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INTRODUCTION

The final weeks of 2021 were quite busy with regard to the coronavirus disease 2019 (COVID-19) pandemic. While the focus rightfully has been on the delta strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the summer, a newly identified mutant variant, omicron, quickly became the dominant strain in the United States by the end of the year. The first case of omicron was identified in the United States on December 1, 2021, but by January 8, the U.S. Centers for Disease Control and Prevention (CDC) said that the omicron variant made up 98.3% of strains detected, eclipsing the delta variant, which stood at 1.7% of circulating strains. The uptick in cases was nationwide, with the colder weather areas such as Boston and New York City affected initially.

Some good news on outpatient therapies has arrived with 2 novel oral agents authorized by the FDA for outpatient treatment. In addition, a frequently used inpatient therapy has now demonstrated benefit in the outpatient setting as well.

This article provides education on the omicron variant, potential ambulatory therapies for COVID-19, and pertinent updates on vaccine therapies as well as other important topics related to prevention of SARS-CoV-2 infections and treatment when they occur.

Omicron Timeline

South Africa first reported a novel SARS-CoV-2 variant just before Thanksgiving to the World Health Organization (WHO), which designated it omicron (B.1.1.529); it had been detected in Botswana and South Africa approximately 2 weeks earlier. On November 29, the United States designated omicron a variant of concern. By the end of the year, omicron had displaced delta as the predominant strain in the United States and many other countries.

Omicron: Tale of the Tape

The omicron variant is characterized by more than 30 mutations in the spike protein,¹ primarily located in the N-terminal domain (NTD) and receptor binding domain (RBD). In addition, the omicron variant RBD binds to human angiotensin converting enzyme 2 (ACE2), the primary means for viral entry into human cells, with increased affinity compared to the original parent Wuhan strain.¹

Clinical Implications of Omicron’s Mutations

While it is still too early to fully know the ultimate manifestations of the many mutations found in the omicron strain, in vitro studies as well as some initial findings internationally have provided some clues regarding how omicron might affect vaccinated and unvaccinated individuals.

Transmissibility

While the delta strain was much more transmissible than the parent (wild type) SARS-CoV-2 strain, omicron appears to be even more transmissible than delta. Once in human cells, omicron replicates faster than the delta variant, which likely produces more virus in exhalations and increases transmissibility. A study from the University of Hong Kong revealed a 70 times faster multiplication rate for the omicron variant compared with the delta variant in the upper airway bronchus. Another study using SARS-CoV-2 omicron pseudoviruses in the laboratory demonstrated 4 times more infectivity of cells compared with parent strain and twice the infectivity of the delta strain.² These data, along with exponential growth in the United States and many other countries, strongly suggest increased transmissibility. However, transmissibility is not the only important variable when evaluating omicron.

Immune Escape

Immune escape or “evasion” refers to the ability of a pathogen to avoid antibodies produced by the human immune system in response to previous infection or vaccination. Because of the SARS-CoV-2 mutations detailed above, the omicron variant exhibits immune escape, even in vaccinated individuals who have received 2 doses of an mRNA vaccine (which was deemed “fully vaccinated” at the time this program was prepared). This immune escape in combination with increased transmissibility most likely explains the explosion of symptomatic cases,³ even in countries with extremely high vaccination or previous infection rates.⁴

Monoclonal Antibodies: Mixed Effectiveness Against the Omicron Variant

Monoclonal antibodies have been a key treatment modality for COVID-19 because they offer an effective ambulatory option that decreases the risk of hospitalization or death in patients identified early with mild-to-moderate disease who are at high risk of complications. Before identification of the omicron variant, 3 monoclonal antibodies were authorized for emergency use by the U.S. Food and Drug Administration (FDA) for treating outpatients with COVID-19: sotrovimab, casirimivab/imdevimab, and bamlanivimab/etesevimab. In addition, the latter 2 products are authorized for postexposure prophylaxis in adolescents and adults (12 years or older and at least 40 kg body weight) who test positive for SARS-CoV-2 and are at high risk of progressing to severe COVID-19.

