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Objective: Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002-2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance., Method: Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance., Results: Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed-accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants' subjective ratings of Everyday Task-Oriented Memory., Conclusions: These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.

Little is known about the consequences of viral infection for pregnant woman or for the fetus. This issue became important with the appearance of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The infection with SARS-CoV-2 causes a respiratory syndrome known as COVID-19. The fast spreading around the world and the fact that without a treatment or vaccine humans are completely exposed, converts emerging viral diseases in a significant risk for pregnant women and their infants. At this time, during SARS-CoV-2 pandemics pregnant women are not considered as a risk population and little is known about the effects of viral infections over the offspring although the amount of emerging evidence showing detrimental effects for the mother and the fetus. This issue highlights the importance to understand the effects of viral infections during pregnancy. In this work, we analyze the effects of viral infections, like SARS-CoV-2 and other related viruses during pregnancy over the mother and the consequences for the offspring.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions., Competing Interests: The authors declare no conflict of interest regarding this manuscript., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors., Methods: A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index., Results: Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03-1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41-5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66-4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07-2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen., Conclusion: Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity., (© 2021. The Author(s).)

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.

Introduction: Many patients with mild or severe COVID-19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection, often of a neurological, cognitive or psychiatric nature. The epidemiological evidence, diagnostic criteria and pathogenesis of post-COVID-19 syndrome are reviewed., Development: Post-COVID-19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID-19, persist for more than 12 weeks and cannot be explained by an alternative diagnosis. The symptoms can fluctuate or cause relapses. It is a heterogeneous condition that includes post-viral chronic fatigue syndrome, sequelae in multiple organs and the effects of severe hospitalisation/post-intensive care syndrome. It has been reported in patients with mild or severe COVID-19 and irrespective of the severity of the symptoms in the acute phase. Between 10% and 65% of survivors who had mild/moderate COVID-19 present symptoms of post-COVID-19 syndrome for 12 weeks or more. At six months, subjects report an average of 14 persistent symptoms. The most common symptoms are fatigue, dyspnoea, anxiety, depression, and impaired attention, concentration, memory and sleep. The underlying biological mechanisms are unknown, although an abnormal or excessive autoimmune and inflammatory response may play an important role., Conclusions: Clinical manifestations are diverse, fluctuating and variable, although fatigue and neurocognitive complaints predominate. There is no defined consensus on post-COVID-19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation.

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.

In the past 20 years, infections caused by coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 have posed a threat to public health since they may cause severe acute respiratory syndrome (SARS) in humans. The Complement System is activated during viral infection, being a central protagonist of innate and acquired immunity. Here, we report some interactions between these three coronaviruses and the Complement System, highlighting the central role of C3 with the severity of these infections. Although it can be protective, its role during coronavirus infections seems to be contradictory. For example, during SARS-CoV-2 infection, Complement System can control the viral infection in asymptomatic or mild cases; however, it can also intensify local and systemic damage in some of severe COVID-19 patients, due to its potent proinflammatory effect. In this last condition, the activation of the Complement System also amplifies the cytokine storm and the pathogenicity of coronavirus infection. Experimental treatment with Complement inhibitors has been an enthusiastic field of intense investigation in search of a promising additional therapy in severe COVID-19 patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In the past 20 years four major viral infectious diseases outbreaks caused hundreds of thousands of deaths worldwide: SARS, Influenza H1N1, MERS, and COVID-19. They all present clinically initially as upper and lower respiratory tract infections and may progress to multi-organ failure., Methods: This study was a systematic review of literature conducted in September 2020 to study extra-pulmonary complications of SARS, FLU, MERS, and current COVID-19. We carried out a systematic search using the keywords in online databases of PubMed, EMBASE, and Google Scholar until June 2020., Objective: This article aims to review the most common extra-pulmonary manifestations of SARS, Influenza, MERS, and COVID-19., Discussion: Several studies have reported extra-pulmonary conditions in patients diagnosed with SARS, Influenza, MERS, and COVID-19, either by direct viral injury or from the systemic response to the initial infection., Conclusion: SARS, Influenza, MERS, and COVID-19 have all been associated with dysfunction of kidneys, endocrine system, neuromuscular symptoms, perinatal complications, and myocardial injury. Progression from pulmonary disease to a systemic condition has a poor outcome and can result in multi-organ failure.

