The contribution of gut-brain axis to development of neurological symptoms in COVID-19 recovered patients: A hypothesis and review of literature.

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer's and Parkinson's disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

Cardiovascular Complications of COVID-19 among Pregnant Women and Their Fetuses: A Systematic Review.

BACKGROUND: COVID-19 is a viral infectious disease leading to a spectrum of clinical complications, especially cardiovascular. Evidence shows that this infection can potentially accompany a worse outcome in pregnant women. Cardiovascular complications in mothers and their fetuses are reported by previous studies. OBJECTIVE: In this systematic review, we aim to investigate the cardiovascular complications of COVID-19 during pregnancy in the mothers and fetus, according to the published literature. METHOD: We systematically searched the online databases of PubMed, Scopus, Web of Science, and Google Scholar, using relevant keywords up to April 2022. We included all observational studies reporting cardiovascular complications among COVID-19-affected pregnant women and their fetuses. RESULTS: We included 74 studies containing 47582 pregnant COVID-19 cases. Pre-eclampsia, hypertensive disorders, cardiomyopathy, heart failure, myocardial infarction, thrombosis formation, alterations in maternal-fetal Doppler patterns, and maternal and fetal arrhythmia were reported as cardiovascular complications. The highest incidences of pre-eclampsia/eclampsia among COVID-19 pregnant cases, reported by studies, were 69% and 62%, and the lowest were 0.5% and 3%. The highest and lowest incidences of fetal bradycardia were 20% and 3%, and regarding fetal tachycardia, 5.4% and 1%, respectively. CONCLUSION: SARS-CoV-2 infection during pregnancy can potentially be associated with cardiovascular complications in the mother, particularly pre-eclampsia and heart failure. Moreover, SARS-CoV-2 infection during pregnancy can potentially cause cardiovascular complications in the fetus, particularly arrhythmia.

COVID-19 causes neuronal degeneration and reduces neurogenesis in human hippocampus.

Recent investigations of COVID-19 have largely focused on the effects of this novel virus on the vital organs in order to efficiently assist individuals who have recovered from the disease. In the present study we used hippocampal tissue samples extracted from people who died after COVID-19. Utilizing histological techniques to analyze glial and neuronal cells we illuminated a massive degeneration of neuronal cells and changes in glial cells morphology in hippocampal samples. The results showed that in hippocampus of the studied brains there were morphological changes in pyramidal cells, an increase in apoptosis, a drop in neurogenesis, and change in spatial distribution of neurons in the pyramidal and granular layer. It was also demonstrated that COVID-19 alter the morphological characteristics and distribution of astrocyte and microglia cells. While the exact mechanism(s) by which the virus causes neuronal loss and morphology in the central nervous system (CNS) remains to be determined, it is necessary to monitor the effect of SARS-CoV-2 infection on CNS compartments like the hippocampus in future investigations. As a result of what happened in the hippocampus secondary to COVID-19, memory impairment may be a long-term neurological complication which can be a predisposing factor for neurodegenerative disorders through neuroinflammation and oxidative stress mechanisms.

Coronavirus disease and male fertility: a systematic review.

BACKGROUND: Based on the information from other SARS-CoV infections in the patients recovered from COVID-19, particularly cases in the reproductive age, gonadal function evaluation and andrological consultation comprising semen analysis are recommended. MAIN BODY: Based on the COVID-19 infected patients' seminal fluid analyses, SARS-CoV-2 may employ the male reproductive system as a transmission pathway. It has been also demonstrated that angiotensin-converting enzyme 2 (ACE2) can be strongly expressed at the protein levels in the testicular cells. The high expression of ACE2 in testes suggests that testes in the COVID-19 infected males can have an important role in the viral persistence and this subject needs further investigations. Several researchers have examined males recovered from COVID-19, but still, large-scale experiments are needed to determine the effects of SARS-CoV-2 on the male reproductive system as well as viral transmission risk. CONCLUSION: Comprehensive researches are required to figure out the presence of the SARS-CoV-2 virus in seminal fluid as well as its sexual transmissibility and impact on sperm characteristics.

Challenges of cancer immunotherapy and chemotherapy during the COVID-19 pandemic.

People at high risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), including patients dealing with malignancies and patients on immunosuppressive anticancer therapies, need to be followed carefully as the pandemic continues. Challenges in continuing cancer management and patient monitoring are of concern given the importance of timing in cancer therapy. Alternative treatment decisions and priorities are also important considerations. The efficacy and safety of various cancer treatments in patients with COVID-19 are other important considerations. In this systematic review, we summarize the potential risks and benefits of cancer treatments applied to patients with COVID-19 and malignant tumors. Using the PubMed and Scopus databases, we reviewed studies involving cancer therapy and COVID-19 to address the recent discoveries and related challenges of cancer therapy in patients with COVID-19 and cancer.

Complement inhibition: A possible therapeutic approach in the fight against Covid-19.

