COVID-19 in 2025: Addressing disease burden, access inequities and economic impact
Introduction
Despite advancements in vaccination and treatment, COVID-19 was responsible for 1.8% of all deaths in the United States during the week of January 4-11, 2025.1-3 The virus disproportionately affects high-risk populations including elderly and immunocompromised individuals and those with key chronic comorbidities.4-6
This article explores the burden of COVID-19, advancements in its prevention and treatment, inequities in health care access, potential strategies to address inequities and economic and societal impacts of the disease, with a particular focus on progression to severe disease and long COVID-19. Managed healthcare is uniquely situated to optimize patient outcomes, improve resource use and promote economic efficiency.
Burden of disease
On a global scale, peak SARS-CoV-2 infection rates have decreased since 2021.7 Despite this trend, the weekly infection rates have fluctuated, with the peak infection rate being higher in 2024 than in 2023 (17.8% vs. 14.5%).8 As of November 2024, the most prevalent SARS-CoV-2 variants in the US are KP.3.1.1 and XEC, which is the only variant currently being monitored by the World Health Organization with increasing global prevalence.9,10 As a low-risk variant, XEC has not been associated with reports of increased disease severity compared to other Omicron variants.10 However, compared to the prior KP.3 variant, XEC and KP.3.1.1 have significantly higher infectivity rates.11
CLINICAL BURDEN: SEVERE COVID-19 AND LONG COVID
This higher infectivity is relevant for patients at elevated risk of severe COVID-19, which is defined as disease resulting in hospitalization, admission to the intensive care unit (ICU), intubation, mechanical ventilation or death.12 As of January 29, 2025, the overall rate of COVID-19-related hospitalizations during the 2024-2025 season was 38.0 per 100,000 people.13 Among 1,320 adults hospitalized with COVID-19 in 12 US states between October 2023 and April 2024, 18.4% were admitted to an ICU, 8.4% were given mechanical ventilation and 6.9% died while hospitalized.14
The higher infectivity rate of current COVID-19 variants is also relevant for patients who experience long COVID, an infection-related chronic condition characterized by symptoms persisting for at least 3 months.15 Long COVID presents variously, either exacerbating existing conditions (eg, cardiovascular disease, chronic kidney disease, diabetes) or presenting new ones (eg, fatigue, sleep disturbance, dyspnea and brain fog).15-20 This prolonged condition can follow COVID-19 infection of any severity and impact individuals regardless of prior health status. Long COVID may diminish patients’ quality of life and impair their ability to work, attend school and participate in activities of daily life.15,21,22 As of September 2024, approximately 17.9% (95% CI, 17.3%-18.6%) of all US adults have ever experienced long COVID, according to results from a National Center for Health Statistics survey of 45,717 individuals.23
Risk factors
The presence of key comorbidities increases the risk of developing severe COVID-19.6 These comorbidities include immunocompromised states; chronic diseases of the lungs or kidneys; diabetes; hypertension; obesity; cardiovascular, neurologic, or mental health conditions; and some types of disabilities.5,6,24-27 Having more than one of these comorbidities further increases risk.6
Advanced age, as well as certain race and geographical status, increase the risk of COVID-19-related mortality. In 2023, 488.1 of every 100,000 individuals aged at least 85 years died from COVID-19-related disease.4 By race, individuals with non-Hispanic White or American Indian/Alaskan Native ancestry are at highest risk, with 2023 COVID-19-related mortality rates of 19.6 per 100,000 individuals and 18.7 per 100,000 individuals in these populations, respectively.4 Persons living in high-density population centers like apartment and mobile home communities are also at increased risk of transmission and mortality.28,29
Patients at higher risk of experiencing long COVID include women and those with severe acute illness, unvaccinated status, elevated body mass index, cardiovascular disease or autoimmune disorders.30-33
ECONOMIC BURDEN
The economic impact of COVID-19 continues to be substantial. In a Markov-based modeling study, the total costs of the disease on the US health care system during the 2023-2024 vaccination season were estimated to be $54.7 billion. Direct costs related to vaccination, outpatient services, hospitalization and long COVID totaled $37.3 billion; indirect costs related to lost productivity due to vaccination, COVID-19 disease and long COVID reached $17.4 billion.34