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has been accompanied by various gastrointestinal (GI) and renal manifestations in significant portion of infected patients. Beside studies on the respiratory complications of coronavirus infection, understanding the essential immunological processes underlying the different clinical manifestations of virus infection is crucial for the identification and development of effective therapies. In addition to the respiratory tract, the digestive and urinary systems are the major sources of virus transmission. Thus, knowledge about the invasion mechanisms of SARS-CoV-2 in these systems and the immune system responses is important for implementing the infection prevention strategies. This article presents an overview of the gut and renal complications in SARS-CoV-2 infection. We focus on how SARS-CoV-2 interacts with the immune system and the consequent contribution of immune system, gut, and renal dysfunctions in the development of disease., (© 2020 The Scandinavian Foundation for Immunology.)

The current pandemic of SARS-COV 2 infection (Covid-19) is challenging health systems and communities worldwide. At the individual level, the main biological system involved in Covid-19 is the respiratory system. Respiratory complications range from mild flu-like illness symptoms to a fatal respiratory distress syndrome or a severe and fulminant pneumonia. Critically, the presence of a pre-existing cardiovascular disease or its risk factors, such as hypertension or type II diabetes mellitus, increases the chance of having severe complications (including death) if infected by the virus. In addition, the infection can worsen an existing cardiovascular disease or precipitate new ones. This paper presents a contemporary review of cardiovascular complications of Covid-19. It also specifically examines the impact of the disease on those already vulnerable and on the poorly resourced health systems of Africa as well as the potential broader consequences on the socio-economic health of this region., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

SARS-CoV-2 infection, resulting in Coronavirus disease 2019 (COVID-19), has significantly affected the entire world. It was labelled a pandemic by World Health Organization. Although it commonly produces respiratory symptoms, neurological features have been described. Neurological manifestations may vary from non-specific symptoms such as headache, dizziness, myalgia and/or fatigue, olfactory or taste dysfunction to specific syndromes including meningitis, stroke, acute transverse myelitis and Guillain-Barre syndrome. This review describes potential pathogenetic mechanisms and neurological manifestations of COVID-19 along with its management. Considering structural and pathogenetic similarity of SARS-CoV-2 with SARS-CoV and MERS viruses, we compared their neurological manifestations and mentioned few features expected in COVID-19 in future. Interestingly, many COVID-19 cases may present with pure neurological manifestations at onset with non-neurological features manifesting few days later and we propose the term "Neuro-COVID syndrome" for such cases. Awareness of neurological manifestations may facilitate its management and improve outcome in such patients.

