was slower than in other trials, which led to improved tolerability. On day 1, patients received 500 mg. On days 2–5, participants received 500 mg twice daily. On day 6 and beyond, participants received 500 mg in the morning and 1000 mg in the evening through day 14, at which point therapy was stopped.⁸

The potential antiviral effects of metformin in unvaccinated patients are similar to ritonavir-boosted nirmatrelvir and therefore need to be studied in a primarily vaccinated population, ideally in a study comparing treatment with or without ritonavir-boosted nirmatrelvir. The best outcomes were achieved when metformin was initiated closer to symptom onset, providing more rationale for a primary antiviral mechanism of action. If these results are confirmed, metformin would offer a very affordable, well-tolerated, safe therapy for potentially decreasing the risk of long COVID.

CAN COVID-19–INDUCED DYSGEUSIA PERSIST FOR LONG PERIODS OF TIME?

Sensory disturbances have been a hallmark symptom among patients with SARS-CoV-2 infections. During the initial stages of the pandemic, anosmia, more commonly known as lack of smell, was reported frequently. This could persist for many, many months. Potential causes included age and genetic factors. Anosmia was frustrating for patients and could lead to complications such as anorexia, resulting in weight loss. Fortunately, this adverse effect has not presented as frequently with recently dominant, mutated SARS-CoV-2 strains.^9,10

While the incidence of anosmia has decreased, dysgeusia remains a target of conversation for several reasons. First, one of the primary therapeutic agents, ritonavir-boosted nirmatrelvir, is known to cause dysgeusia because of its ritonavir component. While reported in about 6% of patients in earlier trials, recent studies found dysgeusia 1 in 4 patients. Long-term dysgeusia has been reported in some patients with complaints lasting 6 months or longer, and this can lead to decreased appetite and weight loss.

A recent study sought to identify a pathophysiologic explanation for prolonged dysgeusia in patients with COVID-19. Investigators performed biopsies of the fungiform papillae (raised protrusions on the tongue that detect flavor, temperature, and touch), primarily from the center of the tongue near the midline, in 16 participants with molecularly confirmed SARS-CoV-2 infection. Of the 16 patients, 10 who were still experiencing dysgeusia after 6 months or more had a second biopsy. All patients had evidence of SARS-CoV-2 in the epithelial layer and the connective tissues of the tongue. Continuing immune activity was detected in 11 of 16 participants based on increased concentrations of both cytotoxic CD8 T cells and interleukin 1 beta within the fungiform papillae. Several patients had taste recovery even after more than 11 months of symptoms.¹¹

More evidence is needed to determine if treatment decreases the risk of long-term dysgeusia, as none of these patients received antiviral or monoclonal antibody COVID-19 treatments. Patients should be reassured that long-term dysgeusia is a rare phenomenon and typically resolves even after lasting for several months.

REMDESIVIR DOSING MODIFIED FOR RENALLY INSUFFICIENT PATIENTS

A major clinical practice conundrum within the field of antimicrobial agents, including antiviral agents, is the lack of data in renally insufficient patients, especially those with an estimated glomerular filtration rate (eGFR) of 30 mL/min or less. Remdesivir was the first and only intravenous antiviral agent authorized and later approved by the FDA for the treatment of COVID-19. It was initially approved for but not recommended in patients with an eGFR of <30 mL/min.

The labeling has now been modified. No dosage adjustment is recommended in patients with any degree of renal impairment, including patients on dialysis. Remdesivir may be given at any time of day and on dialysis days, which is important from a practical administration standpoint. This contrasts with many other antimicrobial agents whose daily doses must be delayed until after dialysis to decrease drug removal.

Studies described in the product labeling support the new recommendation. In participants with acute kidney injury, chronic kidney disease, or end-stage renal disease, no safety signals beyond previously recognized ones were identified.

Other antiviral agents currently approved or authorized for COVID-19 have differing recommendations for patients with eGFR <30 mL/min. Molnupiravir does not require any dosage adjustments for any degree of renal dysfunction, similar to the new label for remdesivir. The nucleoside analog metabolite of molnupiravir, N4-hydroxycytidine or NHC, is not significantly cleared renally and would not be expected to accumulate in renal dysfunction. With use permitted only under an emergency use authorization, molnupiravir is not a first-line oral agent for ambulatory patients because of its limited efficacy compared with remdesivir and ritonavir-boosted nirmatrelvir.

