The Promise of Growth Hormone Therapy for Post-COVID Neurologic Symptoms


The spread of the SARS-CoV-2 virus and subsequent COVID-19 pandemic has profoundly affected the global population, with over 770 million confirmed cases and almost 7 million deaths reported globally as of December 2023. The pandemic has not only caused acute illnesses but also led to a condition known as “long-COVID” or post-acute sequelae of COVID-19 (PASC), where symptoms persist for months or even years after the initial infection. This article delves into the complexities of PASC, its symptoms, prevalence, underlying mechanisms, and potential treatments, with a particular focus on recent findings and ongoing research.

Prevalence and Symptoms of Long-COVID

Following the acute phase of COVID-19, a subset of individuals continues to experience a range of symptoms collectively referred to as PASC. Among the most common symptoms are post-exertional malaise, gastrointestinal problems, and neurologic symptoms such as fatigue and brain fog. The variability in the definition and characteristic symptoms of PASC has led to a wide range of occurrence rate estimates, from as low as 6% to over 50% of symptomatic COVID-19 patients. This disparity underscores the need for a standardized definition and diagnostic criteria for PASC.

Risk Factors and Demographic Variations

Not all individuals who contract COVID-19 develop PASC. Factors contributing to the development of PASC include the severity of the initial disease and the viral variant involved. PASC is more prevalent in individuals infected with pre-Omicron variants and those who experienced more severe initial symptoms. Additionally, women are approximately twice as likely to report PASC symptoms compared to men, highlighting a potential gender-related predisposition that warrants further investigation.

Potential Mechanisms Underlying PASC

The exact mechanisms causing PASC are not fully understood, but several hypotheses have been proposed. These include lingering viral reservoirs, excessive blood clotting, organ and tissue damage, reactivation of dormant pathogens, inflammatory cascades, hormonal disruptions, and microbial dysbiosis. These factors may individually or collectively contribute to the persistence of symptoms in PASC patients.

Metabolic and Hormonal Disturbances

COVID-19 has been associated with metabolic and hormonal disturbances affecting multiple organs and systems. Altered pituitary function, including reduced plasma growth hormone (GH), has been observed in both the acute and post-acute phases of the disease. Recent studies have found that reduced GH secretion persists in individuals with neurologic PASC symptoms more than six months after the initial infection. This persistence of reduced GH secretion and its impact on neurologic symptoms such as fatigue and brain fog draw parallels to other conditions like brain injury-associated fatigue and altered cognition (BIAFAC).

Gut Dysbiosis and GI Complaints

PASC is also linked to gastrointestinal complaints, and gut dysbiosis is implicated in long-term recovery from COVID-19. The altered gut microbiome may contribute to symptoms by affecting the bioavailability of amino acids and neurotransmitters, further complicating recovery and symptom management.

Growth Hormone Therapy: A Pilot Study

In light of the observed GH deficiency in PASC patients, a pilot study was conducted to assess the efficacy of GH treatment in alleviating neurologic symptoms. The study found that GH treatment significantly improved self-reported measures of fatigue, depression, mood, and quality of life in PASC patients. However, these improvements did not extend to changes in body composition, metabolism, or formal cognitive testing, suggesting that GH treatment may mask symptoms without addressing the underlying cause.

Subject-Reported Outcomes

The pilot study revealed significant improvements in fatigue-specific measures, including the Brief Fatigue Inventory (BFI) and the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). These instruments demonstrated a profound reduction in fatigue with GH treatment, with symptoms progressively improving over the treatment course and reverting toward baseline after treatment cessation.

Sleep Disturbance and Quality of Life

Sleep disturbance is highly correlated with PASC, and sleep apnea may be a risk factor for its development. Although the study showed a non-significant trend toward improved sleep quality with GH treatment, the overall quality of life measures indicated a progressive improvement, which reverted upon treatment cessation. This suggests a potential link between sleep quality and overall quality of life in PASC patients.

Cognition and Neurologic Symptoms

Formal neurocognitive testing did not indicate significant cognitive improvements within six months of GH treatment, although self-assessed cognitive measures showed significant improvement. This discrepancy highlights the need for longer treatment durations and more sensitive testing methods to capture subtle changes in cognition.

Metabolism and Body Composition

GH treatment did not significantly alter resting energy expenditure (REE), body mass, or body composition in the study’s duration. This contrasts with prior studies in TBI patients, suggesting that the shorter treatment duration or the newer onset of PASC symptoms may account for the lack of significant metabolic changes.

Physical Performance

GH treatment did not affect maximum effort physical performance measures but significantly improved self-metered measures of physical performance at submaximal effort. This indicates that improvements in physical performance with GH treatment may stem from central neurologic effects rather than peripheral physical strength and ability.

Study Limitations and Future Directions

The small sample size and lack of a placebo group are notable limitations of the pilot study. The uneven distribution of male and female participants also complicates the interpretation and application of the findings. Further studies with larger sample sizes, balanced gender representation, and extended treatment durations are needed to confirm the efficacy of GH therapy in PASC patients.

In conclusion, PASC continues to pose a significant challenge for many COVID-19 survivors, affecting their quality of life and productivity. The findings from the pilot study on GH therapy offer a glimmer of hope for symptomatic relief but underscore the need for continued research to understand and treat this condition effectively. As the medical community gains more insights into the mechanisms underlying PASC, it is imperative to develop targeted therapies that address the root causes and provide long-term relief for those affected.

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