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The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the ensuing COVID-19 pandemic had far-reaching and multifaceted effects on global health. This paper provides a comprehensive overview of the physical, extrapulmonary, and psychological manifestations associated with COVID-19. It highlights the wide-ranging impact of the virus on various organ systems, including the respiratory, cardiovascular, renal, gastrointestinal, ocular, dermatologic, and nervous systems. Additionally, it explores the complex connections between COVID-19 infection and neuropsychiatric symptoms, shedding light on the potential underlying mechanisms. The paper also delves into the phenomenon of "long COVID," a condition characterized by persistent symptoms extending well beyond the disease's acute phase. It discusses the diverse and often debilitating symptoms that individuals with long COVID may experience, encompassing physical, cognitive, and psychological aspects. The complexity and variability of long COVID underscore the challenges it poses to healthcare professionals and the importance of ongoing research to understand its underlying mechanisms. Furthermore, the paper touches on the current state of knowledge regarding the aetiology of long COVID and the various approaches to symptom management and treatment. While a definitive cure remains elusive, efforts are underway to alleviate the burden of long COVID through pharmacological interventions, physical therapy, cognitive-behavioral therapy, and support networks. This paper comprehensively explores COVID-19's far-reaching effects, emphasizing the need for a holistic and interdisciplinary approach to understanding and managing the diverse manifestations of this global health challenge. Ongoing research and collaborative efforts are essential in addressing the complex and evolving nature of COVID-19 and its aftermath.

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A 50-year-old female who presented to our hospital for recurrent diarrhea was found to have worsening aminotransferase and alkaline phosphatase levels. Workup revealed lymphadenopathy and hepatomegaly prompting a biopsy of the liver and axillary lymph node, confirming a diagnosis of hepatic sarcoidosis. Our patient later developed cutaneous sarcoidosis. She is currently asymptomatic and is followed by gastroenterology, pulmonary, and dermatology. Recognition of extrapulmonary manifestations of sarcoidosis is important for proper management of patients. Treatment often requires a multidisciplinary approach when more than one organ system is involved.

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This review describes the appearance of extrapulmonary tuberculosis manifestations in comprehensive and multiparametric ultrasound imaging. The aim is to increase awareness of typical ultrasound findings regarding extrapulmonary tuberculosis, correlate those with pathological features, and facilitate differential diagnosis. Point of care ultrasound protocols can be used as a screening method in high-risk populations, although the negative findings do not exclude tuberculosis. Conversely, the diagnosis of extrapulmonary tuberculosis can never be made using ultrasound alone, as many ultrasound findings in extrapulmonary tuberculosis are non-specific. However, ultrasound-based sampling techniques can significantly facilitate the collection of samples for microbiological or molecular proof of tuberculosis, as well as facilitating the establishment of alternative diagnoses.

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Tuberculosis is a highly infectious respiratory disease due to Mycobacterium tuberculosis (MTb). The most common manifestation of MTb is pulmonary tuberculosis, but some patients can present with extrapulmonary manifestations as their initial presentation. Tuberculous pleurisy and pleural effusion are among the most common extrapulmonary manifestations of MTb. The treatment of pleural MTb is the same as the treatment for pulmonary disease, with a four-drug regimen with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) under directly observed therapy (DOT). Drainage of the pleural effusion is usually not recommended in tuberculosis pleural effusion. We present a case of a complex, loculated pleural effusion due to MTb in an otherwise healthy middle-aged male who responded rapidly and completely to an early, short course of intrapleural tissue plasminogen activator and dornase alfa (TPA/DNase) therapy.

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Legionnaires' disease is caused by a potentially life-threatening infection with the opportunistic Gram-negative bacilli species Legionella pneumophila, which is transmitted via inhalation or aspiration of water droplets. Legionnaires' commonly presents as atypical community-acquired pneumonia with accompanying diarrhea. Although hepatic and renal involvement are relatively uncommon, in this report, we present a case of Legionella pneumonia with acute hepatitis.

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Although usually more associated with the lungs, sarcoidosis can have multiple extrapulmonary manifestations. We present a case of a patient with previous biopsy-proven sarcoidosis who was admitted to the hospital secondary to worsening shortness of breath. The patient was found to be positive for Respiratory Syncytial Virus (RSV) which was believed to have exacerbated his pulmonary symptoms. He was treated with IV steroids, nebulizers, and antibiotics which ultimately helped relieve his symptoms. In terms of his sarcoidosis, he was previously treated in the past with steroids in regards to this pathology (which is the mainstay of treatment); while on the regimen, the patient noted his breathing was improved. Of note, he did also have a history of renal cell carcinoma (RCC) status post nephrectomy which was initially evaluated for possible sarcoidosis involvement. This medical therapy could also have been the reason his sarcoidosis did not progress to involve other organs.

