Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III

• Sponsor: Anahuac University (Other)
• Overall Status: Completed
• CT.gov ID: NCT04507867
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Actual Duration (Months): 7.1
• Patients Per Site Per Month: 11.3

Study Details

Study Description

Brief Summary

The disease caused by SARS-CoV-2, has derived a pandemic in which its evolution and complications depend on the immune capacity of the host. The virus has been characterized by presenting an inflammatory cascade, increased by the overproduction of proinflammatory cytokines, the decrease in metalloenzymes and also the rapid spread of the virus. There are several lines of treatment, however, nutritional treatment only considered a caloric intake. For this reason, this study will evaluate the evolution of patients with COVID-19 assisted by nutritional support system and the effect of this therapy in reducing complications and comorbidities.

Research question: Will the nutritional support system reduce complications in stage III positive COVID-19 patients with comorbidities (type 2 DM, SAH, overweight / obesity with BMI <35), with a better benefit than that achieved with the conventional nutritional treatment ?.

Hypothesis: The nutritional support system will reduce the complications of patients with COVID-19 in stage III with comorbidities. General Objective: To determine the effect of the use of a nutritional support system on complications in patients with COVID-19 in stage III with comorbidities.

Methodology: A controlled, blinded, randomized clinical trial will be conducted in patients with COVID-19, hospitalized at the ISSEMYM Toluca Arturo Montiel Rojas Medical Center, who meet the inclusion criteria. The evolution of the group of patients receiving the nutritional support system (NSS) and the normal diet implemented by the hospital will be evaluated against the group of patients receiving only the diet, using clinical examination, laboratory and cabinet tests during their hospital stay.

Statistical analysis: for independent groups with normal distribution, Student's T will be applied. If the distribution does not meet normality criteria, a Mann Whitney U will be performed; Two-way ANOVA will be applied to monitor the groups over time with normal distribution. If the distribution does not meet normality criteria, a Friedman test will be performed, in both cases post hoc tests will be performed. The results will be analyzed using version 6 of the Graphpad Prism software.

Condition or Disease	Intervention/Treatment	Phase
COVID19; Diabetes Mellitus; Hypertension; Obesity; Overweight; Oxygen Saturation; Mortality; Inflammation	Dietary Supplement: Nutritional support system (NSS); Other: Conventional nutritional support designed by hospital nutritionists	N/A

Detailed Description

Patients in the COVID-19 area, who are treated at the ISSEMYM Toluca Arturo Montiel Rojas Medical Center, located in Paseo Tollocan, Av. Baja Velocidad km 575, Barrio de Sta Clara, Toluca de Lerdo, México; both sexes, with the presence of comorbidities (type 2 DM, SAH, overweight or obesity BMI <35) and in stage III of the disease.

Consecutive cases. With systematic randomized allocation using a sequence of random numbers built with the Excel program divided into two groups. Once the participants of the COVID-19 area have been selected, patients and / or family members will be spoken to to explain the protocol and obtain the signatures of the letters of informed consent. Assignment to the research group will be carried out randomly.

Once the patients have been admitted to the study, the following will be carried out: test of COVID-19 by means of PCR, thorax tomography, complete clinical history, Mini Nutritional Assessment (MNA), food diary, list of clinical variables designed by us, complete blood count, coagulation profile, serum electrolytes, blood chemistry (6-elements), lipidic profile, liver function tests, ferritin, fibrinogen, C-reactive protein, procalcitonin and D-dimer. Anthropometric measurements will also be carried out (height, weight, BMI, muscle mass %, fat % and visceral fat%).

The follow-up will be carried out daily for 21 days or earlier, if they are discharged from the hospital due to improvement in the evolution, at that moment the patient concludes the study. The following points will be supervised, recording the information in files and photos, since the hospital security protocol does not allow to extract stationery from the

COVID-19 area:

1. Application and consumption of NSS supplementation as appropriate.

2. Morning and evening vital signs.

3. Daily clinical evaluation (It includes variables such as oxygen flow, activity level, integrity of the hair, skin and nails, evaluation of the sense of taste and smell, pain, gastrointestinal symptoms, bowel movements, prescribed medications, mood, among others).

4. Anthropometric measurements using a scale every 2 days (only if the patient is stable and can maintain balance).

5. Food diaries of each patient.

6. Laboratory studies every 3 days (previously mentioned).

In the same way, the following will be taken into account: the number of days hospitalized, number of patients who progress to ventilation, number of patients who die, number of patients who are extubated and number of days after extubation.

