INTRODUCTION

There is cautious optimism as our society concludes year 3 of the coronavirus disease 2019 (COVID-19) pandemic. When the omicron variant first began circulating, cases and hospitalizations rose initially, primarily due to its enhanced transmissibility and immune-evading properties compared to previous strains. In subsequent months, overall case numbers, hospitalizations, and deaths have declined, even with continually easing societal restrictions, such as indoor masking. Potential reasons for the decline include widespread availability of effective vaccines, decreased severity of disease with the predominant omicron variant, the overall prevalence of infection-related immunity, and availability of effective, Food and Drug Administration (FDA)-approved oral COVID-19 treatments for ambulatory patients with mild-to-moderate disease as well as hospitalized patients with severe COVID-19.

Omicron BA.5 was the dominant strain for several weeks, peaking in August 2022 at more than 80% of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in weekly data from the U.S. Centers for Disease Control and Prevention (CDC). It has now been overtaken by a collection of more resistant subvariants, including BQ.1, BQ1.1, and BF.7.

Going forward in the winter season in the Northern Hemisphere, will these new variants have an increased risk of severe disease? Will any of our currently available therapeutic agents be effective against the omicron variant? Will greater population immunity through previous disease and/or vaccination help prevent disease? What newer agents are in the COVID-19 therapeutic pipeline?

This continuing education program provides frontline pharmacists and pharmacy technicians answers to these questions along with information on other pertinent COVID-19 topics.

PREVENTION OF COVID-19: VARIANTS AND VACCINES

Current Omicron Subvariants and Availability of Effective Treatments

Any discussion of the prevention of COVID-19 begins with an assessment of the variants currently circulating. In an interview reported in Stat, the head of FDA’s vaccines division expressed concern about the rapidity of mutations found in clinical isolates of SARS-CoV-2, especially given the declining uptake of booster doses among Americans. The original mRNA-1273 vaccines were developed based on the antigenicity of the spike protein found in the parent strain isolated in Wuhan, China. As discussed below, a bivalent COVID-19 vaccine is available that covers the omicron BA.4 and BA.5 subvariants.

At the time this program was prepared in November 2022, the CDC recognized a dozen omicron subvariants. BA.5 had been the most commonly circulating subvariant in the United States but was declining from a peak of 87% in late August to 29.7% of isolates during the week of November 6–12. Dominant in the United States were BQ1.1 (24.1%), BQ.1 (20.1%), BF-7 (7.8%), and BA.4.6 (5.5%).

Several of these fastest-spreading variants are expected to be resistant to currently used monoclonal antibodies for SARS-CoV-2, according to a November 10, 2022, statement from the National Institute of Health (NIH) COVID-19 Treatment Guidelines Panel. The spike proteins of newest subvariants likely evade vaccine-induced neutralizing antibodies based on their genetic make-up.¹

Recently, researchers tested the in vitro activity of a documented BA.2.75 variant strain isolated from a patient traveling from India to Japan. A number of agents were tested for neutralizing capabilities, including monoclonal antibodies as well as antiviral agents. Bebtelovimab was the only monoclonal antibody tested that efficiently neutralized BA.2.75. Tixagevimab-cilgavimab inhibited the subvariant as well but overall neutralizing activity was less than with the parent strain. Other monoclonal antibodies that have previously been used in the pandemic, such as sotrovimab and casirivimab-imdevimab, provided mild-to-moderate inhibition that was much less than against the parent strain. The BA.2.75 subvariant was susceptible to the 3 antivirals tested (remdesivir, molnupiravir, and nirmatrelvir). While these data are helpful, they only represent neutralizing in vitro capability; clinical outcomes are required to guide recommendations and ultimately patient care.²

A number of evolving subvariants, such as BQ1 and XBB, could drive additional waves of COVID-19 diseases due to immune-evading properties. XBB, which was most recently discovered in China, displays significantly greater immune-escape properties than BA.2.75 versus bebtelovimab and tixagevimab-cilgavimab in vitro.³ Close monitoring of these subvariants and their overall disease virulence and clinical response to currently recommended agents is prudent becauseseveral are spreading in the United States as the colder weather season of 2022–2023 begins.

