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Research Article
*Corresponding Author: Samar Osama Ahmed Hassan, Ain Shams University Hospital, Cairo, Egypt.
Citation: Samar Osama Ahmed Hassan, Ahmed Nour El-Din Hassan, Manal Sabry Mohamed, Mohamed Nabil Badawy Al Ashram, Mina Michael Nesim, et al., (2023), The Effects of Probiotic Lactobacillus Acidophilus and Colchicine on The Control of Symptoms, Duration, And Disease Progression of Mild and Moderate Cases of Covid-19: A Randomized Controlled Clinical Trial, Clinical Medical Reviews and Reports, 5(4); DOI:10.31579/2690-8794/162
Copyright: © 2023, Samar Osama Ahmed Hassan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 01 June 2023 | Accepted: 15 June 2023 | Published: 23 June 2023
Keywords: probiotics; colchicine; COVID-19; RCT; ain shams university
Background
Coronavirus disease 2019 (COVID-19) is a newly emerging human disease caused by a novel coronavirus, causing a global pandemic crisis. Probiotics and/or colchicine may be considered as options for treatment since they have anti-viral, anti-inflammatory, and immunomodulatory effects.
Objective
To assess the effectiveness of probiotic supplements (Lactobacillus acidophilus) and colchicine on symptoms, duration, and progression of mild and moderate cases of COVID-19 infection.
Methods
A three-arm randomized controlled clinical trial was carried out in the triage clinic of the family medicine department at Ain Shams University Hospitals on 150 participants who had been diagnosed as COVID-19 patients with mild and moderate severity. Patients aged below 18 years or above 65 years with any co-morbidities, pregnant or lactating females, and severe COVID-19 confirmed cases were excluded. Randomization was done by using sealed envelopes containing codes for intervention or control. Patients are followed up for improvement of their symptoms with no development of new symptoms over the course of two weeks.
Results
A total of 150 patients with mild and moderate severity of COVID-19 were enrolled in the study, 50 patients in each arm; around one third (34.7%) of the participants were aged between 29 and 39 years; one-quarter (24.7%) were aged between 18 and 28 years and 40.6% were aged 40 years and above. The mean duration of symptoms improvement was 12, 11 and 12 in the colchicine, probiotic, and control groups, respectively. Improvement of inflammatory markers over time occurred in each of the three groups, with no statistically significant difference between them.
Conclusion
Probiotic Lactobacillus acidophilus and colchicine shows no significant effect on the symptoms, duration, and progression of mild and moderate cases of COVID-19.
A novel coronavirus was discovered to be the source of a cluster of pneumonia cases in Wuhan (China), which led to an outbreak throughout China and then to a global pandemic. In February of 2020, the World Health Organization officially recognized COVID-19 (coronavirus disease 2019 [1].
COVID-19 disease frequently manifests as a fever, dry cough, shortness of breath, and breathing difficulties. Some of the less frequent symptoms include anosmia, sore throat, runny nose, vomiting, and diarrhea [2].
Dysbiosis of the gut microbiome, immunological dysregulation, hyperinflammation, and a cytokine storm are hallmarks of COVID-19 illness [3]. Probiotics are defined as” live bacteria that provide health benefits to the host when given in sufficient doses” [4].
Early reports from Wuhan indicate that 2–10% of COVID-19 patients exhibited gastrointestinal symptoms, including diarrhea, vomiting, and abdominal pain. 10% of patients experienced one to two days of nausea and diarrhea prior to the onset of fever and respiratory symptoms [5].
The severity of COVID-19 disease was correlated with the diversity of the gut microbiota, and alterations in the gut microbiota persisted even after the virus eliminated, suggesting that the virus may have a long-lasting negative impact on the homoeostasis of the human microbiome [6].
As an intestinal microbe regulator, probiotics help to improve the immune system, lessen allergic reactions, and play a crucial part in antiviral immunomodulation. They also increase the gastrointestinal microbiota's capacity to modulate immunological activity [7].