The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has recently been spread to almost all countries around the world. Although most people are immunocompetent to SARS-CoV-2, a small group develops hyper-inflammation that leads to complications like acute respiratory distress syndrome, disseminated intravascular coagulation, and multi-organ failure. Emerging evidence demonstrates that the complement system exerts a crucial role in this inflammatory reaction. Additionally, patients with the severe form of Covid-19 show over-activation of the complement in their skin, sera, and lungs. This study aims to summarise current knowledge concerning the interaction of SARS-CoV-2 with the complement system and to critically appraise complement inhibition as a potential new approach for Covid-19 treatment.

T helper type (Th1/Th2) responses to SARS-CoV-2 and influenza A (H1N1) virus: From cytokines produced to immune responses.

Cytokines produced by T helper cells (Th cells) have essential roles in the body's defense against viruses. Type 1 T helper (Th1) cells are essential for the host defense toward intracellular pathogens while T helper type 2 (Th2) cells are considered to be critical for the helminthic parasites' elimination swine-origin influenza A (H1N1) virus, a disease led to an epidemic in 2009 and rapidly spread globally via human-to-human transmission. Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic in 2020 and is a serious threat to the public health. Pulmonary immunopathology is the leading cause of death during influenza and SARS-CoV-2 epidemics and pandemics. Influenza and SARS-CoV-2 cause high levels of cytokines in the lung. Both inadequate levels and high levels of specific cytokines can have side effects. In this literature review article, we want to compare the Th1 and Th2 cells responses in SARS-CoV-2 and H1N1.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19.

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies.

BACKGROUND: Recently, it has been shown that coronavirus disease 2019 (COVID-19), which has caused a pandemic since December 2019, can be accompanied by some neurological disorders. This study aimed to assess the prevalence of the most common neurological symptoms and comorbidities and systematically review the literature regarding the most prevalent neurological complications of COVID-19 infection. METHODS: All relevant studies had been collected from PubMed, Scopus, Embase, and Web of Science databases. All extracted data were analyzed using Stata version 11.2. The I2 index was applied, and a random-effects model or a fixed-effects model was used for pooled estimation to assess the heterogeneity of studies. Furthermore, Egger and Beeg's tests were used to evaluate the publication bias. RESULTS: Fifty-seven studies (26 observational and 31 case reports) were included (including 6,597 COVID-19 patients). The most prevalent general symptoms were fever, cough, and dyspnea with 84.6% (95% CI: 75.3-92.1; I2 = 98.7%), 61.3% (95% CI: 55.3-67.0; I2 = 94.6%), and 34.2% (95% CI: 25.6-43.4; I2 = 97.7%), respectively. Neurological symptoms observed among COVID-19 patients were fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea with 42.9% (95% CI: 36.7-49.3; I2 = 92.8%), 35.4% (95% CI: 11.2-64.4; I2 = 99.2%), 28.9% (95% CI: 19.9-38.8; I2 = 96.3%), 25.3% (95% CI: 1.6-63.4; I2 = 99.6%), 10.1% (95% CI: 2.7-21.0; I2 = 99.1%), 6.7% (95% CI: 3.7-10.5; I2 = 87.5%), and 5.9% (95% CI: 3.1-9.5; I2 = 94.5%). The most prevalent neurological comorbidity in COVID-19 was cerebrovascular disease with 4.3% (95% CI: 2.7-6.3; I2 = 78.7%). CONCLUSION: The most prevalent neurological manifestations of COVID-19 include fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea. Cerebrovascular disorders can either act as a risk factor for poorer prognosis in COVID-19 patients or occur as a critical complication in these patients. Guillain-Barre syndrome, encephalitis, and meningitis have also been reported as complications of COVID-19.

Seroprevalence of Immunoglobulin M and G Antibodies against SARS-CoV-2 Virus: A Systematic Review and Meta-Analysis Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new global health threat. OBJECTIVES: to analyze the effectiveness of the measurement of specific antibodies to SARS-CoV2 (IgM and IgG) for the diagnosis of COVID-19 and to analyze the rate of SARS-CoV2 seroprevalence in the population. METHODS: 11 relevant studies, published before June 5, 2020, were included in this meta-analysis. These studies were identified by searching the MEDLINE and Scopus databases. The final selected studies were analyzed using STATA version 14. Publication bias was examined using both Egger's test and Funnel plots. Moreover, the I² statistic has been used to evaluate and verify heterogeneity. RESULTS: The 11 relevant studies selected for the present meta-analysis cover a total of 996 infection cases. According to the results, the average rate of positive cases for IgM (AU/mL) was 2.10 (95% CI: 1.65-2.55; I2=92.2%), and the sensitivity in individuals with positive IgM test was 63% (95% CI: 47-79; I2=94.9%). In addition, the average rate of positive cases for IgG (AU/mL) was 67.44 (95% CI: 28.79-106.09; I2=99.4%), and the sensitivity in individuals with positive IgG test was 79% (95% CI: 67-90; I2=89.5%). CONCLUSIONS: According to this analysis, detection of anti-SARS-CoV-2 IgM and IgG antibodies may assist early detection of SARS-CoV2 infection. Whether antibodies against SARS-CoV-2 confer protective immunity warrants further studies.