Bivalent COVID-19 Vaccine Authorized for Fall Season

One of the perceived primary advantages of the mRNA vaccines is the ability to quickly modify mRNA component of the vaccine (shown in Figure 1) in response to changes in circulating variants. Since initial FDA authorization and ultimate approval of Pfizer/BioNTech’s Comirnaty and Moderna’s Spikevax brands of COVID-19 —both of which target the parent strain of SARS-CoV-2 — the companies have been working to strategically respond to epidemiologic trends of variant strains and produce an updated vaccine that would use mRNA technology to maximize prevention of COVID-19, including severe disease manifested by hospitalization and death.

The recently authorized “bivalent” COVID-19 vaccines contain mRNA from the original vaccine parent strain and an mRNA component in between the omicron BA.4 and BA.5 lineages that were causing the most disease in fall 2022. The Pfizer/BioNTech bivalent vaccine was initially authorized in those 12 years of age and older, and the Moderna bivalent option in patients 18 years of age and older. Later authorizations lowered the ages to 5 years for Pfizer/BioNTech and 6 years for Moderna.

The FDA authorizations for the bivalent vaccines were based primarily on clinical safety and effectiveness data from each of the mRNA parent vaccine studies in conjunction with immunogenicity data specific to a bivalent COVID-19 vaccine that possessed mRNA from the omicron BA.1 lineage. Nonclinical data using mRNA from the parent strain as well as mRNA the BA.4 and BA.5 strains have in common were used to support the final FDA authorization. Clinical outcome data specific to these vaccine boosters are needed to determine overall real-world effectiveness, especially if current variants are replaced my new ones within omicron or newly emerged SARS-CoV-2 strains.

Here are some important logistics regarding integration of these bivalent mRNA vaccines into current vaccination schedules:

1. The bivalent vaccines are authorized as single booster doses.
2. They may be administered at least 2 months after completion of a primary series (2 doses for children aged 5 years or older and adults; 3 doses for those with immunocompromising conditions who are 5 years or older) or a booster COVID-19 vaccination.
3. Approval of the bivalent mRNA vaccines removes the authorization for the monovalent (original) boosters for patients 12 years and older.

Figure 1. The mRNA vaccines can be easily adapted to new SARS-CoV-2 strains by changing he genetic material delivered to host tissues in step 1 of this process to match mutations in the spike proteins protruding from the viral membrane.

Authorization Expanded for Novavax Product

Novavax’s adjuvanted COVID-19 vaccine, NVX-CoV2373, received its original emergency use authorization as a 2-dose primary series for adults in July 2022, expanded a month later to include adolescents aged 12–17 years. In October 2022, FDA authorized the use of NVX-CoV2373 as a first booster in adults aged 18 years or older.

Novavax’s protein subunit vaccine, administered in 2 doses 3 to 8 weeks apart, is the fourth authorized COVID-19 vaccine in the United States (including the Janssen/Johnson & Johnson product). It is produced with spike protein and an adjuvant to bolster immune response. Protein subunit technology is already used in many familiar vaccines, including those for influenza, hepatitis B, and acellular pertussis. NVX-CoV2373 provides an additional and more familiar option for those who have not yet received a primary vaccination series.The hope is that people who were concerned about the newer technology used to produce mRNA vaccines will overcome their vaccine hesitancy and be open to receiving vaccination with the Novavax option.

Preceding initial authorization, Novavax’s studies showed vaccine effectiveness of 90.4% for preventing “mild, moderate, and severe COVID-19” in clinical trials, though effectiveness was a lower 78.6% in those at or above 65 years of age. These trials were conducted before the delta and omicron variant surges, so applicability in today’s SARS-CoV-2 variant and subvariants is limited. In clinical trials, side effects were consistent with those of the mRNA vaccines, including pain, tenderness, redness, and swelling at the injection site, headache, fever, and nausea.

In August, the European Medicines Agency recommended that Novavax include a warning for the possibility of myocarditis and pericarditis with their vaccine. Novavax claims no such concerns about heart inflammation were raised during clinical trials, and that myocarditis is most often caused by viral infections. Nevertheless, more study is to follow and the warning will be included. Myocarditis and pericarditis have also occurred rarely following administration of the mRNA vaccines.⁴

As a condition of authorization in the United States, Novavax is also required to include a warning about both kinds of heart inflammation in the fact sheet for providers of the vaccine. Providers and Novavax must report any instances of myocarditis or pericarditis as adverse events to VAERS. Patients are encouraged to seek medical attention if they experience signs of these conditions, including shortness of breath, arrhythmia, or chest pain.

