Various Treatments for Long COVID

Overseen By KENNY WILLIAMS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Well- Konnect Healthcare Services and Research Firm

Disqualifiers: Myocarditis, Pericarditis, Severe renal impairment

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 5 days for Paxlovid, 1 month between Moderna doses

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals experiencing long COVID symptoms, such as fatigue, brain fog, and joint pain, following a COVID-19 infection. Researchers are testing the Moderna COVID-19 vaccine and Paxlovid (Ritonavir-Boosted Nirmatrelvir) to assess their potential benefits. The goal is to identify and understand biomarkers (biological indicators) and develop personalized treatment plans. Individuals with long COVID symptoms persisting for more than four weeks may be suitable candidates for this study. As a Phase 4 trial, the treatments are already FDA-approved and have proven effective, and this research aims to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that participants must not take any medications that could interfere with the study results. It's best to discuss your specific medications with the study team.

What is the safety track record for these treatments?

Previous studies have shown that the Moderna COVID-19 Vaccine is generally safe. Most side effects are mild, such as a sore arm or fatigue. Serious side effects, like heart-related issues, are rare but have been reported, especially after the second dose. Recipients are usually observed for 15 minutes after the shot to ensure their well-being.

Research indicates that Paxlovid (Ritonavir-Boosted Nirmatrelvir) is well-tolerated for treating COVID-19, with most side effects being mild and temporary. Some individuals may notice changes in taste or experience diarrhea. Safety data is more limited for its use in long COVID, but it is already approved to treat mild to moderate COVID-19.

Both treatments have been widely used, and safety data continues to be collected. Always consult a healthcare provider with any concerns or questions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for Long COVID because they offer innovative approaches to managing lingering symptoms. The Moderna COVID-19 Vaccine (2023-2024 Formula) is unique as it specifically targets the Omicron variant XBB.1.5, which could potentially enhance immune protection against this prevalent strain. Meanwhile, Ritonavir-Boosted Nirmatrelvir (Paxlovid) stands out due to its oral administration, which makes it convenient for nonhospitalized patients, and its ability to rapidly address COVID-19 symptoms and reduce the risk of progression. These treatments might provide faster and more tailored responses compared to the current standard of care options for Long COVID, which often involve supportive therapies and symptom management.

What evidence suggests that this trial's treatments could be effective for long COVID?

This trial will compare the effects of the Moderna COVID-19 Vaccine and Ritonavir-Boosted Nirmatrelvir (Paxlovid) on long COVID symptoms. Research has shown that the Moderna COVID-19 Vaccine may alleviate long COVID symptoms. Studies have found that COVID-19 vaccines, including Moderna, can protect against long COVID and help treat its symptoms. The vaccine effectively prevents COVID-19 and helps the body produce antibodies to fight the virus.

For Ritonavir-Boosted Nirmatrelvir (Paxlovid), research indicates it reduces the risk of severe COVID-19 and can lower the chances of experiencing long COVID symptoms like brain fog. Clinical studies have shown that Paxlovid effectively reduces severe illness and can help prevent long-term symptoms, benefiting both vaccinated and unvaccinated individuals. ^{1 4 6 7 8}

Who Is on the Research Team?

Kawana J Williams, Ph.D.

Principal Investigator

The National Institute of Health All of Us Research Program At Well-Konnect Healthcare Services and Research Center

Are You a Good Fit for This Trial?

This trial is for individuals who have had a positive COVID-19 diagnosis and are experiencing long-haul symptoms like fatigue, breathlessness, brain fog, heart issues, pain, or mood changes for more than 4 weeks. The study aims to tailor treatment plans using various interventions.

Inclusion Criteria

Participants must be able to communicate effectively in English or have a translator available

I have been diagnosed with COVID-19.

I still have symptoms even after getting over the initial sickness.

Exclusion Criteria

I am under 18 years old.

I have had myocarditis in the past.