Early data from several studies strongly indicate that the omicron variant escapes several of these monoclonal antibodies as well as others being evaluated, likely leading to ineffective therapy. The Infectious Diseases Society of America (IDSA) guidelines summarize the currently available studies, noting that casirivimab/imdevimab and bamlanivimab/etesevimab provide no neutralization efficacy.

Notably, sotrovimab — which has to date been the least used monoclonal antibody in the United States — retains activity against the omicron variant because its preserved epitope is primarily positioned outside of the mutated RBD.

Because of these findings, the Office of the Assistant Secretary for Preparedness and Response halted any further distribution of casirivimab/imdevimab or bamlanivimab/etesevimab as it is unlikely that these agents will retain activity against the omicron variant. This was rescinded on December 31 because of potential albeit unlikely prevalence of potential delta variants in a particular geographic area. Sotrovimab shipments resumed the week of December 23, with an additional 300,000 doses expected during January 2022. This allocation is not likely to meet demand considering the criteria outlined in the emergency use authorization that allow many patients to qualify for treatment.

Any “Good” News With the Omicron Variant?

Despite all the bad news with regard to omicron’s increased transmissibility and immune escape, some news about this variant is cautiously optimistic. First, the same reference above out of Hong Kong that demonstrated a much higher replication rate also found omicron to have less lower respiratory tract (lung) infectivity; if this is confirmed as more clinical data become available, it likely means less severe disease. An in vitro lab study out of the UK also demonstrated decreased lung infectivity compared with the delta variant.⁵ Real-world data from countries where omicron has circulated the longest have demonstrated significantly lower numbers of patients requiring hospitalization, especially intensive care unit admissions, indicating less severe disease. In Scotland, an article submitted for publication but not yet peer-reviewed showed a nearly two-thirds reduction in COVID-19-related hospitalizations due to omicron variant. Initial reports out of the United Kingdom and South Africa are also positive, suggesting significantly decreased hospitalizations caused by the omicron variant compared with the delta variant. Important to note is that these reports are from countries with very high vaccination rates, including boosters, and/or a high incidence of previous COVID-19 infection. The most recent data out of California, a highly vaccinated population, demonstrates also less severe disease and shorter lengths of stay with the omicron variant.

A recent MMWR report, which described an omicron cluster outbreak in Nebraska, demonstrated a shorter incubation period compared with delta (approximately 3 days) and a milder clinical syndrome than previous strains in patients who had been previously infected or vaccinated.⁶ if these characteristics of increased transmissibility and immune escape with less severe disease prove true for the omicron variant, the COVID-19 pandemic will likely be pushed toward more of an endemic state, in which nearly every U.S. citizen will have acquired immunity through vaccination and/or infection.

Vaccine Protection Against the Omicron Variant

An analysis of data from the Israeli Clalit Health Services for people 50 years of age or older demonstrated a mortality benefit for those who received a booster dose of BNT162b2 (Pfizer/BioNTech) at least 5 months after receiving 2 doses of that vaccine (0.16 vs. 2.98 deaths per 100,000 persons; adjusted hazard ratio of 0.10 [95% CI 0.07-0.14; P <0.001]).⁷ However, because of the short timeframe during which omicron has been the dominant strain in many countries, data are limited concerning how well vaccines work in a predominantly omicron-infected population.

A yet-to-be-peer-reviewed article demonstrated that a 2-dose vaccine series of BNT162b2 provides minimal vaccine effectiveness (33%) versus symptomatic SARS-CoV-2 caused by the omicron variant. Providing a booster dose of the same vaccine increases vaccine effectiveness to about 75% at 2 weeks or more after receiving the booster dose. Prevention of severe disease for the currently defined “fully vaccinated” schedule of 2 doses was higher at about 70% for those with the omicron variant.⁸ Because of the small number of cases of omicron infections in this study as well as the lag time required for these cases to occur and resolve, severe disease prevention through booster doses could not be evaluated within the timeframe of the study.