A descriptive analysis will be carried out for each continuous variable. These variables will be expressed as mean ± standard deviation and standard error. It will be done according to the distribution of the data; For independent groups with a normal distribution, Student's T will be applied. If the distribution does not meet normality criteria, a Mann Whitney U will be performed; For the follow-up of dependent groups with normal distribution, two-way ANOVA will be applied. If the distribution does not meet normality criteria, a Friedman test will be performed, in both cases post hoc tests will be performed, taking into account that a significant value of p of < 0.05. The results will be analyzed using version 6 of the Graphpad Prism software.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: exploratory study, it is a controlled, blinded, randomized clinical trial design.exploratory study, it is a controlled, blinded, randomized clinical trial design.
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: blinding was planned for patients and evaluators (treating physicians , care provider and laboratory personnel)
• Primary Purpose: Treatment
• Official Title: Effect of a Nutritional Support System to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III
• Actual Study Start Date: Sep 7, 2020
• Actual Primary Completion Date: Apr 10, 2021
• Actual Study Completion Date: Apr 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: control group Patients who received the standard diet	Other: Conventional nutritional support designed by hospital nutritionists; Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.
Experimental: Intervention group Patients who received the nutritional support system (NSS) and the standard diet	Dietary Supplement: Nutritional support system (NSS); Combination of three B vitamins (B1, B6 and B12) "Neurobion" 10 mg solution for IM injection, One every 24 hours for the first 5 days. Probiotics Saccharomyces boulardii CNCM I-745 "Floratil". One morning and one evening 250 mg capsule during the first 6 days One envelope of NSS-1 in the morning and one envelope in the afternoon mixed with 400 ml of water each, contain nutritional support system.; Other: Conventional nutritional support designed by hospital nutritionists; Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.

Outcome Measures

Primary Outcome Measures

1. Overall Survival [40 days.]

   Overall survival, the total number of patients included in the study and completed a 40-day follow-up.

2. Overall Mortality at Day 40 [40 days.]

   Total number of patients who died before day 40 of follow-up.

Secondary Outcome Measures

1. Survival in Intubated Patients at Day 40 [40 days]

   Total number of patients who were intubated, extubated, discharged and completes the 40 day follow-up

2. Mortality in Intubated Patients at Day 40 [40 days]

   Patients who were intubated during their hospital stay and died before completing follow-up on day 40.

3. Progression to Mechanical Ventilation Assistance [10 days.]

   total number of patients included in the study who progressed to mechanical ventilation during the first 10 days of hospital stay.

4. Participants With Normal Bristol Scale at Day 3 [day 3]

   The Bristol Stool Form Scale categorizes stools into one of seven stool types ranging from type 1 (hard lumps) to type 7 (watery diarrhea). Type 3 and 4 were considered "Normal".

5. Hidric Balance on Day 3 [It is evaluated on day 3 of hospital stay (duration approximately 10 minutes).]

   The ratio between the water assimilated into the body and that lost from the body, in milliliters.

6. Oxigen Saturation >90% on Day 3 [day 3.]

   the total number of patients with oxygen saturation >90% on day 3 of their hospital stay.

7. PHQ-9 Test [baseline and hospital discharge]

   Is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders, includes 9 items, which evaluate the presence of depressive symptoms based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders version 4, during the last 2 weeks, how often the patient presented depressive symptoms. According to the sum of the score obtained, the following 4 categories will be considered: 0-4 minimum existence or absence of depressive symptoms; 5-9 = mild depressive symptoms; 10-14 = moderate depressive symptoms; 15-19 = moderate to severe depressive symptoms; 20-27 = severe depressive symptoms.

8. Oxigen Flow (Intragroup) [baseline and day 3]

   Difference in oxygen delivery between the baseline period and day 3 of hospital stay in each group.

9. qSOFA at Day 3 [Baseline and Day 3]

   Quick-Sequential Organ Failure Assessment (qSOFA) score gives 0 to 3 points. ≥2 in the setting of suspected infection had a high predicted in-hospital mortality rate and could be considered septic.

10. Number of Defectations on Day 3 [Day 3]

    Refers to the subjective sensation of increased abdominal pressure without an increase in abdominal size, the number of defecations were quantified at day 3 and compared between both groups.

11. Number of Participants With Distension on Day 3 [Day 3]

    Is a visible increase in abdominal girth.1. Present, 2. Absent.