With indications similar to remdesivir, ritonavir-boosted nirmatrelvir offers an FDA-approved option for COVID-19. Its use in renally insufficient patients has not been adequately studied, and thus the FDA approval does not recommend the use of the combination in patients with eGFR <30 mL/min. Dosage decreases are recommended in patients with eGFRs of 30–59 mL/min. Data with recommendations in this population would be helpful, as pharmacists can prescribe this agent.

REMDESIVIR EFFECTIVENESS IN IMMUNOCOMPROMISED PATIENTS

Remdesivir was one of the first therapeutic agents for COVID-19 granted emergency use authorization and later approved by the FDA. However, clinical evidence supporting its benefit has been controversial, with some but not all studies demonstrating benefit in comparison with placebo. While a number of medications have been authorized since remdesivir, few are currently available for hospitalized patients, as ritonavir-boosted nirmatrelvir and molnupiravir are indicated for inpatient use only when the primary admitting issue is not COVID-19. In addition, monoclonal antibody therapy is not recommended because of lack of effectiveness against the currently circulating variants. Other authorized/approved therapies have significant immunosuppressing effects, such as baricitinib or tocilizumab, and are recommended primarily in severe illness. These would also not be optimal for an immunosuppressed population, such as those receiving cancer chemotherapy.

The immunosuppressed population could benefit from treatment, but it has been poorly represented in most COVID-19 treatment trials to date. A recent study published in Clinical Infectious Diseases evaluated remdesivir’s use in hospitalized, immunocompromised patients. Overall, patients receiving remdesivir therapy had a decrease in 14-day mortality compared with patients who did not receive remdesivir participants (11.1% vs. 15.4%). Mortality at 28 days was also lower in the remdesivir group (17.7% vs. 22.4%). ¹²

Because immunocompromised patients are unlikely to respond well to vaccinations, remdesivir therapy is an option for this and other high-risk populations. The modified label for remdesivir discussed earlier for renally insufficient populations, lack of known drug interactions, and good tolerability will likely lead to remdesivir continuing to be a first-line agent for the treatment of COVID-19 in hospitalized patients. More data are welcome for this agent in the ambulatory, immunocompromised patient population to prevent admissions.¹³

NIRMATRELVIR EFFECTIVE IN YOUNGER VACCINATED POPULATIONS?

When ritonavir-boosted nirmatrelvir was authorized and then approved by the FDA for the treatment of mild-to-moderate COVID-19, the supporting data were mostly from studies showing decreased hospitalizations and deaths in an unvaccinated population. Fast forwarding to the present, questions have been raised regarding overall antiviral effectiveness in a primarily vaccinated population. In addition, much of the effectiveness of antiviral therapy appears to be driven by older populations with significant comorbidities. Ritonavir-boosted nirmatrelvir, unlike intravenous remdesivir, is involved in several clinically significant drug interactions because of the potent CYP 450 inhibition of ritonavir. These factors make it critical to identify the optimal ambulatory populations with COVID-19 who would benefit while also minimizing the risk of drug interactions and potential toxicity.

A cohort study of fully vaccinated adult patients aged 18–50 years attempted to answer some of these questions. Compared with participants not treated with ritonavir-boosted nirmatrelvir (the untreated cohort), people receiving the drug combination (the treated cohort) were significantly less likely to have a primary outcome of all-cause emergency department visits, hospitalization, and mortality (4.9% vs. 7.0%, a 30% relative risk reduction). The primary endpoint was driven by all-cause hospitalization and death; emergency department visits were not significantly decreased between the groups. Constitutional symptoms were more common along with cardiorespiratory symptoms in the untreated cohort. Smell/taste alteration was not significantly different between the groups, only occurring in less than 1% of both patient populations (identification of these patients depended on record documentation). Lower respiratory tract infections were reported less frequently in the treated cohort. When evaluating outcomes by individual comorbidities, patients with cancer or cardiovascular disease had significant benefit with treatment, but patients with chronic lower respiratory tract disorders (e.g., asthma or COPD) or no serious comorbidity did not benefit from therapy.¹⁴

The findings of this study will likely be compared and contrasted with the upcoming release of results from the Platform Adaptive trial of NOvel antivirals for eArly treatment of COVID-19 in the Community, or the “PANORAMIC” trial. This study demonstrated benefit in younger, vaccinated patients with significantly more comorbidities than the general younger population. Younger patients without comorbidities did not benefit from Paxlovid therapy. Continued study of a primarily vaccinated, but also previously infected population, will be key going forward to fully elucidate the role of antiviral therapies, such as ritonavir-boosted nirmatrelvir, to best give benefit while limiting overall risk of drug interactions.