Data supporting the use of NVX-CoV2373 as a booster following the 2-dose primary series comes from the phase 3 PREVENT trial. Booster doses, given 6 months after a primary series, induced antibodies similar to those induced by the primary series. Likewise, during the phase 2 COV-BOOST trial, the booster was effective when used in a mix-and-match strategy with other primary COVID-19 vaccines.⁵

To date, limited uptake of NVX-CoV2373 has occurred across the United States. As of mid- November 2022, the COVID-19 data tracker reported delivery of 932,500 doses of Novavax’s COVID-19 vaccine in the United States. Of those, approximately 50,000 had been administered. The federal government has purchased 3.2 million doses of NVX-CoV2373 through a $1.6 billion contract through the U.S. Department of Health and Human Services and the Department of Defense.

COVID-19 TREATMENTS

Effectiveness of Ritonavir-Boosted Nirmatrelvir Against the Omicron Variant

Ritonavir-boosted nirmatrelvir (Paxlovid, Pfizer) has shown promising results since its emergency use authorization in December 2021. This protease inhibitor combination can be taken by ambulatory patients to prevent progression to severe disease. It is currently recommended in the NIH COVID-19 Treatment Guidelines as a first-line therapy for nonhospitalized adults and pediatric patients aged 12 years or older who have mild-to-moderate COVID-19 and a high risk of disease progression, and are within 5 days of symptom onset. Ritonavir-boosted nirmatrelvir can be used in patients hospitalized with a diagnosis other than COVID-19 when they meet the 3 criteria used for ambulatory patients.

Ritonavir-boosted nirmatrelvir produced excellent outcomes in patients who were primarily unvaccinated during the delta wave. Data are limited regarding efficacy against the B.1.1.529 (omicron) variant, especially now that more people have documented immunity through vaccination, previous infection, or both.

One observational retrospective analysis of a large Israeli dataset during the omicron surge indicated that patients with prior immunity can benefit from treatment with ritonavir-boosted nirmatrelvir. Among 3,902 individuals treated with ritonavir-boosted nirmatrelvir (90% had prior immunity) and a matched cohort (78% with prior immunity), rates of COVID-related hospitalization and mortality were significantly lower among older adults (65 years or older) who received ritonavir-boosted nirmatrelvir than in the untreated cohort. However, this finding did not hold true for younger patients (40–64 years of age), as rates of hospitalization or mortality due to COVID-19 were not significantly different between the cohorts.⁶

Beyond this likely benefit of ritonavir-boosted nirmatrelvir in an older population infected primarily with the omicron strain, more questions remain regarding its ultimate role in younger patients, especially those with prior immunity. Potentially significant drug-drug interactions with ritonavir as well as likely high pharmacoeconomic cost to prevent 1 hospital admission, especially in a younger population, suggests a need for further studies of ritonavir-boosted nirmatrelvir.

Paxlovid Rebound: Latest Data

In May 2022, the CDC issued an official health advisory about COVID-19 rebound after ritonavir-boosted nirmatrelvir therapy. Recent studies attempt to answer several questions about this puzzling phenomenon. How should COVID-19 rebound be defined? Is diagnosis based on symptoms, positive SARS-CoV-2 tests, or a combination of those factors? Does COVID-19 rebound happen only after ritonavir-boosted nirmatrelvir therapy? Or does it occur in people treated with other agents, such as molnupiravir? Can it happen in patients who received no treatment for COVID-19?

In clinical studies, COVID-19 has generally been defined as recurrence of symptoms with positive viral tests following an initial symptomatic infection of SARS-CoV-2. In 3 separate case reports, patients infected with omicron variants received ritonavir-boosted nirmatrelvir therapy on day 1 of symptoms, later had at least 5 days during which they were asymptomatic, and rebounded with both recurrent symptoms as well as higher viral loads similar to initial presentation. All patients displayed the same genetic sequence of omicron variant, suggesting rebound and not reinfection with a different variant. No SARS-CoV-2 protease mutations were present that would suggest antiviral resistance to nirmatrelvir.⁷

Case reports also indicate that patients with rebound COVID-19 after ritonavir-boosted nirmatrelvir therapy can transmit the virus to close contacts; patients should be counseled about the possibility of rebound with recurrence of infectivity. Combining the above 3 cases with 10 other cases in which the virus was not sequenced, the researchers found higher viral loads and instances of transmission to close contacts during the rebound periods. All 13 of these cases occurred in previously vaccinated patients who had received at least 1 mRNA booster within the previous 7 months of infection. No patients were immunocompromised and 2 patients likely transmitted the infection to close contacts during the rebound timeframe.⁷