Modelling data from the United Kingdom suggest a booster effectiveness rate versus severe disease of approximately 80.1% for omicron strains. Limited data regarding the mRNA-1273 vaccine (Moderna) shows that a booster dose increased omicron neutralization titers, but more data are needed to evaluate patient outcomes.⁹ A recent release from Johnson & Johnson/Janssen demonstrated booster doses with their vaccine demonstrated 85% effectiveness in preventing hospitalizations in South Africa during the recent period in which omicron was the dominant strain (82%–98% of strains).

Booster Recommendations Updated

Prevention of COVID-19 disease, especially severe disease marked by hospitalization and death, through vaccination and boosters is a priority, especially given the increase in cases that are occurring with the omicron variant. While the severity of omicron at this time appears to be less than the delta variant, the increased transmissibility and immune escape will likely result in high numbers of cases with subsequent stress on the health care system. In addition, data suggest that T-cell immune response from vaccines should remainsl effective versus the omicron variant.

The booster injection recommendation has been progressively expanded among a number of different populations. All Americans 18 years of age or older are now eligible for a booster vaccination, defined as a dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) 5 months or more after the initial 2-dose series with either of those vaccines or 2 months after an initial Johnson & Johnson/Janssen vaccine. In addition, 12–17-year-olds are eligible for a booster vaccination at 5 months after an initial Pfizer/BioNTech vaccine series (the only one authorized for this age group). As of January 9, 2022, just over one-third of patients eligible for a booster dose have received one (36.3%), including 60.4% of patients 65 years of age or older having received a booster injection.

Remdesivir: An Option in the Outpatient Setting?

Interest continues to increase in therapies that may be given earlier in the course of COVID-19 — and preferably to ambulatory patients — to reduce their chances of developing the inflammatory cascade that can lead to severe disease, hospitalization, and death. Remdesivir (Veklury) is an antiviral agent that works via RNA polymerase inhibition and therefore should be most beneficial earlier in COVID-19 when SARS-CoV-2 is rapidly replicating. However, to date, its use has been restricted to the inpatient setting for patients hospitalized with COVID-19.

A recently published trial, the PINETREE study, evaluated remdesivir in ambulatory patients with COVID-19 who had symptoms identified within 7 days of enrollment. Participants had confirmed SARS-CoV-2 within 4 days of screening for entry into the study. They also had at least 1 risk factor for progression to severe disease, such as obesity, age of 60 years or older, or diabetes mellitus. Participants were excluded if they were requiring or would be expected to require supplemental oxygen. Participants were randomized in a double-blind manner to placebo or remdesivir 200 mg IV on day 1 followed by 100 mg IV on days 2 and 3. The primary efficacy endpoint was the composite of hospitalization or death by day 28. The primary safety endpoint was any adverse event. Results showed that the primary endpoint occurred in 0.7% of remdesivir patients and 5.3% of placebo patients, resulting in hazard ratio of 0.13; CI 0.03–0.59; P = 0.008. The reduced risk was driven by a decrease in hospitalizations, as no patients died by day 28. No significant adverse events were linked to remdesivir.¹⁰

Similar to monoclonal antibodies, the need for intravenous administration of remdesivir presents logistical challenges that oral agents lack. While use of remdesivir would be considered an off-label use if ambulatory patients with COVID-19 are treated, guidelines from both the National Institutes of Health (NIH) and IDSA recommend that remdesivir be considered in this setting along with monoclonal antibodies.^11,12

As detailed earlier, sotrovimab is the monoclonal antibody expected to retain activity against the omicron variant. However, the large number of potentially eligible patients with confirmed COVID-19 in this setting is much greater than the number of available doses both now and for the foreseeable future. That could open the door for off-label use of remdesivir in ambulatory patients with mild-to-moderate COVID-19 of recent onset (≤7 days) who are at high risk of progressing to severe disease.¹²

Shortened Isolation and Quarantine Periods

As concern mounted about the surge in SARS-CoV-2 infections caused primarily by omicron variant and related employee absences, the CDC has shortened isolation and quarantine periods for health care workers. Most transmission of omicron occurs 1 to 2 days before symptom onset and during the first 2 to 3 days of symptoms. Workers with COVID-19 who are asymptomatic after 7 days and have a negative test may return to work. If staffing shortages are present, a case-by-case assessment may be made to allow for shorter isolation periods. Health care workers who have been fully vaccinated and received a booster injection are not required to quarantine at home after a high-risk exposure.