Severe disease accounts for an outsized portion of these expenditures. In the same study, COVID-19-related hospitalization alone was estimated to account for $22.1 billion in seasonal cost.34 Per person, median inpatient costs for 161,824 patients hospitalized with COVID-19 from February 2023 through February 2024 ranged from $9,494 (IQR, $5,812-$15,678) for those not admitted to the ICU (n = 132,691) to $33,555 (IQR, $18,721-$60,398) for those in the ICU receiving invasive mechanical ventilation (n = 11,374) according to results of a claims-based analysis of PINC AI Healthcare Database data (all 2023/2024 US$).35 Median lengths of stay for these cohorts were 4 days (IQR, 2-6 days) and 9 days (IQR, 4-15 days), respectively, and increased with age.35
The economic burden of long COVID is not yet fully known, as many individuals still are affected by this syndrome. Cases of long COVID were anticipated to cost $2.6 trillion over the course of 2021 when assuming quality-adjusted life expectancy decreases of 35% and the value of a year of life.36 Results of a study of COVID-19 Research Database claims data from January 2019 through March 2021 for 250,514 infected individuals who had not been hospitalized with severe symptoms demonstrated an increase in monthly healthcare costs of $223.60 (95% CI, $218.34-$228.85; p-value < 0.001) over six months.37 Although healthcare use was the highest during the month when patients received a COVID-19 diagnosis and showed a gradual decline over 5 months, healthcare costs at month six were higher than those noted before diagnosis.37
Burden on healthcare workers and staffing
During the height of the COVID-19 pandemic, the capacity of hospitals was strained as weekly ICU occupancy increased by up to 38.9 percentage points.38 At that time, 55% of surveyed healthcare workers (N = 209) reported worse mental health than before the pandemic, 45.5% felt burned out at least 3 times per week, and 35.4% stated an intent to leave healthcare within 5 years.39 Although the national rate of hospital staff turnover was lower in 2023 (20.7%) than it was during its peak in 2021 (25.9%), it remained almost 3% higher than the pre-pandemic rate of 2019 (17.8%), demonstrating the enduring impact of COVID-19 on the health care system.40
Disease prevention
COVID-19 vaccines decrease hospitalizations, ICU admissions and death.41,42 Moreover, the efficacy of monovalent COVID-19 messenger RNA vaccines used from February 2022 to January 2023 in preventing invasive mechanical ventilation and death was 76% for up to 6 months and 56% after 1 year.43 Also, vaccination with booster vaccines has been associated with lower risk of hospitalization and of supplemental oxygenation use if a patient is hospitalized.44,45 The Centers for Disease Control and Prevention (CDC) makes recommendations for COVID-19 vaccination in immunocompetent adults 19 years and older, which are summarized in the Table.46
Treatment landscape
Current outpatient treatment options for COVID-19 are associated with reduced time to symptom resolution as well as decreased rates of hospitalization, admission to ICUs, oxygenation or mechanical ventilation and mortality in patients at high risk of disease progression.47-52 Therefore, early diagnosis and therapy with antivirals or high-titer convalescent plasma is recommended while viral loads are high to ensure maximal treatment effect and to prevent hospitalization and further need for healthcare resources.52 Infectious Disease Society of America guideline-recommended therapies to treat patients with mild to moderate COVID-19 are summarized in the Figure and described below.52-54
REMDESIVIR
Remdesivir (Veklury; Gilead Sciences), an intravenous (IV) antiviral that inhibits SARS-CoV-2 RNA-dependent RNA polymerase and prevents viral replication of SARS-CoV-2, was approved by the FDA in 2020; it is indicated to treat COVID-19 in patients who are hospitalized or at high risk for progression.55,56 In the PINETREE randomized clinical trial (RCT), administration of remdesivir therapy within seven days of symptom onset decreased hospitalizations or death from any cause at 28 days by 87% in 279 treated patients versus administration of placebo, which was given to 283 patients (HR, 0.13; 95% CI, 0.03-0.59; p-value = 0.008).50 Side effects occurred at a greater rate in the placebo group than in the remdesivir group (46.3% vs. 42.3%).50
Analysis of real-world evidence from a retrospective propensity matched study of high-risk outpatients with COVID-19 demonstrated results similar to those found in PINETREE, namely a lower 28-day all-cause hospitalization among 1,252 patients given remdesivir compared with 2,499 patients given placebo (adjusted HR, 0.39; 95% CI, 0.23-0.67; p-value < 0.001).57
