Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.

Chemokines and chemokine receptors during COVID-19 infection.

Chemokines are crucial inflammatory mediators needed during an immune response to clear pathogens. However, their excessive release is the main cause of hyperinflammation. In the recent COVID-19 outbreak, chemokines may be the direct cause of acute respiratory disease syndrome, a major complication leading to death in about 40% of severe cases. Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection. Here, we review the role of chemokines and their receptors in COVID-19 pathogenesis to better understand the disease immunopathology which may aid in developing possible therapeutic targets for the infection.

Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment.

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.

CXCL10 Chemokine: A Critical Player in RNA and DNA Viral Infections.

Chemokines constitute a group of small, secreted proteins that regulate leukocyte migration and contribute to their activation. Chemokines are crucial inflammatory mediators that play a key role in managing viral infections, during which the profile of chemokine expression helps shape the immune response and regulate viral clearance, improving clinical outcome. In particular, the chemokine ligand CXCL10 and its receptor CXCR3 were explored in a plethora of RNA and DNA viral infections. In this review, we highlight the expression profile and role of the CXCL10/CXCR3 axis in the host defense against a variety of RNA and DNA viral infections. We also discuss the interactions among viruses and host cells that trigger CXCL10 expression, as well as the signaling cascades induced in CXCR3 positive cells.

Peripheral blood cell anomalies in COVID-19 patients in the United Arab Emirates: A single-centered study.

Introduction: In this study, we aimed at exploring the morphologic and quantitative abnormalities in the peripheral blood counts of coronavirus disease 2019 (COVID-19) patients. Methods: A cohort of 131 COVID-19 patients was recruited at University Hospital Sharjah (UHS), UAE. Their peripheral blood smears were examined for morphological evaluation. Also, their clinical laboratory investigations and radiological findings were retrieved from the medical records. Our cohort consisted of 63 males and 68 females with an age of 63.6 ± 18.6 years. Results: The presence of atypical lymphocytes was observed in around 80% of the recruited COVID-19 patients. Further, monocytes with toxic cytoplasmic vacuoles were identified in 55% of the cases. Neutrophil-associated changes, including pseudo-Pelger-Huët, bands, and long nuclear endoplasm, were reported in around 25-35% of the patients. RBCs associated changes such as microcytic and hypochromic RBCs, as well as targetoid, dacrocytes, ovalocytes, echinocytes/burr cells, and schistocytes, were described. According to disease severity, RBCs chromicity was found to be significantly different between stable and critical patients. COVID-19 patients with CO-RADS 5 showed a similar change in RBCs as well as a decrease in the neutrophils with hypogranular cytoplasm. Conclusion: Peripheral blood smear assessment in COVID-19 patients could provide information about the disease state and pulmonary involvement.

Profiling Levels of Serum microRNAs and Soluble ACE2 in COVID-19 Patients.

Background: The main mechanism of viral entry in COVID-19 infection is through the angiotensin-converting enzyme 2 (ACE2) receptor present in the lungs. Numerous studies suggested a clinical significance of risk factors, such as gender, obesity, and diabetes on the soluble form of ACE2 (sACE2) and related miRNAs in COVID-19 infection. This study aims to investigate the serum level of sACE2 and 4 miRNAs (miR-421, miR-3909, miR-212-5p, and miR-4677-3p) in COVID-19 patients and assess their associations with clinicopathological parameters. Methods: Serum samples were collected from non-diabetic and diabetic COVID-19 patients and healthy controls. sACE2 levels were quantified using ELISA, and serum miRNA levels were measured using qPCR. In addition, laboratory blood tests were retrieved from the clinical records of COVID-19 patients. Results: sACE2 levels were upregulated in COVID-19 patients regardless of sex, diabetes status, or obesity. Furthermore, the four investigated miRNAs were upregulated in COVID-19 patients and were positively correlated with each other. Furthermore, miR-421, miR-3909, and miR-4677-3p were positively associated with sACE2, suggesting a strong link between these markers. Notably, miR-212-5p was selectively upregulated in moderate, male, and non-obese COVID-19 patients. Interestingly, miR-212-5p was correlated with D-dimer, while sACE2 was correlated with coagulation tests, such as aPTT and platelets, indicating their potential as markers of coagulopathy in COVID-19. Additionally, there was a positive correlation between sACE2 and C-reactive protein in diabetic COVID-19 patients, indicating a promising role of this marker in the inflammatory status of these patients. Conclusions: sACE2 and its regulatory miRNAs were upregulated and correlated with laboratory investigations of COVID-19 patients, thus indicating their clinical significance as biomarkers in COVID-19 infection.