For the general public with confirmed COVID-19 infection, the isolation period has been decreased from 10 days to 5 days under certain conditions. Those who are asymptomatic after 5 days of isolation or have symptom improvement may leave isolation as long as masks are worn in public to minimize potential spread. In addition, patients must be afebrile before leaving isolation. Those who are fully vaccinated and have received a booster shot do not have to quarantine when exposed to COVID-19 per CDC definitions but should wear a well-fitting mask when around others for 10 days. Those who do not meet these criteria should quarantine for 5 days followed by strict mask usage for an additional 5 days.

New Monoclonal Antibody for Pre-exposure Prevention of COVID-19

On December 8, 2021, FDA approved an emergency use authorization (EUA) for a new long-acting monoclonal antibody combination. Tixagevimab co-packaged with cilgavimab (Evushield) became the first and thus far only product authorized for pre-exposure prophylaxis of COVID-19 in patients 12 years of age or older who weigh at least 40 kg. Tixagevimab and cilgavimab are both SARS-CoV-2 spike protein-targeted attachment inhibitors derived from Chinese hamster ovary cells with prolonged elimination half-lives of approximately 80–90 days. The authorization was based primarily on the results of the PROVENT study, which demonstrated a 77% reduction in COVID-19–acquired infection across a 6-month period of evaluation.

Tixagevimab/cilgavimab is administered intramuscularly in 2 separate, consecutive, one-time injections (150 mg of each component administered in separate syringes and at separate sites [preferably 1 in each of the gluteal muscles) to patients with moderately to severely compromised immune systems secondary to medical conditions (e.g., active cancer) or immunosuppressive medications (e.g., transplant rejection medications such as mycophenolate mofetil). A detailed list of immunosuppressive qualifying conditions is in the FDA-approved fact sheet for this product. In addition, patients who have a history of severe reaction to COVID-19 vaccine or vaccine components are eligible for this therapy.

Two Oral Agents Authorized for Ambulatory Treatment of COVID-19

Nearly 2 years into the COVID-19 pandemic, an early Christmas present arrived when FDA authorized 2 oral antiviral medications on back-to-back days. Both products should be available by prescription only in early 2022, according to an initial distribution plan.

Nirmatrelvir/ritonavir

Authorized first was nirmatrelvir/ritonavir, with the trade name Paxlovid, which will be manufactured by Pfizer. It is currently authorized for mild-to-moderate COVID-19 in ambulatory adults and adolescents aged 12 years or older who weigh at least 40 kg and are at high risk of severe disease manifested by hospitalization or death. It should be given to the patient as soon as possible and within 5 days of symptom onset. The treatment regimen consists of 2 nirmatrelvir 150 mg tablets plus 1 ritonavir 100 mg tablet twice daily for 5 days; these 30 tablets are dispensed in blister packs. Patients with moderate renal impairment, defined as estimated glomerular filtration rate (eGFR) of 30 mL/min to <60 mL/min should receive 2 tablets (1 nirmatrelvir 150 mg tablet plus 1 ritonavir 100 mg tablet) twice daily for 5 days (20 tablets total). This agent is not recommended for use in patients with eGFR less than 30 mL/min.

Nirmatrelvir is a peptidomimetic inhibitor of the main protease (Mpro) of SARS-CoV-2, also referred to as 3C-like protease (3CLpro) or nsp5 protease. This is likely why one of the physical markings on the side of the nirmatrelvir tablet is “3CL” with “PFE” on the other side for Pfizer. Ritonavir is a well-known protease inhibitor in human immunodeficiency virus (HIV) 1 therapy, but it exerts no activity against SARS-CoV-2 Mpro; it is used as a pharmacokinetic booster for nirmatrelvir, similar to its role in combination with other protease inhibitors in HIV therapy.