The prognostic value of comorbidity for the severity of COVID-19: A systematic review and meta-analysis study.

BACKGROUND AND OBJECTIVES: With the increase in the number of COVID-19 infections, the global health apparatus is facing insufficient resources. The main objective of the current study is to provide additional data regarding the clinical characteristics of the patients diagnosed with COVID-19, and in particular to analyze the factors associated with disease severity, lack of improvement, and mortality. METHODS: 102 studies were included in the present meta-analysis, all of which were published before September 24, 2020. The studies were found by searching a number of databases, including Scopus, MEDLINE, Web of Science, and Embase. We performed a thorough search from early February until September 24. The selected papers were evaluated and analyzed using Stata software application version 14. RESULTS: Ultimately, 102 papers were selected for this meta- analysis, covering 121,437 infected patients. The mean age of the patients was 58.42 years. The results indicate a prevalence of 79.26% for fever (95% CI: 74.98-83.26; I2 = 97.35%), 60.70% for cough (95% CI: 56.91-64.43; I2 = 94.98%), 33.21% for fatigue or myalgia (95% CI: 28.86-37.70; I2 = 96.12%), 31.30% for dyspnea (95% CI: 26.14-36.69; I2 = 97.67%), and 10.65% for diarrhea (95% CI: 8.26-13.27; I2 = 94.20%). The prevalence for the most common comorbidities was 28.30% for hypertension (95% CI: 23.66-33.18; I2 = 99.58%), 14.29% for diabetes (95% CI: 11.88-16.87; I2 = 99.10%), 12.30% for cardiovascular diseases (95% CI: 9.59-15.27; I2 = 99.33%), and 5.19% for chronic kidney disease (95% CI: 3.95-6.58; I2 = 96.42%). CONCLUSIONS: We evaluated the prevalence of some of the most important comorbidities in COVID-19 patients, indicating that some underlying disorders, including hypertension, diabetes, cardiovascular diseases, and chronic kidney disease, can be considered as risk factors for patients with COVID-19 infection. Furthermore, the results show that an elderly male with underlying diseases is more likely to have severe COVID-19.

Coronavirus diseases and pregnancy: COVID-19,SARS, and MERS.

Around the end of December 2019, a new beta-coronavirus from Wuhan City, Hubei Province, China began to spread rapidly. The new virus, called SARS-CoV-2, which could be transmitted through respiratory droplets, had a range of mild to severe symptoms, from simple cold in some cases to death in others. The disease caused by SARS-CoV-2 was named COVID-19 by WHO and has so far killed more people than SARS and MERS. Following the widespread global outbreak of COVID-19, with more than 132758 confirmed cases and 4955 deaths worldwide, the World Health Organization declared COVID-19 a pandemic disease in January 2020. Earlier studies on viral pneumonia epidemics has shown that pregnant women are at greater risk than others. During pregnancy, the pregnant woman is more prone to infectious diseases. Research on both SARS-CoV and MERS-CoV, which are pathologically similar to SARS-CoV-2, has shown that being infected with these viruses during pregnancy increases the risk of maternal death, stillbirth, intrauterine growth retardation and, preterm delivery. With the exponential increase in cases of COVID-19 throughout the world, there is a need to understand the effects of SARS-CoV-2 on the health of pregnant women, through extrapolation of earlier studies that have been conducted on pregnant women infected with SARS-CoV, and MERS-CoV. There is an urgent need to understand the chance of vertical transmission of SARS-CoV-2 from mother to fetus and the possibility of the virus crossing the placental barrier. Additionally, since some viral diseases and antiviral drugs may have a negative impact on the mother and fetus, in which case, pregnant women need special attention for the prevention, diagnosis, and treatment of COVID-19.

Critical complications of COVID-19: A descriptive meta-analysis study.

The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review.

After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population.

Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia.

Studies have found increased rates of dysosmia in patients with Novel Coronavirus disease 2019 (COVID-19). However, the mechanism that causes olfactory loss is unknown. The primary objective of this study was to explore local proinflammatory cytokine levels in the olfactory epithelium in patients with COVID-19. Biopsies of the olfactory epithelium were taken from patients with confirmed COVID-19 as well as uninfected controls. Levels of tumor necrosis factor α (TNF-α) and interleukin-1-beta (IL-1ß) were assessed using ELISA and compared between groups. Average TNF-α levels were significantly increased in the olfactory epithelium of the COVID-19 group compared to the control group (P < 0.05). However, no differences in IL-1ß were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.