New Insights into the Role of the Complement System in Human Viral Diseases.

The complement system (CS) is part of the human immune system, consisting of more than 30 proteins that play a vital role in the protection against various pathogens and diseases, including viral diseases. Activated via three pathways, the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP), the complement system leads to the formation of a membrane attack complex (MAC) that disrupts the membrane of target cells, leading to cell lysis and death. Due to the increasing number of reports on its role in viral diseases, which may have implications for research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this review aims to highlight significant progress in understanding and defining the role of the complement system in four groups of diseases of viral etiology: (1) respiratory diseases; (2) acute liver failure (ALF); (3) disseminated intravascular coagulation (DIC); and (4) vector-borne diseases (VBDs). Some of these diseases already present a serious global health problem, while others are a matter of concern and require the collaboration of relevant national services and scientists with the World Health Organization (WHO) to avoid their spread.

Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19.

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Mild versus Severe Liver Injury in SARS-CoV-2 Infection.

BACKGROUND: Abnormal liver function has been reported in patients with COVID-19 infection. The aim of our study was to report on the prevalence of liver injury in our cohort, to evaluate the association of mild versus severe liver injury with mortality in COVID-19 patients and to scrutinize the temporal pattern of viral detection and liver injury. METHODS: We present data from a German cohort of 147 SARS-CoV-2 infected patients. The patients were divided into 3 groups according to their liver status during treatment. The first group included patients without elevated alanine aminotransferase or bilirubin, the third group patients meeting the biochemical criteria of acute liver failure (ALF), and the second group all other patients. RESULTS: Liver injury was detected in 75 (50.7%) and 93 (63%) patients by admission and during treatment, respectively. ALF was associated with the male sex, younger age, and higher BMI. Mortality was associated with the presence of ALF (OR = 9.423, 95% CI: 2.410-36.858) in contrast to milder liver injury (OR 1.101, 95% CI: 0.435-2.791). In 30% of patients with mild liver injury and in 50% of ALF patients, peak liver injury was observed at a time point when the virus was no longer detectable in the respiratory tract. CONCLUSION: Mild liver injury was not associated with worse outcome in our cohort, and the pattern of liver injury did not fit well to the theory of SARS-CoV-2 directly causing liver impairment. Instead, severe liver injury in our cohort was associated multiple-organ failure and acute vascular events.

COVID-19 presenting as fulminant hepatic failure: A case report.

INTRODUCTION: Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic has spread from Wuhan, China in December, 2019 to 216 countries and territories as of September 10, 2020 with 27.74 million cases and 899,911 confirmed deaths. The spectrum of disease is most commonly seen as a viral pneumonia with high grade fevers, shortness of breath, dry cough, and chest pain with radiologic evidence of bilateral, interstitial, ground glass opacities, and peripheral lung consolidation. Liver chemistries are frequently abnormal, with transaminases shown to be one-two times the upper limit of normal in most instances. The full spectrum of gastrointestinal involvement of the SARS-CoV-2 infection has yet to be fully seen.Patient concerns: We present a case of a young woman with SLE who developed severe abdominal pain, nausea and vomiting, rapidly progressing to acute hepatic failure and tested positive for SARS-CoV-2 infection. She had no respiratory symptoms. DIAGNOSIS: A thorough work-up of acute liver failure including liver biopsy confirmed acute hepatitis with viral like changes. Common viral causes of liver failure were ruled out. The patient had no recent travel history. INTERVENTIONS: The patient was started on hydroxychloroquine due to SLE, treated with N-Acetyl-Cysteine, and methylprednisolone. OUTCOMES: The patient improved with resolution of encephalopathy and normalization of her liver chemistries without any development of respiratory illness. CONCLUSION: This case details a unique presentation of likely SARS-CoV-2 infection. Until now, the literature has primarily described a respiratory illness and liver injury with mild transaminase elevations. Significant liver injury progressing to acute liver failure should be considered in those with SARS-CoV-2 infection.

Fulminant hepatic failure: A rare and devastating manifestation of Coronavirus disease 2019 in an 11-year-old boy.

Although several typical manifestation of novel coronavirus disease 2019 (COVID-19) including respiratory symptoms, weakness, fever, and fatigue have been reported, some rare and novel manifestations have also been observed, particularly in children. We report a pediatric case of fulminant hepatic failure associated with COVID-19. Although the patient was treated for acute fulminant hepatic failure in the context of COVID-19, he died following the progression of the disease to stage 4 hepatic failure with encephalopathy and brain death.

SARS, MERS and COVID-19: clinical manifestations and organ-system complications: a mini review.

Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) are caused by three distinct coronaviruses belonging to the same genus. COVID-19 and its two predecessors share many important features in their clinical presentations, and in their propensity for progression to severe disease which is marked by high rates of morbidity and mortality. However, comparison of the three viral illnesses also reveals a number of specific differences in clinical manifestations and complications, which suggest variability in the disease process. This narrative review delineates the pulmonary, cardiac, renal, gastrointestinal, hepatic, neurological and hematologic complications associated with these three respiratory coronaviruses. It further describes the mechanisms of immune hyperactivation-particularly cytokine release syndrome-implicated in the multi-organ system injury seen in severe cases of MERS, SARS and COVID-19.

Patterns of liver injury in COVID-19 - a German case series.

BACKGROUND: Reports of liver injury in patients with novel coronavirus disease 2019 (COVID-19) are emerging from China and the USA. A wide variety of liver function test abnormalities and few cases of severe liver failure have been reported. No data on the hepatic phenotype from Europe are available at current. METHODS: We report a case series of 44 consecutive patients hospitalized for COVID-19 in Germany. RESULTS: At the time of admission, aspartate aminotransferase greater than the upper limit of normal was present in 70%, while alanine aminotransferase was elevated in 15.8%. Markers of cholestatic liver injury were altered only in a minority of patients. During hospitalization, 31% and 22% experienced increasing aspartate aminotransferase and alanine aminotransferase, respectively, when transaminases were normal at admission. Severe liver injury defined by 3×> upper limit of normal was observed in 9.1% over a mean time of 10.5 days. Importantly, patients exhibited cytotoxicity including lactate dehydrogenase and creatinine kinase elevations, but no signs of relevant liver function impairment. CONCLUSION: In summary, in a case series of hospitalized patients in Germany, cytotoxicity in the absence of severe liver dysfunction at admission and only few cases suggestive of severe liver injury during hospital were observed.