Recent developments in SARS-CoV-2 vaccines: A systematic review of the current studies.

Designing and manufacturing efficient vaccines against coronavirus disease 2019 (COVID-19) is a major objective. In this systematic review, we aimed to evaluate the most important vaccines under construction worldwide, their efficiencies and clinical results in healthy individuals and in those with specific underlying diseases. We conducted a comprehensive search in PubMed, Scopus, EMBASE, and Web of Sciences by 1 December 2021 to identify published research studies. The inclusion criteria were publications that evaluated the immune responses and safety of COVID-19 vaccines in healthy individuals and in those with pre-existing diseases. We also searched the VAERS database to estimate the incidence of adverse events of special interest (AESI) post COVID-19 vaccination. Almost all investigated vaccines were well tolerated and developed good levels of both humoural and cellular responses. A protective and efficient humoural immune response develops after the second or third dose of vaccine and a longer interval (about 28 days) between the first and second injections of vaccine could induce higher antibody responses. The vaccines were less immunogenic in immunocompromised patients, particularly those with haematological malignancies. In addition, we found that venous and arterial thrombotic events, Bell's palsy, and myocarditis/pericarditis were the most common AESI. The results showed the potency of the SARS-CoV-2 vaccines to protect subjects against disease. The provision of further effective and safe vaccines is necessary in order to reach a high coverage of immunisation programs across the globe and to provide protection against infection itself.

Takotsubo syndrome and COVID-19: A systematic review.

Background and Aims: Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is characterized by acute and transient left ventricular dysfunction and has increased during the COVID-19 pandemic. Herein, we aim to review studies on TTS that were associated with COVID-19 infection, vaccine, and other COVID-19-related etiologies including psychosocial stressors. Methods: We systematically searched PubMed, EMBASE, and Scopus up to May 12, 2022. We included case reports, case series, and original articles that reported at least one TTS case associated with COVID-19, or TTS cases after receiving COVID-19 vaccines, or TTS cases secondary to psychological stress due to the COVID-19 pandemic. The quality assessment was conducted using the Joanna Briggs Institute checklist. Results: Sixty-seven articles including 102 cases were included. Hypertension was the most frequently accompanying comorbidity (N = 67 [65.6%]) and the mean left ventricular ejection fraction was 36.5%. Among COVID-19 patients, the in-hospital mortality rate was 33.3%. On the other hand, only one COVID-19-negative individual expired (2.3%). The most common presenting clinical symptom was dyspnea in 42 (73.6%) patients. the mean time interval from the first symptom to admission was 7.2 days. The most common chest imaging finding was ground-glass opacity which was reported in 14 (31.1%) participants. The most common abnormalities were T-wave inversion in 35 (43.2%) and ST-segment elevation in 30 (37%). Brain natriuretic peptide and troponin were elevated in 94.7% and 95.9% of participants, respectively. Conclusion: The TTS in patients with COVID-19 is almost rare, whereas it could lead to a great mortality and morbidity. An individual with COVID-19, especially an elderly woman, presented with dyspnea in addition to a rise in brain natriuretic peptide and troponin should be evaluated for TTS.

Takotsubo syndrome and COVID‐19: A systematic review

Background and Aims Takotsubo syndrome (TTS), also known as stress cardiomyopathy, is characterized by acute and transient left ventricular dysfunction and has increased during the COVID‐19 pandemic. Herein, we aim to review studies on TTS that were associated with COVID‐19 infection, vaccine, and other COVID‐19‐related etiologies including psychosocial stressors. Methods We systematically searched PubMed, EMBASE, and Scopus up to May 12, 2022. We included case reports, case series, and original articles that reported at least one TTS case associated with COVID‐19, or TTS cases after receiving COVID‐19 vaccines, or TTS cases secondary to psychological stress due to the COVID‐19 pandemic. The quality assessment was conducted using the Joanna Briggs Institute checklist. Results Sixty‐seven articles including 102 cases were included. Hypertension was the most frequently accompanying comorbidity (N = 67 [65.6%]) and the mean left ventricular ejection fraction was 36.5%. Among COVID‐19 patients, the in‐hospital mortality rate was 33.3%. On the other hand, only one COVID‐19‐negative individual expired (2.3%). The most common presenting clinical symptom was dyspnea in 42 (73.6%) patients. the mean time interval from the first symptom to admission was 7.2 days. The most common chest imaging finding was ground‐glass opacity which was reported in 14 (31.1%) participants. The most common abnormalities were T‐wave inversion in 35 (43.2%) and ST‐segment elevation in 30 (37%). Brain natriuretic peptide and troponin were elevated in 94.7% and 95.9% of participants, respectively. Conclusion The TTS in patients with COVID‐19 is almost rare, whereas it could lead to a great mortality and morbidity. An individual with COVID‐19, especially an elderly woman, presented with dyspnea in addition to a rise in brain natriuretic peptide and troponin should be evaluated for TTS.

Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review.

Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 10⁹ /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.

A systematic review and meta-analysis of immune response against first and second doses of SARS-CoV-2 vaccines in adult patients with hematological malignancies.

BACKGROUND: Cancer patients particularly those with hematological malignancies are at higher risk of affecting by severe coronavirus disease 2019 (COVID-19). Due to the immunocompromised nature of the disease and the immunosuppressive treatments, they are more likely to develop less antibody protection; therefore, we aimed to evaluate the immunogenicity of COVID-19 vaccines in patients with hematological malignancies. METHODS: A comprehensive systematic search was conducted in PubMed, Scopus, and Web of Science databases, as well as Google scholar search engine as of December 10, 2021. Our primary outcomes of interest comprised of estimating the antibody seropositive rate following COVID-19 vaccination in patients with hematological malignancies and to compare it with those who were affected by solid tumors or healthy subjects. The secondary outcomes were to assess the vaccine's immunogenicity based on different treatments, status of the disease, and type of vaccine. After the two-step screening, the data were extracted and the summary measures were calculated using a random-effect model. RESULTS: A total of 82 articles recording 13,804 patients with a diagnosis of malignancy were included in the present review. The seropositive rates in patients with hematological malignancies after first and second vaccine doses were 30.0% (95% confidence interval (95%CI): 11.9-52.0) and 62.3% (95%CI 56.0-68.5), respectively. These patients were less likely to develop antibody response as compared to cases with solid tumors (RR 0.73, 95%CI 0.67-0.79) and healthy subjects (RR 0.62, 95%CI 0.54-0.71) following complete immunization. Chronic lymphocytic leukemia (CLL) patients had the lowest response rate among all subtypes of hematological malignancies (first dose: 22.0%, 95%CI 13.5-31.8 and second dose: 47.8%, 95%CI 41.2-54.4). Besides, anti-CD20 therapies (5.7%, 95%CI 2.0-10.6) and bruton's tyrosine kinase inhibitors (26.8%, 95%CI 16.9-37.8) represented the lowest seropositiveness post first and second doses, respectively. Notably, patients who were in active status of disease showed lower antibody detection rate compared to those on remission status (RR 0.87, 95%CI 0.76-0.99). Furthermore, lower rate of seropositivity was found in patients received BNT162.b2 compared to ones who received mRNA-1273 (RR 0.89, 95%CI 0.79-0.99). CONCLUSION: Our findings highlight the substantially low rate of seroprotection in patients with hematological malignancies with a wide range of rates among disease subgroups and different treatments; further highlighting the fact that booster doses might be acquired for these patients to improve immunity against SARS-CoV-2.

A Review on the Possible Pathophysiology of Potassium Abnormalities in COVID-19

Coronavirus disease 2019 (COVID-19) is a catastrophic contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Electrolyte disturbances are common complications of COVID-19. The present article examined the potential mechanisms of hypokalemia and hyperkalemia in patients suffering from COVID-19, in order to raise awareness of potassium disorders in SARS-CoV-2 infections. PubMed, Scopus, and Google Scholar were searched with keywords, such as “COVID-19”, “SARS-CoV-2”, “2019-nCoV”, “Hypokalemia”, “Hyperkalemia”, “Serum potassium”, and “Etiology”, “Pathophysiology” up to April 20, 2021 without any search filters. We included articles that proposed potential mechanisms for potassium abnormalities in COVID-19 patients. Furthermore, we used backward and forward citation searching. Potassium abnormalities are considered to be important electrolyte disturbances, with reported incidences ranging from < 5% to > 50% in patients affected by SARS-CoV-2. Therefore, understanding the etiologies of potassium abnormalities could help to improve disease outcome. Utilization of ACE2 by SARS-CoV-2 in the renal cells, viral-induced tubular injury, and gastrointestinal abnormalities, such as anorexia, diarrhea, and vomiting may predispose COVID-19 patients to developing hypokalemia. Furthermore, depleted magnesium levels make hypokalemia refractory to treatments. In addition, hyperkalemia may occur because of reduced urinary output, as a consequence of renal failure. Changes in blood pH and medication-induced side-effects are other possible reasons for the deviation of potassium levels from the normal range. The etiology of potassium abnormalities in COVID-19 patients is multifactorial. Therefore, the early detection and management of potassium disorders is vital and would improve the outcome of patients with COVID-19. DOI: 10.52547/ijkd.6552