NIRMATRELVIR/RITONAVIR
Nirmatrelvir, an oral antiviral that prevents viral replication of SARS-CoV-2 via inhibition of the cysteine protease Mpro, is combined with ritonavir to enhance pharmacokinetic and therapeutic effect.58 Use of nirmatrelvir/ritonavir (NMV/r) (Paxlovid; Pfizer) was approved by the FDA in 2023 to treat mild to moderate COVID-19 in adults with high risk for progression.59 In the EPIC-HR RCT, those who received NMV/r within three days of symptom onset (n = 697) had an 88.9% relative risk reduction in COVID-19-related hospitalizations or death from any cause at 28 days when compared with those given placebo (n=682) (p-value< 0.001).47 Use of NMV/r within five days of symptom onset reduced COVID-19 hospitalization rates or death from any cause at 28 days by 87.8% when compared with placebo (p-value < 0.001).47 Results of the subsequent EPIC-SR RCT, which included 1,296 SARS-Cov-2-positive patients who had onset of symptoms within the prior five days and who were either unvaccinated with no risk of severe disease or vaccinated and at risk for severe disease, demonstrated that 0.8% (5 of 654) of patients given NMV/r versus 1.6% (10 of 634) of those given placebo were hospitalized for COVID-19 or died from any cause.48 In both trials, side effects, serious side effects, and side effects leading to discontinuation occurred in similar rates between the NMV/r and placebo groups, with dysgeusia and diarrhea occurring more frequently in the NMV/r groups.47,48
Real-world data from a retrospective propensity matched study of nonhospitalized, vaccinated adult patients with COVID-19 also demonstrated a lower rate of all-cause emergency department (ED) visits, hospitalizations or death at 30 days among patients given NMV/r within five days of diagnosis as compared with those not given the combination therapy (OR, 0.5; 95% CI, 0.39-0.67; p-value < 0.005).60
MOLNUPIRAVIR
Molnupiravir (Lagevrio; Merck), an oral antiviral prodrug of β-D-N4-hydroxycytidine that impairs SARS-CoV replication, received emergency use authorization (EUA) by the FDA in 2021; it is authorized for the treatment of patients with mild to moderate COVID-19 who are at risk for progression and are unable to receive other FDA-approved medications.61,62 The MOVe-OUT trial included 1,433 patients with SARS-COV-2 and risk for disease progression; use of molnupiravir reduced the risk of hospitalization or death by 2.8% (95% CI, 0.0%-5.7%) when compared with placebo.51 Side effects were reported in greater rates in the placebo vs. the molnupiravir groups (33.0% vs. 30.4%).
Analysis of real-world data for 26,554 patients treated with molnupiravir demonstrated that, within 28 days of treatment initiation, only 6.5% of patients visited the ED and 0.1% required oxygen or mechanical ventilation.63
In addition to a reduction in severe COVID-19, antiviral therapy is also associated with a reduced risk of long COVID. Evidence from a meta-analysis of nine clinical studies of 866,066 total patients indicated that initiation of molnupiravir or NMV/r treatment within approximately five days of diagnosis was associated with a 77% reduction in risk of post-COVID conditions when compared with no antiviral treatment (95% CI, 68%-88%).64
HIGH-TITER CONVALESCENT PLASMA
High-titer COVID-19 convalescent plasma is recommended for patients with mild to moderate COVID-19 at high risk of progression when there are no other treatment options.52 In December 2024, the FDA granted OneBlood, a blood center, full approval to provide licensed high-titer plasma from people who have recovered from symptomatic SARS-CoV-2 infection for use in patients with COVID-19 who have immunocompromise-immunosuppressive disease or who are receiving immunosuppressant treatments and who are at risk of progression to severe disease.53,54 The results of a meta-analysis of 23 RCTs and a 20,000-person registry study indicated that compared with study controls, COVID-19 convalescent plasma may reduce hospitalization (RR, 0.74; 95% CI, 0.56-0.98), but it carries an increased risk of side effects (RR, 1.08; 95% CI, 0.94-1.26).52
OTHER THERAPIES
Neutralizing monoclonal antibodies are not currently recommended, as Omicron subvariants are not susceptible to these therapies.52 Agents under investigation for treatment of COVID-19 include ensitrelvir, an antiviral with activity against Omicron subvariants.65,66 Synergistic antiviral alternatives are also being considered to avoid drug interactions involving cytochrome P450 3A4.58,67,68
Economic impact of COVID-19 prevention and treatment