Infection with SARS-CoV-2 significantly altered the fecal microbiomes of all 15 patients, according to a study of confirmed COVID-19 patients in Hong Kong. This imbalance of intestinal microbiota persisted even after SARS-CoV-2 clearance [8].
Colchicine is an anti-inflammatory drug frequently prescribed for the treatment and prevention of crystals induced arthritis, such as gout, systemic auto-inflammatory illnesses such Bechet’s disease and familial Mediterranean fever [9]. Inhibiting neutrophil chemotaxis and activity in response to vascular damage is its mode of action [10].
One of the clinical trials called COLCORONA 2020 was directed by the Montreal Heart Institute and conducted in Brazil, Canada, Greece, South Africa, Spain, and the United States conducted by Tardif. et al. in 2021. The trial revealed that the effect of colchicine on clinical symptoms of COVID-19- community-treated individuals was not statistically significant difference between the colchicine group and controls [11].
Colchicine may lessen mortality and the need for mechanical ventilation in mild-to-moderate COVID-19 patients, according to a systematic review and meta-analysis conducted by Siemieniuk et al. in 2020 [12].
Consequently, probiotics and/or colchicine may be viable treatment options for COVID-19 patients. To examine the efficacy of probiotics and colchicine in the treatment of COVID-19, it is necessary to conduct additional clinical trials and provide clinicians with evidence, as there are currently insufficient studies to support this conclusion.
The aim of the current study was to assess the effectiveness of probiotic supplements (Lactobacillus acidophilus) and colchicine on symptoms, duration, and progression of mild and moderate cases of COVID-19 infection.
Patients And Methods
Study design and setting
A three-arm randomised controlled clinical trial was done as part of the investigation over the course of a year at the Triage Clinic of the Family Medicine Department at Ain Shams University Hospitals.
Inclusion criteria
Patients with mild and moderate COVID-19 severity, aged 18 to 64.
Exclusion criteria
Patients with COVID-19 who are under 18 or over 65, have co-morbid conditions, are pregnant or lactating mother, or have severe confirmed COVID-19 were excluded from the trial.
Participants in the research and sampling
A total of 150 individuals who satisfied the inclusion criteria had their data gathered between the beginning of July 2021 and the end of August 2022.
Patients were chosen from the Triage/COVID-19 Outpatient Clinic, and each one had the following procedures: Sociodemographic information was gathered for the clinical history, including age, gender, marital status, place of residence, smoking history, etc. Medical information included weight, current medications, symptoms (onset, course, and duration), and the presence of co-morbidities. The temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation are all measured during a thorough general examination.
Patients who met the CDC's criteria for suspicion had radiographic and laboratory confirmation using the tests PCR-COVID-19, Complete Blood Count, CRP, Ferritin and D-Dimer, as well as High-resolution CT chest.
Patients were categorised as mild and moderate based on laboratory and radiographic results once the diagnosis was confirmed.
The participants were divided into 3 groups:
Group A (Colchicine group) consisted of COVID-19 patients with mild to moderate disease who received the recommended course of care in accordance with the protocol established by the Egyptian Supreme Council of University Hospitals, as well as Colchicine tablets (0.5 mg) three times per day for three days and subsequently twice per day for four days [13].
Patients in Group B (Probiotic group) with mild and moderate COVID-19 severity got probiotics in the form of oral sachets once daily for two weeks in addition to protocol prescribed by the Egyptian Supreme Council of University Hospitals.
Group C (Control group) consists of COVID-19 patients with mild and moderate severity who received the recommended course of care in accordance with the protocol established by the Egyptian Supreme Council of University Hospitals (yet to be published) (Vitamin C 500 mg twice daily, Vitamin D3 2000–4000 IU/day, Zinc 75 mg once daily for two weeks, and necessary protocol of management based on case assessment and severity).
Randomization
To distribute intervention or control codes, the researcher utilised sealed envelopes.