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Sarcoidosis is a well-characterized inflammatory disease that affects multiple organ systems and can have long-term devastating outcomes if not identified and treated appropriately. The disease is most prevalent among young to middle-aged African American women. It most commonly presents with pulmonary involvement, though there are reported cases of sarcoidosis without pulmonary involvement. Pulmonary presentations can be biopsied, diagnosed, and treated with primary immunomodulation with great treatment success. Here, we present an unusual presentation of sarcoidosis as granulomatosis mucositis in the salivary gland and concurrent rare complication of sarcoid myositis in the rectus femoris in a patient with no evidence of pulmonary involvement throughout the duration of their clinical course. Further, we discuss differential diagnoses related to this patient's presentation as well as the efficacy of treatment modalities available in the management of this disease.

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Early recognition and prompt management are crucial for improving survival in COVID-19 patients, and after 2 years of the pandemic, many efforts have been made to obtain an early diagnosis. A key factor is the use of fast microbiological techniques, considering also that COVID-19 patients may show no peculiar signs and symptoms that may differentiate COVID-19 from other infective or non-infective diseases. These techniques were developed to promptly identify SARS-CoV-2 infection and to prevent viral spread and transmission. However, recent data about clinical, radiological and laboratory features of COVID-19 at time of hospitalization could help physicians in early suspicion of SARS-CoV-2 infection and distinguishing it from other etiologies. The knowledge of clinical features and microbiological techniques will be crucial in the next years when the endemic circulation of SARS-CoV-2 will be probably associated with clusters of infection. In this review we provide a state of the art about new advances in microbiological and clinical findings of SARS-CoV-2 infection in hospitalized patients with a focus on pulmonary and extrapulmonary characteristics, including the role of gut microbiota.

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Although fever and respiratory symptoms are the main clinical expression of COVID-19 disease, important extrapulmonary complications that affect the majority of the organs and systems may occur. Multisystemic involvement can mainly be attributed to the generalized location of ACE2 receptors throughout the body, which act as the main point of entry for the virus. Systemic manifestations may occasionally appear before the typical symptoms, although they generally occur later or are sequelae of the disease. Thromboembolic complications are concerning due to their frequency and severity; they are the result of a hypercoagulable state with multiple possible clinical manifestations. Cardiac, neurological, gastrointestinal, renal, endocrine-metabolic, skin, and ocular complications may occur. The manifestations and specific therapeutic aspects of COVID-19 disease in pregnant women as well as implications of the disease on children are discussed. The corresponding tests must be performed in all patients with a clinical suspicion of COVID-19 in order to confirm the diagnosis of the infection. The specific diagnostic tests that are indicative of involvement of different organs are guided based on clinical suspicion. These tests are conducted on an individual basis taking into account the isolation measures required and the severity of each case. Likewise, the corresponding treatment is administered according to criteria that generally similar to those for the general population.

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Introduction: Coronavirus Disease 2019 (COVID-19) is predominantly manifested as respiratory distress. There are growing reports of extrapulmonary clinical manifestations of COVID-19 in addition to the respiratory symptoms. COVID-19 has been associated with the thyroid function through Angiotensin-converting enzyme 2 (ACE2), the central mechanism through Thyroid Stimulating Hormone (TSH), and direct replication of the virus. Case presentation: A 26-year-old woman presented with complaints of palpitation and abdominal pain for three days. Because the symptoms were worsening, she was brought to the emergency room. Her temperature was 37.9 °C without any symptoms of cough, coryza, sneezing, nor headache. Physical examination revealed tremor, tachycardia with 162 beats per minute (bpm), excessive sweating, hyperreflexia of patellar reflex, and no prominent lump in the neck. Electrocardiography (ECG) showed supraventricular tachycardic rhythm (SVT) and 150 J cardioversions were performed. The ECG converted to sinus rhythm, regular, with 120 bpm. Thyroid function tests showed an elevated fT4 level (>7.77 ng/dL) and low TSH level (<0.005 µIU/mL). Chest X-ray showed slight cardiomegaly without prominent abnormality in the lungs that was confirmed with thoracic computerized tomography. The result of the rapid antigen test for COVID-19 was positive and confirmed with polymerase chain reaction testing. She was then treated in the intensive isolation room with remdesivir, anti-hyperthyroid, and supportive therapy. As her condition improved, she was shifted to a non-intensive isolation room and was discharged from the hospital at day 7. Discussion: COVID-19 could present as a thyroid crisis as the initial clinical manifestation. Clinicians should be aware that presentation of thyroid dysfunction in a patient without previous endocrine disease could be due to COVID-19 infection. Early recognition, anti-hyperthyroid therapy, and following isolation procedures for COVID-19 are required in the emergency condition.

