Managing COVID-19 in the 2025-2026 Respiratory Season

Evidence-Based Guidelines for Prevention, Diagnosis, and Treatment

Schedule a Consultation

Key Message

COVID-19 remains a significant public health concern in the 2025-2026 respiratory season. While the disease burden is lower than at the pandemic's peak, it continues to cause substantial morbidity and mortality, particularly among vulnerable populations. Updated vaccines and effective treatments are available.

Current Epidemiological Situation

The Centers for Disease Control and Prevention (CDC) predicts that the combined peak hospitalizations from COVID-19, influenza, and RSV during the 2025-2026 season will likely be similar to the 2024-2025 season. However, COVID-19 summer activity has been increasing, which may impact the timing and magnitude of fall and winter disease activity.

2024-2025 Season Impact

Preliminary CDC estimates show 2.4 to 3.8 million outpatient visits, 270,000-440,000 hospitalizations, and 32,000-51,000 deaths caused by COVID-19 during the respiratory season.

Circulating Variants

As of late 2025, dominant variants include XFG (Stratus), NB.1.8.1 (Nimbus), and JN.1-related lineages, showing enhanced transmissibility and some immune escape properties.

Population Immunity

While many people have prior infection and/or vaccination, booster uptake has declined, increasing risk of severe outcomes especially among the unvaccinated and immunocompromised.

The 2025-2026 Respiratory Virus Landscape

The upcoming 2025-2026 fall and winter season demands a strategic shift away from single-pathogen planning. The co-circulation of COVID-19, influenza, and Respiratory Syncytial Virus (RSV) presents an integrated threat to public health, making a comprehensive outlook a strategic imperative for effective hospital resource management and the maintenance of public trust.

For the 2025-2026 season, the CDC expects a similar combined number of peak hospitalizations from COVID-19, influenza, and RSV compared to the previous season. The CDC bases its assessment on historical trends, expert opinion, and scenario modeling to provide a baseline for public health preparedness.

Important Note

The confidence in this combined forecast is low to moderate. This is qualified by inherent uncertainty stemming from the historic variability in both the timing and magnitude of hospital demand for each of the three diseases. While the combined peak has been relatively consistent over the past three years, the individual peaks for each virus can occur at different times, complicating precise predictions.

The Evolving COVID-19 Threat

While the overall respiratory burden may track similarly to last year, the trajectory of COVID-19 presents unique and significant risks that require detailed examination. The CDC forecasts that the peak weekly hospitalization rate for COVID-19 will be similar to or higher than the 2024-2025 season, an assessment made with moderate confidence.

The CDC's modeling outlines two primary scenarios for COVID-19 hospitalization rates, highlighting the pivotal role of viral evolution, particularly the potential emergence of a new variant with enhanced immune-escape properties:

Scenario Projected Peak Weekly Hospitalization Rate (per 100,000)
Scenario A: Assumes no new SARS-CoV-2 variant with significant immune escape emerges 3.8 to 5.9
Scenario B: Assumes a variant with moderate immune-escape properties emerges in November 6.7 to 9.5

Key Variables to Monitor

Several key variables could contribute to a higher-than-expected peak:

  • The emergence of a new SARS-CoV-2 variant with increased immune evasion or clinical severity
  • Lower-than-expected uptake of the updated COVID-19 vaccine
  • Lower vaccine effectiveness against hospitalization compared to the previous year's immunizations

Vaccination Strategy: The Frontline Defense

Vaccination is the frontline defense for mitigating the impact of COVID-19 and other respiratory viruses. The central tenets of this strategy are the deployment of updated vaccine formulations designed to match currently circulating viral variants and the application of targeted guidance to protect the most vulnerable populations.

2025-2026 Vaccine Formulation

To ensure the 2025-2026 formula more closely matches currently circulating viruses, the U.S. Food and Drug Administration (FDA) has advised manufacturers to develop a monovalent JN.1-lineage-based vaccine, preferentially using the LP.8.1 strain.

mRNA Vaccines

Moderna (Spikevax): Utilizing the LP.8.1 template. Note that for the 2025-2026 season, Moderna is the only FDA-authorized option for children aged 6 months to 4 years.

Pfizer-BioNTech (Comirnaty): Authorized for ages 5 years and older.

Protein Subunit Vaccine

Novavax (Nuvaxovid): Formulated with the JN.1 strain. This provides a critical alternative for individuals who are hesitant about mRNA technology or who have experienced reactogenicity with lipid nanoparticle-based vaccines. Authorized for ages 12 and older.

Vaccination Recommendations

Population Recommendation
General Population - Adults 65+ Should receive vaccination
Adults 19-64 with risk factors Should receive vaccination
Healthcare workers Annual vaccination strongly recommended
Children 6 months to 18 years One dose recommended, especially for those with risk factors
Immunocompromised patients Strong recommendation; may need additional doses based on degree of immunosuppression
Pregnant individuals Vaccination recommended to protect both mother and fetus

Co-administration Safety

With the concurrent circulation of influenza and RSV, co-administration is operationally critical. Data supports the safety of administering the COVID-19 vaccine alongside influenza vaccine, RSV vaccine (for eligible adults), and Tdap. Administer in separate limbs when possible to minimize local injection site reactions.

Treatment Strategies

Severity Classification

Treatment decisions are based on disease severity:

Mild to Moderate

SpO2 >94% on room air. Outpatient management with antiviral therapy for high-risk patients.

Severe

SpO2 ≤94% on room air, requiring supplemental oxygen. Hospitalization typically required.

