Extrapulmonary Manifestations Of COVID-19 Research Articles

Extra-pulmonary manifestations of COVID-19: A comprehensive review

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has predominantly been recognized for its respiratory impact. However, as the pandemic has progressed, it has become evident that SARS-CoV-2 affects multiple organ systems beyond the lungs, resulting in a wide array of extra-pulmonary manifestations. These manifestations encompass cardiovascular, neurological, gastrointestinal, hepatic, renal, dermatological, hematological, endocrine, musculoskeletal, ocular, immunological, and psychiatric complications. This review aims to provide a comprehensive understanding of these extra-pulmonary manifestations, highlighting their clinical significance, underlying mechanisms, and implications for patient management. Recognizing these manifestations is critical for improving patient outcomes and informing ongoing research and therapeutic strategies.

Characteristics and biomarkers associated with mortality in COVID-19 patients presenting to the emergency department.

This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n=41; 8.6%) and cardiac manifestations (n=31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796-0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.

A Pictorial Essay Describing the CT Imaging Features of COVID-19 Cases throughout the Pandemic with a Special Focus on Lung Manifestations and Extrapulmonary Vascular Abdominal Complications.

With the Omicron wave, SARS-CoV-2 infections improved, with less lung involvement and few cases of severe manifestations. In this pictorial review, there is a summary of the pathogenesis with particular focus on the interaction of the immune system and gut and lung axis in both pulmonary and extrapulmonary manifestations of COVID-19 and the computed tomography (CT) imaging features of COVID-19 pneumonia from the beginning of the pandemic, describing the typical features of COVID-19 pneumonia following the Delta variant and the atypical features appearing during the Omicron wave. There is also an outline of the typical features of COVID-19 pneumonia in cases of breakthrough infection, including secondary lung complications such as acute respiratory distress disease (ARDS), pneumomediastinum, pneumothorax, and lung pulmonary thromboembolism, which were more frequent during the first waves of the pandemic. Finally, there is a description of vascular extrapulmonary complications, including both ischemic and hemorrhagic abdominal complications.

Pulmonary and Extra Pulmonary Manifestations of COVID-19

Global public health emergency: COVID-19, triggered by SARS-CoV-2. A thorough search was conducted using Web of Science, PubMed, and Scopus databases, and 36 relevant studies were identified. COVID-19 has spread to over 200 nations, causing 14 million infections as of July 18, 2020. SARS-CoV-2 affects more than only the respiratory system, causing fever, cough, and dyspnea. COVID-19 extrapulmonary symptoms are little documented [1]. This study covers COVID-19's cardiovascular and neurological symptoms. COVID-19's clinical characteristics will be compared to SARS and MERS. The goal is to raise knowledge of the organ systems impacted by SARS-CoV-2 and explain the clinical similarities and distinctions of these disorders. COVID-19 patients also have arrhythmias. COVID-19 individuals also experience gastrointestinal problems. These symptoms include moderate diarrhea to severe vomiting and abdominal discomfort. COVID-19 has pulmonary and extrapulmonary symptoms. The most prevalent symptoms are pulmonary (ARDS, pneumonia, and respiratory failure) and extrapulmonary (cardiovascular and gastrointestinal). Understanding these symptoms helps physicians treat COVID-19 patients [2]. COVID-19 causes pneumonia, ARDS, and respiratory failure. Severe COVID-19 can lead to ARDS. Lung inflammation causes fluid collection and respiratory problems. X- rays and CT scans can detect COVID-19-related pneumonia. Severe COVID-19 patients often have a respiratory failure when their lungs cannot provide adequate oxygen.

The potential link between Covid-19 and multiple myeloma: A new saga.