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Background: Since the beginning of the coronavirus disease of 2019 (COVID-19) pandemic, concerns raised by the growing number of deaths worldwide. Acute respiratory distress syndrome (ARDS) and extrapulmonary complications can correlate with prognosis in COVID-19 patients. This study evaluated the association of systemic complications with mortality in severely affected COVID-19 patients. Materials and Methods: This retrospective study was done on 51 intensive care unit (ICU)-admitted COVID-19 adult patients who were admitted to the ICU ward of Khorshid hospital, affiliated with Isfahan University of Medical Sciences. Only the patients who had a definite hospitalization outcome (dead vs. survivors) were included in the study. Daily clinical and paraclinical records were used to diagnose in-hospital complications in these patients. Results: The sample was comprised of 37 males (72.5%) and 14 females (27.4%). The median age of patients was 63 years (Min: 20, Max: 84), with the mortality rate of 47.1%. In total, 70.6% of patients had at least one coexisting disorder. Chronic kidney disease was associated with the worse outcome (29.16% of dead patients against 3.70 of survived ones). Mechanical ventilation was used in 58.8% of patients. Patients who had received invasive ventilation were more likely to die (87.50% of dead patients against 7.40 of survivors), Complications including sepsis and secondary infections (odds ratio: 8.05, confidence interval: 2.11-30.63) was the strongest predictors of mortality. Conclusion: Complications including sepsis and secondary infections can increase the risk of death in ICU-admitted COVID-19 patients. Therefore, it is substantial that the physicians consider preventing or controlling these complications.

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BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a heterogenous disease with a median survival of 3-4 years. Patients with mutations in telomere-related genes exhibit extrapulmonary signs and symptoms. These patients represent a distinct phenotype of IPF with worse survival. As genetic analyses are not available for most patients with IPF, we sought to determine the predictive value of extrapulmonary signs and symptoms of a telomere syndrome in patients with IPF. METHODS: We retrospectively studied 409 patients with IPF. Clinical characteristics, laboratory results and family history suggestive of a telomere syndrome were related to leukocyte telomere length measured by quantitative PCR and patient outcomes. RESULTS: The cohort included 293 patients with sporadic IPF and 116 patients with a background of familial pulmonary fibrosis. Any or a combination of a clinical history (haematological disease, liver disease, early greying of hair, nail dystrophy, skin abnormalities), a family history or haematological laboratory abnormalities (macrocytosis, anaemia, thrombopenia or leukopenia) suggestive of a telomere syndrome was present in 27% of IPF patients and associated with shorter leukocyte telomere length and shorter survival (p = 0.002 in a multivariate model). In sporadic IPF, having either a clinical history, family history or haematological laboratory abnormalities was not significantly associated with decreased survival (p = 0.07 in a multivariate model). CONCLUSION: Taking a careful clinical and family history focused on extrapulmonary manifestations of a telomere syndrome can provide important prognostic information in patients with IPF, as this is associated with shorter survival.

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BACKGROUND & AIM: Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD. METHODS: This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1 s (FEV1) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV1%predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups. RESULTS: Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p = 0.029). In line with a large difference in FEV1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p < 0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1 m, p = 0.001, and 25.9%predicted, p < 0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups. CONCLUSION: Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD.

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Human adenovirus(HAdV)is a double-stranded DNA virus with multiple serotypes.Owing to their genetic heterogeneity, HAdVs display broad tissue tropism and can infect several organs or tissues.Besides the most common respiratory system, different types of HAdV can enter into multi-tissue and cells of the whole body through different receptors and mechanisms, directly destroy the host cells and also trigger immune response that course further damages.Then a variety of extrapulmonary manifestations would appear, such as gastroenteritis, encephalitis, myocarditis, hemorrhagic cystitis, hemophagocytosis and conjunctivitis, which seriously threaten the health of children.

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Mycoplasma pneumoniae (MP) is one of the main causes of both upper and lower respiratory infections in school-aged children, accounting for up to 40% of community-acquired pneumonia. Younger children are also affected, and extrapulmonary manifestations have been recently reported in the pediatric population. We carried out a retrospective analysis of MP-positive patients admitted to the Pediatric Emergency Unit of S. Orsola Malpighi University Hospital in Bologna, the largest tertiary pediatric referral center in the Emilia-Romagna region, Northern Italy, between 2012 and 2020. We identified 145 patients with MP infection (82 males and 63 females), 27% of which were younger than 2 years; the median age was 5 years (interquartile range 1-9). The clinical presentation partially differed between age groups. School-aged children were more likely to have a chest X-ray-confirmed pneumonia (p = 0.013), while younger children required oxygen therapy more often (p = 0.048). Seventy-four children (51%) showed extrapulmonary manifestations, mainly gastrointestinal (30%) and dermatological (14%). Neurological symptoms were more frequent in children older than 6 years (p = 0.006). The rate of other extrapulmonary manifestations did not differ significantly between age groups. This study shows that MP infection is a frequent cause of pediatric hospitalization, including of children younger than 2 years. Clinicians should be aware of the variable clinical expressions of MP, including extrapulmonary manifestations, to achieve a correct diagnosis and determine appropriate treatment.

