Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIMS: Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS: We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS: Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS: Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.

The effect of microbiome-modulating probiotics, prebiotics and synbiotics on glucose homeostasis in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIM/HYPOTHESIS: The globally escalating diabetes epidemic is responsible for significant morbidity and mortality. Microbiome-modulating nutraceuticals have been investigated for their potential to restore metabolic and floral homeostasis in type 2 diabetic patients METHODS: A systematic review, meta-analyses and meta-regressions were conducted to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of glucose homeostasis based on a multi-database search of clinical trials published through April 10, 2022. Data was pooled using random effects meta-analyses and reported as mean differences with 95% confidence intervals (CIs), followed by univariate linear model meta-regression. RESULTS: Data from 68 trial comparisons across 58 studies (n = 3835) revealed that, compared to placebo/control group, administration of pro/pre/synbiotics was associated with statistically significant changes in fasting plasma glucose (-12.41 mg/dl [95% CI: -15.94; -8.88], p 0.0001), glycated hemoglobin (-0.38% [95% CI: -0.47; -0.30], p 0.0001), fasting insulin (-1.49 µU/mL [95% CI: -2.12; -0.86], p 0.0001), HOMA-IR (-0.69 [95% CI: -1.16; -0.23], p = 0.0031) and QUICKI (0.0148 [95% CI: 0.0052; 0.0244], p = 0.0025), but not C-peptide (-0.0144 ng/mL [95% CI: -0.2564; -0.2275], p = 0.9069). Age, baseline BMI, baseline biomarker value, pro/prebiotic dosage, trial duration, nutraceutical type, and recruitment region significantly affected the potential of pro/pre/synbiotics use as personalized diabetes adjunct therapy. Lastly, we discuss unexplained observations and directives for future trials, with the aim of maximizing our understanding of how microbiome-modulating nutraceuticals can treat various metabolic diseases CONCLUSIONS: Pro/pre/synbiotic supplementation improved glucose homeostasis in diabetic patients. Our results support their potential use as adjunct therapy for improving glycemia and insulinemia alongside pharmacological therapeutics.

Communities of culturable yeasts and yeast-like fungi in oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar.

This report is the first investigation of yeast biodiversity from the oligotrophic hypersaline coastal waters of the Arabian Gulf surrounding Qatar. Yeasts and yeast-like fungi, were cultured from seawater sampled at 13 coastal areas surrounding Qatar over a period of 2 years (December 2013-September 2015). Eight hundred and forty-two isolates belonging to 82 species representing two phyla viz., Ascomycota (23 genera) and Basidiomycota (16 genera) were identified by molecular sequencing. The results indicated that the coastal waters of the Qatari oligotrophic marine environment harbor a diverse pool of yeast species, most of which have been reported from terrestrial, clinical and aquatic sources in various parts of the world. Five species, i.e., Candida albicans, C. parapsilosis, C. tropicalis, Pichia kudriavzevii and Meyerozyma guilliermondii (n = 252/842; 30% isolates) are known as major opportunistic human pathogens. Fifteen species belonging to nine genera (n = 498/842; 59%) and 12 species belonging to seven genera (n = 459/842; 55%) are hydrocarbon degrading yeast and pollution indicator yeast species, respectively. Ascomycetous yeasts were predominant (66.38%; 559/842) as compared to their basidiomycetous counterparts (33.6%; 283/842). The most isolated yeast genera were Candida (28%; 236/842) (e.g., C. aaseri, C. boidinii, C. glabrata, C. intermedia, C. oleophila, C. orthopsilosis, C. palmioleophila, C. parapsilosis, C. pseudointermedia, C. rugopelliculosa, C. sake, C. tropicalis and C. zeylanoides), Rhodotorula (12.7%; 107/842), Naganishia (8.4%; 71/842), Aureobasidium (7.4%; 62/842), Pichia (7.3%; 62/842), and Debaryomyces (6.4%; 54/842). A total of eleven yeast species ( n = 38) isolated in this study are reported for the first time from the marine environment. Chemical testing demonstrated that seven out of the 13 sites had levels of total petroleum hydrocarbons (TPH) ranging from 200 to 900 µg/L, whereas 6 sites showed higher TPH levels (> 1000-21000 µg/L). The results suggest that the yeast community structure and density are impacted by various physico-chemical factors, namely total organic carbon, dissolved organic carbon and sulphur.