Other Outcome Measures

1. Saturation Without Supplementary Oxygen [day 40]

   The oxygen saturation without supplementary oxygen is taken at the control appointment 40 days after hospital discharge.

2. Need for Home Oxygen Flow [Day 40]

   The need to continue with supplemental oxygen at hospital discharge. Categories: 1. Yes, 2. No.

3. Time of Home Oxigen Use [day 40]

   It is recorded for how many days the treating doctor asked the patients to continue to administer supplemental oxygen after hospital discharge

4. Post Covid Syndrome [Day 40.]

   Persistence of clinical signs and symptoms that arise after developing COVID-19, and are not explained by an alternative diagnosis. 1. Present. 2. Absent.

5. Weight Decrease [Day 40]

   Is defined as at least a 5% reduction in weight from the baseline level.Total number of patients with weight loss at the end of follow-up at day 40

6. Gastrointestinal Symptoms [Day 40]

   Total number of patients with gastrointestinal symptoms at the end of follow-up at day 40.Those symptoms perceived abdominal region (pain, burn, pressure, nausea, vomiting)

7. Number of Deceased Patients Stratified by Fibrinogen Level. [Baseline]

   Association between the presentation of certain laboratory parameters taken at baseline with the overall mortality of discharged patients compared to deceased patients.

8. Number of Deceased Patients Stratified by Procalcitonin Level. [Baseline]

   Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

9. Number of Deceased Patients Stratified by Ureic Nitrogen Level [Baseline]

   Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

10. Number of Deceased Participants Stratified by RCP Level [Baseline]

    Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

11. Number of Deceased Participants Stratified by Neutrophils Level [Baseline]

    Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

12. Number of Deceased Participants Stratified by Leukocytes Level [Baseline]

    Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

13. Number of Deceased Participants Stratified by Urea Level [Baseline]

    Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients admitted to the ISSEMYM Toluca Medical Center "Arturo Montiel Rojas ", diagnosed with COVID-19 confirmed by PCR.

• Patients in need of supplemental O2 with nasal prongs or reservoir-mask for satO2 <90% and respiratory distress.

• With concomitant diseases such as cardiovascular disease, diabetes mellitus 2, hypertension, overweight or obesity BMI <35.

• Both sexes.

• Over 30 years old.

• The patient tolerate oral feeding.

• Signing of the letter of informed consent.

Exclusion Criteria:

• Detachment from treatment.

• Admission to the ICU for any reason.

• Patients who do not tolerate the oral route.

• Reactions to treatment that compromise the health of patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ISSEMYM "Arturo Montiel Rojas" Medical Center	Toluca de Lerdo	Mexico State	Mexico	52140

Sponsors and Collaborators

• Anahuac University

Investigators

• Principal Investigator: Fernado Leal Martínez, Ph.D, Anahuac University

Study Documents (Full-Text)

• Study Protocol - Jul 28, 2020
• Statistical Analysis Plan - Jul 28, 2021
• Informed Consent Form - Jul 28, 2020

More Information

Additional Information:

• BMI Classification Percentile And Cut Off Points
• Diabetes Mellitus Type 2
• Cardiovascular Disease
• Hyperlipidemia
• Dyspnea
• Chapter 84: Nausea and Vomiting
• Acute Headache
• Myalgia
• Diarrhea
• Physiology, Respiratory Rate
• Oxygen Saturation
• How is body temperature regulated and what is fever?
• Oxygen Administration
• Antihypertensive Medications
• Antibiotics
• Antacids
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
• Chapter 151: Hemoglobin and Hematocrit
• Chapter 152: Red Cell Indices
• Histology, White Blood Cell
• Blood Glucose Monitoring
• Physiology, Cholesterol
• Alanine Amino Transferase
• Chapter 101: Serum Albumin and Globulin
• Calories: Total Macronutrient Intake, Energy Expenditure, and Net Energy Stores

Publications

None provided.

• Responsible Party: Fernando Leal-Martinez, Doctor in Clinical Nutrition, Anahuac University
• ClinicalTrials.gov Identifier: NCT04507867
• Other Study ID Numbers: 202036
• First Posted: Aug 11, 2020
• Last Update Posted: Oct 15, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Fernando Leal-Martinez, Doctor in Clinical Nutrition, Anahuac University: COVID19; Nutritional support; SARS-COV-2; Pneumonia; Supplementation; Probiotics
• Additional relevant MeSH terms: COVID-19; Inflammation; Overweight

Study Results

Participant Flow

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Period Title: Overall Study
STARTED	40	40
COMPLETED	33	39
NOT COMPLETED	7	1

