Human Monkeypox: A Comprehensive Narrative Review and Analysis of the Public Health Implications.

Recently, numerous cases of monkeypox were reported from several non-endemic countries in Europe, North America, and Oceania, suggesting an unusual and alarming public health issue, particularly considering that the disease is not directly related to human or animal travels. Attention is currently being drawn to this phenomenon since more than 70% of the global population is no longer vaccinated against smallpox. Indeed, the smallpox vaccination also confers some indirect degree of protection against other poxviruses, including monkeypox. We performed a narrative review to describe the existing literature with regard to monkeypox using the MEDLINE, EMBASE, and Scopus databases. This review aims to provide updated evidence of findings on the epidemiology, clinical features, diagnosis, management, and prevention of monkeypox, also considering the concurrent zoonotic pandemic caused by the COVID-19 coronavirus, SARS-CoV-2.

What are the recommendations for returning athletes who have experienced long term COVID-19 symptoms?

Currently, there is limited research reporting the symptoms of long COVID among athletes, and the recommendations for athletes returning to competition/training who have experienced long COVID symptoms. Therefore, the aim of this systematic review is to synthesise the recommendations for returning athletes who have experienced long COVID symptoms. The protocol was registered in PROSPERO under CRD42021265939. Two authors searched the electronic databases PubMed, Embase, Scopus, the Cochrane Library, Web of Science, CINAHL, PsycINFO, and SPORTDiscus from August 2019-July 2021. Search terms included words related to "long COVID", "athlete" and "return". Data extraction was completed for each study by two independent investigators for: (1) first author name; (2) year of publication; (3) journal; (4) Definition of athlete (i.e. elite or non-elite) (5) Recommendations reported. A total of 220 records were found. Following title and abstract screening, 61 studies were eligible for full text screening. Overall, no studies, commentaries, editorials or reviews provided specific recommendations for "long COVID" defined as COVID-19 signs and symptoms lasting for over 4 weeks as a result of COVID-19 infection. In addition, we found no studies which reported symptoms of athletes suffering from long COVID. Despite the lack of evidence, we did find eight separate professional recommendations for managing "long-term effects" and "ongoing" or "prolonged" symptoms and COVID-19 complications among athletes. Practitioners should be aware of both mental and physical symptoms of long COVID, and additional considerations may be required for athletes who have undergone intensive care. The present review provides a list of recommendations based on existing literature that may be followed and implemented for returning athletes.Key MessagesFurther research, including longitudinal research of athletes who have tested positive for COVID-19, is required to develop evidenced-based guidelines for athletes with ongoing COVID-19 symptoms.Prior to returning to play after COVID-19 infection, a thorough medical history, physical and psychological examination should be conducted by a medical professional.Athletes should continue to monitor and record their own physical and psychological markers of health.

Autoimmunity roots of the thrombotic events after COVID-19 vaccination.

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

Urgent Need for Field Surveys of Coronaviruses in Southeast Asia to Understand the SARS-CoV-2 Phylogeny and Risk Assessment for Future Outbreaks.

Phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on a single isolate of bat coronaviruses (bat CoVs) which does not adequately represent genetically related coronaviruses (CoVs) [...].

COVID-19 Vaccines and Thrombosis-Roadblock or Dead-End Street?

Two adenovirus-based vaccines, ChAdOx1 nCoV-19 and Ad26.COV2.S, and two mRNA-based vaccines, BNT162b2 and mRNA.1273, have been approved by the European Medicines Agency (EMA), and are invaluable in preventing and reducing the incidence of coronavirus disease-2019 (COVID-19). Recent reports have pointed to thrombosis with associated thrombocytopenia as an adverse effect occurring at a low frequency in some individuals after vaccination. The causes of such events may be related to SARS-CoV-2 spike protein interactions with different C-type lectin receptors, heparan sulfate proteoglycans (HSPGs) and the CD147 receptor, or to different soluble splice variants of the spike protein, adenovirus vector interactions with the CD46 receptor or platelet factor 4 antibodies. Similar findings have been reported for several viral diseases after vaccine administration. In addition, immunological mechanisms elicited by viral vectors related to cellular delivery could play a relevant role in individuals with certain genetic backgrounds. Although rare, the potential COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) requires immediate validation, especially in risk groups, such as the elderly, chronic smokers, and individuals with pre-existing incidences of thrombocytopenia; and if necessary, a reformulation of existing vaccines.