Covid-19 is considered a primary respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury and acute respiratory distress syndrome (ARDS). In addition, though, extra-pulmonary manifestations of Covid-19 have been shown. Furthermore, severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2) infection may coexist with several malignancies, including multiple myeloma (MM). This critical literature review aimed to find the potential association between SARS-CoV-2 infection and MM in Covid-19 patients with underlying MM. Narrative literature and databases search revealed that ARDS is developed in both MM and Covid-19 due to hypercalcemia and proteasome dysfunction. Notably, the expression of angiogenic factors and glutamine deficiency could link Covid-19 severity and MM in the pathogenesis of cardiovascular complications. MM and Covid-19 share thrombosis as a typical complication; unlike thrombosis in Covid-19, which reflects disease severity, thrombosis does not reflect disease severity in MM. In both conditions, thromboprophylaxis is essential to prevent pulmonary thrombosis and other thromboembolic disorders. Moreover, Covid-19 may exacerbate the development of acute kidney injury and neurological complications in MM patients. These findings highlighted that MM patients might be a risk group for Covid-19 severity due to underlying immunosuppression and most of those patients need specific management in the Covid-19 era.

Body Weight May Have a Role on Neuropathy and Mobility after Moderate to Severe COVID-19: An Exploratory Study.

Background and Objectives: Among the extra-pulmonary manifestations of COVID-19, neuromuscular signs and symptoms are frequent. We aimed to assess the correlation between neuromuscular abnormalities (electrophysiological) and mobility measures (Berg Balance Scale and Timed-Up-and-Go test) twice, at least 6 weeks after hospital discharge and 6 months later, taking into account cognitive performance, nutrition, muscle strength, and submaximal exercise capacity. Materials and Methods: 43 patients (51.4 ± 9.3 years old) accepted to participate in the study; they had a dyspnea score ≤ 3 (Borg scale), and no history of neurology/neuromuscular/orthopedic disorders, but high frequency of overweight/obesity and weight loss during hospital stay. The two evaluations included physical examination, cognitive assessment, nutritional evaluation, muscle strength (hand-grip and quadriceps dynamometry), electromyography, Barthel Index, Six-Minute- Walk-Test (6MWT), Berg Balance Scale and Timed-Up-and-Go test. Bivariate and repeated measures covariance analyses were performed (significance level of 0.05). Results: Electrophysiological abnormalities were evident in 67% of the patients, which were associated with diminished performance on the 6MWT, the Berg Balance Scale and the Timed-Up-and-Go test. At each evaluation and between evaluations, scores on the Berg Balance Scale were related to the body mass index (BMI) at hospital admission and the 6MWT (MANCoVA R ≥ 0.62, p = 0.0001), while the time to perform the Timed-Up-and-Go test was related to the electrophysiological abnormalities, weight loss during hospital stay, sex, handgrip strength, and the 6MWT (MANCoVA, R ≥ 0.62, p < 0.0001). We concluded that, after hospital discharge, patients with moderate to severe COVID-19 may have neuromuscular abnormalities that can be related to BMI/weight loss, and contribute to mobility decrease. In patients with moderate to severe COVID-19 and high BMI/ large weight loss, neuromuscular and intended mobility assessments could be required to provide early rehabilitation. Apart from the 6MWT, handgrip dynamometry and the Timed-Up-and-Go test were useful tools to quickly assess fitness and mobility.

Ursolic acid and SARS-CoV-2 infection: a new horizon and perspective.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) has been identified as the source of a world coronavirus pandemic in 2019. Covid-19 is considered a main respiratory disease-causing viral pneumonia and, in severe cases, leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although, extrapulmonary manifestations of Covid-19 like neurological, cardiovascular, and gastrointestinal have been confirmed. Exaggerated immune response and release of a high amount of pro-inflammatory cytokines may progress, causing a cytokine storm. Consequently, direct and indirect effects of SARS-CoV-2 infection can evolve into systemic complications due to the progression of hyper inflammation, oxidative stress and dysregulation of the renin-angiotensin system (RAS). Therefore, anti-inflammatory and antioxidant agents could be efficient in alleviating these disorders. Ursolic acid has anti-inflammatory, antioxidant, and antiviral effects; it reduces the release of pro-inflammatory cytokines, improves anti-inflammatory cytokines, and inhibits the production of reactive oxygen species (ROS). In virtue of its anti-inflammatory and antioxidant effects, ursolic acid may minimize SARS-CoV-2 infection-induced complications. Also, by regulating RAS and inflammatory signaling pathways, ursolic acid might effectively reduce the development of ALI in ARDS in Covid-19. In this state, this perspective discusses how ursolic acid can mitigate hyper inflammation and oxidative stress in Covid-19.

