Endocrine, Metabolic and Microbiome Influence on the Post COVID-19 Syndrome
Condition: Covid19
MeSH terms: COVID-19
Study type: Observational

Summary: 
      The aim of this study is characterize the endocrine, metabolic and microbiomes of patients
      with post-COVID syndrome and patients that have recovered from COVID without lingering
      symptoms.
    

Detailed description: 
      The onset of the COVID-19 pandemic has led to a subset of patients that, once recovered from
      the acute infection, also experience an intractable and debilitating set of lingering
      symptoms termed post-COVID syndrome. The most common symptoms include anxiety, shortness of
      breath, continued loss of the sense of smell and taste, loss of appetite with subsequent
      weight loss, sleep difficulties, severe fatigue, cognitive dysfunction (foggy brain) and
      increased frailty. These patients frequently present to the emergency room looking for
      symptom management because they are unable to perform normal activities of daily living and
      maintain job performance. Thus, it is critical to characterize the baseline endocrine,
      metabolic, inflammatory and microbiome alterations in the post-COVID syndrome patients to
      better identify and manage the symptoms to prevent potential long-term health consequences.

      University of Texas Medical Branch (UTMB) has established a post-COVID clinic for management
      of these patients, but it is recognized that a more complete clinical picture of the
      underlying mechanisms driving these lingering symptoms is needed.

      Persistent and long-lasting health problems are common in patients after COVID-19 infection.
      In a recent study of patients that had been hospitalized with COVID-19, two months after
      discharge, 87% reported at least one lingering symptom (joint pain, fatigue, breathing
      issues, etc), more than 50% reported more than three lingering issues, and over 40% reported
      a reduction in their of quality of life. Another study found that at 1-month after
      hospitalization for COVID-19, 74% reported persistent issues related to shortness of breath
      and a decrease in both physical and mental health. Preliminary data from the UTMB Post-COVID
      Recovery clinic agree with these two recent reports. In a recent study, 1 1/2 months after
      COVID-19 diagnosis, patients reported on average 10 of the 18 common symptoms (with 90%
      having chest pain, 87% dyspnea, 75% fatigue, and 90% with cognitive changes). While the
      previous studies examined patients that had severe COVID-19 infections, >50% of the patients
      were never hospitalized, yet have numerous persistent symptoms. This has serious implications
      for the ability of patients to return to work, downstream effects on mental health due to
      sometimes drastic lifestyle and work capacity changes, and the ability to engage in
      activities or hobbies enjoyed prior to COVID-19 illness.

      Notably, the cluster of symptoms associated with post-COVID syndrome include profound fatigue
      and cognitive dysfunction, which are strikingly consistent with a syndrome that the
      investigators clinical research team has described in patients after traumatic brain injury
      (TBI) designated Brain Injury Associated Fatigue and Altered Cognition (BIAFAC). Over the
      last 12 months the investigators have reported the characteristics of BIAFAC syndrome. In
      particular, TBI patients with BIAFAC present with lingering and profoundly debilitating
      symptoms including severe fatigue, cognitive dysfunction (foggy brain), sleep disturbances,
      and the inability to perform activities of daily living that persist for years post-injury.
      Mechanistically the investigators have explored the role of the gut microbiome discovering
      altered communities in TBI patients in long-term care facilities compared with controls. The
      investigators also established that many TBI patients with BIAFAC also present with abnormal
      growth hormone (GH) secretion, and when treated with recombinant GH, a majority of patients
      have significant improvement of both fatigue and impaired cognition. While studies are
      underway to understand the details of the mechanism causing BIAFAC and why GH treatment
      alleviates symptoms in these patients, the investigators are intrigued that the symptom
      phenotype with post-COVID patients overlaps with many BIAFAC symptoms. It is possible that
      post-COVID syndrome may be addressed through similar treatment strategies including the
      potential for prebiotic/probiotic enhancement of microbiome health.

      In the current pilot proposal, the investigators will characterize the baseline endocrine,
      metabolic, inflammatory and gut microbiome alterations in post-COVID syndrome patients and
      patients who recovered without lingering symptoms from COVID infection. These patients will
      be compared to the investigators extensive database of BIAFAC patients and normal controls.
      From this critical baseline data, the investigators will develop carefully defined clinical
      research trials that will test potential treatments for alleviating the syndrome. The
      investigators hypothesize that an imbalanced endocrine axis stemming from COVID-19 infection
      leads to metabolic, inflammatory and microbial dysregulation resulting in the onset of
      persistent post-COVID symptoms.

      Specific Aims

      Specific Aim 1: Characterize the baseline physiological measures of endocrine function,
      metabolism, inflammation, and composition of the gut and nasal microbiome of patients
      reporting symptoms of post-COVID syndrome.

      Specific Aim 2: Assess baseline neuropsychological measures of fatigue, sleep, and cognition
      for patients reporting symptoms of post-COVID syndrome.

      Specific Aim 3: Correlate physiological and neuropsychological measures of post-COVID
      patients and compare those measures to the investigators extensive database of BIAFAC
      patients and normal controls.

      Specific Aim 4: Characterize the microbiome of patients with post-COVID syndrome and compare
      to: a)our database of healthy control subjects, b) our database of symptomatic BIAFAC
      patients, c) new collected samples of patients with a history of COVID who did not develop
      post-COVID syndrome.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        1. Subjects recovered from COVID without lingering symptoms (nPASC)

          2. Subjects with post-COVID syndrome (PASC)
      
Keywords: cognitive impairment; fatigue