Data from the phase 2 and 3 controlled study EPIC-HR used to support the FDA authorization of ritonavir-boosted nirmatrelvir suggest that periods of rebound occurred in patients who were randomized to placebo as well as ritonavir-boosted nirmatrelvir. Nasopharyngeal swabs were collected on day 1 of enrollment and days 3, 5, 10, and 14. Recurrence was defined as a half-log increase in SARS-CoV-2 viral load on day 10 or day 14 if 1 value was available or on days 10 and 14 if both values were available. Rebound was documented similarly in both groups, occurring in 2.3% and 1.7% of patients taking ritonavir-boosted nirmatrelvir and placebo, respectively. In 1 patient who had been hospitalized, rebound occurred after discharge.⁸

Patients experiencing rebound have more frequently had underlying medical conditions than those without rebound. In a study undergoing peer review, COVID-19 rebound occurred with both ritonavir-boosted nirmatrelvir therapy and molnupiravir therapy, which is not currently a first-line therapy for COVID-19 as outlined by current NIH guidelines. Rates and relative risks of rebound at days 7 and 30 among 13,644 eligible patients for the first half of 2022 are shown in Table 1. Rebound as evaluated by infection, COVID-19 related symptoms, and hospitalizations was similar in patients taking ritonavir-boosted nirmatrelvir and molnupiravir for rebound outcomes. Propensity score matching demonstrated no significant differences between ritonavir-boosted nirmatrelvir and molnupiravir therapy for rebound COVID-19 infection, symptoms, or hospitalizations.⁹

What does all of this information suggest for ritonavir-boosted nirmatrelvir rebound? Rebound is likely more common in real-world practice than is reflected in registry studies and often depends on the definition used in the study evaluations of rebound (e.g. detection of virus, symptoms, or both). Various studies were conducted during periods with differences in circulating variants such as delta and omicron, and higher rebound rates occurred with the omicron variant. Rebound symptoms may occur with ritonavir-boosted nirmatrelvir or molnupiravir treatment, and rebound does not appear to be associated with antiviral resistance.

Pharmacists should counsel patients receiving ritonavir-boosted nirmatrelvir therapy that rebound symptoms are possible after asymptomatic periods that are often mild and do not require further treatment. Further studies are needed to further elucidate etiology of rebound viral replication and subsequent COVID-19 symptoms.

Making Sense of “Paxlovid Mouth”

Pharmacovigilance is an important component of evaluation of medications when they are in general use. Therapies for COVID-19 are no exception, including drugs such as ritonavir-boosted nirmatrelvir that are available under emergency use authorizations. Reassuringly to this point, overall safety and tolerability of COVID-19 antiviral agents appears to be excellent. This is aided by their overall 5-day short treatment course for both ritonavir-boosted nirmatrelvir and molnupiravir. However, an interesting and yet predictable adverse effect of Paxlovid has emerged; it is known in consumer media as “Paxlovid mouth.”

Scientifically, this adverse effect is best described as dysgeusia, a general term for an overall taste disturbance. The types of taste disturbances are varied and can include a bitter, metallic, salty, sour, or even rancid taste. A number of drugs have been associated with dysgeusia, including metformin, metronidazole, captopril, and protease inhibitors used in the management of human immunodeficiency virus, including ritonavir.¹⁰

The nirmatrelvir component of Paxlovid could be contributing to a higher incidence of dysgeusia, perhaps because of its inherent bitterness, the manufacturer told a reporter from The Atlantic. These effects should not be confused with COVID-19–induced anosmia (lack of smell) or dysgeusia, which were associated with initial COVID-19 infections early in the pandemic with the original strain of SARS-CoV-2. While these can still occur, they are much less common with currently circulating variants.