Renal Health Improvement in Diabetes through Microbiome Modulation of the Gut-Kidney Axis with Biotics: A Systematic and Narrative Review of Randomized Controlled Trials.

Diabetes mellitus is the most common endocrine disorder worldwide, with over 20% of patients ultimately developing diabetic kidney disease (DKD), a complex nephropathic complication that is a leading cause of end-stage renal disease. Various clinical trials have utilized probiotics, prebiotics, and synbiotics to attempt to positively modulate the gut microbiome via the gut-kidney axis, but consensus is limited. We conducted a multi-database systematic review to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of renal health in diabetes, based on studies published through 10 April 2022. Adhering to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, relevant articles were systematically screened and extracted by independent reviewers; subsequently, results were systematically compiled, analyzed, and expanded through a narrative discussion. A total of 16 publications encompassing 903 diabetic individuals met the inclusion criteria. Our findings show that some studies report statistically significant changes in common renal markers, such as serum creatinine, estimated glomerular filtration rate, blood urea nitrogen/urea, microalbuminuria, and uric acid, but not on serum albumin, sodium, potassium, phosphorous, or total urine protein. Interestingly, these nutraceuticals seem to increase serum uric acid concentrations, an inflammatory marker usually associated with decreased renal health. We found that probiotics from the Lactobacillus and Bifidobacterium families were the most investigated, followed by Streptococcus thermophilus. Prebiotics including inulin, galacto-oligosaccharide, and resistant dextrin were also examined. The single-species probiotic soymilk formulation of Lactobacillus plantarum A7 possessed effects on multiple renal biomarkers in DKD patients without adverse events. We further investigated the optimum nutraceutical formulation, discussed findings from prior studies, described the gut-kidney axis in diabetes and DKD, and finally commented on some possible mechanisms of action of these nutraceuticals on renal health in diabetics. Although probiotics, prebiotics, and synbiotics have shown some potential in ameliorating renal health degradation in diabetes via gut-kidney axis crosstalk, larger and more convincing trials with focused objectives and next-generation nutraceutical formulations are required to investigate their possible role as adjunct therapy in such patients.

Reclassification of Facklamia ignava, Facklamia sourekii and Facklamia tabacinasalis as Falseniella ignava gen. nov., comb. nov., Hutsoniella sourekii gen. nov., comb. nov., and Ruoffia tabacinasalis gen. nov., comb. nov., and description of Ruoffia halotolerans sp. nov., isolated from hypersaline Inland Sea of Qatar.

A Gram-stain-positive, non-pigmented, coccus-shaped, facultatively anaerobic and α-hemolytic bacterium designated as INB8T was isolated from a hypersaline marine water sample collected at the Inland Sea of Qatar. The isolate was able to grow at 25-40 °C (optimum, 30 °C), at pH 5-11 and with 2-8% NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain INB8T was placed within the family Aerococcaceae with the highest sequence similarity to Facklamia tabacinasalis CCUG 30090T (99.5%), followed by Facklamia hominis CCUG 36813T (93.9%), Facklamia sourekii Y17312T (93.8%), Facklamia ignava CCUG 37419T (93.6%), Facklamia miroungae CCUG 42728T (93.5%), Suicoccus acidiformans ZY16052T (93.5%), Facklamia languida CCUG 37842T (93.2%), Ignavigranum ruoffiae (93.1%), and Dolosicoccus paucivorans DSM 15742T (90.8%). Average nucleotide identity and digital DNA-DNA hybridization values between strain INB8T and F. tabacinasalis CCUG 30090T were determined to be 94.5% and 58.9% respectively, confirming strain INB8T represents a novel species. The major fatty acids were C14:0, C16:0, C18:0 and C18:1 ω9c. The G + C content of strain INB8T determined from the genome was 36.3 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic information, it is proposed that Facklamia tabacinasalis should be reclassified as Ruoffia tabacinasalis, Facklamia ignava be reclassified as Falseniella ignava, and Facklamia sourekii be reclassified Hutsoniella sourekii. It is further proposed that strain INB8T should be classified as a species of the genus Ruoffia for which the name Ruoffia halotolerans sp. nov. is proposed. The type strain is INB8T (= LMG 30291T = CCUG 70701T = QCC/B60/17T).