I have had pericarditis in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive alternative treatments for long-haul COVID-19 symptoms, including Moderna COVID-19 Vaccine and Ritonavir-Boosted Nirmatrelvir (Paxlovid)

5 days for Paxlovid, 1 month between Moderna doses

Multiple visits for treatment administration

Longitudinal Observation and Intervention Implementation

Participants are observed and interventions are implemented to address long-haul COVID-19 symptoms

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral (e.g., Psychotherapy, Lifestyle Counseling)
• Biopsychological
• Genetic (including gene transfer, stem cell and recombinant DNA)
• Moderna COVID-19 Vaccine
• Multidisciplinary approach
• Physiological Evaluation
• Ritonavir-Boosted Nirmatrelvir (Paxlovid)

Trial Overview The study tests multiple treatments including lifestyle counseling, Paxlovid (an antiviral medication), physiological evaluations, the Moderna vaccine, and other approaches to manage long COVID symptoms and improve health outcomes.

How Is the Trial Designed?

Group I: Moderna COVID-19 Vaccine Active Control 7 Interventions

Unvaccinated individuals: Two doses of Moderna COVID-19 Vaccine (2023-2024 Formula) are administered. The second dose is administered 1 month after the first. Moderna COVID-19 Vaccine to include the 2023-2024 formula. The Moderna COVID-19 Vaccine (2023-2024 Formula) includes a monovalent (single) component that corresponds to the Omicron variant XBB.1.5 of SARS-CoV-2. The Moderna COVID-19 Vaccine (2023-2024 Formula) is authorized for all doses administered to individuals 6 months through 11 years of age to prevent COVID-19. The Moderna COVID-19 Vaccine, Bivalent is no longer authorized for use in the United States. Moderna COVID-19 Vaccine is a suspension for injection. A single dose is 0.25 mL. (3) History of a severe allergic reaction (e.g., anaphylaxis) to any component of Moderna COVID-19 Vaccine or following a previous dose of a Moderna COVID-19 vaccine.

Group II: Ritonavir-Boosted Nirmatrelvir (Paxlovid) Active Control 7 Interventions

The COVID-19 Treatment Guidelines Panel (the Panel) recommends using nirmatrelvir 300 mg with ritonavir 100 mg (Paxlovid) orally (PO) twice daily for 5 days in nonhospitalized adults with mild to moderate COVID-19 who are at high risk of disease progression (). Treatment should be initiated as soon as possible and within 5 days of symptom onset. Ritonavir-boosted nirmatrelvir is available through an FDA EUA for the treatment of mild to moderate COVID-19 in nonhospitalized adolescents aged 12 to 17 years and weighing ≥40 kg.4 For recommendations on using ritonavir-boosted nirmatrelvir in nonhospitalized children with COVID-19.

Moderna COVID-19 Vaccine is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Moderna COVID-19 Vaccine for:

• Prevention of COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older

Approved in European Union as Spikevax for:

• Prevention of COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older

Approved in Canada as Moderna COVID-19 Vaccine for:

• Prevention of COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older

Approved in Japan as Spikevax for:

• Prevention of COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older

Approved in Switzerland as Moderna COVID-19 Vaccine for:

• Prevention of COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older

Who Is Running the Clinical Trial?

Well- Konnect Healthcare Services and Research Firm

Lead Sponsor

Trials

1

Recruited

100+

All of Us Research Program at the National Institute of Health

Collaborator

Trials

1

Recruited

100+

Published Research Related to This Trial

Nirmatrelvir-ritonavir (Paxlovid®) is an oral treatment for Covid-19 that has been available since February 4, 2022.

It is specifically designed for individuals at very high risk of developing severe forms of the disease, highlighting its targeted use for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. Buxeraud, J., Faure, S., Fougere, É.[2022]

A booster dose of the mRNA vaccines BNT162b2 and mRNA-1273 significantly increases the durability of antibodies against SARS-CoV-2, providing enhanced long-term protection compared to the initial two-dose series.

Antibody levels after the mRNA-1273 booster were found to be higher than those after the BNT162b2 booster, indicating that the Moderna vaccine may offer superior antibody responses in the months following the booster.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273. Ailsworth, SM., Keshavarz, B., Richards, NE., et al.[2023]

Nirmatrelvir, a component of Paxlovid, shows a stronger interaction with the SARS-CoV-2 main protease (Mpro) compared to ritonavir, suggesting it plays a key role in the drug's antiviral efficacy.

