Covid19
Conditions
Keywords
cognitive impairment, fatigue
Brief summary
The aim of this study is characterize the endocrine, metabolic and microbiomes of patients with post-acute sequelae SARS-CoV-2 infection (PASC) 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-acute sequelae SARS-CoV-2 infection (PASC). 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 PASC 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 PASC patients overlaps with many BIAFAC symptoms. It is possible that PASC 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 PASC 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 PASC. Specific Aim 2: Assess baseline neuropsychological measures of fatigue, sleep, and cognition for patients reporting symptoms of PASC. Specific Aim 3: Correlate physiological and neuropsychological measures of PASC and compare those measures to the investigators extensive database of BIAFAC patients and normal controls. Specific Aim 4: Characterize the microbiome of patients with PASC 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 PASC.
Interventions
None listed
Sponsors
The University of Texas Medical Branch, Galveston
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
COVID Non-Symptomatic controls (nPASC) Inclusion criteria 1. Male or female with a history of COVID with diagnosis confirmed by PCR test. 2. Minimum of 6 months since diagnosis of COVID by PCR test. 3. Ages 18 to 80 years. 4. Participant is willing and able to give informed consent for participation in the study.
Exclusion criteria
1. Current COVID infection. 2. Unable to walk unassisted. 3. Significant heart, liver, kidney, blood or respiratory disease as determined by Principal Investigator. 4. Uncontrolled diabetes mellitus. 5. Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma). 6. Current alcohol or drug abuse. 7. History of psychosis. 8. Pregnancy or become pregnant during the trial. 9. Subjects who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results. 10. Other medical condition or medication administration deemed exclusionary by the study investigators. COVID Symptomatic Subjects (PASC) Inclusion Criteria: 1. Male or female with a history of COVID with diagnosis confirmed by PCR test. 2. Has been seen at UTMB Post COVID clinic. 3. Minimum of 6 months since diagnosis of COVID by PCR test. 4. Ages 18 to 80 years. 5. Score of 3 or higher on any question 1-3 of the Brief Fatigue Inventory (BFI) questionnaire. 6. Participant is willing and able to give informed consent for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression Measured by the Beck Depression Inventory-II | baseline | The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of 3 indicating a severe symptoms and a score of 0 indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe. |
| Follicle Stimulating Hormone (FSH) | baseline | Follicle Stimulation Hormone (FSH) will be measured in serum. |
| Insulin-Like Growth Factor-1 (IGF1) | baseline | Insulin-Like Growth Factor-1 (IGF1) will be measured in serum. Results will be reported in ng/mL. |
| Sex Hormone Binding Globulin (SHBG) | baseline | Sex Hormone Binding Globulin (SHBG) will be measured in serum. Results will be reported in nmol/L. |
| Total Testosterone | baseline | Total testosterone will be measured in serum of male subjects. Results will be reported in ng/dL. |
| Free Testosterone | baseline | Free testosterone will be measured in serum of male subjects. Results will be reported in pg/mL. |
| Prolactin | baseline | Prolactin will be measured in serum. Results will be reported in ng/mL. |
| Thyroid Stimulating Hormone (TSH) | baseline | Thyroid Stimulating Hormone (TSH) will be measured in serum. Results will be reported in mUI/L. |
| C Reactive Protein (CRP) | baseline | C Reactive Protein (CRP) will be measured in serum. |
| Vitamin B12 | baseline | Vitamin B12 will be measured in serum. |
| Vitamin D 25OH | baseline | Vitamin D 25OH will be measured in serum. |
| Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption | Before glucose consumption | Glucose will be measured in serum before (0 minutes) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only. |
| Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 120 minutes after glucose consumption | Glucose will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only. |
| Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption | Before glucose consumption | Insulin will be measured in serum before (0 min) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only. |
| Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 120 minutes after glucose consumption | Insulin will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only. |
| Glucose Derived CO2 as Measured by Breath During the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 120 minutes after glucose consumption | Glucose derived CO2 will be measured in breath samples at 120 minutes after oral consumption of 75g glucose isotopically labeled with 150 mg \[U-13C6\] glucose. Glucose-derived breath CO2 data are analyzed by measuring the ratios of 13CO2 to 12CO2 in single breath samples using an UBiT-IR300 infrared spectrophotometer (Otsuka Electronics, Hirakata, Osaka, Japan). The UBIT-IR300 calculates the difference in 13CO2 abundance from the baseline breath sample to each timed sample and expresses this as per mille delta over baseline (%DOB). OGTT will be performed on PASC subjects only. |