Prevention and treatment of COVID-19 is associated with direct and indirect cost savings. These include direct cost savings related to reduced hospitalizations, ICU admissions, length of stay, ED or urgent care visits and supplemental oxygenation use.44,45 Among patients who require hospitalization for severe COVID-19, for instance, those who have received NMV/r have shorter hospital stays, are less likely to require intensive care or require mechanical ventilation and are more likely to be discharged to home/self-care than are patients who have not.49 Similarly, among patients who were hospitalized with COVID-19 at the Mayo Clinic in Rochester, Minnesota, from November 2020 to November 2021 and started on remdesivir in the inpatient setting, hospital costs were $7,447 lower for the 530 patients who transitioned remdesivir treatment in the outpatient setting than for the 2,290 patients who continued treatment in the hospital ($9,097 vs. $16,544; p-value < 0.01).69
According to a 2022 estimate from the Institute for Clinical and Economic Review, outpatient treatment of COVID-19 using NMV/r or molnupiravir may have avoided per patient hospitalization costs of approximately $26,000 to $76,000 (2022 US$).70 Results of a more recent (2024) mathematical modeling study estimated that outpatient use of NMV/r in 20% of symptomatic patients alone would have saved the US health care system an estimated $56.95 billion to $171.17 billion in 2022.71
Treatment can also reduce costs related to long COVID. A Centers for Medicare & Medicaid Services (CMS) budget impact model predicted that for a simulated 1 million-member US health plan, exclusive treatment of 29,999 adults at high risk of severe COVID-19 with NMV/r would increase total 1-year costs (including drug and hospitalization costs) by $2,733,745 (2023 US$) compared with treatment with remdesivir, molnupiravir or supportive care.72 However, when the model accounted for long COVID, exclusive treatment with NMV/r resulted in a cost savings of $1,510,780.72
Preventing COVID-19-related hospitalization is also associated with reduced home care and nursing facility use. In a study of Premier Healthcare Database COVID-19 Special Release data for 1,454,780 adult patients with COVID-19, 11.6% and 15.1% of patients, respectively, required home health services or care in rehabilitation/skilled nursing facilities after hospitalization for COVID-19.73 Conversely, just 0.4% of individuals managed as outpatients were discharged to home health, and only 0.8% were sent to rehabilitation/skilled nursingcare.73
Just as COVID-19 treatment points to a faster recovery and ability to return to work, COVID-19 vaccination is associated with increased economic productivity. Globally, COVID-19 vaccination from January 2020 to December 2021 was estimated to avert $340.9 billion in indirect costs due to lost labor.74 In the US, introduction of the COVID-19 vaccine was associated with increases in working hours when compared with prior months according to an analysis of data from the US Current Population Survey.75 Indeed, in a study evaluating data from screening questionnaires completed at CVS Health test sites by 430 US patients who tested positive for SARS-CoV-2 in 2022, those who were vaccinated had 19.4% (95% CI, 10.6%-28.3%; p-value < 0.001) less time lost to absenteeism and 11.2% (95% CI 2.5%-19.9%; p-value = 0.012) less work productivity time lost one week after diagnosis.76
Access landscape
As of January 24, 2025, only 22.8% (95% CI, 22.1%-23.5%) of adults in the United States have received 2024-2025 COVID-19 vaccines.77 Patients less likely to stay up to date with COVID-19 vaccines include those who have no insurance, live in rural settings, have concern for unknown serious side effects, perceive a lack of evidence to support vaccination, distrust the government/pharmaceutical companies and/or have American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander heritage.78,79 Additionally, out-of-pocket costs are likely to decrease patient adherence to COVID-19 vaccinations, as removal of cost-sharing increases vaccination for other diseases.80
Accessibility to outpatient COVID-19 therapies has been hindered by high costs of the medications, limited access and logistical difficulty in administering IV agents.81 Additionally, the decreased availability and increased cost of COVID-19 testing has impaired the early diagnosis of COVID-19 and initiation of therapies within a short window after identification.81 Provider skepticism of the evidence for antiviral use, hampered identification of eligible patients and patient skepticism due to misinformation have also contributed to decreased use of these agents.81 Social demographic factors may play a role, as 46% of Hispanic or Latino individuals and 38% non-Hispanic Black populations report unawareness of the advantages of receiving antiviral therapy.82 Finally, lower vaccination rates and use of outpatient COVID-19 therapies occur in those with lower incomes.79,83
