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

Trial Summary

What is the purpose of this trial?

Investigators are conducting a study on alternative treatments for patients who have received an current or previous positive COVID-19 diagnosis with mild-serve symptoms or undiagnosable condition after testing positive for severe acute COVID-19 infection and are experiencing long-haul symptoms. The symptoms of long COVID can include extreme tiredness (fatigue), shortness of breath, memory and concentration issues (brain fog), heart palpitations, dizziness, joint pain, muscle aches, cough, headaches, anxiety, and depression. It's important to note that there are various other symptoms that individuals can experience after a COVID-19 infection, such as loss of smell, chest pain or tightness, difficulty sleeping (insomnia), pins and needles, depression, anxiety, tinnitus, earaches, nausea, diarrhea, stomach aches, loss of appetite, cough, headaches, sore throat, and changes to the sense of smell or taste. To be included in the study, participants must have had symptoms for more than 4 weeks. The goal of the study is to measure biomarkers, identify new ones through clinical trials, and individualize and optimize treatment plans, which may or may not include COVID-19 post-market antivirals, vaccines, and medical care. It's essential to conduct thorough clinical trials to understand the long-term effects of COVID-19 and to develop personalized treatment plans for individuals experiencing long-haul symptoms.

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.

Is the Moderna COVID-19 Vaccine (mRNA-1273, Spikevax) generally safe for humans?

The Moderna COVID-19 Vaccine (mRNA-1273, Spikevax) has been associated with mild to serious reactions, including rare cases of myocarditis (heart inflammation) and delayed inflammatory myositis (muscle inflammation). However, it has been approved by the US Food and Drug Administration, indicating an acceptable safety profile for general use. ^{1 2 3 4 5}

How is the drug Paxlovid unique for treating Long COVID?

Paxlovid, a combination of nirmatrelvir and ritonavir, is unique because it targets the main protease of the virus, potentially reducing symptoms of Long COVID. Unlike other treatments, it is taken orally and has shown benefits in some Long COVID cases, although longer courses are still being explored. ^{6 7 8 9 10}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of the NVX-CoV2373 COVID-19 vaccine in randomized placebo-controlled clinical trials. [2023]

3. Singapore 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Enhanced SARS-CoV-2 IgG durability following COVID-19 mRNA booster vaccination and comparison of BNT162b2 with mRNA-1273. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. [2021]

6. France pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Impact of extended-course oral nirmatrelvir/ritonavir (Paxlovid) in established Long COVID: Case series and research considerations. [2023]

8. Netherlands 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). [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

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

10. Germany pubmed.ncbi.nlm.nih.gov

The impact of early therapies for COVID-19 on death, hospitalization and persisting symptoms: a retrospective study. [2023]