In phase 2/3 studies that led to the FDA emergency use authorization of ritonavir-boosted nirmatrelvir, dysgeusia was documented in approximately 5% to 6% of participants, was reported as mild, and did not necessitate discontinuation of therapy in most cases. The mechanism causing these clinical effects is currently unknown. Theories include an inflammatory response in the oral mucosa as well as receptor malfunction. The bitter taste most often occurs during the time the medication is present in the body and resolves relatively soon after cessation of the final dose. This is very different from the anosmia/dysgeusia resulting from COVID-19, which can persist for many, many months after cessation of other symptoms, with most patients recovering their sense of smell within a year of infection.¹¹

During counseling, pharmacists should reassure patients that dysgeusia is more of a nuisance when it occurs and that the medication may be safely continued. Premature discontinuation of therapy could be problematic, as has been reported with other medications such as metformin. Nonadherence in the highest-risk patients could lead to hospital admission, which this outpatient oral therapy is intended to avoid. Patients should be counseled that the dysgeusia should cease shortly after completing the 5-day course of ritonavir-boosted nirmatrelvir.

While there are no specific recommendations from the manufacturer on ways to prevent dysgeusia, a number of options, including coating the mouth with a spoonful of peanut butter or chocolate milk, have been advocated by some infectious diseases specialists. Cinnamon gum has been recommended by some due to its ability to overpower the taste buds as well as increase saliva production locally that may inhibit worsening of dysgeusia when the mouth is dried out.

TEACHING OLD DOGS NEW TRICKS: METFORMIN, IVERMECTIN, AND FLUVOXAMINE FOR COVID-19?

Throughout the pandemic, a large number of older drugs have been tested for COVID-19. Often, an initial positive finding in a lower quality trial is not confirmed when studied more rigorously. For example, hydroxychloroquine with azithromycin or as monotherapy was originally used by many prescribers based on lower quality studies. These benefits were not confirmed in higher quality studies, and this agent is not recommended for use in COVID-19 in NIH guidelines.

Metformin is a first-line antidiabetic agent with in vitro activity against SARS-CoV-2. This agent also possesses anti-inflammatory activity, decreasing interleukin production and risk of thrombosis. Ivermectin has in vitro activity against SARS-CoV-2 at levels much higher than achievable in humans. While smaller studies have shown no benefit, concerns over underdosing necessitate more study, particularly when it is used in populations with an overall low risk. Fluvoxamine has anti-inflammatory properties as well and in the TOGETHER trial, performed well when used early in the disease course in high-risk patients.¹²

A recent higher-quality study assessed the efficacy of these repurposed drugs and found them all to be lacking. In a 2x3 factorial design study, adults with overweight or obesity had similar outcomes with the 3 drugs and placebo with respect to hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visits, hospitalizations, and death. The fluvoxamine doses in this study were 50 mg twice daily; higher doses may be needed for this drug to work as an antiviral agent. Ivermectin did not show any benefit in any subgroup, even at a dose higher than those used previously. Metformin was interesting in that when evaluating emergency department visits, hospitalization, or death (removing self-reported hypoxemia), it was statistically beneficial. Other outcomes had numerically lower odds ratios, but these did not reach statistical significance. With its low overall cost and favorable tolerability when titrated appropriately, metformin would be a reasonable choice for further testing.¹³

MONOCLONAL ANTIBODIES

Real-World Outcomes of Bebtelovimab: The Growing Problem of Resistant Omicron Subvariants

While many different monoclonal antibodies have been authorized over the course of the pandemic, only bebtelovimab is currently recommended in NIH guidelines due to its activity against the omicron subvariants. This advantage is currently diminishing as subvariants that are likely resistant to bebtelovimab have become the dominant strains circulating in the United States.

Approval of the EUA for bebtelovimab was based largely on in vitro data. A recent publication out of the northeast United States provides clinical data from a retrospective cohort study. The retrospective cohort study compared high-risk ambulatory patients with a positive SARS-CoV-2 test who were treated in spring 2022 with a single intravenous dose of bebtelovimab and matched patients. The adjusted odds ratio of hospitalization or death was 0.50 (95% CI 0.31-0.80). Among propensity score-matched patients, the risk of hospitalization or death was 3.1% in the treated group and 5.5% in the non-treated group (conditional OR = 0.53; 95% CI 0.32-0.86). The greatest benefit of treatment was in older patients, immunocompromised patients, and fully vaccinated patients.¹⁴

While those data are encouraging, a statement from the NIH COVID-19 Treatment Guidelines Panel provides levity about the emerging subvariants: “When resistant Omicron subvariants (e.g., BQ.1, BQ.1.1) represent the majority of infections in the region, clinicians cannot rely on bebtelovimab to be effective for the treatment of COVID-19. Ritonavir-boosted nirmatrelvir, remdesivir, and molnupiravir are expected to be active against these resistant subvariants.”¹⁵

Pipeline Updates: Sabizabulin and Vilobelimab

As we continue to transition from pandemic to endemic status for SARS-CoV-2 and COVID-19, more therapeutics are welcomed to reinforce the armamentarium of safe and effective agents. A number of options are currently being evaluated, including some with novel mechanisms of action that may work independently or complement current therapies, including therapies for severely ill inpatients.