The primary study demonstrating efficacy and ultimately securing authorization by the FDA was the EPIC-HR study. This was a randomized, double-blinded, placebo-controlled trial in ambulatory patients with laboratory confirmed SARS-CoV-2. Similar to the monoclonal antibody studies, participants had a prespecified risk factor for progression to severe disease or were 60 years of age or older. An important exclusion criterion was previous COVID-19 or SARS-CoV-2 vaccination.

The primary outcome in this study was hospitalization or death due to COVID-19 through day 28 of monitoring. It was decreased among participants in the nirmatrelvir/ritonavir group compared with placebo, with a relative risk reduction of 88% in the final analysis. Among 2,085 total participants evaluated within 5 days of symptom onset, the primary outcome occurred in 0.8% of those receiving active therapy and 6% of those on placebo (P <0.0001). No deaths occurred among participants receiving nirmatrelvir/ritonavir, compared with 12 deaths in the placebo arm.

These results held up across a number of subgroups, with the only subgroup not showing better outcomes being participants who had received or were expected to receive COVID-19 monoclonal antibodies. Among participants treated within 3 days of symptom onset, the primary outcome occurred in 0.7% of those on active therapy and 6.5% of those on placebo (P <0.0001). In a subgroup analysis of participants whose viral load was measured (n = 499), nirmatrelvir/ritonavir decreased viral load significantly compared with placebo patients by 10-fold).

The EPIC-SR study evaluated nirmatrelvir/ritonavir in adults with standard risk (low risk of hospitalization or death) or vaccinated adults with 1 or more risk factors for progression to severe disease. Compared with results in participants receiving placebo, the intervention group did not meet the primary endpoint of alleviation of all COVID-19 symptoms for 96 consecutive hours. A decrease in hospitalizations (secondary endpoint) of 70% relative to placebo was demonstrated, representing 0.7% of participants receiving nirmatrelvir/ritonavir and 2.4% of those on placebo (P = 0.051), a difference that did not quite meet statistical significance in this follow-on analysis of 80% of enrolled participants; final statistics and results from the full group will follow.

Ritonavir is a potent CYP3A inhibitor that is involved in several important drug interactions. A number of these interactions are well documented because of ritonavir’s use in people living with HIV. However, with protease inhibitors no longer being a first-line recommended agent for HIV therapy, brushing up on potential interactions with nirmatrelvir/ritonavir is a good idea, as pharmacists are likely to receive many questions from prescribers and need to intervene to avoid contraindicated combinations of medications. For example, a number of common medications are not recommended for use with nirmatrelvir/ritonavir, such as rivaroxaban (Xarelto), colchicine, sildenafil, salmeterol, and simvastatin; concomitant use with ritonavir could lead to accumulation and toxicity of these interacting agents.

Atorvastatin, digoxin, and quetiapine are among the drugs that interact with nirmatrelvir/ritonavir but might be needed to manage other conditions. In such situations, monitoring is useful for avoiding toxicity. Immunosuppressants, such as cyclosporine and tacrolimus, would require very close serum monitoring with nirmatrelvir/ritonavir therapy. If monitoring not feasible, nirmatrelvir/ritonavir should be avoided. A detailed list of potential drug interactions is provided in the nirmatrelvir/ritonavir fact sheet. Another excellent resource for in depth evaluation of potential drug interactions with nirmatrelvir/ritonavir is available at no cost on the University of Liverpool website.

For a number of drug interactions, clinical judgment is required because of divergent recommendations of manufacturers based on ritonavir use in HIV therapy and other expert resources. For example, consider the interaction of ritonavir with a commonly prescribed anticoagulant, apixaban. Apixaban is a substrate of P-glycoprotein and is metabolized by primarily CYP3A4. Therefore, accumulation of apixaban is possible secondary to ritonavir inhibition, leading to an increased risk of bleeding. However, the nirmatrelvir/ritonavir fact sheet does not list an interaction of apixaban with ritonavir. The apixaban product labeling recommends reducing apixaban doses of 5 or 10 mg twice daily by 50% when co-administered with ritonavir. If patients are taking apixaban 2.5 mg twice daily, co-administration with ritonavir is not recommended.¹³

On the other hand, the University of Liverpool drug interaction website recommends avoiding the combination, although the site notes this advice is based on very little evidence. A boxed warning in the apixaban product labeling cautions that abrupt cessation of therapy is associated with increased risk of thrombotic events and premature discontinuation is therefore not recommended when avoidable. A risk–benefit assessment will be required for a number of potential interactions, especially those with high-risk agents such as apixaban, even during courses of nirmatrelvir/ritonavir lasting only 5 days.