| Sleep Quality as Measured by Pittsburgh Sleep Quality Index | baseline | Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total \< 5 associated with good sleep quality. Total \> 5 associated with poor sleep quality. |
| Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration | Before glucagon administration | Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of human growth hormone. 1 mg glucagon (for subjects over 90 kg, 1.5 mg glucagon) will be injected intramuscularly (IM) in the deltoid muscle of the subject and blood will be drawn at specified time points. Results will be reported as ng/mL. |
| Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration | 90 minutes after glucagon administration | Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at time point 90 minutes after glucagon injection to test for levels of human growth hormone. Results will be reported as ng/mL. |
| Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration | 120 minutes after glucagon administration | Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 120 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL. |
| Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration | 150 minutes after glucagon administration | Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 150 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL. |
| Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration | 180 minutes after glucagon administration | Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 180 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL. |
| Basal Metabolic Rate as Measured by Resting Energy Expenditure | baseline | Resting Energy Expenditure will be measured by capturing the expired breath of subjects while at rest with a metabolic cart over a 30 minute time period. Data from the first 5 minutes will be discarded and the remaining 25 minutes of data will be averaged to calculate the resting energy expenditure. Data will be reported as kilocalories/day Procedure will be performed on PASC subjects only. |
| Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) Before Cortrosyn Administration | Before Cortrosyn administration | Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of cortisol. 0.25 mg Cortrosyn will be administered and additional serum (3.5 mL) will be collected at specified time points. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only. |
| Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 30 Minutes After Cortrosyn Administration | 30 minutes after Cortrosyn administration | Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 30 minutes after Cortrosyn administration to test for levels of cortisol. Procedure will be performed on PASC subjects only. Results will be reported as ug/dL. |
| Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 60 Minutes After Cortrosyn Administration | 60 minutes after Cortrosyn administration | Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 60 minutes after Cortrosyn administration to test for levels of cortisol. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only. |
| Cognitive Function as Measured by Montreal Cognitive Assessment | baseline | The Montreal Cognitive Assessment (MoCA) will be used to assess cognition. The Montreal Cognitive Assessment (MoCA) is a rapid assessment of cognition. The MoCA consists of 9 questions with the following subcategories: visuospatial/executive, naming, memory, language, abstraction, delayed recall and orientation. The MoCA has been used extensively to detect cognitive impairment in many conditions, including head trauma. Version 7.1 will be used. Scores range from 0 to 30, higher score being a better outcome. |
| Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale | baseline | The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort). The average of the scores for all 15 items is regarded as the GSRS total score. A higher score indicates a worse outcome. |
| Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory | baseline | Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. |
| Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults | baseline | Symptoms of growth hormone deficiency will be measured using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free T4 | baseline | Free T4 measured at baseline |
Countries
United States
Participant flow
Recruitment details
This study was conducted from May 2021 to May 2022. Subjects for PASC group were recruited from the UTMB post-COVID clinic. Subjects for the nPASC group were recruited from the community. All subjects were required to have a confirmed PCR diagnosis of SARS-CoV-2 at least 6 months prior to enrollment as well as confirmed negative at enrollment. Confirmed SARS-CoV-2 infection dates for subjects ranged from June 2020 to August 2021, before the emergence and dominance of the Omicron variant.