In preclinical modeling evaluations, sabizabulin has demonstrated dual antiviral and anti-inflammatory properties. It works by disrupting formation of microtubule filaments that are needed for viral infection, including by SARS-CoV-2. In a clinical trial of 204 patients with hospitalized patients with moderate-to-severe COVID-19, this agent was superior to placebo at a planned interim analysis for mortality (55.2% reduction, from 45.1% with placebo to 22.2% with sabizabulin). Secondary outcomes favored sabizabulin as well, with a 43% relative risk reduction in days in intensive care, 49% reduction in mechanical ventilation days, and a 26% reduction in hospital length of stay. Adverse events were similar with placebo and sabizabulin.¹⁶

The FDA’s Pulmonary-Allergy Drugs Advisory Committee considered an EUA request for sabizabulin in November 2022. In a split vote of 8 to 5, the panel recommended against approval at this time given the small number of participants in the clinical trial. FDA usually but not always follows the recommendation of advisory panels.

Vilobelimab is an intravenous, anti-C5a monoclonal antibody that is being evaluated for the treatment of patients with severe COVID-19 and for severe sepsis and septic shock.^17,18 Complement system activation through C5a — a known anaphylatoxin — increases white blood cells at the infection site, inducing tissue injury and microclotting. While promising in these trials, more data are needed for a full evaluation by FDA.

LONG COVID UPDATE

Significant progress has been made with COVID-19 vaccines to decrease hospitalization and death from severe manifestations of disease. In addition, many safe and effective intravenous and oral therapies for both inpatients and outpatients have significantly improved outcomes. However, one area of significant concern going forward is the longer-term lingering effects of COVID-19 that persist after the acute phase of infection. Due to the ubiquitous presence of the ACE2 receptor throughout the body, long COVID symptoms have been reported in several organ systems, with central nervous system (e.g. brain fog) symptoms and nonspecific shortness of breath and/or fatigue frequently reported. Because of the nature of these concerns, longer studies are now being completed to provide more details on long COVID.

An initial study published in January 2022 from the Brookings Institution conservatively estimated that approximately 1.5 million job vacancies in the United States could be due to long COVID, accounting for approximately 15% of the labor shortage at the time. This analysis was limited due to the time course required to properly evaluate these longer-term symptoms. In June 2022, the U.S. Census Bureau and the CDC’s National Center for Health Statistics added 4 questions about long COVID to the Household Pulse Survey to gather more specific information about long COVID prevalence. If survey participants confirmed they had tested positive for COVID-19, they were asked these questions:

1. How would you describe your coronavirus symptoms when they were at their worst?
2. Did you have any symptoms lasting 3 months or longer that you did not have prior to having coronavirus or COVID-19?
3. Do you have symptoms now?
4. Do these long-term symptoms reduce your ability to carry out day-to-day activities compared with the time before you had COVID-19?

Survey results demonstrated that approximately 16 million working Americans currently have long COVID symptoms, with 12.5% to 25% of these currently out of work due to symptoms. The annual cost of lost productivity is somewhere between $170 billion and $230 billion annually. Due to the tremendous impact of this disease on society, these recommendations have been discussed for minimizing the occurrence and the impact of long COVID:

1. Better prevention and treatment options
2. Expanded paid sick leave
3. Improved employer accommodations
4. Wider access to disability insurance
5. Enhanced data collection

While these initiatives are appropriate and welcome, prevention may be the most critical aspect. While long COVID symptoms are more strongly associated with severe disease that is minimized by vaccinations, it has occurred in patients whose symptoms were mild to moderate in severity. In addition, data are limited demonstrating any decrease in these symptoms even when treated with currently authorized antiviral or antibody agents. When asked by patients about long COVID, pharmacists can refer patients to the CDC resources for information. Many of these symptoms resolve in patients over time, and this can be reassuring to patients who have unfortunately been affected with long COVID. The NIH continues to support research into long COVID and its both in adults and children and its physical and mental health impact.

REFERENCES

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