Molnupiravir

The second oral antiviral agent authorized by the FDA was molnupiravir (no trade name yet in United States), manufactured by Merck. It is currently authorized for mild-to-moderate COVID-19 disease in ambulatory patients 18 years or older who are at high risk of severe disease manifested by hospitalization or death. As with nirmatrelvir/ritonavir, molnupiravir should be taken as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset. Molnupiravir is not recommended in pediatric patients because of the possibility of bone and cartilage toxicity. It is also not recommended for use in pregnant women because of concerns over potential embryo-fetal toxicity.

The treatment regimen consists of 4 molnupiravir 200 mg capsules (800 mg) orally every 12 hours for 5 days, with or without food, for total of 40 capsules for entire treatment course. If patients remember a missed dose within 10 hours of the usual time of administration, they should take the dose and resume normal dosing schedule; if more than 10 hours has passed, the dose should be skipped and the next one taken at the scheduled time. No specific dosage adjustments are required for renal or hepatic impairment, and to date, no significant drug interactions have been identified.

Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication by misdirecting the SARS-CoV-2 polymerase and ultimately making the virus noninfectious and unable to replicate. Most of the data leading to FDA authorization were based on the MOVe-OUT trial published recently in the New England Journal of Medicine. A total of 1,433 participants were randomized in a double-blind, placebo-controlled manner to 5 days of molnupiravir 800 mg twice daily or placebo. Participants were ambulatory individuals who were unvaccinated, had laboratory-confirmed SARS-CoV-2, and had signs and symptoms consistent with mild-to-moderate disease within 5 days of enrollment. All patients also had at least 1 risk factor for progression to severe disease, similar to the EPIC-HR trial. The primary efficacy endpoint was hospitalization or death at day 29.¹⁴

At a prespecified interim analysis once 50% of patients had been enrolled, molnupiravir had demonstrated a nearly 50% reduction in the primary endpoint relative to placebo. However, by the final analysis, this had decreased to an approximate 30% decrease in the primary endpoint compared with placebo (6.8% vs. 9.7%; 95% CI –5.9 to –0.1). Prespecified results showed that molnupiravir significantly reduced baseline viral load compared with placebo at days 3, 5, and 10. There was 1 death in the molnupiravir arm and 9 deaths in the placebo arm, all considered by investigators to be COVID-19 related.¹⁴

These results are puzzling for a few reasons. First, while most subgroups benefitted from molnupiravir therapy, compared with placebo, participants in the following subgroups had better results with placebo¹⁴:

• Patients with SARS-CoV-2 nucleocapsid antibodies at baseline (indicating prior infection)
• Patients with low viral load at baseline
• Patients with diabetes at baseline
• Patients who identified as Asian only, Black only, Native American only, or mixed Black–Native American–White
• Patients enrolled in the Asia-Pacific region

Some of these subgroups had wide confidence intervals, especially those with small sample sizes.¹⁴

In the PINETREE study discussed earlier, the primary endpoint was reduced significantly, similar to results with nirmatrelvir/ritonavir, despite not demonstrating the significant viral load reduction observed in the molnupiravir trial.¹⁰ Phase 2 studies with molnupiravir demonstrated less benefit later in the disease course, defined as more than 3 to 5 days after symptom presentation or admission to the hospital for COVID-19. In MOVe-OUT, approximately half of enrolled patients received therapy within 72 hours of symptom onset. For these reasons, the IDSA and NIH guidelines recommend molnupiravir only when other potential ambulatory options are not available/optimal.^11,12

The FDA’s decision to block pharmacists from ordering oral antivirals such as molnupiravir or nirmatrelvir/ritonavir is disappointing, as this further delays receipt of effective therapy after confirmation of SARS-CoV-2 infections. Pharmacists are well trained to order these agents, including screening for potentially harmful drug interactions with ritonavir.