Baseline Characteristics

Arm/Group Title	Control Group	Intervention Group	Total
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.	Total of all reporting groups
Overall Participants	40	40	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (10.3)	51.5 (11.4)	52.7 (10.9)
Sex: Female, Male (Count of Participants)
Female	13 32.5%	15 37.5%	28 35%
Male	27 67.5%	25 62.5%	52 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	40 100%	40 100%	80 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Mexico	40 100%	40 100%	80 100%
Overweight (Count of Participants)
Count of Participants [Participants]	38 95%	36 90%	74 92.5%
Obesity Type I-II (Count of Participants)
Count of Participants [Participants]	14 35%	13 32.5%	27 33.8%
Diabetes Mellitus 2 (Count of Participants)
Count of Participants [Participants]	13 32.5%	11 27.5%	24 30%
Cardiovascular Disease and/or Hypertension (Count of Participants)
Count of Participants [Participants]	17 42.5%	10 25%	27 33.8%
Hyperlipidemia (Count of Participants)
Count of Participants [Participants]	11 27.5%	7 17.5%	18 22.5%
Number of Participants with Gastrointestinal Disease (Count of Participants)
Count of Participants [Participants]	14 35%	13 32.5%	27 33.8%
Total Risk Factors (number of risk factors) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of risk factors]	2.92 (1.42)	2.57 (1.35)	2.75 (1.39)
Number of Participants with Dyspnea (Count of Participants)
Count of Participants [Participants]	24 60%	26 65%	50 62.5%
Nausea and Vomiting (Count of Participants)
Count of Participants [Participants]	6 15%	7 17.5%	13 16.3%
Hyposmia (Count of Participants)
Count of Participants [Participants]	12 30%	15 37.5%	27 33.8%
Dysgeusia (Count of Participants)
Count of Participants [Participants]	18 45%	20 50%	38 47.5%
Number of Participants with Headache (Count of Participants)
Count of Participants [Participants]	26 65%	29 72.5%	55 68.8%
Number of Participants with Myalgia (Count of Participants)
Count of Participants [Participants]	32 80%	30 75%	62 77.5%
Number of Participants with Diarrhea (Count of Participants)
Count of Participants [Participants]	18 45%	12 30%	30 37.5%
Number of Participants with Anorexia (Count of Participants)
Count of Participants [Participants]	20 50%	21 52.5%	41 51.3%
Total of symptoms (number of symptoms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of symptoms]	7.05 (2.11)	6.8 (2.23)	6.92 (2.16)
Bristol scale "normal" (T3-4) (Count of Participants)
Count of Participants [Participants]	9 22.5%	5 12.5%	14 17.5%
Number of defecations (Number of defecations per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Number of defecations per day]	0.54 (0.6)	0.52 (0.73)	0.53 (0.66)
Number of Participants with Abdominal Distension (Count of Participants)
Count of Participants [Participants]	28 70%	28 70%	56 70%
Breathing Frequency (breaths per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [breaths per minute]	21.18 (3.01)	21.48 (3.01)	21.32 (2.99)
Oxygen Saturation (oxygen saturation percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [oxygen saturation percentage]	92.73 (4.17)	94 (3.18)	93.36 (3.74)
Resting Heart Rate (beats per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats per minute]	70.7 (15.4)	75.5 (9.88)	73.07 (13.07)
Body Temperature (ºC) (degrees Celsius (ºC)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees Celsius (ºC)]	36.27 (0.73)	36.25 (0.62)	36.25 (0.67)
Liters of Supplemental Oxygen (L/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [L/min]	5.9 (3.82)	6 (3.29)	5.97 (3.54)
qSOFA Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.425 (0.59)	0.65 (0.62)	0.53 (0.61)
MNA (Mini Nutritional Assessment) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.13 (2.26)	11.38 (1.65)	11.25 (1.97)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.35 (3.89)	29.98 (4.07)	29.66 (3.97)
Hydric Balance (milliliters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters]	-203.4 (966)	-301.5 (1167)	-254.1 (1056)
Antihypertensive medication (Count of Participants)
Count of Participants [Participants]	13 32.5%	9 22.5%	22 27.5%
Antidiabetics medication (Count of Participants)
Count of Participants [Participants]	9 22.5%	11 27.5%	20 25%
Antilipids medication (Count of Participants)
Count of Participants [Participants]	3 7.5%	3 7.5%	6 7.5%
Antibiotics medication (Count of Participants)
Count of Participants [Participants]	1 2.5%	4 10%	5 6.3%
Antiacids (Count of Participants)
Count of Participants [Participants]	6 15%	6 15%	12 15%
NSAIDs medication (Count of Participants)
Count of Participants [Participants]	8 20%	12 30%	20 25%
Hemoglobin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	15.53 (2.22)	15.54 (2.08)	15.53 (2.14)
Mean Corpuscular Hemoglobin Concentration (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	33.39 (1.4)	33.46 (1.17)	33.42 (1.28)
Platelets (10^3 platelets / μL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 platelets / μL]	222.2 (53.93)	248.4 (139.9)	235.3 (106.1)
Leukocytes (10^3 leukocytes / μL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^3 leukocytes / μL]	8.97 (4.15)	8.46 (4.36)	8.72 (4.23)
Neutrophils (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	83.5 (8.87)	80.78 (9.29)	82.14 (9.12)
Glycemia (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	135.4 (59.39)	134.8 (58.83)	135.12 (58.73)
Total cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	142.8 (42.82)	135 (23.53)	138.98 (34.65)
Triglycerides (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	147.5 (58.92)	132.8 (37.39)	140.2 (49.6)
AST (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	48.06 (28.81)	46.4 (49.65)	47.2 (40.3)
ALT (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	47.69 (31.9)	50.44 (50.88)	49.06 (42.21)
Albumin (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	3.53 (0.44)	3.57 (0.41)	3.55 (0.42)
Ferritin (ng/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/ml]	1070 (899.3)	1270 (1142)	1167 (1022)
Fibrinogen (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	592.2 (170.4)	607.4 (162.9)	600 (165.3)
CRP (mg/l) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/l]	157.3 (106.7)	135.3 (94.92)	146.3 (100.9)
D dimer (μg/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μg/ml]	291.2 (179.9)	444.9 (954.9)	368 (686.4)
Serum Creatinine (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	0.88 (0.31)	0.86 (0.22)	0.87 (0.27)
Urea (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	33.95 (15.84)	32.95 (10.78)	33.42 (13.47)
Blood urea nitrogen (BUN) (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	15.87 (7.39)	15.43 (5.02)	15.65 (6.29)
Glomerular filtration rate (GFR) (mL/min/1.73 m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73 m^2]	90.15 (20.2)	93.59 (17.4)	91.84 (18.82)
Procalcitonin (μg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μg/L]	0.364 (0.6)	0.18 (0.188)	0.27 (0.45)
basal energy intake (kilocalories) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilocalories]	1411 (46.2)	1376 (36.3)	1393.5 (43.3)

