Conventional Treatment Options: What’s Most Likely to Work?

Antiviral Drugs

Antiviral drugs help minimize the symptoms and duration of active viral infections. However, antiviral drug development lagged the progress of antibiotics used to treat bacterial infections. One reason is that viruses have a protein coat surrounding a nucleic acid genome. The protein coat is called a capsid. Instructions for making the protein subunits of the capsid are encoded in the nucleic acid genome of the virus.

It’s a simple construction but highly effective for rapid replication. And is an obstacle that makes it difficult for drugs to eliminate or inhibit viruses.

Another reason antivirals don’t work well is unlike bacteria, viruses are not living things. They do not share the hallmarks of living things like metabolism or the ability to reproduce independently. To reproduce, a virus infects a living cell causing the cell to create copies of the virus. This characteristic makes it challenging to design antivirals to target viruses without killing normal cells. In addition, antiviral drugs have the potential for serious side effects. For example, Paxlovid provides some benefits during acute COVID but can cause diarrhea, abdominal pain, nausea, malaise, and other adverse symptoms.

However, over time, researchers were not idle. They found ways to target critical enzymes, like reverse transcriptase in HIV. Reverse transcriptase is an enzyme encoded from the genetic material of retroviruses that catalyzes the transcription of retrovirus RNA into DNA. But even these highly effective antiretroviral drugs don’t eliminate the virus. They control its growth and spread, indirectly improving immune status and reducing symptoms, but do not completely destroy the virus. HIV patients must take antiretrovirals for life.

Other successful antiviral drug treatments are those for Hepatitis C Virus (HCV).  There’s no effective vaccine for HCV, but direct-acting antiviral cures more than 95% of those infected with HCV.

In the original SARS epidemic of 2003, over 90 percent of patients in Hong Kong, an epicenter of the disease, were treated with Ribavirin, one of the only broad-spectrum antiviral drugs available at that time. However, it caused anemia in more than half of patients, failed to lower viral load, and was ineffective in most cases—this misconception about effectiveness resulted in the contagious spread to healthcare workers. Twenty years later, in the era of the COVID-19 pandemic, we’re only slightly better at controlling SARS coronaviruses.

Antiviral Drugs For SARS-CoV-2

There is no antiviral drug that targets the virus that causes COVID. One reason is that SARS-CoV-2 quickly generates lots of mutations resistant to antivirals. Some antivirals worked when first used on patients, but treatment failure developed due to rapid variant and sub-lineage evolution. The most used antivirals, Paxlovid and Molnupriavir, provide only modest benefits.

Drugs for Symptom Control

Treating symptoms is standard practice in allopathic medicine. Symptoms of Long COVID are so numerous that drugs are limited to the main symptoms. These drugs include wakefulness drugs for drowsiness and fatigue, analgesics and anti-inflammatories for joint pain, and antidepressants for mood changes.

• Anti-inflammatory Drugs: A 2022 study found that colchicine, a drug used for gout, did not significantly improve acute COVID patients’ symptoms but may have reduced complications and deaths. However, a 2023 clinical study found it improved brain fog, fatigue, and joint aches in Long COVID patients.
• Fluvoxamine: SARS-CoV-2 can invade the nervous system and enter the brain, causing an imbalance in serotonin, a neurotransmitter linked to depression and fatigue. Selective serotonin reuptake inhibitors (SSRIs), like fluvoxamine, have shown minor benefit for improving mood in some Long COVID patients.

In my clinical experience, the benefits of symptomatic use of pharmaceutical drugs are modest, and there is concern for cross-reactions when taking too many prescriptions. At the time of this blog, we’re still looking for better symptomatic treatments.

Off-label and Repurposed Drugs

Patients are requesting, and some doctors are prescribing off-label meds since there’s no FDA-approved drug for Long COVID. However, the options are limited, and the results are marginal.

Drugs In Development

Long COVID is a sizeable market, so it’s not surprising that drugs are in the pipeline. One is a peptide-based drug, NACE2i, developed by QIMR Berghofer to treat persistent inflammation. NACE2i can stop viral replication and protect against re-infection. It can also prevent inflammation and promote lung tissue repair. It sounds impressive. But FDA approval is pending.

What Drugs Are Most Likely to Help Beat Long COVID?

None of these pharmaceutical drugs target specific disease processes that cause Long COVID. Though non-specific drug treatments, like LDN, may help reduce symptoms in some cases. However, all drugs have side effects, which I call the ‘limited benefit but high-risk potential’ method for Long COVID treatment.

Note About Glucocorticoids in Acute COVID Infection: High doses of steroids were used in SARS and MERS but caused more harm than benefit. Chinese studies in early 2020 found methylprednisolone effective in reducing deaths among hospitalized COVID patients. However, subsequent negative experiences with steroid drugs resulted in guidelines against the routine use of glucocorticoids for COVID patients. However, in a reversal of policy, in late 2020, the WHO recommended glucocorticoids for 7-10 days in critically ill patients. Do risks outweigh benefits?

Synthetic glucocorticoids can cause long-lasting HPA axis disruption in some patients. Adrenal function shuts down, so less cortisol is produced. The main symptom is severe persistent fatigue. Some cases will return to normal in time. Others may have a permanently weakened adrenal function, causing a chronic fatigue state like in ME/CFS and Long COVID.

Since the HPA axis is already disrupted and cortisol levels tend to be low, I do not recommend glucocorticoids for Long COVID cases.