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review.

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

Ningiella ruwaisensis gen. nov., sp. nov., a member of the family Alteromonadaceae isolated from marine water of the Arabian Gulf.

Strain B66T was isolated from a marine water sample collected at Al Ruwais, located on the northern tip of Qatar. Cells were Gram-stain-negative, strictly aerobic and short- rod-shaped with a polar flagellum. The isolate was able to grow at 15-45 °C (optimum, 30 °C), at pH 5-11 (optimum, pH 6.5-8) and with 0-6 % NaCl. 16S rRNA gene sequence analysis revealed that strain B66T was affiliated with the family Alteromonadaceae, sharing the highest sequence similarities to the genera Alteromonas (93.7-95.4 %), Aestuariibacter (94.0-95.1 %), Agaribacter (93.3-93.7 %), Glaciecola (92.0-93.7 %), Marisendiminitalea (93.2-93.3 %) and Planctobacterium (92.9 %). In the phylogenetic trees, strain B66T demonstrated the novel organism formed a distinct lineage closely associated with Aestuariibacter and Planctobacterium. Major fatty acids were C16 : 0, summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c/iso-C15 : 0 2-OH and iso-C15 : 0 3-OH. The major respiratory quinone was ubiquinone-8 and the major polar lipids are phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content derived from the genome was 43.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain B66T is considered to represent a novel species and genus for which the name Ningiella ruwaisensis gen. nov., sp. nov., is proposed. The type strain is B66T (=QCC B003/17T=LMG 30288 T=CCUG 70703T).

Cystobasidium halotolerans sp. nov., a novel basidiomycetous yeast species isolated from the Arabian Gulf.

Two strains, 1Y129 and 3Y383, which represent a single novel anamorphic yeast species, were isolated from the Arabian Gulf surrounding Qatar. The two strains have identical sequences in the D1/D2 domains of the large subunit (LSU) and the internal transcribed spacer (ITS) regions of the rRNA gene. On the basis of this sequence analysis the two strains were found to be closely related to Cystobasidium slooffiae CBS5706T with 97. 3 % nucleotide substitutions (12 nt; four gaps) in D1/D2 regions of the LSU rRNA and 97.0 % nucleotide substitutions (14 nt; two gaps) in ITS regions. In contrast to Cystobasidium halotolerans sp. nov., the related species Cystobasidium slooffiae, Cystobasidium minutum and Cystobasidium fimetarium were unable to assimilate d-galactose, soluble starch, galactitol, methanol or nitrate, and grew at 37 °C. The name proposed for this undescribed species is Cystobasidium halotolerans sp. nov. The ex-type strain is QCC/Y31/17 (=MUCL057192=CGMCC2.5570).

Measles pneumonitis, an important cause to recognize in the era of COVID-19: a case report.

Measles is an acute febrile viral illness with a characteristic rash. It is usually present in children. Due to the vaccine's development and wide use, serious complications are quite infrequent in vaccine-covered areas. Case Presentation: A 36-year-old immunocompetent woman presented with a fever and a macular rash affecting the face and upper trunk. She was found to have transaminitis and later developed bilateral pulmonary infiltrates with decreased oxygen saturation. After extensive work, the measles PCR returned positive results. The patient was treated conservatively until she recovered. Discussion: Measles pneumonitis is a rare complication that usually occurs in immunosuppressed patients. Due to the coronavirus disease pandemic, diagnosis can be difficult, especially if the presentation is not classic. Conclusion: We report this case to emphasize the importance of correct diagnosis and proper management.

Alcohol and Atrial Fibrillation: A Pathophysiologic Perspective.

Atrial fibrillation (AF) is the most common cardiac arrhythmia responsible for significant morbidity and mortality. Its burden on patients and the health care system is only expected to increase. Several studies have established a dose-response relationship between the amount and frequency of alcohol consumption and the incidence of new onset AF independent of sex, age, and other risk factors. This causal relationship is mediated by the impact alcohol consumption has on conduction properties of the atrium, structural and cellular effect on cardiac myocytes, and dysregulation of the autonomic nervous system. This article reviews the current literature supporting the link between alcohol consumption and AF while attempting to provide an insight into pathophysiological mechanisms.