Clinical and Laboratory Profile of Hospitalized Symptomatic COVID-19 Patients: Case Series Study From the First COVID-19 Center in the UAE.

Introduction: COVID-19 is raising with a second wave threatening many countries. Therefore, it is important to understand COVID-19 characteristics across different countries. Methods: This is a cross-sectional descriptive study of 525 hospitalized symptomatic COVID-19 patients, from the central federal hospital in Dubai-UAE during period of March to August 2020. Results: UAE's COVID-19 patients were relatively young; mean (SD) of the age 49(15) years, 130 (25%) were older than 60 and 4 (<1%) were younger than 18 years old. Majority were male(47; 78%). The mean (SD) BMI was 29 (6) kg/m2. While the source of contracting COVID-19 was not known in 369 (70%) of patients, 29 (6%) reported travel to overseas-country and 127 (24%) reported contact with another COVID-19 case/s. At least one comorbidity was present in 284 (54%) of patients and 241 (46%) had none. The most common comorbidities were diabetes (177; 34%) and hypertension (166; 32%). The mean (SD) of symptoms duration was 6 (3) days. The most common symptoms at hospitalization were fever (340; 65%), cough (296; 56%), and shortness of breath (SOB) (243; 46%). Most of the laboratory values were within normal range, but (184; 35%) of patients had lymphopenia, 43 (8%) had neutrophilia, and 116 (22%) had prolong international normalized ratio (INR), and 317 (60%) had high D-dimer. Chest x ray findings of consolidation was present in 334 (64%) of patients and CT scan ground glass appearance was present in 354 (68%). Acute cardiac injury occurred in 124 (24%), acute kidney injury in 111 (21%), liver injury in 101 (19%), ARDS in 155 (30%), acidosis in 118 (22%), and septic shock in 93 (18%). Consequently, 150 (29%) required ICU admission with 103 (20%) needed mechanical ventilation. Conclusions: The study demonstrated the special profile of COVID-19 in UAE. Patients were young with diabetes and/or hypertension and associated with severe infection as shown by various clinical and laboratory data necessitating ICU admission.

Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients.

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.

COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies.

In March 2020, COVID-19 infection caused by SARS-CoV-2 has been declared to be a global pandemic, where its complications, severity and mortality are reported to be due to the released inflammatory cytokines or the so-called cytokine storm. This is quite similar to that observed in the autoimmune and chronic inflammatory rheumatic disease, rheumatoid arthritis (RA). It was hypothesized that RA patients are at a higher risk of acquiring COVID-19; however, recent studies reported that they are not when compared to the rest of the population. In this review, we aim to highlight the mutual pathological features, cytokine profiles and risk factors between COVID-19 and RA. Also, many researchers are currently working to explore therapeutic agents that could aid in the eradication of COVID-19 infection. Due to the similarity between the inflammation status in COVID-19 and RA, many anti-rheumatic drugs such as hydroxychloroquine, tocilizumab, baricitinib and anakinra were proposed to be therapeutic modalities for COVID-19 infection.

Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection?

COVID-19 infection caused by the newly discovered coronavirus severe acute respiratory distress syndrome virus-19 (SARS-CoV-2) has become a pandemic issue across the globe. There are currently many investigations taking place to look for specific, safe and potent anti-viral agents. Upon transmission and entry into the human body, SARS-CoV-2 triggers multiple immune players to be involved in the fight against the viral infection. Amongst these immune cells are NK cells that possess robust antiviral activity, and which do not require prior sensitization. However, NK cell count and activity were found to be impaired in COVID-19 patients and hence, could become a potential therapeutic target for COVID-19. Several drugs, including glatiramer acetate (GA), vitamin D3, dimethyl fumarate (DMF), monomethyl fumarate (MMF), natalizumab, ocrelizumab, and IFN-ß, among others have been previously described to increase the biological activities of NK cells especially their cytolytic potential as reported by upregulation of CD107a, and the release of perforin and granzymes. In this review, we propose that such drugs could potentially restore NK cell activity allowing individuals to be more protective against COVID-19 infection and its complications.