The burden of stroke and its attributable risk factors in the Middle East and North Africa region, 1990-2019.

Stroke is one of the leading causes of mortality and morbidity across the globe. Providing comprehensive data on the burden of stroke in the Middle East and North Africa (MENA) could be useful for health policy makers in the region. Therefore, this article reported the burden of stroke and its attributable risk factors between 1990 and 2019 by age, sex, type of stroke, and socio-demographic index. Data on the point prevalence, death, and disability-adjusted life-years (DALYs), due to stroke, were retrieved from the Global Burden of Disease study 2019 for the 21 countries located in the MENA region from 1990 to 2019. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals (UIs). In 2019, the regional age-standardised point prevalence and death rates of stroke were 1537.5 (95% UI: 1421.9-1659.9) and 87.7 (78.2-97.6) per 100,000, which represent a 0.5% (- 2.3 to 1.1) and 27.8% (- 35.4 to - 16) decrease since 1990, respectively. Moreover, the regional age-standardised DALY rate in 2019 was 1826.2 (1635.3-2026.2) per 100,000, a 32.0% (- 39.1 to - 23.3) decrease since 1990. In 2019, Afghanistan [3498.2 (2508.8-4500.4)] and Lebanon [752.9 (593.3-935.9)] had the highest and lowest age-standardised DALY rates, respectively. Regionally, the total number of stroke cases were highest in the 60-64 age group and was more prevalent in women in all age groups. In addition, there was a general negative association between SDI and the burden of stoke from 1990 to 2019. Also, in 2019, high systolic blood pressure [53.5%], high body mass index [39.4%] and ambient particulate air pollution [27.1%] made the three largest contributions to the burden of stroke in the MENA region. The stroke burden has decreased in the MENA region over the last three decades, although there are large inter-country differences. Preventive programs should be implemented which focus on metabolic risk factors, especially among older females in low SDI countries.

Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities.

Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.

Cardiac complications following mRNA COVID-19 vaccines: A systematic review of case reports and case series.

There have been several local and systemic adverse events associated with mRNA COVID-19 vaccines. Pericarditis, myocarditis and myocardial infarction are examples of cardiac complications related to these vaccines. In this article, we conducted a systematic review of case reports and case series to identify the clinical profile, investigations, and management of reported cardiac complications post-mRNA COVID-19 vaccines. We systematically searched PubMed, Scopus, Web of Science, and Google Scholar, as well as the medRxiv preprint server, with terms including: 'SARS-CoV-2', 'COVID-19', 'messenger RNA vaccine*', 'mRNA-1273 vaccine', 'BNT162 vaccine', 'myocarditis', 'pericarditis', 'stroke' and 'Myocardial Ischemia' up to 25 September 2021. Studies were excluded if they were not case reports or case series, or reported cases from non-mRNA vaccines. Case reports and case series were included that investigated the potential cardiac complications associated with mRNA COVID-19 vaccines. The JBI checklist was used to assess quality and data synthesis was conducted using a qualitative methodology called narrative synthesis. Sixty-nine studies, including 43 case reports and 26 case series, were included. Myocarditis/myopericarditis and pericarditis were the most common adverse events among the 243 reported cardiac complications, post mRNA COVID-19 vaccination. Males with a median age of 21 years had the highest frequency of myocarditis. Almost three quarters (74.4%) of cases with myocarditis had received the BNT162b2 vaccine and 87.7% had received the second dose of the vaccine. Chest pain (96.1%) and fever (38.2%) were the most common presentations. CK-MB, troponin, and NT-proBNP were elevated in 100%, 99.5% and 78.3% of subjects, respectively. ST-segment abnormality was the most common electrocardiogram feature. Cardiac magnetic resonance imaging, which is the gold-standard approach for diagnosing myocarditis, was abnormal in all patients diagnosed with myocarditis. Non-steroidal anti-inflammatory drugs were the most prescribed medication for the management of myocarditis. Apart from inflammatory conditions, some rare cases of Takotsubo cardiomyopathy, myocardial infarction, myocardial infarction with non-obstructive coronary arteries, and isolated tachycardia were also reported following immunisation with mRNA COVID-19 vaccines. We acknowledge that only reviewing case reports and case series studies is one potential limitation of our study. We found that myocarditis was the most commonly reported adverse cardiac event associated with mRNA COVID-19 vaccines, which presented as chest pain with a rise in cardiac biomarkers. Further large-scale observational studies are recommended.