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

Lymphopenia is commonly observed in SARS and COVID-19 patients although the lymphocyte count is not always below 0.8 × 10 9 /L in all the patients. It is suggested that lymphopenia serves as a useful predictor for prognosis in the patients. It is also hypothesized that lymphopenia is related to glucocorticoids and apoptosis. However, the ordering between lymphopenia and apoptosis appears different between SARS and COVID-19 patients, ie, lymphopenia is prior to apoptosis in SARS patients whereas apoptosis is prior to lymphopenia in COVID-19 patients. This paper attempts to figure out this contradiction through three players, lymphopenia, glucocorticoids, and apoptosis. Although the literature does not provide a solid explanation, the level of glucocorticoids could determine the ordering between lymphopenia and apoptosis because the administration of high doses of glucocorticoids could lead to lymphopenia whereas low doses of glucocorticoids could benefit patients. In the meantime, this paper raises several questions, which need to be answered in order to better understand the whole course of COVID-19., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Introduction: The past two decades have been marked by three epidemics linked to emerging coronaviruses. The COVID-19 pandemic highlighted the existence of neurological manifestations associated with SARS-CoV-2 infection and raised the question of the neuropathogenicity of coronaviruses. The aim of this review was to summarize the current data about neurological manifestations and diseases linked to human coronaviruses., Material and Methods: Articles have been identified by searches of PubMed and Google scholar up to September 25, 2020, using a combination of coronavirus and neurology search terms and adding relevant references in the articles., Results: We found five cohorts providing prevalence data of neurological symptoms among a total of 2533 hospitalized COVID-19 patients, and articles focusing on COVID-19 patients with neurological manifestations including a total of 580 patients. Neurological symptoms involved up to 73% of COVID-19 hospitalized patients, and were mostly headache, myalgias and impaired consciousness. Central nervous system (CNS) manifestations reported in COVID-19 were mostly non-specific encephalopathies that represented between 13% and 40% of all neurological manifestations; post-infectious syndromes including acute demyelinating encephalomyelitis (ADEM, n=13), acute necrotizing encephalopathy (ANE, n=4), Bickerstaff's encephalitis (n=5), generalized myoclonus (n=3) and acute transverse myelitis (n=7); other encephalitis including limbic encephalitis (n=9) and miscellaneous encephalitis with variable radiologic findings (n=26); acute cerebrovascular diseases including ischemic strokes (between 1.3% and 4.7% of COVID-19 patients), hemorrhagic strokes (n=17), cerebral venous thrombosis (n=8) and posterior reversible encephalopathy (n=5). Peripheral nervous system (PNS) manifestations reported in COVID-19 were the following: Guillain-Barré syndrome (n=31) and variants including Miller Fisher syndrome (n=3), polyneuritis cranialis (n=2) and facial diplegia (n=2); isolated oculomotor neuropathy (n=6); critical illness myopathy (n=6). Neuropathological studies in COVID-19 patients demonstrated different patterns of CNS damage, mostly ischemic and hemorrhagic changes with few cases of inflammatory injuries. Only one case suggested SARS-CoV-2 infiltration in endothelial and neural cells. We found 10 case reports or case series describing 22 patients with neurological manifestations associated with other human coronaviruses. Among them we found four MERS patients with ADEM or Bickerstaff's encephalitis, two SARS patients with encephalitis who had a positive SARS-CoV PCR in cerebrospinal fluid, five patients with ischemic strokes associated with SARS, eight MERS patients with critical illness neuromyopathy and one MERS patient with Guillain-Barré Syndrome. An autopsy study on SARS-CoV patients demonstrated the presence of the virus in the brain of eight patients., Conclusion: The wide range of neurological manifestations and diseases associated with SARS-CoV-2 is consistent with multiple pathogenic pathways including post-infectious mechanisms, septic-associated encephalopathies, coagulopathy or endothelitis. There was no definite evidence to support direct neuropathogenicity of SARS-CoV-2., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

COVID-19 has spread worldwide, including the United States, United Kingdom, and Italy, along with its site of origin in China, since 2020. The virus was first found in the Wuhan seafood market at the end of 2019, with a controversial source. The clinical symptoms of COVID-19 include fever, cough, and respiratory tract inflammation, with some severe patients developing an acute and chronic lung injury, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). It has already claimed approximately 300 thousand human lives and the number is still on the rise; the only way to prevent the infection is to be safe till vaccines and reliable treatments develop. In previous studies, the use of mesenchymal stem cells (MSCs) in clinical trials had been proven to be effective in immune modulation and tissue repair promotion; however, their efficacy in treating COVID-19 remains underestimated. Here, we report the findings from past experiences of SARS and MSCs, and how SARS could also induce PF. Such studies may help to understand the rationale for the recent cell-based therapies for COVID-19.

Introduction: The novel Coronavirus Disease (COVID-19) outbreak currently puts health care workers at high risk of both physical and mental health problems. This study aimed to identify the risk and protective factors for mental health outcomes in health care workers during coronavirus epidemics., Methods: A rapid systematic review was performed in three databases (March 24, 2020) and a current COVID-19 resource (May 28, 2020). Following study selection, study characteristics and effect measures were tabulated, and data were synthesized by using vote counting. Meta-analysis was not possible because of high variation in risk factors, outcomes and effect measures. Risk of bias of each study was assessed and the certainty of evidence was appraised according to the GRADE methodology., Results: Out of 2605 references, 33 observational studies were selected and the identified risk and protective factors were categorized in ten thematic categories. Most of these studies (n = 23) were performed during the SARS outbreak, seven during the current COVID-19 pandemic and three during the MERS outbreak. The level of disease exposure and health fear were significantly associated with worse mental health outcomes. There was evidence that clear communication and support from the organization, social support and personal sense of control are protective factors. The evidence was of very low certainty, because of risk of bias and imprecision., Conclusion: Safeguarding mental health of health care workers during infectious disease outbreaks should not be treated as a separate mental health intervention strategy, but could benefit from a protective approach. This study suggests that embedding mental health support in a safe and efficient working environment which promotes collegial social support and personal sense of control could help to maximize resilience of health care workers. Low quality cross-sectional studies currently provide the best possible evidence, and further research is warranted to confirm causality., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: the activities of the Belgian Red Cross include the provision of psychosocial first aid to laypeople. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The novel coronavirus (SARS-CoV-2) has distinct clinical manifestations that can vary from an asymptomatic condition to severe acute respiratory failure. Phenotypes are attributable to different pathophysiological mechanisms and require different treatment strategies. The assessment and identification of different phenotypes can guide therapy configurations such as oxygen therapy, non-invasive ventilation, airway management, and tracheal intubation. Further studies are essential to provide information on the influence of phenotypes in the decision of rehabilitation strategies. The sequelae left in the respiratory system of COVID-19 survivors and its limitations will be a challenge for rehabilitation services worldwide. Lung injuries are directly related to the phenotypes presented, and depending on the degree of these injuries, rehabilitation strategies can be targeted. We believe that differentiating patients, according to their respective phenotypes, can improve decision-making in treatment and individualized rehabilitation.

Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease that has quickly become a worldwide threat to health, mainly causing severe acute respiratory syndrome. In addition to the widely described respiratory syndrome, COVID-19 may cause life-treating complications directly or indirectly related to this infection. Among these, thrombotic complications have emerged as an important issue in patients with COVID-19 infection, particularly in patients in intensive care units. Thrombotic complications due to COVID-19 are likely to occur due to a pro-coagulant pattern encountered in some of these patients or to a progressive endothelial thrombo-inflammatory syndrome causing microvascular disease. In the present authors' experience, from five different hospitals in Italy and the UK, imaging has proved its utility in identifying these COVID-19-related thrombotic complications, with translational clinical relevance. The aim of this review is to illustrate thromboembolic complications directly or indirectly related to COVID-19 disease. Specifically, this review will show complications related to thromboembolism due to a pro-coagulant pattern from those likely related to an endothelial thrombo-inflammatory syndrome., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments., (© 2020 Published by Elsevier Inc.)

Purpose: The first case of coronavirus disease 2019 (COVID-19) was identified and confirmed in December 2019 in Wuhan, China. COVID-19 is gradually posing a serious threat to global public health. In this review the characteristics and mechanism of kidney injury caused by SARS-CoV, MERS-CoV and SARS-CoV-2 infection are summarized and contrasted. In particular, urine-oral transmission, prevention and management of the kidney injury caused by SARS-CoV-2 are emphasized., Materials and Methods: We searched PubMed® for English language articles published since 2003 with the keywords "SARS," "MERS," "COVID-19" or "kidney injury." ClinicalTrials.gov was queried for ongoing studies. We also used relevant data from websites, including the Centers for Disease Control and Prevention and European Centre for Disease Prevention and Control., Results: Similar to 2 other coronaviruses including SARS-CoV and MERS-CoV, SARS-CoV-2 caused severe respiratory syndrome with rapid progression and kidney injury. The infection process of SARS-CoV-2 is mediated by specifically binding to angiotensin-converting enzyme 2. Cases of COVID-19 combined with kidney impairment are associated with a higher risk of mortality than those without comorbidities. The pathological changes of the kidney are mainly due to local SARS-CoV-2 replication or indirectly by pro-inflammatory cytokine response. In addition, studies have confirmed the isolation of infectious SARS-CoV-2 in urine, raising the possibility of urine-oral transmission. Ultimately this is significant for preventing potential urine-oral transmission and improving the cure rate of acute kidney injury with COVID-19., Conclusions: Emerging evidence supports that in patients with SARS-CoV-2 infections the prevalence of kidney injury is high and usually leads to a poor prognosis. Optimal prevention and management of kidney injury will benefit patients with COVID-19.