Critical

Requiring mechanical ventilation, high-flow oxygen, non-invasive ventilation, or ECMO.

Antiviral Treatments for Mild-to-Moderate COVID-19

First-Line: Nirmatrelvir/Ritonavir (Paxlovid)

Indication: High-risk adults with mild-to-moderate COVID-19

Dosing:

  • eGFR >60: 300/100 mg every 12 hours for 5 days
  • eGFR 30-60: 150/100 mg every 12 hours for 5 days
  • eGFR <30: 300/100 mg day 1, then 150/100 mg daily days 2-5

Efficacy: 83% relative risk reduction in hospitalization

Key consideration: Check for drug-drug interactions (ritonavir is CYP3A4 inhibitor)

Alternative: Remdesivir (Veklury)

Indication: High-risk patients with mild-to-moderate COVID-19 when nirmatrelvir/ritonavir is contraindicated

Dosing: 200 mg IV day 1, then 100 mg IV days 2-3

Efficacy: 87% reduction in hospitalization risk

Advantage: No renal dose adjustment needed; minimal drug interactions

Limitation: Requires IV administration for 3 consecutive days

Last Resort: Molnupiravir (Lagevrio)

Indication: High-risk adults with no other treatment options

Dosing: 800 mg orally twice daily for 5 days

Efficacy: Modest benefit (14% reduction in hospitalization, imprecise estimate)

Contraindications: Pregnancy, Age <18 years, Requires contraception during and after treatment

Treatment for Severe and Critical COVID-19

Hospitalized Patients with Severe Disease (SpO2 ≤94%)

  • Dexamethasone 6 mg daily (IV or PO) for 10 days or until discharge - Strong evidence for mortality benefit
  • Consider adding IL-6 inhibitors (tocilizumab) or JAK inhibitors (baricitinib) in patients with elevated inflammatory markers (CRP) and progressive severe disease
  • Remdesivir may be considered (decreases time to recovery, but no mortality benefit demonstrated)

Critically Ill Patients (Mechanical Ventilation/ECMO)

  • Dexamethasone 6 mg daily - strongly recommended
  • IL-6 inhibitors (tocilizumab preferred) - recommended with elevated CRP
  • Baricitinib - can be used if IL-6 inhibitors unavailable
  • Remdesivir - not recommended (no demonstrated benefit)

Pre-Exposure Prophylaxis

Pemivibart (Pemgarda)

Indication: For moderately to severely immunocompromised individuals 12+ years unable to mount adequate vaccine response

Dosing: 4,500 mg IV every 3 months

Timing: Administer at least 2 weeks after COVID-19 vaccination

Efficacy: Clinical data from the CANOPY trial demonstrated a 76% relative risk reduction in symptomatic COVID-19 compared to placebo over a 12-month period

Risk: 0.6% risk of anaphylaxis

At CarePoint Infusion Center, we provide Pemgarda infusion therapy for eligible immunocompromised patients throughout Northeast Ohio.

Special Considerations

Immunocompromised Patients

This population requires tailored management:

  • Enhanced vaccination schedules (may require additional doses)
  • Consider pre-exposure prophylaxis with pemivibart
  • Early antiviral treatment with first symptoms
  • May have prolonged viral shedding requiring extended isolation
  • Close monitoring for treatment failure and rebound

Pregnant Individuals

  • At higher risk for severe COVID-19 outcomes
  • Vaccination strongly recommended for maternal and fetal protection
  • Early antiviral treatment if infected (nirmatrelvir/ritonavir or remdesivir preferred)
  • Avoid molnupiravir due to fetal harm concerns

Key Takeaways for Managing the 2025-2026 Season

Integrated Threat Assessment

While the combined hospital burden from COVID-19, influenza, and RSV may remain stable, planning must account for the distinct possibility of a higher COVID-19 hospitalization peak driven by potential new variants.

Aggressive Vaccination Strategy

Timely vaccination with the FDA-advised JN.1-lineage-based COVID-19 formula is the primary defense against severe disease. This must be reinforced with targeted campaigns for vulnerable populations.

Surveillance Infrastructure

Support expanded global surveillance through initiatives like the WHO's enhanced GISRS platform for early threat detection and variant monitoring.

Long COVID Care

Healthcare systems must build capacity to provide holistic, symptom-based care for the estimated 6% of individuals globally who develop Long COVID. When your clinician recommends supportive hydration and micronutrient repletion during viral recovery, learn about our IV multivitamin infusion therapy for respiratory illness recovery at CarePoint.

Serving Northeast Ohio Communities

CarePoint Infusion Center provides comprehensive COVID-19 prevention and treatment services, including Pemgarda pre-exposure prophylaxis for immunocompromised patients throughout Northeast Ohio. We serve patients from Cleveland, Beachwood, Akron, and surrounding communities in Cuyahoga County and beyond.

We conveniently serve patients from:

Cleveland Beachwood Hudson Solon Westlake Shaker Heights University Heights Lyndhurst South Euclid Mayfield Heights Warrensville Heights Orange Village Pepper Pike Chagrin Falls Akron Canton Youngstown

And throughout Cuyahoga County and Northeast Ohio. Contact us today to schedule your consultation.

Take the Next Step

If you are at high risk for severe COVID-19 or have questions about prevention and treatment strategies, our experienced team at CarePoint Infusion Center is here to help. We provide evidence-based care and support for patients throughout Northeast Ohio.

Contact Us Today Learn About Pemgarda

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of medical conditions. Individual results may vary. Treatment recommendations may change as new data emerges.

Additional Resources

Learn more about COVID-19 prevention and treatment: