Long Covid Action Project (LCAP) ACT NOW Campaign

Subject: Urgent Need for Diagnostic Tools and Targeted Therapies for Long COVID

Dear NIH, Senate HELP Committee, and Researchers,

The Long Covid Action Project's CURE Committee (LCAP-CURE) applauds the NIH's efforts to investigate potential treatments for Long Covid through the RECOVER-TLC initiative. Multiple studies have proven that viral persistence is the driver of Long Covid. However, we believe a critical obstacle hinders the meaningful progress: the lack of a reliable diagnostic biomarker test for Long Covid and a means to measure RNA viral load.

Without these essential tools, there is no reliable method to accurately assess the effectiveness of any therapeutic intervention.

• Diagnostic Challenge: A definitive diagnostic test is crucial to:

• Rule out other conditions that may mimic Long Covid symptoms.

• Ensure that research participants are accurately diagnosed with Long Covid.

• RNA Viral Load Measurement Challenge:

• Quantifying RNA viral load is essential to understand the disease's progression and to objectively measure the impact of potential treatments.

• This data is critical for determining whether a therapeutic intervention is effectively reducing viral persistence, a key factor in Long Covid.

An effective diagnostic and viral load test must measure RNA. Proteomic testing is not a sufficient diagnostic of Long Covid. An accurate diagnostic must also measure more than just spike. You can read more about what constitutes an effective test here.

Recommended Approach:

LCAP-CURE demands the prioritization of evaluating medications with antiviral properties for their potential efficacy in treating Long Covid. We are proposing evaluation of a subset of preexisting antivirals and monoclonal antibodies as well as medications with immune modulating and antiviral properties, some of which are currently in clinical trials. This approach is based on the growing evidence that persistent viral infection plays a significant role in the development and continuation of Long Covid symptoms.

LCAP-CURE has assembled a list of some of the most promising therapeutics that merit further study.

LCAP-CURE combed through research and news articles and compiled a list of therapeutics that seem most promising to address viral persistence and replication that drive Long Covid. LCAP-CURE has cast a wide net in compiling this list of therapeutics we believe deserve more research. Our list of medications consists of drugs currently on the market to treat other conditions, drugs currently undergoing clinical trials, and drugs for which trials have not yet begun. Each of the medications listed have antiviral properties, or are immune modulating drugs or other drugs of interest such as biologics, including monoclonal antibodies, polyclonal antibodies, and immunoglobulins. In all, LCAP-Cure is submitting 17 antivirals, 14 biologics, and 18 other drugs for a total of 49 drugs so far for consideration by the NIH. LCAP-Cure will be submitting each of these through the NIH RECOVER-TLC portal. They are also attached below and here is a summary of those therapeutics on our website.

It is imperative that research avoids two pitfalls in trialing medications:

• Designing clinical trials that are too short

• Most antivirals require months of consistent and continuous use before improvement can take place.

• Short-term trials of medications can lead to drug resistance, in effect disqualifying a patient from re-trialing a drug for the appropriate amount of time.

• Studying treatments as monotherapies

• Just as HIV requires a combination of antivirals, treatment of Long Covid needs a multi-prong approach to address viral persistence, increase the effectiveness of the drugs, and reduce the chance of developing drug resistance. Monotherapy will not suffice.

• Adding monoclonal or polyclonal antibodies to a treatment regimen in tandem with antivirals can reduce the RNA viral load in patients.

Recommendations:

1. Prioritize Diagnostic Development: Invest in the development and validation of a sensitive and specific diagnostic biomarker test for Long Covid.

2. Establish RNA Viral Load Measurement: Develop and implement standardized methods for measuring RNA viral load in individuals with suspected Long Covid.

3. Focus on Antiviral, Monoclonal Antibody and Polyclonal Antibody Therapies: Investigate antiviral therapies, both alone and in combination with other medications (such as monoclonal antibodies), as potential first-line treatments for Long Covid.

4. Combination Therapies: Explore combination therapies to address the complex nature of Long Covid and enhance treatment outcomes.

Urgency:

The ongoing impact of Long Covid on individuals and society demands urgent action. The "let it rip" approach to COVID-19 has resulted in a significant number of individuals suffering from debilitating long-term health consequences. We urge the NIH, the Senate HELP Committee, and all scientists involved in Long Covid research to prioritize the development of diagnostic tools and the investigation of targeted antiviral therapies.

Thank you for your consideration.

Sincerely,

Long Covid Action Project CURE Committee