A recent genetic association study 1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative) 2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.

Coronaviruses cause respiratory and gastrointestinal disorders in animals and humans. The current SARS-CoV-2, the COVID-19 infectious agent, belongs to a subgroup called betacoronavirus including the SARS-CoV and MERS-CoV responsible for epidemics in 2002 and 2012, respectively. These viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ACE2) expressed in neurons and glial cells. Infections with SARS-CoV, MERS-CoV, and now SARS-CoV-2 also produce neurological signs such as acute cerebrovascular disease, impaired consciousness, and muscle injury, as well as dizziness, hypogeusia, hyposmia, hypoxia, neuralgia, and hypoxic encephalopathy. For this reason, close attention should be paid to the neurological manifestations of COVID-19 patients.

An 18-year-old man presented with persistent isolated headache 2 weeks after recovering from acute COVID-19 illness. Extensive cerebral venous sinus thrombosis (CVST) was detected on CT venogram despite him having no other thrombotic risk factors. CVST can complicate COVID-19. A high index of clinical suspicion is warranted as it can often have a subtle presentation with paucity of neurological symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 60-year-old man presented with sudden onset right-sided chest pain and gradually worsening shortness of breath on exertion. Eleven days earlier, he had an admission with COVID-19 pneumonitis requiring 8 days of continuous positive airway pressure. He was tachypnoeic with a respiratory rate of 24 breaths/min, oxygen saturations on room air of 91%. Examination revealed reduced air entry and a resonant percussion note over the right hemithorax. Chest radiograph suggested a complex right pneumothorax; however, a CT chest was notable for widespread right-sided bullous lung disease. After a day of observation on a COVID-19 ward (and a repeat radiograph with a stable appearance), he was discharged with a 2-week follow-up with the respiratory team, safety netting advice and ambulatory oxygen. This case suggests that bullous lung disease may be a complication of severe COVID-19 pneumonitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19. Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications., Methods: This systematic review serves to summarize available information regarding the potential effects of different types of CoV on the nervous system and describes the range of clinical neurological complications that have been reported thus far in COVID-19., Results: Two hundred and twenty-five studies on CoV infections associated neurological manifestations in human were reviewed. Of those, 208 articles were pertinent to COVID-19. The most common neurological complaints in COVID-19 were anosmia, ageusia, and headache, but more serious complications, such as stroke, impairment of consciousness, seizures, and encephalopathy, have also been reported., Conclusion: There are several similarities between neurological complications after SARS-CoV-1, MERS-CoV and COVID-19, however, the scope of the epidemics and number of patients are very different. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Accordingly, comprehensive knowledge of these complications will help health care providers to be attentive to these complications and diagnose and treat them timely., Competing Interests: Declaration of Competing Interest Authors have no relevant financial disclosure to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in late 2019 and has led to an ongoing pandemic. COVID-19 typically affects the respiratory tract and mucous membranes, leading to pathological involvement of various organ systems. Although patients usually present with fever, cough, and fatigue, less common manifestations have been reported including symptoms arising from thrombosis and thromboembolism. A spectrum of dermatologic changes is becoming recognized in patients with COVID-19 who initially present with respiratory symptoms. The mechanism behind these manifestations remains unclear. This report presents the case of a 47-year-old Hispanic man who developed cutaneous vasculitic lesions and gangrene of the toes following admission to hospital with COVID-19 pneumonia. CASE REPORT COVID-19 has been associated with cardiovascular disease entities including stroke, acute coronary syndrome, venous thromboembolism, and peripheral vascular disease. We present a case in which a 47-year-old Hispanic man arrived at the Emergency Department with COVID-19 and was admitted for respiratory failure. Despite anticoagulation initiated on admission in the presence of an elevated D-dimer, the patient developed gangrene of all his toes, which required bilateral transmetatarsal amputation. CONCLUSIONS This case shows that dermatologic manifestations may develop in patients who initially present with COVID-19 pneumonia. These symptoms may be due to venous thrombosis following SARS-CoV-2 vasculitis, leading to challenging decisions regarding anticoagulation therapy. Randomized controlled trials are needed to evaluate the efficacy of anticoagulation, to choose appropriate anticoagulants and dosing, and to assess bleeding risk.