COVID-19 Related Myositis in a Patient Recently Diagnosed with Pre B Cell Acute Lymphoblastic Leukemia

Myositis is not a common finding in patients diagnosed with COVID-19. Up to now, a few cases of COVID-19 associated with myositis have been reported.&#x0D; A 26-year-old man was referred to the hematology clinic due to leukocytosis and bicytopenia in his lab tests. The patient had no symptoms at the visit session. Following the evaluation, he was hospitalized with the diagnosis of pre-B cell Acute Lymphoblastic Leukemia (ALL) and was considered a chemotherapy regimen consisting of vincristine, methotrexate, cytarabine, and prednisolone. Prior to initiating the treatment, he was diagnosed with COVID-19 with manifestations of fever and dyspnea on the 20th day of hospitalization. The positive Polymerase Chain Reaction (PCR) test confirmed the diagnosis. On the 8th day of COVID-19 related clinical and paraclinical manifestations, the patient was complaining about a vague severe pain in the pelvic region predominantly around his hips. A pelvic MRI was performed to rule out critical etiologies and perimuscular and intramuscular edema was revealed. Creatine Phosphokinase (CPK) and Lactate Dehydrogenase (LDH) were elevated in the lab tests.&#x0D; His pain was diminished in few days spontaneously and diagnosis of myositis was confirmed.&#x0D; Myositis can be one of the extra-pulmonary manifestations of COVID-19. Therefore, finding out the association between myositis and COVID-19 can be beneficial for the early diagnosis and prevention of misleading.

Molecular consequences of SARS-CoV-2 liver tropism

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.

COVID-19-Associated Biventricular Takotsubo Syndrome Complicated with Cardiogenic Shock (Clinical Case)

Acute myocardial dysfunction (AMD) remains prominent among extrapulmonary manifestations of COVID-19. Takotsubo syndrome (TS) is one of the causes of AMD development. TS incidence in patients with COVID-19 is currently unknown. The report presents a clinical case of an elderly female patient on maintenance hemodialysis with severe COVID-19. During the session of therapeutic plasma exchange (TPE), the patient had an episode of ventricular fibrillation followed by cardiogenic shock development and ECG changes, similar to myocardial infarction. Echocardiographic (Echo) data showed a distinctive pattern of biventricular TS with a significant systolic function decrease in both ventricles. Emergency CT angiography ruled out obstructive lesions of coronary arteries. Full recovery of both ventricles systolic function, regression of ECG changes, and complete resolution of cardiogenic shock were observed within the next week. The subsequent course of the disease was complicated by sepsis and multiple organ failure which determined the lethal outcome.The autopsy findings excluded coronarogenic and viral myocardial damage. The presented case demonstrates a life-threatening TS pattern in patients with severe COVID-19. TPE procedure should be treated as a possible trigger of TS.