Another factor contributing to inequities in preventing and treating COVID-19 is poor communication between providers and patients.83,84 For instance, a provider may not clarify that some patient comorbidities put them at an increased risk of severe COVID-19 disease; this may be accompanied by decreased motivation to discuss therapy options and discrepant patient perception of their own risk factors.81,85
STRATEGIES TO IMPROVE ACCESS
Since the outbreak of the COVID-19 pandemic, federal, state and local governments; pharmaceutical companies; managed care organizations (MCOs) and insurers have all worked to reduce barriers to accessing COVID-19 vaccines and treatment. For example, as part of the CARES Act, insurance companies provide COVID-19 vaccinations to patients for no cost at in-network providers.86
Other government initiatives to address inequitable access have included mobile vaccination and test-to-treat programs incorporating mobile treatment units and telemedicine.87-89 In Massachusetts, mobile vaccination units have reached individuals having different demographics than the general vaccinated population in the state and in targeted communities.87 A comprehensive approach in New York City incorporated testing, virtual urgent care service and home delivery programs to deliver same- or next-day oral antivirals to residents at no cost.88 In Los Angeles County, COVID-19 test results were sent digitally with educational materials and prompts to assess eligibility for antivirals.89 Eligible patients received a call with a provider to disseminate antivirals via delivery or pharmacy pickup.89
The ability to communicate with providers via telemedicine may have facilitated better patient understanding of COVID-19 therapy and more therapy usage in a Medicare population, as well.83 For this population, Medicare programs have addressed inequities through US government patient assistance programs (PAPs) or rebates with Pfizer for NMV/r; these programs have expanded the availability of NMV/r via the PAP/rebates during this respiratory virus season.90 Medicaid programs are plan-specific as of January 2025, and some patients may qualify for the federal PAP.90 Patients receiving molnupiravir or remdesivir may be able to enroll in the Merck or Gilead PAPs, respectively.91
MCOs are uniquely positioned to coordinate the care of patients testing positive for COVID-19. During the height of the pandemic, MCOs increased community networks with community-based organizations to increase outreach and access to vaccines and antiviral therapies.92,93 MCOs can collaborate with public health officials and providers to improve vaccine access, provider recommendations and public health messaging; they can work with trusted community messengers to prevent the spread of health misinformation.94 These organizations can also survey patients who test positive for SARS-CoV-2 to identify those at risk for progression to severe COVID-19, initiate monitoring via telehealth visits and optimize treatment for both COVID-19 and comorbidities.95
Payers can improve access to prophylactic measures for and treatment of COVID-19 by covering guideline-recommended therapies at no to minimal cost to members. The CMS recommends that at least one oral antiviral be available on Part D formularies, which encourages a $0 cost-sharing tier.96
Formulary decisions for use of vaccines and oral antivirals should account for the clinical and financial benefits of preventing severe disease and long COVID, including reducing hospital costs, costs related to prolonged recovery at a rehabilitation or skilled nursing facility and management of comorbid diseases during hospitalization or rehabilitation.
Conclusion
The burden of COVID-19 remains substantial, but advancements in vaccination, treatment and access strategies have provided pathways to mitigate the disease’s impact. Vaccination and early intervention with antiviral therapies are crucial to reducing death and hospitalizations and to preventing long COVID and its affiliated costs. Continuing to work toward providing equitable access is essential to enable all populations to receive preventive care and treatments and benefit the economy. Managed healthcare organizations are pivotal in ensuring effective use of resources to care for patients considered at high risk for severe COVID-19 and thus reducing the overall societal burden of this disease.
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