COVID-19: Clinical Spectrum—It's Multiorgan Syndrome

COVID-19 outbreak caused by SARS-CoV-2 has emerged as a global challenge for the entire health care system worldwide. It has affected the developed as well as developing countries markedly. What began as pneumonia-like illness later evolved into a multiorgan disease leading to severe morbidity and even death. The clinical data and global literature explicitly suggest that in addition to respiratory symptoms, the COVID-19 patients may present with hematological, cardiovascular, renal, gastrointestinal, neurological, ocular, and skin manifestations. The underlying mechanism for multisystem involvement is the expression of angiotensin-converting enzyme 2 (ACE2) receptors at multiple extrapulmonary tissues. Injury to various organs may be attributed to cytokine storms or to disturbances of coagulation and vascular endothelium. The aim of this review is to emphasize the impact of SARS CoV-2 infection on not only the lungs but other organ systems too. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Microbiological and Clinical Findings of SARS-CoV-2 Infection after 2 Years of Pandemic: From Lung to Gut Microbiota.

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.

Association of systemic complications with mortality in coronavirus disease of 2019: A cohort study on intensive care unit patients.

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.

Thyrotoxicosis occurrence in SARS-CoV-2 infection: A case report.

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.

Atypical Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children: A Systematic Review.

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.

Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity.

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.

Extrapulmonary complications of COVID-19: A multisystem disease?

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.

Peculiar clinical presentation of COVID-19 and predictors of mortality in the elderly: A multicentre retrospective cohort study.

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.

Acute myocarditis as the main clinical manifestation of SARS-CoV 2 infection.

We describe a case of acute myocarditis, which was reported as the main COVID-19 clinical manifestation, with a favorabile outcome. In addition to symptoms, laboratory tests (BNP and troponin), echocardiogram and cardiac MRI contributed to diagnosis. Regardless heart biopsy was not obtained, it is likely an immunological pathogenesis of this condition which pave the way to further therapeutic implications, since there are currently no standardized treatments.

Adolescent COVID-19-Associated Fatal Rhabdomyolysis.

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.