How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels?

Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) is the causative agent of current coronavirus disease 2019 (COVID-19) pandemic. Electrolyte disorders particularly potassium abnormalities have been repeatedly reported as common clinical manifestations of COVID-19. Here, we discuss how SARS-CoV-2 may affect potassium balance by impairing the activity of epithelial sodium channels (ENaC). The first hypothesis could justify the incidence of hypokalemia. SARS-CoV-2 cell entry through angiotensin-converting enzyme 2 (ACE2) may enhance the activity of renin-angiotensin-aldosterone system (RAAS) classical axis and further leading to over production of aldosterone. Aldosterone is capable of enhancing the activity of ENaC and resulting in potassium loss from epithelial cells. However, type II transmembrane serine protease (TMPRSS2) is able to inhibit the ENaC, but it is utilized in the case of SARS-CoV-2 cell entry, therefore the ENaC remains activated. The second hypothesis describe the incidence of hyperkalemia based on the key role of furin. Furin is necessary for cleaving both SARS-CoV-2 spike protein and ENaC subunits. While the furin is hijacked by the virus, the decreased activity of ENaC would be expected, which causes retention of potassium ions and hyperkalemia. Given that the occurrence of hypokalemia is higher than hyperkalemia in COVID-19 patients, the first hypothesis may have greater impact on potassium levels. Further investigations are warranted to determine the exact role of ENaC in SARS-CoV-2 pathogenesis.

Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.

BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.

Different incidences of acute kidney injury (AKI) and outcomes in COVID-19 patients with and without non-azithromycin antibiotics: A retrospective study.

In late December 2019, an outbreak of a novel coronavirus which caused coronavirus disease 2019 (COVID-19) was initiated. Acute kidney injury (AKI) was associated with higher severity and mortality of COVID-19. We aimed to evaluate the effects of comorbidities and medications in addition to determining the association between AKI, antibiotics against coinfections (AAC) and outcomes of patients. We conducted a retrospective study on adult patients hospitalized with COVID-19 in a tertiary center. Our primary outcomes were the incidence rate of AKI based on comorbidities and medications. The secondary outcome was to determine mortality, intensive care unit (ICU) admission, and prolonged hospitalization by AKI and AAC. Univariable and multivariable logistic regression method was used to explore predictive effects of AKI and AAC on outcomes. Out of 854 included participants, 118 patients developed AKI in whom, 57 used AAC and 61 did not. Hypertension and diabetes were the most common comorbidities in patients developed AKI. AAC, lopinavir/ritonavir, ribavirin, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and corticosteroids had significant higher rate of administration in patients developed AKI. AAC were associated with higher deaths (odds ratio [OR] = 5.13; 95% confidence interval (CI): 3-8.78) and ICU admission (OR = 5.87; 95%CI: 2.81-12.27), while AKI had higher OR for prolonged hospitalization (3.37; 95%CI: 1.76-6.45). Both AKI and AAC are associated with poor prognosis of COVID-19. Defining strict criteria regarding indications and types of antibiotics would help overcoming concomitant infections and minimizing related adverse events.