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival, the total number of patients included in the study and completed a 40-day follow-up.
Time Frame	40 days.

Outcome Measure Data

Analysis Population Description

the total number of patients who were enrolled and included in the study and who survived or not at the end of follow-up at day 40.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Count of Participants [Participants]	33 82.5%	39 97.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	The total number of patients who did or did not survive to day 40 of follow-up.
	Type of Statistical Test	Other
	Comments	Kaplan-Meier method for overall survival.
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Log Rank
	Comments

2. Primary Outcome

Title	Overall Mortality at Day 40
Description	Total number of patients who died before day 40 of follow-up.
Time Frame	40 days.

Outcome Measure Data

Analysis Population Description

total number of patients who were enrolled in the study and died prior to day 40 of follow-up

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Count of Participants [Participants]	7 17.5%	1 2.5%

3. Secondary Outcome

Title	Survival in Intubated Patients at Day 40
Description	Total number of patients who were intubated, extubated, discharged and completes the 40 day follow-up
Time Frame	40 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	7	3
Count of Participants [Participants]	2 5%	2 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	the total number of patients who were intubated and survived at the end of day 40 follow-up.
	Type of Statistical Test	Other
	Comments	Kaplan-Meier method
Statistical Test of Hypothesis	p-Value	0.495
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Mortality in Intubated Patients at Day 40
Description	Patients who were intubated during their hospital stay and died before completing follow-up on day 40.
Time Frame	40 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	7	3
Count of Participants [Participants]	5 12.5%	1 2.5%

5. Secondary Outcome

Title	Progression to Mechanical Ventilation Assistance
Description	total number of patients included in the study who progressed to mechanical ventilation during the first 10 days of hospital stay.
Time Frame	10 days.