In 2020 during the CoronaVirus Disease19 (COVID19) pandemic caused by da SARS-CoV-2, the weakness of e-health (electronic health) (ie the lack of direct contact between physician and patient) may prove to be a strength, given the high contagiousness and relative lethality of the virus. In Italy the lack of preparation for supporting the patient load (shortage of personal protection devices, shortage of Intensive Care Unit) beds in comparison with other European Countries, and the poor early diagnostic and therapeutic activity has led us to suggest a project that uses an online platform between General Practitioners and patients in order to reduce moving infected individuals and to perform the diagnosis and treatment early on., (© 2020 John Wiley & Sons Ltd.)

Respiratory failure and acute kidney injury (AKI) are associated with high mortality in SARS-CoV-2-associated Coronavirus disease 2019 (COVID-19). These manifestations are linked to a hypercoaguable, pro-inflammatory state with persistent, systemic complement activation. Three critical COVID-19 patients recalcitrant to multiple interventions had skin biopsies documenting deposition of the terminal complement component C5b-9, the lectin complement pathway enzyme MASP2, and C4d in microvascular endothelium. Administration of anti-C5 monoclonal antibody eculizumab led to a marked decline in D-dimers and neutrophil counts in all three cases, and normalization of liver functions and creatinine in two. One patient with severe heart failure and AKI had a complete remission. The other two individuals had partial remissions, one with resolution of his AKI but ultimately succumbing to respiratory failure, and another with a significant decline in FiO 2 requirements, but persistent renal failure. In conclusion, anti-complement therapy may be beneficial in at least some patients with critical COVID-19., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Since December 2019, the world is affected by an outbreak of a new disease named COVID-19, which is an acronym of 'coronavirus disease 2019'. Coronaviruses (CoV) were assumed to be associated with mild upper respiratory tract infections, such as common cold. This perception changed in time due to occurrence of the Severe Acute Respiratory Syndrome (SARS) caused by SARS-CoV in 2002 and the Middle East Respiratory Syndrome (MERS) caused by MERS-CoV in 2012, both inducing an epidemic severe viral pneumonia with potentially respiratory failure and numerous extra-pulmonary manifestations. The novel coronavirus, SARS-CoV-2, is likewise a causative pathogen for severe viral pneumonia with the risk of progression to respiratory failure and systemic manifestations. In this review, we will give a summary of the neurological manifestations due to SARS and MERS, as those might predict the neurological outcome in the novel COVID-19. Additionally, we provide an overview of the current knowledge concerning neurological manifestations associated with COVID-19, to the extent that literature is already available as the pandemic is still ongoing.