LONG-TERM IMMUNOLOGICAL CONSEQUENCES OF COVID-19 ON HEALTH

SARS-Cov-2 (severe acute respiratory syndrome coronavirus) that initially came to notice in December 2019 is the agent responsible for COVID-19 is still spreading rapidly worldwide and it is presently a potent danger to the world and also to the economy. Patients with COVID-19 are still at risk of Acute Respiratory Distress Syndrome (ARDS), respiratory failure, and death. Those patients whose aged more than sixty years with comorbidities, children, and healthcare workers are highly vulnerable to this virus patient shows various symptoms most commonly cough, fever, difficulty in breathing, fatigue, sore throat. The infection could be categorized into three stages: mild infection, the pulmonary stage, and the inflammatory stage. As the COVID-19 pandemic continues, it has been clear that infection caused due to SARS-Cov-2 might be responsible for the unpredicted long-term health consequences. In addition to this, it has acute respiratory manifestations, adversely SARS-Cov-2 also affects the other organ systems. However, there is limited to the management of COVID-19 related conditions of the extrapulmonary systems. After recovery, patients remain at risk for lung disease, heart disease, and mental ailment. There may be long-term consequences of adverse effects they observed in the course of COVID-19 and during its treatment. This review provided information about the extrapulmonary manifestations of COVID-19 that may impair the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. Also, the main purpose of this article is to describe the current concern of the extra pulmonary complications that were caused due to COVID-19 and also to improve the management and diagnosis of these patients.

Rehabilitation Strategies for Cognitive and Neuropsychiatric Manifestations of COVID-19.

Purpose of ReviewExtrapulmonary manifestations of COVID-19 are abundant, including after recovery of acute SARS-CoV-2 infection. This review seeks to explore the cognitive and neuropsychiatric manifestations of COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC), including Long COVID syndromes. Furthermore, the review will discuss rehabilitation strategies for the emerging neurological consequences of COVID-19 to help those experiencing long-term effects of COVID-19.Recent FindingsThere is emerging evidence depicting the neural involvement of COVID-19. Health priorities have shifted from understanding pathogenesis and treatment of pulmonary symptoms to targeting the acute and chronic sequelae of COVID-19, including cognitive and neuropsychiatric symptoms. The sequelae of COVID-19 often co-occur with other medical problems and is best managed by assessment and care across multiple disciplines. Symptoms following infection are similar to those found by other syndromes and disorders that disrupt the central nervous system.SummaryThe acute and chronic sequelae of COVID-19 have become major targets of current health care providers given its significant public health impact, inclusive of cognitive and neuropsychiatric sequelae. Assessment and referral to rehabilitation based on each individual’s needs and symptoms can decrease morbidity and improve quality of life.

A RARE AND FATAL CASE OF ACUTE FULMINANT LIVER FAILURE INDUCED BY COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The SARS-CoV-2 virus, in accordance with the name designated to it by viral taxonomists, primarily causes severe acute respiratory distress syndrome. A challenge of this novel coronavirus has been discovering and preventing its indiscriminate and catastrophic effect on other organs. We present a rare case of the SARS-CoV-2 virus precipitating fulminant hepatic failure in a patient without respiratory symptoms or prior evidence of liver disease. CASE PRESENTATION: A 60 year-old female with history of atrial fibrillation, emphysema, and renal cell carcinoma status post left radical nephrectomy presented with weakness and fatigue. On day 12 of admission, she became hemodynamically unstable due to atrial fibrillation with rapid ventricular response, requiring electrical cardioversion, emergent intubation and transfer to ICU. Repeat SARS-CoV-2 PCR test was positive, although negative on admission. Dexamethasone, vancomycin and piperacillin-tazobactam were initiated, and one dose of Remdesivir was given after an unremarkable liver panel. No further Remdesivir was given, as six hours later, the patient had abrupt worsening of her liver function tests, with eventual peak AST of 2610 IU/L, ALT of 14860 IU/L and INR of 9.12. Fibrinogen was 136 mg/dL, ammonia 290 mcmol/L, lactate 11.51 mmol/L and IL-6 143.9 pg/mL. Viral causes for acute hepatitis were negative and abdominal ultrasound was unremarkable. The patient was treated with N-acetylcysteine, methylprednisolone, lactulose and rifaximin. She was ineligible for transfer to a liver transplant center due to her COVID-19 positive status. Unfortunately, despite conservative management, patient expired after developing severe disseminated intravascular coagulation, renal failure, and refractory septic shock. DISCUSSION: In recent literature, SARS-CoV-2 has primarily been recognized for causing mild liver injury, while fulminant hepatic failure is a rare occurrence (1,2). Remdesivir, which this patient received only one dose of, is known to cause mild transaminitis. It has been shown to cause severe liver injury only when used in combination with amiodarone, due to the latter's role as a moderate inhibitor of CYP3A4 and p-glycoprotein (3). This patient did not have exposure to hepatotoxic agents, prolonged state of shock, evidence of metastatic liver lesions or acute viral hepatitis to explain profound liver failure. Hence, we postulate that the SARS-CoV-2 virus may have directly targeted the hepatobiliary cells. Further studies of the pathophysiology of liver injury from this virus may allow better prevention and treatment. CONCLUSIONS: Understanding SARS-CoV-2's effects on a hepatocellular level may allow for anticipatory monitoring and prevention of liver damage from this virus. For those more severely affected, better treatments would help avoid the difficult course of emergency liver transplantation and resultant need for lifelong immunosuppression. REFERENCE #1: Gupta A, Mahhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID19. Nature Medicine 26:1017-1032, July 2020 REFERENCE #2: Melquist S, Estepp K, Aleksandrovich Y, et al. COVID-19 presenting as fulminant hepatic failure. Medicine 99:issue 43, October 23, 2020 doi 10.1097 REFERENCE #3: Remdesivir in LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet). National Institute of Diabetes and Digestive and Kidney Diseases, November 4, 2020; https://www.ncbi.nlm.nih.gov/books/NBK564049/?report=printable DISCLOSURES: No relevant relationships by Chester Choi, source=Web Response No relevant relationships by Madlena Nalbandian, source=Web Response No relevant relationships by Eulia Tlisov, source=Web Response

Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.

Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2–induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2–induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.

Extrapulmonary Manifestations of Covid-19: A Review

Extrapulmonary Manifestations of Covid-19: A Review

A cross-sectional study of pulmonary and extrapulmonary manifestations of COVID-19

Background: While the name of the virus indicates respiratory disease, and the respiratory spread of COVID-19 has been well documented in the literature, the ongoing pandemic has shown that the virus is not confined to just the lung. Hence, physicians should be aware of the “many faces” that this singular disease can present with, for timely diagnosis and prompt initiation of best treatment options. Materials and Methods: A total of 1754 patients with confirmed COVID-19 infection were admitted at a rural tertiary care center, Karnataka, India. This study is a cross-sectional study done for a period of 6 months from July 2020 to December 2020. Demographic data, clinical manifestations, laboratory parameters, management, and outcomes were recorded and compared. Results: Out of 1754 COVID-19 patients, pulmonary manifestations were seen in 1222 patients, extrapulmonary manifestations in 360 patients, and 172 patients were asymptomatic. Males were affected more than females, with a male-to-female ratio of 1.2:1. Most common pulmonary manifestation seen was cough in 83.06%, followed by fever in 67.59%. Most common extrapulmonary manifestation seen was neurological followed by gastrointestinal in 60.83% and 35.8% patients, respectively. Fatality in patients with pulmonary manifestations was 5% and extrapulmonary manifestation was 3%. All patients were managed according to standard COVID-19 treatment protocol. Conclusion: Early recognition of COVID-19 infections remains a big challenge. COVID-19 can have diverse range of clinical manifestations. Hence, COVID-19 infection should be considered in the differential of any systemic disease during the current pandemic, even in the absence of pulmonary manifestations like fever or cough.

Peculiarities of antimicrobial therapy of viral and bacterial pneumonia in patients with coronavirus disease

Background. The coronavirus pandemic (COVID-19) currently dominates all health problems. Adequate initial antimicrobial therapy of viral and bacterial pneumonia in patients with COVID-19 requires compliance with a number of features that are fundamentally important in the context of global growth of resistance of pathogenic flora to antimicrobial drugs.&#x0D; Objective. To describe the features of antimicrobial therapy of viral and bacterial pneumonia in patients with COVID-19.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. Severe coronavirus infection triggers an avalanche-like generalized inflammatory response with rapid vascular endothelial damage. Lungs is the main target organ of this aggression. A significant part of all endothelial cells of the body is concentrated in the lungs, so the cascade of multiorgan disorders begins with them. Liver, intestines, kidneys and muscles are the organs that suffer from extrapulmonary manifestations of COVID-19. SARS-CoV-2 сoronavirus also has neurotropism, so it is able to affect the nervous system, both central and peripheral. The pathogenesis, diagnosis and treatment of COVID-19 should be considered in terms of the approaches used in sepsis. This disease is characterized by the following laboratory changes: increased content of C-reactive protein, leukocytosis or leukopenia, lymphopenia, neutrophilia, increased activity of alanine and aspartate aminotransferases, creatine phosphokinase, lactate dehydrogenase, bilirubin and creatinine concentrations. However, sufficiently sensitive and specific markers for the diagnosis and prediction of COVID-19 are currently lacking. Until the results of the polymerase chain reaction for SARS-CoV-2 and, consequently, the confirmation of COVID-19, are absent, all patients with severe pneumonia and acute respiratory distress syndrome should be treated as patients with acute severe community-acquired pneumonia. Empirical combination antibiotic therapy should be started immediately. Patients over 60 years of age with pre-existing comorbidities need special attention. The spectrum of microbial flora in such patients includes Streptococcus pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, gram-negative enterobacteria. This must be taken into account when choosing an antibiotic. In presence of intracellular pathogens, fluoroquinolones have an advantage over macrolides and tetracyclines. Due to the growing resistance of hospital flora to macrolides and the high risk of resistance to them in outpatient flora, the initial use of fluoroquinolones is one of the main trends in modern antibiotic therapy. The advantages of levofloxacin are the possibility of administration in short courses (750 mg once a day for 5 days), a wide activity spectrum, the ability to overcome the basic mechanisms of resistance, a good safety profile. Intravenous administration of levofloxacin is not inferior to the effectiveness of the combination of β-lactams and macrolides and can be completed by transferring the patient to oral treatment. For the treatment of patients at risk of Pseudomonas aeruginosa infection, combination therapy is prescribed – antipseudomonad cephalosporins of III-IV generation in combination with aminoglycosides, ciprofloxacin or levofloxacin. Alternatively, carbapenems are prescribed in combination with aminoglycosides (tobramycin – Braxon, “Yuria-Pharm”) or fluoroquinolones (levofloxacin – Leflocin, “Yuria-Pharm”). When methicillin-resistant Staphylococcus aureus is detected, the use of linezolid (Linelid, “Yuria-Pharm”) is advisable. Antibiotic therapy is often accompanied by fungal infections. In severe cases of the latter, as well as in pulmonary aspergillosis voriconazole (Vizealot, “Yuria-Pharm”) is prescribed.&#x0D; Conclusions. 1. Severe coronavirus infection triggers an avalanche-like generalized inflammatory reaction with rapid damage to the vascular endothelium. 2. In the presence of intracellular pathogens, fluoroquinolones have an advantage over macrolides and tetracyclines. 3. The initial use of fluoroquinolones is one of the main trends in modern antibiotic therapy. 4. In the detection of methicillin-resistant Staphylococcus aureus, it is advisable to use linezolid. 5. In severe fungal infections and pulmonary aspergillosis, voriconazole is prescribed.