Follow-up
Participants were contacted twice a week by phone to assess their symptoms (increase or decrease, duration, and development of new symptoms), compliance with treatment, daily temperature, oxygen saturation, need for oxygen inhalation, need for hospital admission, need for ICU admission, need for mechanical ventilation, and improvement in inflammatory markers level (CBC, CRP, ferritin, and D-dimer).
Final assessment
Release from isolation 10 days after start of symptoms or 10 days after the patient's first positive swab [14].
14 days after the initiation of therapy, individuals were polled about whether their symptoms had improved or remained the same, and Complete Blood Count, CRP, Ferritin, and D-Dimer were retested.
End point
The trial lasted until the sample size was reached, the patient's symptoms had improved, and no new symptoms had appeared. It also continued until there was no longer a requirement for hospitalization or ICU admissions or the occurrence of adverse events (AES) or severe adverse events (SAEs) during the course of the study.
Ethical Considerations:
Administrative and ethical committee board approvals (no. MD 88/2020) to carry out the study at Ain Shams University Hospitals were obtained (Approval date 19/6/2021). An informed consent was obtained from the patients which addressed all the steps of the study as well as their right to withdraw from the study at any time. Privacy and confidentiality of data was also assured. This study was executed according to the code of ethics of the World Medical Association (Declaration of Helsinki) for studies on humans.
Data Analysis:
The collected data were introduced and statistically analyzed by utilizing the Statistical Package for Social Sciences (SPSS) version 20 for windows. Qualitative data were defined as numbers and percentages. Chi-Square test, Fisher’s exact test were used for comparison between categorical variables as appropriate. Quantitative data were tested for normality by Kolmogorov-Smirnov test. Normal distribution of variables was described as mean and standard deviation (SD), and independent sample t-test was used for comparison between groups. For comparison of Lab investigation before and after the treatment Mc Nemar test was used for qualitative binary variables, While Marginal Homogeneity test was used for nominal variables. P value ≤ 0.05 was statistically significant.
Of the participants in the present clinical trial, around one-third (34.7%) were between the ages of 29 and 39, one-quarter (24.7%) were between the ages of 18 and 28, and 40.6% were older than 40. 68% of people live in cities, 57% in rural regions, and 25% in urban slum. 23 percent of them smoked, 92% were married, 49% had graduate degrees, and 71% were housewives. Regarding demographic information, there was no statistically significant difference between the three groups (Table 1).
| Variable | Total | Treatment groups | P-value | |||||||
| Control group | Colchicine group | Probiotic group | ||||||||
| N | % | N | % | N | % | N | % | 0.870 | ||
| Age | 18–28 Y | 37 | 24.7% | 9 | 18.0% | 15 | 30.0% | 13 | 26.0% | |
| 29–39 Y | 52 | 34.7% | 19 | 38.0% | 16 | 32.0% | 17 | 34.0% | ||
| 40–50 Y | 30 | 20.0% | 10 | 20.0% | 9 | 18.0% | 11 | 22.0% | ||