Outcome Measure Data

Analysis Population Description

Proportion of patients from control group and intervention group were analyzed with the Kaplan-Meier method comparing both groups to MVA progression

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Count of Participants [Participants]	7 17.5%	3 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	total number of patients included in the study who progressed to mechanical ventilation during the first 10 days of hospital stay.
	Type of Statistical Test	Other
	Comments	Kaplan-Meier method
Statistical Test of Hypothesis	p-Value	0.186
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Participants With Normal Bristol Scale at Day 3
Description	The Bristol Stool Form Scale categorizes stools into one of seven stool types ranging from type 1 (hard lumps) to type 7 (watery diarrhea). Type 3 and 4 were considered "Normal".
Time Frame	day 3

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group, measured at day 3 of hospital stay . Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	24	31
Count of Participants [Participants]	8 20%	13 32.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group, measured at day 3 of hospital stay. It was categorized as follows: 1. normal bristol scale at day 3; 2. abnormal bristol scale at day 3.
	Type of Statistical Test	Superiority
	Comments	Fisher exact test
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Hidric Balance on Day 3
Description	The ratio between the water assimilated into the body and that lost from the body, in milliliters.
Time Frame	It is evaluated on day 3 of hospital stay (duration approximately 10 minutes).

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at day 3 of hospital stay . Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	17	18
Mean (Standard Deviation) [milliliters]	123.4 (453.8)	456.6 (485.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group, measured at day 3 of hospital stay . Deceased patients were excluded.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	t-test, 1 sided
	Comments

8. Secondary Outcome

Title	Oxigen Saturation >90% on Day 3
Description	the total number of patients with oxygen saturation >90% on day 3 of their hospital stay.
Time Frame	day 3.

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at day 3 of hospital stay . Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Count of Participants [Participants]	34 85%	37 92.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at day 3 of hospital stay . Deceased patients were excluded.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.241
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	PHQ-9 Test
Description	Is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders, includes 9 items, which evaluate the presence of depressive symptoms based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders version 4, during the last 2 weeks, how often the patient presented depressive symptoms. According to the sum of the score obtained, the following 4 categories will be considered: 0-4 minimum existence or absence of depressive symptoms; 5-9 = mild depressive symptoms; 10-14 = moderate depressive symptoms; 15-19 = moderate to severe depressive symptoms; 20-27 = severe depressive symptoms.
Time Frame	baseline and hospital discharge

Outcome Measure Data

Analysis Population Description

Intragroup analysis between the control group and the intervention group for different parameters, measured at baseline and at hospital discharge.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	6	10
Baseline	3.66 (2.5)	5.3 (3.4)
Hospital discharge	1.50 (2.8)	1.9 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group
	Comments	Intragroup analysis at the control group, the measurement was performed at baseline and at hospital discharge.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.187
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intervention Group
	Comments	Intragroup analysis at the intervention group, the measurement was performed at baseline and at hospital discharge.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Oxigen Flow (Intragroup)
Description	Difference in oxygen delivery between the baseline period and day 3 of hospital stay in each group.
Time Frame	baseline and day 3

Outcome Measure Data

Analysis Population Description

Intragroup and Intergroup analysis between the control group and the intervention group for the difference in oxygen delivery between the baseline period and day 3 of hospital stay in each group.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Baseline	5.9 (3.8)	6 (3.2)
Day 3	6 (4.4)	4.5 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group
	Comments	Intragroup analysis of the control group in oxygen delivery, the difference between the baseline period and day 3 of hospital stay.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.919
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intervention Group
	Comments	Intragroup analysis of the control group in oxygen delivery, the difference between the baseline period and day 3 of hospital stay.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	qSOFA at Day 3
Description	Quick-Sequential Organ Failure Assessment (qSOFA) score gives 0 to 3 points. ≥2 in the setting of suspected infection had a high predicted in-hospital mortality rate and could be considered septic.
Time Frame	Baseline and Day 3

Outcome Measure Data

Analysis Population Description

Intragroup analysis of both groups, the difference in the qSOFA measurement at baseline and at day 3 will be analyzed.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	40	40
Baseline	0.42 (0.59)	0.65 (0.62)
Day 3	0.51 (0.57)	0.43 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group
	Comments	Intragroup analysis of the control group, the difference in the qSOFA measurement at baseline and at day 3 will be analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intervention Group
	Comments	Intragroup analysis of the intervention group, the difference in the qSOFA measurement at baseline and at day 3 will be analyzed.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	t-test, 2 sided
	Comments