EP05 COVID-19 and the biliary tree: atypical manifestations of disease during the pandemic

Case report - IntroductionCOVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, and first described in Wuhan, China in December 2019, has affected more than 19 million patients worldwide and resulted in more than 700,000 deaths at the time of writing1. Patients with rheumatic diseases and those receiving immunosuppressive treatment are felt to be at greater risk of complications from this illness, though registry and trial data should help refine our understanding of these risks. We hereby describe a case of COVID-19 complicating an unusual rheumatic illness, resulting in severe multi-system disease and premature death.Case report - Case descriptionA 69 year-old male presented to rheumatology and haematology with symmetrical polyarthritis, thrombocytopenia (18 x 109/L), eosinophilia (25.4 x 109/L), raised C-reactive protein (CRP, 43 mg/L), positive rheumatoid factor (>200), antinuclear antibody (ANA) and anti-Ro. Bone marrow biopsy did not demonstrate evidence of haematological malignancy. Seropositive rheumatoid arthritis and connective tissue disease overlap were diagnosed, and treatment with Prednisolone 60mg daily was initiated. Despite rituximab and intravenous immunoglobulins, thrombocytopenia deteriorated on reducing corticosteroids, however the addition of mycophenolate mofetil (MMF) allowed gradual prednisolone tapering to 3mg daily. Hydroxychloroquine was briefly added but discontinued due to headaches. MMF was discontinued after he developed fungal pneumonia followed by jaundice. Liver biopsy was consistent with drug-induced cholestasis, attributed to co-amoxiclav, and his liver function tests (LFTs) improved on ursodeoxycholic acid. Following a further deterioration in thrombocytopenia, hyperferritinaemia and new onset erythema nodosum, he had a repeat bone marrow examination. This demonstrated large areas of fibrosis and granulomatous inflammation with a dense, pleomorphic T-cell infiltrate, but no haemophagocytosis. Haematologists felt this was reactive and prednisolone dose was increased to 10mg daily.Six months later he developed cholangitis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a tight 4cm stricture of the distal common bile duct (CBD) within the head of pancreas, which was diffusely swollen without any clear focal mass. Serum amylase was mildly elevated (316 units/L). Concurrent CT thorax, abdomen and pelvis demonstrated bilateral ground-glass changes within the lungs, and a SARS-CoV-2 nasopharyngeal PCR test was positive, though he had no respiratory symptoms or oxygen requirement at that stage.Sadly, four days after the CT scan and before a planned endoscopic retrograde cholangiopancreatography (ERCP) could be performed, he became markedly hypoxic with plain chest x-ray features suggestive of COVID-19 pneumonia. Despite medical management, including doubling of his prednisolone dose, he rapidly deteriorated and died.Case report - DiscussionThis case highlights an unusual presentation of COVID-19 in a patient with a complex background of inflammatory arthritis with immune-mediated thrombocytopenia. At the time of his final illness, these conditions were managed with steroid monotherapy. Based on the COVID-19 risk matrix recommended by the British Society for Rheumatology, he was not identified as a patient requiring shielding.Cholangitis was the major problem precipitating his final admission to hospital, and at the time of admission he had no respiratory symptoms. One week prior to this admission, his father-in-law had died of COVID-19 pneumonia, though they had not been in recent direct contact. Interstitial lung changes were incidentally noted on a CT performed to identify the cause of cholangitis, which prompted the nasopharyngeal PCR that detected SARS-CoV-2. This occurred prior to widespread routine testing of hospital inpatients for SARS-CoV-2 by PCR. Unfortunately he then rapidly developed COVID-19 pneumonia and died before the underlying cause of cholangitis could be definitively identified, though an MRCP demonstrated an obstructed CBD within a diffusely swollen pancreas, where a differential diagnosis of pancreatic malignancy or autoimmune pancreatitis was suggested by the reporting radiologist. There are emerging case reports of COVID-19 resulting in significant pancreatic injuryand a further recent laboratory analysis has suggested that ACE2 receptors, which are utilised by SARS-CoV-2 to gain entry to host cells, are highly expressed on cholangiocytes at a comparable level to type II alveolar cells. Whilst the ultimate cause of cholangitis will remain unknown in this patient, this case highlights the potential for atypical presentations and extra-pulmonary manifestations of COVID-19. Case report - Key learning points COVID-19 is a multi-system illness which can cause significant extra-pulmonary as well as pulmonary pathology, with emerging reports that the biliary tract and pancreas are frequently affected.Evidence to inform accurate prediction of which patients with rheumatic diseases are at highest risk of acquiring severe COVID-19 disease remains insufficient, with current shielding guidelines based on expert consensus.This case highlights the importance of widespread testing for COVID-19 in hospital patients, as not all patients carrying the SARS-CoV-2 virus will demonstrate classical respiratory features of the disease at the point of admission.