| 51–60 Y | 31 | 20.7% | 12 | 24.0% | 10 | 20.0% | 9 | 18.0% | ||
| Sex | Male | 66 | 44.0% | 20 | 40.0% | 23 | 46.0% | 23 | 46.0% | 0.780 |
| Female | 84 | 56.0% | 30 | 60.0% | 27 | 54.0% | 27 | 54.0% | ||
| Smoking | No | 115 | 76.7% | 41 | 82.0% | 38 | 76.0% | 36 | 72.0% | 0.490 |
| Yes | 35 | 23.3% | 9 | 18.0% | 12 | 24.0% | 14 | 28.0% | ||
| Marital status | Single | 36 | 24.0% | 8 | 16.0% | 14 | 28.0% | 14 | 28.0% | 0.740 |
| Married | 92 | 61.3% | 33 | 66.0% | 29 | 58.0% | 30 | 60.0% | ||
| Divorced | 5 | 3.3% | 2 | 4.0% | 1 | 2.0% | 2 | 4.0% | ||
| Widow | 17 | 11.3% | 7 | 14.0% | 6 | 12.0% | 4 | 8.0% | ||
| Education | Illiterate | 22 | 14.7% | 8 | 16.0% | 8 | 16.0% | 6 | 12.0% | 0.760 |
| Read and write | 10 | 6.7% | 5 | 10.0% | 3 | 6.0% | 2 | 4.0% | ||
| Primary | 9 | 6.0% | 1 | 2.0% | 5 | 10.0% | 3 | 6.0% | ||
| Preparatory | 7 | 4.7% | 3 | 6.0% | 3 | 6.0% | 1 | 2.0% | ||
| Secondary | 12 | 8.0% | 4 | 8.0% | 4 | 8.0% | 4 | 8.0% | ||
| Intermediate institute | 40 | 26.7% | 15 | 30.0% | 12 | 24.0% | 13 | 26.0% | ||
| University graduate | 49 | 32.7% | 14 | 28.0% | 14 | 28.0% | 21 | 42.0% | ||
| Postgraduate | 1 | 0.7% | 0 | 0.0% | 1 | 2.0% | 0 | 0.0% | ||
| Occupation | Non-working/housewife | 71 | 47.3% | 26 | 52.0% | 25 | 50.0% | 20 | 40.0% | 0.610 |
| unskilled manual worker | 4 | 2.7% | 1 | 2.0% | 3 | 6.0% | 0 | 0.0% | ||
| skilled manual worker/farmer | 14 | 9.3% | 4 | 8.0% | 4 | 8.0% | 6 | 12.0% | ||
| Trades/business | 9 | 6.0% | 4 | 8.0% | 3 | 6.0% | 2 | 4.0% | ||
| semi-professional | 30 | 20.0% | 10 | 20.0% | 8 | 16.0% | 12 | 24.0% | ||
| Professional | 22 | 14.7% | 5 | 10.0% | 7 | 14.0% | 10 | 20.0% | ||
| Residence | Urban slum | 25 | 16.7% | 7 | 14.0% | 6 | 12.0% | 12 | 24.0% | 0.550 |
| Rural | 57 | 38.0% | 20 | 40.0% | 20 | 40.0% | 17 | 34.0% | ||
| Urban | 68 | 45.3% | 23 | 46.0% | 24 | 48.0% | 21 | 42.0% | ||
Table 1: Comparisons between the three treatment groups regarding the sociodemographic characteristics.
Test of Sig, Chi-square test.
Table 2 summarizes clinical information, such as the number of new symptoms, their duration, and their persistence after two weeks. In the colchicine, probiotic, and control groups, the mean symptom duration was 12, 11 and 12, respectively, with no statistically significant differences. After two weeks, the majority of patients (54%, 46% and 56%) had residual symptoms with no difference between the three groups. Hospitalization rate was 14%, 2% and 10% in the colchicine, probiotic, and control groups respectively, with no statistically significant differences.
| Variable | Total | Control group | Colchicine group | Probiotic group | P-value | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Duration of symptoms improvement (post) | Mean (SD) | 12 (4) | 12 (3) | 12 (4) | 11 (4) | 0.837** | ||||
| Min-Max | (5–30) | (5–21) | (7–30) | (5–25) | ||||||
| residual symptoms (post) | NO | 72 | 48% | 22 | 44% | 23 | 46% | 27 | 54% | 0.57 |
| Yes | 78 | 52% | 28 | 56% | 27 | 54% | 23 | 46% | ||
| Hospitalization (post) | NO | 137 | 91.3% | 45 | 90% | 43 | 86% | 49 | 98% | 0.09 |
| Yes | 13 | 8.7% | 5 | 10% | 7 | 14% | 1 | 2% | ||
Table 2: Comparisons between the three treatment groups regarding the clinical data.
Test of Sig: ANOVA**: *Sig P value ≤ 0.05.