Knowledge, Awareness, and Attitude of Healthcare Stakeholders on Alzheimer's Disease and Dementia in Qatar.

Dementia is characterized by progressive cognitive decline, memory impairment, and disability. Alzheimer's disease (AD) accounts for 60-70% of cases, followed by vascular and mixed dementia. Qatar and the Middle East are at increased risk owing to aging populations and high prevalence of vascular risk factors. Appropriate levels of knowledge, attitudes, and awareness amongst health care professionals (HCPs) are the need of the hour, but literature indicates that these proficiencies may be inadequate, outdated, or markedly heterogenous. In addition to a review of published quantitative surveys investigating similar questions in the Middle East, a pilot cross-sectional online needs-assessment survey was undertaken to gauge these parameters of dementia and AD among healthcare stakeholders in Qatar between 19 April and 16 May 2022. Overall, 229 responses were recorded between physicians (21%), nurses (21%), and medical students (25%), with two-thirds from Qatar. Over half the respondents reported that >10% of their patients were elderly (>60 years). Over 25% reported having contact with >50 patients with dementia or neurodegenerative disease annually. Over 70% had not undertake related education/training in the last 2 years. The knowledge of HCPs regarding dementia and AD was moderate (mean score of 5.3 ± 1.5 out of 7) and their awareness of recent advances in basic disease pathophysiology was lacking. Differences existed across professions and location of respondents. Our findings lay the groundwork for a call-to-action for healthcare institutions to improve dementia care within Qatar and the Middle East region.

'Is It Brain Talking to the Ear': Neuro-otological Evaluation of Tinnitus Using Auditory Brainstem Response Audiometry.

Tinnitus is hypothesized to be an auditory phantom phenomenon resulting from spontaneous neuronal activity somewhere along the auditory pathway. The neural abnormalities underlying tinnitus are largely unknown. We evaluated the functional characteristics and the auditory system synchronization using Auditory Brainstem Response (ABR) in normal hearing tinnitus patients. In this observational comparative cross-sectional study, patients with chief complaints of Tinnitus and equal number of age and sex matched controls without hearing loss and tinnitus were enrolled. All patients underwent a full ENT assessment, pure tone audiometry and Brainstem evoked response audiometry (BERA) tests. The study population consisted of 100 patients with tinnitus, 55 controls without tinnitus and 45 controls with tinnitus. Statistical analysis showed significant relation (p < 0.05) between hearing loss and tinnitus between cases and controls with tinnitus, between absolute latency of wave III amongst cases and controls without tinnitus, Interpeak Latency between wave III and V amongst cases and controls with tinnitus and interpeak latency of wave I and wave III amongst controls without and with tinnitus. Brainstem evoked response audiometry results that we obtained from the patients of tinnitus and controls with and without tinnitus are different from one person to another. This suggests impaired neural firing synchronization and transmission in the central auditory pathway in tinnitus patients. These findings also indicate that the pathology underlying tinnitus is not the same in every individual, with possible brainstem involvement in some cases.

The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review.

Background: One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods: Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results: From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion: Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.

A multi-targeted approach to identify potential flavonoids against three targets in the SARS-CoV-2 life cycle.

The advent and persistence of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2)-induced Coronavirus Disease (COVID-19) pandemic since December 2019 has created the largest public health emergency in over a century. Despite the administration of multiple vaccines across the globe, there continues to be a lack of approved efficacious non-prophylactic interventions for the disease. Flavonoids are a class of phytochemicals with historically established antiviral, anti-inflammatory and antioxidative properties that are effective against cancers, type 2 diabetes mellitus, and even other human coronaviruses. To identify the most promising bioactive flavonoids against the SARS-CoV-2, this article screened a virtual library of 46 bioactive flavonoids against three promising targets in the SARS-CoV-2 life cycle: human TMPRSS2 protein, 3CLpro, and PLpro. By examining the effects of glycosylation and other structural-activity relationships, the presence of sugar moiety in flavonoids significantly reduces its binding energy. It increases the solubility of flavonoids leading to reduced toxicity and higher bioavailability. Through protein-ligand contact profiling, it was concluded that naringin formed more hydrogen bonds with TMPRSS2 and 3CLpro. In contrast, hesperidin formed a more significant number of hydrogen bonds with PLpro. These observations were complimented by the 100 ns molecular dynamics simulation and binding free energy analysis, which showed a considerable stability of docked bioflavonoids in the active site of SARS-CoV-2 target proteins. Finally, the binding affinity and stability of the selected docked complexes were compared with the reference ligands (camostat for TMPRSS2, GC376 for 3CLpro, and GRL0617 for PLpro) that strongly inhibit their respective SARS-COV-2 targets. Overall analysis revealed that the selected flavonoids could be potential therapeutic agents against SARS-CoV-2. Naringin showed better affinity and stability for TMPRSS2 and 3CLpro, whereas hesperidin showed a better binding relationship and stability for PLpro.

Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals.

The analysis of beating rate provides information on the modulatory action of the autonomic nervous system on the heart, which mediates adjustments of cardiac function to meet hemodynamic requirements. In patients with myocardial infarction, alterations of heart rate variability (HRV) have been correlated to the occurrence of arrhythmic events and all-cause mortality. In the current study, we tested whether experimental rodent models of myocardial infarction recapitulate dynamics of heart rate variability observed in humans, and constitute valid platforms for understanding mechanisms linking autonomic function to the development and manifestation of cardiovascular conditions. For this purpose, HRV was evaluated in two engineered mouse lines using electrocardiograms collected in the conscious, restrained state, using a tunnel device. Measurements were obtained in naïve mice and animals at 3-∼28 days following myocardial infarction, induced by permanent coronary artery ligation. Two mouse lines with inbred and hybrid genetic background and, respectively, homozygous (Homo) and heterozygous (Het) for the MerCreMer transgene, were employed. In the naïve state, Het female and male mice presented prolonged RR interval duration (∼9%) and a ∼4-fold increased short- and long-term RR interval variability, with respect to sex-matched Homo mice. These differences were abrogated by pharmacological interventions inhibiting the sympathetic and parasympathetic axes. At 3-∼14 days after myocardial infarction, RR interval duration increased in Homo mice, but was not affected in Het animals. In contrast, Homo mice had minor modifications in HRV parameters, whereas substantial (> 50%) reduction of short- and long-term RR interval variation occurred in Het mice. Interestingly, ex vivo studies in isolated organs documented that intrinsic RR interval duration increased in infarcted vs. non-infarcted Homo and Het hearts, whereas RR interval variation was not affected. In conclusion, our study documents that, as observed in humans, myocardial infarction in rodents is associated with alterations in heart rhythm dynamics consistent with sympathoexcitation and parasympathetic withdrawal. Moreover, we report that mouse strain is an important variable when evaluating autonomic function via the analysis of HRV.

The Interplay Between the Immune System, the Renin-Angiotensin-Aldosterone System (RAAS), and RAAS Inhibitors May Modulate the Outcome of COVID-19: A Systematic Review.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), numerous research has been undertaken to delineate the various effects of the virus which manifests in many ways all over the body. The association between the SARS-CoV-2 invasion mechanism and the renin-angiotensin-aldosterone system (RAAS) receptors, created many debates about the possible consequences of using RAAS-modulating drugs including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) during the pandemic. Many clinical studies were conducted to assess the outcomes of coronavirus disease 2019 (COVID-19) in patients who use ACEi/ARBs following the arguments claiming to discontinue these drugs as a precautionary measure. Although several studies mainly analyzed the outcomes of the disease, this review aimed to compare specific blood markers in both groups of COVID-19 patients to gain better insight into the interaction of ACEi/ARBs with different body functions during the infection. Several databases were searched using a combination of keywords followed by screening and data extraction. Only 28 studies met our inclusion criteria, the majority of which showed no significant difference between the inflammation markers of COVID-19 patients who used or did not use ACEi/ARBs. Interestingly, 6 studies reported lower inflammatory markers in COVID-19 patients who used ACEi/ARBs, and 6 studies reported better outcomes among the same group. We therefore concluded that the use of ACEi/ARBs may not lead to worse prognosis of COVID-19 and may even play a protective role against the hyperinflammatory response associated with COVID-19.