A Review of the Extrapulmonary Manifestations of the 2019 Novel Coronavirus Disease (COVID-19)

Background: Since the onset of the 2019 novel coronavirus disease (COVID-19), many reports have presented the disease as a respiratory disease, thereby limiting diagnosis to presentations with respiratory symptoms. This review critically analyzes and consolidates published literature describing extrapulmonary features of COVID-19. Methods: Recently published full-text literature on the extrapulmonary manifestations of COVID-19 was reviewed. The studies reviewed focused on the cardiovascular, gastrointestinal, nervous, hematopoietic, genitourinary, and musculoskeletal systems; and ocular, otorhinolaryngological, and cutaneous symptoms. Results: A total of 28 original articles were selected and analyzed. The most common extrapulmonary manifestations were acute cardiac injury (7.2-19.7%), arrhythmia (16.7%), and shock (8.7%) in the cardiovascular system; anorexia (83.8%), liver abnormality (14.8-37.2%), diarrhea (3.8-29.3%), abdominal pain (0.4-12.0%), nausea (9.5%), and vomiting (0.8-5.0%) in the gastrointestinal system; acute cerebrovascular disease and loss of consciousness (36.4%) in the nervous system; lymphopenia (40.0%-64.0), leukocytosis (14.3-23.4%), anemia (15.0%), thrombocytopenia (7.0%), elevated D-dimer (42.0%), and prolonged prothrombin time (2.1-6.0%) in the hematopoietic system; and proteinuria (43.9-62.7%), hematuria (26.7%), elevated urea (27.1%) and creatinine (18.6%), and acute kidney injury (3.6-5.1%) in the urinary system. Others include sore throat (28.6%), erythematous rash (15.9%), arthralgia/myalgia (14.8%), widespread urticaria (3.4%), and singular reports of acute myopericarditis, acute lymphocytic myocarditis, meningitis, viral encephalitis, testicular pain, anosmia, and acute conjunctivitis. Conclusion: COVID-19 affects every organ-system and can cause extrapulmonary symptoms with or without respiratory symptoms. A high index of suspicion is required to help healthcare providers achieve early diagnosis, prompt treatment, and reduce the chances of spreading the disease within the community.

Extrapulmonary Manifestations of COVID-19: A Call to Extra Vigilance and Tribute to Dr Li Wenliang

COVID-19 pandemic has covered all continents and virtually all countries of the world infecting millions of people with several hundred thousands of death. It was first brought to the attention of a Chinese ophthalmologist Dr Li Wenliang. The disease which was first believed to be solely associated with the lungs and respiratory system has now shown that the spectrum of organ involvement of the disease is much larger than earlier believed. While lung and pulmonary features still account for a much larger presentation of the disease, other clinical manifestations such as fulminant myocarditis, arteriovenous thromboembolism, disseminated intravascular coagulopathy, intracerebral haemorrhage, diarrhea, hypoxic encephalopathy, septicaemia and detection of SARS-CoV-2 particles in stool, saliva and semen of infected individuals are also becoming less infrequent. Haematologic manifestations of hypercoagulable blood are commonly reported among hospitalized COVID‐19 patients. An elevated D‐Dimer, that is rising in the course of disease may signifies disease deterioration. Prolonged PT and aPTT and increased fibrin degradation products with severe thrombocytopenia have been associated with life-threatening disseminated intravascular coagulation (DIC). Physicians should therefore be on a watch out for these features in the management of patients and be ready to spot out other new surprises by the disease. This should be through deepening of curiosity by health personnel in the assessment and management of patients to spot out early surprises of COVID-19 to strengthen the sustenance of the ongoing control of the pandemic