The study indicates that Paxlovid may remain effective against new COVID-19 variants, such as Omicron, due to the Mpro mutation P132H not affecting the drug's target site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of Paxlovid against COVID-19 is the result of the tight molecular docking between Mpro and antiviral drugs (nirmatrelvir and ritonavir). Dawood, AA.[2023]

A booster dose of the mRNA-1273 COVID-19 vaccine significantly increased neutralizing antibody levels against the original virus and key variants of concern, indicating enhanced immune response after waning immunity from the initial two-dose series.

Both the mRNA-1273 booster and variant-modified boosters were found to be safe and well-tolerated, suggesting they could be effective options for improving protection against emerging SARS-CoV-2 variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Choi, A., Koch, M., Wu, K., et al.[2021]

In a study of 160 healthcare workers, the NVX-CoV2373 vaccine as a second booster resulted in significantly lower antibody responses against SARS-CoV-2 variants compared to mRNA vaccines.

Participants receiving NVX-CoV2373 experienced a higher rate of new SARS-CoV-2 infections but reported fewer adverse events, suggesting a trade-off between safety and immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of heterologous booster with protein-based COVID-19 vaccine (NVX-CoV2373) in healthy adults: A comparative analysis with mRNA vaccines. Sheng, WH., Lin, PH., Cheng, YC., et al.[2023]

The NVX-CoV2373 COVID-19 vaccine demonstrated high efficacy rates of 89.7-90.4% in clinical trials, indicating it is effective in preventing COVID-19 in adults aged 18 and older.

The vaccine has an acceptable safety profile, with most adverse reactions being mild to moderate, and serious adverse events occurring at similar low rates in both NVX-CoV2373 and placebo groups, suggesting it is safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of the NVX-CoV2373 COVID-19 vaccine in randomized placebo-controlled clinical trials. Smith, K., Hegazy, K., Cai, MR., et al.[2023]

A study of 649 outpatients in Italy found that early treatment with antiviral drugs or monoclonal antibodies (mAbs) significantly reduced the risk of developing long COVID symptoms compared to untreated patients.

Specifically, patients treated with antivirals had a 57% lower chance of experiencing any long COVID symptoms, while those treated with mAbs had a 52% lower chance of neuro-behavioral symptoms, highlighting the potential benefits of these therapies in high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of early therapies for COVID-19 on death, hospitalization and persisting symptoms: a retrospective study. Bertuccio, P., Degli Antoni, M., Minisci, D., et al.[2023]

A case series of 13 individuals with Long COVID who took extended courses of oral nirmatrelvir/ritonavir (7.5-30 days) showed that some experienced a meaningful reduction in symptoms, although the benefits were not consistent for all participants.

While some individuals reported improvements, one participant experienced significant side effects (intense stomach pain), highlighting the need for further research to determine who may benefit from this treatment and the optimal duration for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations. Cohen, AK., Jaudon, TW., Schurman, EM., et al.[2023]

In the phase II/III EPIC-HR trial, the combination of nirmatrelvir and ritonavir (Paxlovid™) significantly reduced the risk of severe COVID-19 in symptomatic, unvaccinated adults with mild-to-moderate disease, showing lower rates of hospitalization or death compared to placebo.

Nirmatrelvir plus ritonavir is generally well tolerated, with most side effects being mild or moderate, indicating a favorable safety profile for this treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir plus ritonavir in COVID-19: a profile of its use. Blair, HA.[2023]

This report describes a rare case of delayed inflammatory myositis occurring after the third dose of the mRNA-1273 vaccine, marking the first documented instance of this specific adverse reaction following a booster shot.

The condition was confirmed through biopsy and successfully treated, highlighting the importance of monitoring for unusual side effects even after vaccination, especially with booster doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Delayed Localized Necrotizing Inflammatory Myositis After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccine: A Case Report. Li, JC., Siglin, J., Marshall, MS., et al.[2023]

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