12. Secondary Outcome

Title	Number of Defectations on Day 3
Description	Refers to the subjective sensation of increased abdominal pressure without an increase in abdominal size, the number of defecations were quantified at day 3 and compared between both groups.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Intergroup analysis between both groups to evaluate the number of defecations measured at day 3.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received the standard diet Conventional nutritional support designed by hospital nutritionists: Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.	Patients who received the nutritional support system (NSS) and the standard diet Nutritional support system (NSS): 1.Combination of three B vitamins (B1, B6 and B12) "Neurobion" 10 mg solution for IM injection, One every 24 hours for the first 5 days. 2.Probiotics Saccharomyces boulardii CNCM I-745 "Floratil". One morning and one evening 250 mg capsule during the first 6 days 3. One envelope of NSS-1 in the morning and one envelope in the afternoon mixed with 400 ml of water each, contain nutritional support system. Conventional nutritional support designed by hospital nutritionists: Diet designed by the nutrition department according to comorbidities and intubation probability. Food will be established according to the provisions of the ISSEMYM Toluca Arturo Montiel Rojas Medical Center.
Measure Participants	37	36
Mean (Standard Deviation) [defecations]	0.81 (0.90)	1.41 (1.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between both groups to evaluate the number of defecations measured at day 3.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Number of Participants With Distension on Day 3
Description	Is a visible increase in abdominal girth.1. Present, 2. Absent.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at day 3 of hospital stay. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	31	31
Number [percent of participants]	51.6 129%	19.4 48.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at day 3 of hospital stay. Deceased patients were excluded.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Fisher Exact
	Comments	the shapiro wilk test was used to analyze the distribution of the data.

14. Other Pre-specified Outcome

Title	Saturation Without Supplementary Oxygen
Description	The oxygen saturation without supplementary oxygen is taken at the control appointment 40 days after hospital discharge.
Time Frame	day 40

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	28	38
Mean (Standard Deviation) [percentage]	90.39 (3.4)	92.08 (2.5)

15. Other Pre-specified Outcome

Title	Need for Home Oxygen Flow
Description	The need to continue with supplemental oxygen at hospital discharge. Categories: 1. Yes, 2. No.
Time Frame	Day 40

Outcome Measure Data

Analysis Population Description

Intragroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days of hospital stay. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	27	39
Count of Participants [Participants]	23 57.5%	26 65%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.
Statistical Test of Hypothesis	p-Value	0.078
	Comments
	Method	Fisher Exact
	Comments

16. Other Pre-specified Outcome

Title	Time of Home Oxigen Use
Description	It is recorded for how many days the treating doctor asked the patients to continue to administer supplemental oxygen after hospital discharge
Time Frame	day 40

Outcome Measure Data

Analysis Population Description

Intragroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	17	23
Mean (Standard Deviation) [days]	57.6 (24.6)	43.8 (16.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	t-test, 1 sided
	Comments

17. Other Pre-specified Outcome

Title	Post Covid Syndrome
Description	Persistence of clinical signs and symptoms that arise after developing COVID-19, and are not explained by an alternative diagnosis. 1. Present. 2. Absent.
Time Frame	Day 40.

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	24	34
Count of Participants [Participants]	9 22.5%	8 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group to analyze the presentation of post covid syndrome at the end of follow-up at day 40.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.195
	Comments
	Method	Fisher Exact
	Comments

18. Other Pre-specified Outcome

Title	Weight Decrease
Description	Is defined as at least a 5% reduction in weight from the baseline level.Total number of patients with weight loss at the end of follow-up at day 40
Time Frame	Day 40

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	11	18
Count of Participants [Participants]	8 20%	8 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.135
	Comments
	Method	Fisher Exact
	Comments

19. Other Pre-specified Outcome

Title	Gastrointestinal Symptoms
Description	Total number of patients with gastrointestinal symptoms at the end of follow-up at day 40.Those symptoms perceived abdominal region (pain, burn, pressure, nausea, vomiting)
Time Frame	Day 40

Outcome Measure Data

Analysis Population Description

Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.