These oral agents join a number of potential therapies that can be used in the ambulatory setting to decrease hospitalization and mortality in high-risk patients. The NIH guidelines recommend the following order of preference for these therapies:

1. Nirmatrelvir/ritonavir
2. Sotrovimab
3. Remdesivir
4. Molnupiravir

However, certain characteristics can make use of a nonpreferred agent better in some clinical situations. Table 1 details some of the characteristics used in comparing and choosing a COVID-19 therapy in the ambulatory setting.

Vaccines for Young Children

Pfizer/BioNTech recently provided an update on a trial evaluating BNT162b2 in children 6 months to under 5 years of age. An external independent data monitoring committee review identified a need to evaluate a third dose of 3 µg at least 2 months after the second dose of a 2-dose series to ensure protection of this age group. A prespecified analysis of antibody production was evaluated in patients who were 1 month of age or older following their second dose. Compared with a baseline population of 16–25-year-old participants, noninferiority for those ages 2 to under 5 years was not met. Noninferiority was met for the 6–24-month-old population, and the safety profile was deemed favorable for all participants evaluated. If the third dose of 3 µg is noninferior in each of these populations, an emergency use authorization will be sought by these companies in the first two quarters of 2022.

Vaccinations in this young age group is critical. Young children are the only ones not currently authorized for vaccine dosing, and this continues to impede development of long-term herd immunity. Pediatric hospitalizations have surged as a result of the spread of the omicron variant, with nearly a 50% increase in pediatric admissions during December 2021.

Don’t Forget About Influenza!

While 2020–2021 was an extremely mild season for influenza, early indications are that the 2021–2022 season is an active one. Influenza activity and related hospitalizations are increasing, with the central and eastern United States reporting the earliest activity, primarily among patients aged 5–24 years. Cases in older individuals (>25 years of age) were beginning to increase at the time this program was prepared in January 2022. The strain being most commonly detected was influenza A (H3N2 strain). While some antigenic drift has occurred, most infections have been caused by strains covered by this season’s influenza vaccines. On the CDC website, Fluview is an outstanding resource for week-to-week updates on all things influenza, including a map of current influenza-like illness activity.

The CDC said that influenza vaccination rates are down compared with last season, likely because people are less motivated since last season’s cases were low. However, people need to know that school closures, masks, and physical distancing — all common last season — protect against transmission of the influenza virus. Pharmacists have a tremendous opportunity this season to educate patients on benefits of both influenza and COVID-19 vaccines. Both of these vaccines (including COVID-19 booster shots) can be given simultaneously in a single encounter, keeping in mind that significant arm soreness and local effects are likely, especially if each vaccine is given in a separate arm.

Oral Fluvoxamine as a Potential Outpatient COVID-19 Option

While there have been many failed repurposed agents for COVID-19, a medication recently demonstrated promise. Fluvoxamine, a little-used selective serotonin reuptake inhibitor approved for obsessive-compulsive disorder, was studied in a trial recently reported in Lancet Global Health.

This placebo-controlled, randomized, adaptive platform study was performed in high-risk Brazilian adults with confirmed SARS-CoV-2 who were at risk for severe disease. Fluvoxamine 100 mg orally twice daily for 10 days was compared with placebo (or other treatment groups as part of TOGETHER trial). The primary composite efficacy endpoint was hospitalization (retention in an emergency department setting or transfer to a tertiary hospital because of COVID-19) up to 28 days after randomization (intention to treat). Among nearly 1,500 participants, the primary outcome occurred in 11% of those receiving fluvoxamine and 16% of those on placebo, a statistically significant relative risk reduction (0.68; 95% CI 0.52–0.88). This also surpassed the prespecified threshold of 97.6% at 99.8%.¹⁵

While currently the IDSA and NIH guidelines do not recommend fluvoxamine for the treatment of COVID-19 outside of a clinical trial, further trial findings may ultimately result in a recommendation for fluvoxamine use in ambulatory patients with COVID-19. 

REFERENCES

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