The relationship between blood groups and risk of infection with SARS-CoV-2 or development of severe outcomes: A review.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a global catastrophe that has overwhelmed health care systems. Since initiation of the pandemic, identification of characteristics that might influence risk of infection and poor disease outcomes have been of paramount interest. Blood group phenotypes are genetically inherited characteristics whose association with certain infectious diseases have long been debated. The aim of this review is to identify whether a certain type of blood group may influence an individual's susceptibility to SARS-CoV-2 infection and developing severe outcomes. Our review shows that blood group O protects individuals against SARS-CoV-2, whereas blood group A predisposes them to being infected. Although the association between blood groups and outcomes of COVID-19 is not consistent, it is speculated that non-O blood group carriers with COVID-19 are at higher risk of developing severe outcomes in comparison to O blood group. The interaction between blood groups and SARS-CoV-2 infection is hypothesized to be as result of natural antibodies against blood group antigens that may act as a part of innate immune response to neutralize viral particles. Alternatively, blood group antigens could serve as additional receptors for the virus and individuals who are capable of expressing these antigens on epithelial cells, which are known as secretors, would then have a high propensity to be affected by SARS-CoV-2.

The Efficacy and Potential Mechanisms of Metformin in the Treatment of COVID-19 in the Diabetics: A Systematic Review.

Introduction: Diabetes mellitus (DM) is one of the most common comorbidities among patients with coronavirus disease 2019 (COVID-19) which may exacerbate complications of this new viral infection. Metformin is an anti-hyperglycemic agent with host-directed immune-modulatory effects, which relieve exaggerated inflammation and reduce lung tissue damage. The current systematic review aimed to summarize the available evidence on the potential mechanism of action and the efficacy of metformin in COVID-19 patients with DM. Methods: A systematic search was carried out in PubMed/Medline, EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and Web of Science up to July 30, 2020. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "metformin", and "antidiabetic drug". Results: Fourteen studies were included in our systematic review. Three of them were observational with 6,659 participants. Decreasing insulin resistance, reduction of some inflammatory cytokines like IL-6 and TNF-α, modulation of angiotensin-converting enzyme 2 (ACE2) receptor, and improving neutrophil to lymphocyte ratio are some of the potential mechanisms of metformin in COVID-19 patients with DM. Nine out of fourteen articles revealed the positive effect of metformin on the prognosis of COVID-19 in diabetic or even non-diabetic patients. Moreover, different studies have shown that metformin is more effective in women than men. Conclusions: The use of metformin may lead to improve the clinical outcomes of patients with mild to moderate SARS-CoV-2, especially in diabetic women. Further observational studies should be conducted to clarify the effects of metformin as a part of the treatment strategy of COVID-19.

Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.

At the end of 2019, an emerging outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first reported from Wuhan, China. The first manifestations of patients infected with SARS-CoV-2 was flu-like symptoms, while other type of manifestations, especially gastrointestinal manifestations were discovered recently. As of June 2020, there is no specific drug or treatment strategy for COVID-19, a disease caused by SARS-CoV-2, so different combination of antiviral drugs is currently being used. Gut microbiota mostly consists of four phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The interaction between gut microbiota and immune system through releasing some cytokines such as IL-1ß, IL-2, IL-10, TNF-α, and IFN-γ that play roles in the severity of COVID-19. In this article, a new potential treatment for COVID-19 by fecal microbiota transplantation (FMT) is described. FMT revealed promising results in different diseases, especially recurrent clostridium difficile infection, and it might reduce length of hospital admission and severity of the disease by modification of gut microbiota composition.

Cardiovascular system is at higher risk of affecting by COVID-19.

SARS-CoV-2 has shown its potential to cause severe manifestations among individuals with underlying cardiovascular disease (CVD). The patients infected with SARS-CoV-2 with pre-existing CVD are more likely to relapse. There are several reasons, including the prolonged hospitalization time as a consequence of their more severe illness and aberrant expression of angiotensin-converting enzyme 2 (ACE2) - the cell surface receptor of SARS-COV2 that is present on cardiac cells - and using drugs such as ACE inhibitors and angiotensin receptor blockers (ARBs) that alter the expression of ACE2. Besides, SARS-CoV-2 shares structural similarities with SARS-CoV-1, and that patients recovered from SARS-CoV1 have shown an increased risk of developing inflammatory, metabolic, and cardiac diseases. It makes some concerns that people who recovered from SARS-CoV2 are also liable to develop these chronic conditions later. Further studies should investigate the probability of recurrence of COVID-19 in patients with CVD and the development of approaches for the prevention of chronic inflammatory conditions in patients with CVD who recovered from COVID-19.