The proportion of adverse effects in the colchicine group is shown in Figure 1. In the present trial, 44% of the patients in the colchicine group had gastrointestinal side effects.
Figure 1: See image above for figure legend.
In terms of laboratory results, all the parameters before and after the intervention were statistically significantly (Table 3).
| Variable | Pre | Post | P-value | |||
| N | % | N | % | |||
| Neutrophil | Normal | 96 | 64% | 120 | 80% | 0.05*# |
| Neutropenia | 36 | 24% | 11 | 7.3% | ||
| Neutrophilia | 18 | 12% | 19 | 12.7% | ||
| Lymphocytes | Normal | 80 | 53.3% | 104 | 69.3% | 0.02*# |
| Lymphopenia | 55 | 36.7% | 29 | 19.3% | ||
| Lymphocytosis | 15 | 10% | 17 | 11.3% | ||
| CRP | Normal | 39 | 26% | 91 | 60.7% | < 0.001*$ |
| Increase | 111 | 74% | 59 | 39.3% | ||
| D-dimer | Normal | 64 | 42.7% | 114 | 76% | < 0.0001*$ |
| Increase | 86 | 57.3% | 36 | 24% | ||
| S. ferritin | Normal | 52 | 34.7% | 111 | 74% | < 0.001*$ |
| Increase | 98 | 65.3% | 39 | 26% | ||
Table 3: Comparison between the treatment groups regarding the laboratory data before and after intervention.
*Sig P value; # test of Sig Marginal Homogeneity Test; $ test of sig McNamar Test.
Each of the three groups had improvements in inflammatory markers over time, with no statistically significant differences between them except lymphocyte count post intervention.
| Variable | Total | grouping | P-value | |||||||
| Control group | Colchicine group | Probiotic group | ||||||||
| N | % | N | % | N | % | N | % | |||
Neutrophil (pre) | Normal | 96 | 64% | 33 | 66% | 33 | 66% | 30 | 60% | |
| Neutropenia | 36 | 24% | 12 | 24% | 11 | 22% | 13 | 26% | 0.950 | |
| Neutrophilia | 18 | 12% | 5 | 10% | 6 | 12% | 7 | 14% | ||
Lymphocytes (pre) | Normal | 80 | 53.3% | 26 | 52% | 31 | 62% | 23 | 46% | 0.210 |
| Lymphopenia | 55 | 36.7% | 16 | 32% | 16 | 32% | 23 | 46% | ||
| Lymphocytosis | 15 | 10% | 8 | 16% | 3 | 6% | 4 | 8% | ||
| Neutrophil (post) | Normal | 120 | 80% | 39 | 78% | 41 | 82% | 40 | 80% | |
| Neutropenia | 11 | 7.3% | 3 | 6% | 3 | 6% | 5 | 10% | 0.820 | |
| Neutrophilia | 19 | 12.7% | 8 | 16% | 6 | 12% | 5 | 10% | ||
| Lymphocytes (post) | Normal | 104 | 69.3% | 34 | 68% | 38 | 76% | 32 | 64% | 0.01* |
| Lymphopenia | 29 | 19.3% | 10 | 20% | 12 | 24% | 7 | 14% | ||
| Lymphocytosis | 17 | 11.3% | 6 | 12% | 0 | 0.0% | 11 | 22% | ||
Table 4: Comparison between the three treatment groups regarding laboratory data (CBC parameters) before and after the intervention.