Participants by arm
| Arm | Count |
|---|---|
| Symptomatic Post-COVID 10 patients with Post-COVID syndrome | 10 |
| Non-symptomatic Post-COVID 13 patients with that recovered without lingering symptoms after being infected with COVID | 13 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Symptomatic Post-COVID | Non-symptomatic Post-COVID | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 12 Participants | 22 Participants |
| Age, Continuous | 48.5 years STANDARD_DEVIATION 9.9 | 46.8 years STANDARD_DEVIATION 14.9 | 47.6 years STANDARD_DEVIATION 12.7 |
| BMI | 31.2 (kg/m^2) STANDARD_DEVIATION 5.9 | 30.9 (kg/m^2) STANDARD_DEVIATION 4.5 | 31.0 (kg/m^2) STANDARD_DEVIATION 5.1 |
| COVID Hospitalization | 2 Participants | 0 Participants | 2 Participants |
| Days post-diagnosis | 293.9 days STANDARD_DEVIATION 97.1 | 473.0 days STANDARD_DEVIATION 145.8 | 395.1 days STANDARD_DEVIATION 153.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 12 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 164.2 cm STANDARD_DEVIATION 9.8 | 170.7 cm STANDARD_DEVIATION 8.8 | 167.9 cm STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
| Weight | 85.2 kg STANDARD_DEVIATION 23 | 90.3 kg STANDARD_DEVIATION 16.4 | 88 kg STANDARD_DEVIATION 19.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 13 |
| other Total, other adverse events | 0 / 10 | 0 / 13 |
| serious Total, serious adverse events | 0 / 10 | 0 / 13 |
Outcome results
Primary
Basal Metabolic Rate as Measured by Resting Energy Expenditure
Resting Energy Expenditure will be measured by capturing the expired breath of subjects while at rest with a metabolic cart over a 30 minute time period. Data from the first 5 minutes will be discarded and the remaining 25 minutes of data will be averaged to calculate the resting energy expenditure. Data will be reported as kilocalories/day Procedure will be performed on PASC subjects only.
Time frame: baseline
Population: PASC patients only. 2 patients from the PASC group are missing from measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Basal Metabolic Rate as Measured by Resting Energy Expenditure | 1489.2 kcal/day | Standard Deviation 257.7 |
Primary
Cognitive Function as Measured by Montreal Cognitive Assessment
The Montreal Cognitive Assessment (MoCA) will be used to assess cognition. The Montreal Cognitive Assessment (MoCA) is a rapid assessment of cognition. The MoCA consists of 9 questions with the following subcategories: visuospatial/executive, naming, memory, language, abstraction, delayed recall and orientation. The MoCA has been used extensively to detect cognitive impairment in many conditions, including head trauma. Version 7.1 will be used. Scores range from 0 to 30, higher score being a better outcome.
Time frame: baseline
Population: 1 PASC patient missing from measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Cognitive Function as Measured by Montreal Cognitive Assessment | 27.0 units on a scale | Standard Deviation 2.5 |
| Non-symptomatic Post-COVID | Cognitive Function as Measured by Montreal Cognitive Assessment | 27.9 units on a scale | Standard Deviation 2.8 |
Primary
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 30 Minutes After Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 30 minutes after Cortrosyn administration to test for levels of cortisol. Procedure will be performed on PASC subjects only. Results will be reported as ug/dL.
Time frame: 30 minutes after Cortrosyn administration
Population: PASC patients only~1 PASC patient missing from measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 30 Minutes After Cortrosyn Administration | 17.9 ug/dl | Standard Deviation 2.4 |
Primary
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 60 Minutes After Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 60 minutes after Cortrosyn administration to test for levels of cortisol. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Time frame: 60 minutes after Cortrosyn administration
Population: PASC patients only.~1 PASC patient missing from measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 60 Minutes After Cortrosyn Administration | 21.7 ug/dl | Standard Deviation 2.6 |
Primary
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) Before Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of cortisol. 0.25 mg Cortrosyn will be administered and additional serum (3.5 mL) will be collected at specified time points. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Time frame: Before Cortrosyn administration
Population: PASC patients only.~1 PASC patient is missing from measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) Before Cortrosyn Administration | 5.3 ug/dl | Standard Deviation 2.3 |
Primary
C Reactive Protein (CRP)
C Reactive Protein (CRP) will be measured in serum.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | C Reactive Protein (CRP) | 0.47 mg/dl | Standard Deviation 0.46 |
| Non-symptomatic Post-COVID | C Reactive Protein (CRP) | 0.38 mg/dl | Standard Deviation 0.57 |
Primary
Depression Measured by the Beck Depression Inventory-II
The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of 3 indicating a severe symptoms and a score of 0 indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe.
Time frame: baseline
Population: 1 PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Depression Measured by the Beck Depression Inventory-II | 16.8 units on a scale | Standard Deviation 10.7 |
| Non-symptomatic Post-COVID | Depression Measured by the Beck Depression Inventory-II | 2.2 units on a scale | Standard Deviation 5.4 |
Primary
Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory
Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue.