Arm/Group Title	Control Group	Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
Measure Participants	24	37
Count of Participants [Participants]	4 10%	3 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments	Intergroup analysis between the control group and the intervention group for different parameters, measured at a complete follow-up of 40 days. Deceased patients were excluded.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.266
	Comments
	Method	Fisher Exact
	Comments

20. Other Pre-specified Outcome

Title	Number of Deceased Patients Stratified by Fibrinogen Level.
Description	Association between the presentation of certain laboratory parameters taken at baseline with the overall mortality of discharged patients compared to deceased patients.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Fibrinogen <700 mg/dL	Fibrinogen >700 mg/dL
Arm/Group Description	Patients with fibrinogen levels <700 mg/dl at baseline and died.	Patients with fibrinogen levels > 700 mg/dl at baseline and died.
Measure Participants	61	19
Count of Participants [Participants]	2 5%	6 15%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Fisher Exact
	Comments

21. Other Pre-specified Outcome

Title	Number of Deceased Patients Stratified by Procalcitonin Level.
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Procalcitonin <0.5 ng/mL	Procalcitonin >0.5 ng/mL
Arm/Group Description	Patients with procalcitonin levels <0.5 ng/mL at baseline and died.	Patients with procalcitonin levels >0.5 ng/mL at baseline and died.
Measure Participants	72	8
Count of Participants [Participants]	4 10%	4 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Fisher Exact
	Comments

22. Other Pre-specified Outcome

Title	Number of Deceased Patients Stratified by Ureic Nitrogen Level
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Ureic Nitrogen <22 mg/dL	Ureic Nitrogen >22 mg/dL
Arm/Group Description	Patients with Ureic Nitrogen <22 mg/dL at baseline and died.	Patients with Ureic Nitrogen >22 mg/dL at baseline and died.
Measure Participants	71	9
Count of Participants [Participants]	4 10%	4 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Fisher Exact
	Comments

23. Other Pre-specified Outcome

Title	Number of Deceased Participants Stratified by RCP Level
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	RCP <150 mg/L	RCP >150 mg/L
Arm/Group Description	Patients with RCP <150 mg/L at baseline and died.	Patients with RCP >150 mg/L at baseline and died.
Measure Participants	45	35
Count of Participants [Participants]	1 2.5%	7 17.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Fisher Exact
	Comments

24. Other Pre-specified Outcome

Title	Number of Deceased Participants Stratified by Neutrophils Level
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Neutrophils <80%	Neutrophils >80%
Arm/Group Description	Patients with neutrophils <80% at baseline and died	Patients with neutrophils >80% at baseline and died
Measure Participants	27	53
Count of Participants [Participants]	0 0%	8 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	Fisher Exact
	Comments

25. Other Pre-specified Outcome

Title	Number of Deceased Participants Stratified by Leukocytes Level
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Leukocytes <10x10^3/μL	Leukocytes >10x10^3/μL
Arm/Group Description	Patients with Leukocytes <10x10^3/μL at baseline and died	Patients with Leukocytes >10x10^3/μL at baseline and died
Measure Participants	57	23
Count of Participants [Participants]	3 7.5%	5 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	Fisher Exact
	Comments

26. Other Pre-specified Outcome

Title	Number of Deceased Participants Stratified by Urea Level
Description	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Association between the presentation of certain laboratory parameters taken at baseline compared to overall mortality.

Arm/Group Title	Urea <40 mg/dL	Urea >40 mg/dL
Arm/Group Description	Patients with Urea <40 mg/dL at baseline and died	Patients with Urea >40 mg/dL at baseline and died
Measure Participants	64	16
Count of Participants [Participants]	4 10%	4 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control Group, Intervention Group
	Comments
	Type of Statistical Test	Superiority
	Comments	Association between the presentation of certain laboratory parameters taken in the baseline period, with te overall mortality of discharge patients in comparison with deceased patients
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	40 days.
Adverse Event Reporting Description	Adverse Events and All Cause Mortality monitored for 40 days.
Arm/Group Title	Control Group		Intervention Group
Arm/Group Description	Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center.		Patients who received medical treatment indicated by the hospital and a diet established by the hospital nutrition department of the ISSEMyM Toluca Arturo Montiel Rojas Medical Center. Also it received the Nutritional support system (NSS), which consists of: 10 mg of cyanocobalamin, 100 mg of thiamin and 100 mg of pyridoxine administered intramuscularly every 24 hours for the first 5 days. Probiotics Saccharomyces Boulardii (SB) 50 million CFU daily for 6 days orally. One packet of NSS orally after morning meals and another after evening meals, mixed with 400 ml of water each, during the whole intervention for a maximum of 21 days.
All Cause Mortality
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)		1/40 (2.5%)
Serious Adverse Events
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Control Group		Intervention Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		5/40 (12.5%)
Gastrointestinal disorders
Constipation	0/40 (0%)	0	5/40 (12.5%)	5

Limitations/Caveats

Restriction of resources for laboratory tests, small number of subjects analyzed and restriction of access of measuring instruments to the COVID-19 area.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.