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.

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BACKGROUND: In December 2019, a local outbreak of pneumonia was presented in Wuhan (China) and quickly identified to be caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 was named COVID-19 and was soon declared a pandemic because of the millions of infections and thousands of deaths worldwide. Children infected with SARS-CoV-2 usually develop the asymptomatic or mild type of disease compared to adults. They are also more likely to have atypical and non-specific clinical manifestations than adults. METHODS: A literature search was performed through PubMed and Scopus to summarize the extrapulmonary manifestations of SARS-CoV-2 infection in children since the beginning of the pandemic. Peer-reviewed papers in English were retrieved using the following keywords and combinations: 'pediatric,' 'child,' 'infant,' 'neonate,' 'novel coronavirus,' 'SARS-CoV-2,' 'COVID 19' and 'gastrointestinal,' 'renal,' 'cardiac,' 'dermatologic' or 'ophthalmologic'. We included published case series and case reports providing clinical symptoms and signs in SARS-CoV2 pediatric patients. RESULTS: Although fever and symptoms of upper respiratory infection are the most frequently presented, a variety of other atypical presentations has also been reported. The clinical spectrum includes dermatological, ophthalmological, neurological, cardiovascular, renal, reproductive, and gastrointestinal presentations. In addition, a rare multi-inflammatory syndrome associated with SARS-- CoV-2 infection has been reported in children, often leading to shock and requiring inotropic support and mechanical ventilation. CONCLUSION: Clinicians need to be aware of the wider range of extrapulmonary atypical manifestations of SARS-CoV-2 infection in children, so that appropriate testing, treatment, and public health measures can be implemented rapidly.

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BACKGROUND: The spectrum of COVID-19 clinical manifestations is not yet known. In the elderly, mortality and extrapulmonary involvement appears more frequent than expected. METHODS: A multicentre-retrospective-case-series study of COVID-19 patients, aged ≥65 years, hospitalised between March 1 and June 15, 2020. Patients were classified at admission into 3 groups based on their Clinical Frailty Scale (CFS) score: 1-3 (group A), 4-6 (group B) and 7-9 (group C). RESULTS: Of the 206 patients in the study, 60 (29%) were assigned to group A, 60 (29%) to B and 86 (42%) to C. Significantly more frequent in group C than in B or A were: mental confusion (respectively 65%, 33%, 7%; P < 0.001), kidney failure (39%, 22%, 20%; P = 0.019), dehydration syndrome (55%, 27%, 13%; P < 0.001), electrolyte imbalance (54%, 32%, 25%; P = 0.001), and diabetic decompensation (22%, 12%, 7%; P = 0.026). Crude mortality was 27%. By multivariate logistic regression model independent predictors of death were male sex (adjusted odds ratio (aOR) = 2.87,95%CI = 1.15-7.18), CFS 7-9 (aOR = 9.97,95%CI = 1.82-52.99), dehydration at admission (aOR = 4.27,95%CI = 1.72-10.57) and non-invasive/invasive ventilation (aOR = 4.88,95%CI = 1.94-12.26). CONCLUSIONS: Elderly patients with a high CFS showed frequent extrapulmonary signs at admission, even in the absence of lung involvement. These findings, along with a high CFS, predicted a significant risk of mortality.

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The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID-19 to improve the management and prognosis of patients with COVID-19.

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Coronavirus disease 2019 (COVID-19) has become an urgent global health priority. Although most patients with COVID-19 manifest with fever and respiratory tract symptoms, COVID-19 infections may also involve other organs and extrarespiratory manifestations, including cardiac, gastrointestinal, hepatic, renal, and neurological symptoms. This case describes a 16-year-old boy who presented with fever, sore throat, myalgia, and subsequently with shortness of breath. A diagnosis of COVID-19 was confirmed by polymerase chain reaction. His condition deteriorated and he died within 3 days of admission. An evaluation of his past medical history confirmed an episode of viral illness which had progressed to myositis and rhabdomyolysis 1 year prior. Clinicians should be aware of this complication and maintain a high index of suspicion in cases of COVID-19 presenting with extrapulmonary symptoms.

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