Test of Sig Chi-square test; *Sig P value < 0.05.
| Variable | Total | Grouping | P-value | |||||||
| Control group | Colchicine group | Probiotic group | ||||||||
| N | % | N | % | N | % | N | % | |||
CRP (pre) | Normal | 39 | 26% | 13 | 26% | 15 | 30% | 11 | 22% | 0.660 |
| increase | 111 | 74% | 37 | 74% | 35 | 70% | 39 | 78% | ||
D-dimer (pre) | Normal | 64 | 42.7% | 15 | 30% | 20 | 40% | 29 | 58% | 0.016* |
| increase | 86 | 57.3% | 35 | 70% | 30 | 60% | 21 | 42% | ||
S. ferritin (pre) | Normal | 52 | 34.7% | 16 | 32% | 17 | 34% | 19 | 38% | 0.814 |
| increase | 98 | 65.3% | 34 | 68% | 33 | 66% | 31 | 62% | ||
| CRP (post) | Normal | 91 | 60.7% | 34 | 68% | 26 | 52% | 31 | 62% | 0.254 |
| increase | 59 | 39.3% | 16 | 32% | 24 | 48% | 19 | 38% | ||
D-dimer (Post) | Normal | 114 | 76% | 40 | 80% | 33 | 66% | 41 | 82% | 0.125 |
| increase | 36 | 24% | 10 | 20% | 17 | 34% | 9 | 18% | ||
| S. ferritin (post) | Normal | 111 | 74% | 40 | 80% | 35 | 70% | 36 | 72% | 0.483 |
| increase | 39 | 26% | 10 | 20% | 15 | 30% | 14 | 28% | ||
Table 5: Comparison between the three treatment groups regarding laboratory data (CRP, D-Dimer and Ferritin parameters) before and after the intervention.
Test of Sig Chi-square test; *Sig P value < 0.05.
Discussion
Coronavirus disease 2019 (COVID-19) is an extremely contagious viral infection caused by the SARS-CoV-2 virus, which results in severe acute respiratory syndrome. It has had a catastrophic effect on the demography of the globe. It is now the most crucial aspect of global health. In late December 2019, the first cases of this predominantly respiratory viral illness were reported in Wuhan, Hubei Province, China. SARS-CoV-2 rapidly spread across the globe. On March 11, 2020, the World Health Organization (WHO) had to declare it as a global pandemic.
The 150 COVID-19 non-hospitalized patients in the current trial, which is a three-arm randomized interventional study, ranged in severity from mild to moderate. The participants were randomly assigned to receive the standard treatment protocol alone, the standard treatment protocol plus colchicine, or the standard treatment protocol plus probiotics.
The study's findings regarding the sociodemographic characteristics of the participants show that approximately one third (34.7%) of them are between the ages of 29 and 39 years, one-quarter (24.7%) are between the ages of 18 and 28 years, and forty percent (40.6%) are over the age of 40 years. Of the 150 participants, 84% were female and 66% were male, which is consistent with Doerre and Doblhammer [15] finding that infection rates are highest among the young and Sex ratios show that women at working ages have greater infection risks than males.
In addition, the smoking rate among study participants was 23% which is comparable to that of Farsalinos et al. [16], who discovered that hospitalized COVID-19 patients had a smoking prevalence that was roughly one-fourth of what was predicted.
Notably, there is no statistically significant difference in the sociodemographic features of the three groups, suggesting good matching.
In line with Hakki et al. [17] who found that peak RNA viral load and peak infectious viral load occurred a median of 3 days after symptom onset, the current study revealed that the average duration of symptom onset is the fourth day. As a result, the majority of the study participants sought medical attention at the peak of symptom onset.
Further subgroup analysis revealed that the mean duration of symptoms improvement after intervention is 9.8 days in mild cases and 13 days in moderate cases, with a statistically significant difference between them, which is consistent with Faiq et al. [19] who found the median survival time was 12 days in moderate hospitalized patients. The mean duration of symptoms improvement after intervention is 12 days, and there is no statistically significant difference between the three groups.
Tardif et al. and Dorward et al. [20] trials, which were conducted on 4,488 and 4,997 non-hospitalized participants while Recovery [21] trial was carried out on 19,423 hospitalized participants, found no statistically significant difference between the colchicine and usual care protocol for time of improvement and hospitalizations in the group treated with the standard protocol and colchicine.