Coronavirus infection disease-2019 (COVID-19) gained worldwide fame after deadly outbreak in China and its subsequent spread to many countries. So far, COVID-19 is not fully contained, and new cases are arising on daily bases in various countries. Due to zoonotic nature and human-to-human spread, COVID-19 is considered pandemic with more causalities in developing countries. Full genome analysis revealed its resemblance with severe acute respiratory syndrome (SARS) virus with minor variation in non-structural proteins. Both viruses use the common angiotensin converting enzyme (ACE2) receptor to attach to the epithelial cells of the target organs. Currently, COVID-19 patients are treated with drugs that are used for lungs infections. However, ACE2 has high expression in other human organs such as kidney and testes. Thus, it is assumed that, like SARS, it may have adverse effects on other vital organs, which have dominant expression of ACE2. In testis, SARS affected patients displayed peritubular fibrosis, extensive germ cell disruption, damage of blood-testis barrier integrity and more frequent occurrence of apoptosis. Here, we critically discuss the possible adverse effects of COVID-19 on the testes of patients along with future precautions to overcome the complications of reproductive organs. Key Words: COVID-19; SARS; ACE2, Testes.

BACKGROUND The novel coronavirus disease (COVID-19) has been declared a pandemic. With the ever-increasing number of COVID-19 patients, it is imperative to explore the factors related to the disease to aid patient management until a definitive vaccine is ready, as the disease is not limited to the respiratory system alone. COVID-19 has been associated with various cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The infection is severe in patients with pre-existing cardiovascular disease, and a systemic inflammatory response due to a cytokine storm in severe COVID-19 cases can lead to acute myocardial infarction. CASE REPORT We present the case of a 56-year-old man with cardiovascular risk factors including coronary artery disease, hypertension, ischemic cardiomyopathy, and hyperlipidemia, who had COVID-19-induced pneumonia complicated with acute respiratory distress syndrome. He subsequently developed myocardial infarction during his hospitalization at our facility. He had a significant contact history for COVID-19. He was managed with emergent cardiac revascularization after COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction testing from a nasopharyngeal swab as per hospital policy for admitted patients. Apart from dual antiplatelet therapy, tocilizumab therapy was initiated due to the high interleukin-6 levels. His hospitalization was complicated by hemodialysis and failed extubation and intubation, resulting in a tracheostomy. Upon improvement, he was discharged to a long-term facility with a plan for outpatient follow-up. CONCLUSIONS In high-risk patients with COVID-19-induced pneumonia and cardiovascular risk factors, a severe systemic inflammatory response can lead to atherosclerotic plaque rupture, which can manifest as acute coronary syndrome.

BACKGROUND Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis. Effective anticoagulation therapy may play a dominant role in the management of severe COVID-19 cases. CASE REPORT A 73-year-old man with a 6-day history of fever up to 38.5°C, dyspnea, cough, and fatigue was diagnosed with COVID-19. He had a past medical history significant for hypertension and coronary artery bypass grafting. Two days after hospital admission, the patient developed acute respiratory failure, requiring intubation, mechanical ventilation, and transfer to the intensive care unit (ICU). He received treatment including antibiotics, hydroxychloroquine, tocilizumab, vasopressors, prone positioning, and anticoagulation with enoxaparin at a prophylactic dose. After a 15-day ICU stay, the patient was hemodynamically stable but still hypoxemic; a transthoracic echocardiogram at that time, followed by a transesophageal echocardiogram for better evaluation, revealed the presence of a right atrium thrombus without signs of acute right ventricular dilatation and impaired systolic function. Since the patient was hemodynamically stable, we decided to treat him with conventional anticoagulation under close monitoring for signs of hemodynamic deterioration; thus, the prophylactic dose of enoxaparin was replaced by therapeutic dosing, which was a key component of the patient's successful outcome. Over the next few days he showed significant clinical improvement. The follow-up transesophageal echocardiogram 3 weeks after effective therapeutic anticoagulation revealed no signs of right heart thrombus. CONCLUSIONS The presented COVID-19 case, one of the first reported cases with evidence of right heart thrombus by transesophageal echocardiography, highlights the central role of diagnostic imaging strategies and the importance of adequate anticoagulation therapy in the management of severe COVID-19 cases in the ICU.