NEW AGENT AUTHORIZED FOR COVID-19 IN HOSPITALIZED PATIENTS

Vilobelimab injection was granted an emergency use authorization by the FDA in April 2023 for the treatment of COVID-19 in hospitalized adults (severe COVID-19) when started within 2 days of initiating invasive mechanical ventilator or extracorporeal membrane oxygenation (ECMO). High concentrations of C5a have been demonstrated in patients with severe COVID-19, which would induce inflammation and histamine release and result in tissue damage. Vilobelimab exerts its pharmacologic effect as an anti-C5a monoclonal antibody. Data supporting this authorization are derived primarily from the PANAMO study; results of the phase 3 portion of this trial were published in Lancet Respiratory Medicine.¹⁵

At 46 hospitals primarily in Europe, Asia, Mexico, and South Africa, adults who were mechanically ventilated for 48 hours or less were randomized to vilobelimab 800 mg IV or placebo for a maximum of 6 doses on days 1, 2, 4, 8, 15, and 22. All participants received standard-of-care therapy, and nearly all received corticosteroids (97%) and anticoagulants (98%). The all-cause mortality rate at 28 days was not statistically significantly different in the vilobelimab and placebo groups (32% vs. 42%). When not stratified by hospital site, the 28-day mortality in the vilobelimab arm was 33% lower than in the placebo group, a significant difference. An important limitation of the study is that the Russian sites had high numbers of deaths but were excluded from data analysis.¹⁵

Based on the current data, the NIH COVID-19 treatment guidelines do not recommend either for or against the use of vilobelimab for the treatment of COVID-19. A second trial is likely needed to validate the findings from the PANAMO study before general use can be recommended.

PROVIDING FREE COVID-19 VACCINES FOR UNINSURED PATIENTS

With the cessation of the federal government public health emergency health declaration, a number of citizens who are uninsured or underinsured are at risk of not receiving COVID-19 vaccinations. Approximately 25–30 million adult citizens aged 18–64 years are uninsured in the United States. The CDC has announced the “Bridge Access Program” that will aid both uninsured and underinsured patients. To prepare appropriately for the fall 2023 season, CDC employees are working closely with a number of stakeholders to make the program available and ensure optimal distribution and maximum administration. These stakeholders include the major pharmacy chains, state and local health programs, and vaccine manufacturers. The program is scheduled to end in December 2024.¹⁶

CONCLUSION

Fall 2023 is shaping up to be an interesting season. COVID-19 cases increased over the summer, and FDA and CDC must resolve their differences regarding the composition of the mRNA vaccines. This season could see COVID-19, influenza, and RSV vaccines being administered, which will no doubt lead to a certain amount of consumer confusion and questions for pharmacists.

Timely diagnosis and treatment will continue to be key to improving outcomes and controlling the spread of SARS-CoV-2. As they have since the beginning of the pandemic, pharmacists will be at the forefront of COVID-19 vaccination of patients, providing education about the disease, monitoring for drug interactions, and initiating and dispensing therapeutic agents in a safe and effective manner. including close monitoring of potential drug interactions with ritonavir-boosted nirmatrelvir.

REFERENCES

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14. Faust JS, Kumar A, Shah J, et al. Oral nirmatrelvir and ritonavir for coronavirus disease 2019 in vaccinated, nonhospitalized adults aged 18–50 years. Clin Infect Dis. 2023: ciad400. https://doi.org/10.1093/cid/ciad400
15. Vlaar APJ, Witzenrath M, van Paassen PV, et al. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomized, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022;10:1137-1146.
16. Harris E. Free COVID-19 vaccinations on the way for uninsured adults. JAMA. 2023;330(7):585. doi:10.1001/jama.2023.13133.

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