The results of the current study, however, did not agree with a meta-analysis conducted by Hariyanto et al. [22] who sought to investigate the impact of colchicine as a treatment option for COVID-19 on January 29, 2021. It was revealed that a total of eight studies involving 5778 COVID-19 patients were included in this meta-analysis. Colchicine treatment was linked to better COVID-19 results.
Abdelfattah et al. [23] conducted a retrospective study of 100 patients hospitalized at the Ain Shams University Field Hospital and concluded that colchicine has a significant effect on the participants in terms of duration of symptom improvement and hospitalization.
However, additional clinical trials are required to validate the findings, as they are based on observational studies.
The current study found that 44% of the colchicine group participants experienced gastrointestinal adverse events, particularly at the beginning of the regimen on dose 0.5 mg three times per day for three days, then twice daily for four days. This is consistent with Terkeltaub et al. [24] and Robert et al. [24] studies, which found that 36.5% of participants who took colchicine developed diarrhea.
In addition to clinical improvement, the recent trial evaluated the alternation in hematological parameters of individuals with mild to moderate severity before and after the intervention which was statistically significant and indicates that CBC, CRP, ferritin, and D-dimer may be employed as prognostic and follow-up tools for both disease severity and outcomes. which agrees with Yasmin et al. meta-analysis of five RCTs concluded that CRP and D-dimer levels are crucial in determining the severity of COVID-19 because elevated levels are linked to a poor prognosis. Other studies have also used these parameters to monitor disease severity and outcomes. [25]
Additionally, Qin et al. [26] study revealed that lymphopenia, the most well-known hematological abnormality in patients affected by COVID-19 infection, is seen in up to 85% of severe cases with the severity of lymphopenia linked to outcome. Soraya et al.'s [27] study revealed that leukocytes and neutrophils were significantly higher in severe than in non-severe COVID-19 infected patients. Leukocyte and neutrophil counts also increased as the COVID-19 disease progressed in the severe groups, which is in line with the findings of our study, which show that there is a statistically significant difference between mild and moderate cases with regard to CBC parameters (neutrophils and lymphocytes levels).
Further subgroup analysis revealed no statistically significant difference in inflammatory biomarker levels between the colchicine group and controls, and these results concur with those of Deftereos et al. [28] who found no significant differences in CRP level between the control and colchicine groups.
As opposed to Sarwar et al. [29] who reported from a meta-analysis of six RCTs that Colchicine is effective in decreasing inflammatory biomarkers seen in moderate-to-severe COVID-19 patients. According to Sandhu et al. [30], patients in the colchicine group also had a more pronounced decline in the inflammatory marker’s ferritin (P = 0.012), D-dimer (P = 0.037), and CRP.
On the other hand, the group that received probiotics and the standard of care of treatment shows no statistically significant difference from the controls regarding the time of improvement and for hospitalizations due to COVID-19. In addition, there is no statistically significant difference between the two groups with regard to of biochemical outcomes, which opposes Wischmeyer et al. [[31] who claimed that LGG is well-tolerated and is associated with a longer time to COVID-19 development.
The majority of clinical trials on the use of probiotics during COVID-19 use small sample sizes. Most of them have relied on subjective conclusions. In addition, there has been considerable variation among these studies. Most of the studies and meta-analyses were limited to healthy young adults and excluded the elderly as this population is frequently polymedicated and frequently has multiple comorbidities. Additional clinical trials are required to adequately validate this conclusion. [32].
Conclusion
Probiotic Lactobacillus acidophilus and colchicine shows no significant effect on the symptoms, duration, and progression of mild and moderate cases of COVID-19. Colchicine causes more gastrointestinal adverse effects in the participants. CBC, CRP, ferritin, and D-dimer may be used as prognostic and follow-up tools for both disease severity and outcomes. Further randomised controlled trials with a larger sample size could be conducted to confirm these results.
Declarations
Author contributions:
Each author declares having participated in the activities.
Funding:
None.
Acknowledgments:
None.
Conflict of interest:
None.
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As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