Time frame: baseline
Population: 1 PASC patient is missing from this measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory | 31.0 units on a scale | Standard Deviation 17.3 |
| Non-symptomatic Post-COVID | Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory | -14.0 units on a scale | Standard Deviation 7.4 |
Primary
Follicle Stimulating Hormone (FSH)
Follicle Stimulation Hormone (FSH) will be measured in serum.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Follicle Stimulating Hormone (FSH) | 38.2 mIU/ml | Standard Deviation 35.3 |
| Non-symptomatic Post-COVID | Follicle Stimulating Hormone (FSH) | 24.1 mIU/ml | Standard Deviation 32.7 |
Primary
Free Testosterone
Free testosterone will be measured in serum of male subjects. Results will be reported in pg/mL.
Time frame: baseline
Population: Free testosterone measured in males only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Free Testosterone | 27.9 pg/ml | Standard Deviation 37 |
| Non-symptomatic Post-COVID | Free Testosterone | 76.0 pg/ml | Standard Deviation 4.6 |
Primary
Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort). The average of the scores for all 15 items is regarded as the GSRS total score. A higher score indicates a worse outcome.
Time frame: baseline
Population: 1 PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale | 2.5 units on a scale | Standard Deviation 1 |
| Non-symptomatic Post-COVID | Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale | 1.4 units on a scale | Standard Deviation 0.4 |
Primary
Glucose Derived CO2 as Measured by Breath During the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Glucose derived CO2 will be measured in breath samples at 120 minutes after oral consumption of 75g glucose isotopically labeled with 150 mg \[U-13C6\] glucose. Glucose-derived breath CO2 data are analyzed by measuring the ratios of 13CO2 to 12CO2 in single breath samples using an UBiT-IR300 infrared spectrophotometer (Otsuka Electronics, Hirakata, Osaka, Japan). The UBIT-IR300 calculates the difference in 13CO2 abundance from the baseline breath sample to each timed sample and expresses this as per mille delta over baseline (%DOB). OGTT will be performed on PASC subjects only.
Time frame: 120 minutes after glucose consumption
Population: OGTT will be performed on PASC subjects only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Glucose Derived CO2 as Measured by Breath During the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 40.9 %DOB | Standard Deviation 12.6 |
Primary
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Glucose will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Time frame: 120 minutes after glucose consumption
Population: OGTT will be performed on PASC subjects only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 150.3 mg/dl | Standard Deviation 33.7 |
Primary
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Glucose will be measured in serum before (0 minutes) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Time frame: Before glucose consumption
Population: PASC subjects only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption | 91.9 mg/dl | Standard Deviation 6.9 |
Primary
Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 120 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Time frame: 120 minutes after glucagon administration
Population: One PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration | 2.2 ng/ml | Standard Deviation 2.5 |
| Non-symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration | 5.6 ng/ml | Standard Deviation 6 |
Primary
Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 150 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Time frame: 150 minutes after glucagon administration
Population: One PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration | 2.6 ng/ml | Standard Deviation 2.1 |
| Non-symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration | 5.8 ng/ml | Standard Deviation 3.5 |
Primary
Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 180 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Time frame: 180 minutes after glucagon administration
Population: One PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration | 2.3 ng/ml | Standard Deviation 1.9 |
| Non-symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration | 3.0 ng/ml | Standard Deviation 2.1 |
Primary
Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at time point 90 minutes after glucagon injection to test for levels of human growth hormone. Results will be reported as ng/mL.
Time frame: 90 minutes after glucagon administration
Population: One PASC patient is missing from this measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration | 0.6 ng/ml | Standard Deviation 0.5 |
| Non-symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration | 1.6 ng/ml | Standard Deviation 3.5 |
Primary
Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of human growth hormone. 1 mg glucagon (for subjects over 90 kg, 1.5 mg glucagon) will be injected intramuscularly (IM) in the deltoid muscle of the subject and blood will be drawn at specified time points. Results will be reported as ng/mL.
Time frame: Before glucagon administration
Population: One PASC patient is missing from this measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration | 0.4 ng/ml | Standard Deviation 0.6 |
| Non-symptomatic Post-COVID | Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration | 0.9 ng/ml | Standard Deviation 0.8 |
Primary
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Insulin will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Time frame: 120 minutes after glucose consumption
Population: OGTT will be performed on PASC subjects only. 2 subjects from the PASC group are missing from analysis for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption | 82.0 uIU/ml | Standard Deviation 46.7 |
Primary
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Insulin will be measured in serum before (0 min) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Time frame: Before glucose consumption
Population: OGTT will be performed on PASC subjects only. 2 subjects from PASC are missing this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption | 7.4 uIU/ml | Standard Deviation 4.4 |
Primary
Insulin-Like Growth Factor-1 (IGF1)
Insulin-Like Growth Factor-1 (IGF1) will be measured in serum. Results will be reported in ng/mL.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Insulin-Like Growth Factor-1 (IGF1) | 142.8 ng/ml | Standard Deviation 41.6 |
| Non-symptomatic Post-COVID | Insulin-Like Growth Factor-1 (IGF1) | 137.6 ng/ml | Standard Deviation 56.7 |
Primary
Prolactin
Prolactin will be measured in serum. Results will be reported in ng/mL.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Prolactin | 11.5 ng/ml | Standard Deviation 9.5 |
| Non-symptomatic Post-COVID | Prolactin | 9.5 ng/ml | Standard Deviation 4 |
Primary
Sex Hormone Binding Globulin (SHBG)
Sex Hormone Binding Globulin (SHBG) will be measured in serum. Results will be reported in nmol/L.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Sex Hormone Binding Globulin (SHBG) | 46.4 nmol/L | Standard Deviation 25 |
| Non-symptomatic Post-COVID | Sex Hormone Binding Globulin (SHBG) | 97.7 nmol/L | Standard Deviation 85.8 |
Primary
Sleep Quality as Measured by Pittsburgh Sleep Quality Index
Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total \< 5 associated with good sleep quality. Total \> 5 associated with poor sleep quality.
Time frame: baseline
Population: 1 PASC subject missing from analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Sleep Quality as Measured by Pittsburgh Sleep Quality Index | 11.1 score on a scale | Standard Deviation 4 |
| Non-symptomatic Post-COVID | Sleep Quality as Measured by Pittsburgh Sleep Quality Index | 4.5 score on a scale | Standard Deviation 2.8 |
Primary
Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults
Symptoms of growth hormone deficiency will be measured using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms.
Time frame: baseline
Population: 1 PASC patient is missing from this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults | 13.6 units on a scale | Standard Deviation 7 |
| Non-symptomatic Post-COVID | Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults | 2.4 units on a scale | Standard Deviation 5.1 |
Primary
Thyroid Stimulating Hormone (TSH)
Thyroid Stimulating Hormone (TSH) will be measured in serum. Results will be reported in mUI/L.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Thyroid Stimulating Hormone (TSH) | 2.38 mUI/L | Standard Deviation 1.27 |
| Non-symptomatic Post-COVID | Thyroid Stimulating Hormone (TSH) | 1.60 mUI/L | Standard Deviation 0.95 |
Primary
Total Testosterone
Total testosterone will be measured in serum of male subjects. Results will be reported in ng/dL.
Time frame: baseline
Population: Testosterone reported in male subjects only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Total Testosterone | 508.0 ng/dl | Standard Deviation 81.2 |
| Non-symptomatic Post-COVID | Total Testosterone | 292.5 ng/dl | Standard Deviation 53 |
Primary
Vitamin B12
Vitamin B12 will be measured in serum.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Vitamin B12 | 553.7 pg/ml | Standard Deviation 156.4 |
| Non-symptomatic Post-COVID | Vitamin B12 | 446.1 pg/ml | Standard Deviation 254.3 |
Primary
Vitamin D 25OH
Vitamin D 25OH will be measured in serum.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Vitamin D 25OH | 30.6 ng/ml | Standard Deviation 8.6 |
| Non-symptomatic Post-COVID | Vitamin D 25OH | 41.1 ng/ml | Standard Deviation 10.7 |
Secondary
Free T4
Free T4 measured at baseline
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Symptomatic Post-COVID | Free T4 | 1.05 ng/dl | Standard Deviation 0.16 |
| Non-symptomatic Post-COVID | Free T4 | 1.19 ng/dl | Standard Deviation 0.2 |