Schistosomal appendicitis: Case series and systematic literature review.

BACKGROUND: Globally, schistosomiasis affects at least 240 million people each year with a high proportion of cases in sub-Saharan Africa. The infection presents a wide range of symptoms mainly at the gastrointestinal and urogenital level. Cases of schistosomiasis-related appendicitis are seldom reported. The aim of the present study is to identify the prevalence of schistosomiasis-related appendicitis in Beira, Mozambique and compare to global prevalence. METHODS: We retrospectively reviewed all cases of appendicitis recorded from January 2017 to March 2020 at a single pathology department located in Beira in order to assess the prevalence of schistosomiasis. Moreover, we performed a systematic review on the prevalence of schistosomiasis-related appendicitis in all countries. FINDINGS: A total of 145 appendicitis cases in Beira showed a 13.1% prevalence of schistosomal-related appendicitis. The mean age of patients was 29.1 years, and 14 (73.7%) were male. The systematic review identified 20 studies with 34,790 inpatients with schistosomiasis-related appendicitis with a global prevalence of 1.31% (95% confidence interval (CI): 0.72 to 2.06); a high heterogeneity (I2 = 96.0%) was observed. Studies carried out in Africa reported a significantly higher prevalence of schistosomiasis-related appendicitis (2.75%; 95% CI: 1.28 to 4.68) than those in Middle East (0.49%; 95% CI: 0.18 to 0.95) (p for interaction < 0.0001). CONCLUSIONS: Schistosomiasis infection should be considered as possible cause of appendicitis not only in endemic areas but also in developed countries. Considering that prevention is the best way to control the infection, more efforts should be put in place in order to increase the prevention coverage and avoid the cascading implications for health. This is even more so important in this Coronavirus Disease 2019 (COVID-19) era where the majority of attention and funds are used to fight the pandemic.

Laparoscopy in Low-Income Countries: 10-Year Experience and Systematic Literature Review.

Laparoscopy is a procedure that ultimately reduces hospital stay time and speeds up post-operative recovery. It is mainly performed in high-income countries but its implementation in many low- and middle-income countries (LMICs) is increasing. However, no aggregate data exist regarding the outcomes of this procedure in resource-limited settings. We retrospectively reviewed all cases of laparoscopy recorded from January 2007 to March 2017 at the Department of Surgery of Beira to assess the related outcomes. Moreover, we performed a systematic review of the laparoscopic practices and outcomes in low-income countries. Data from the Department of Surgery of Beira identified 363 laparoscopic procedures, mainly relating to gynecological diseases, cholelithiasis, and appendicectomy with only a 1.6% complication rate (6 cases) and a 1.9% conversion rate (7 cases) to open surgery. The systematic review showed a pooled risk of overall complications significantly lower in laparoscopic vs. open appendicectomy (OR = 0.43; 95% CI 0.19-0.97; I2 = 85.7%) and a significantly lower risk of infection (OR = 0.53; 95% CI 0.43-0.65; I2 = 0.00%). The pooled SMD in operation duration in laparoscopic vs. open appendectomy was 0.58 (95% CI -0.00; 1.15; I2 = 96.52), while the pooled SMD in hospitalization days was -1.35 (95% CI -1.87; -0.82; I2 = 96.41). Laparoscopy is an expensive procedure to adopt as it requires new equipment and specialized trained health workers. However, it could reduce post-operative costs and complications, especially in terms of infections. It is crucial to increase its accessibility, acceptability, and quality particularly in LMICs, especially during this COVID-19 era when the reduction of patient hospitalization is essential.

Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2.

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19.

A unique view of SARS-CoV-2 through the lens of ORF8 protein.

Immune evasion is one of the unique characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributed to its ORF8 protein. This protein modulates the adaptive host immunity through down-regulation of MHC-1 (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the host's interferon-mediated antiviral response. To understand the host's immune perspective in reference to the ORF8 protein, a comprehensive study of the ORF8 protein and mutations possessed by it have been performed. Chemical and structural properties of ORF8 proteins from different hosts, such as human, bat, and pangolin, suggest that the ORF8 of SARS-CoV-2 is much closer to ORF8 of Bat RaTG13-CoV than to that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 in SARS-CoV-2 can be grouped into four classes based on their predicted effects (Hussain et al., 2021) [1]. Based on the geo-locations and timescale of sample collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were found upon sequence similarity analyses and consideration of the amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of the rapidly evolving SARS-CoV-2 through the ORF8.

Hand-Washing Practices among Adolescents Aged 12-15 Years from 80 Countries.

The objectives were to (1) assess the prevalence of hand-washing practices across 80 countries and (2) assess frequency of hand-washing practice by economic status (country income and severe food insecurity), in a global representative sample of adolescents. Cross-sectional data from the Global School-based Student Health Survey 2003-2017 were analyzed. Data on age, sex, hand-washing practices in the past 30 days, and severe food insecurity (i.e., proxy of socioeconomic status) were self-reported. Multivariable logistic regression and meta-analysis with random effects based on country-wise estimates were conducted to assess associations. Adolescents (n = 209,584) aged 12-15 years [mean (SD) age 13.8 (1.0) years; 50.9% boys] were included in the analysis. Overall, the prevalence of hand-washing practices were as follows: never/rarely washing hands before eating (6.4%), after using toilet (5.6%), or with soap (8.8%). The prevalence of never/rarely washing hands after using the toilet (10.8%) or with soap (14.3%) was particularly high in low-income countries. Severe food insecurity was associated with 1.34 (95%CI = 1.25-1.43), 1.61 (95%CI = 1.50-1.73), and 1.44 (95%CI = 1.35-1.53) times higher odds for never/rarely washing hands before eating, after using the toilet, and with soap, respectively. A high prevalence of inadequate hand washing practices was reported, particularly in low-income countries and those with severe food insecurity. In light of the present COVID-19 pandemic and the rapid expansion being observed in low- and middle-income locations, interventions that disseminate good hand-washing practices are urgently required. Such interventions may also have cross-over benefits in relation to other poor sanitation-related diseases.

Child Undernutrition in Sudan: The Social and Economic Impact and Future Perspectives.

The nutrition situation in Sudan is one of the worst in northeast Africa and it is characterized by persistently high levels of acute and chronic malnutrition that have increased over the last two decades. The underlying causes of malnutrition are multi-sectoral and are mainly due to inequalities, inadequate food practices, and limited access to healthcare services. Based on the report The Economic and Social Impacts of Child Undernutrition in Sudan, this study assesses the impact that malnutrition has on health, education, and productivity in Sudan. The country is estimated to have lost an equivalent of about 11.6 billion Sudanese pound (1 United States dollar = 55.3 Sudanese pound) in 2014, which represented 2.6% of the gross domestic product (GDP). Productivity-related losses contributed the largest costs at 1.5% of GDP followed by health and education sectors at 1.1% and 0.1%, respectively. In 2020, the outbreak of the COVID-19 pandemic further exposed the fragility of Sudan's health, social, and economic system. It is mandatory that all stakeholders address child nutrition as a main concern and stunting is incorporated in the center of the development agenda. In particular, the national development frameworks should be updated to ensure the reduction of the stunting prevalence and to put in place a comprehensive multi-sectoral nutrition policy, strategy, and plan of action.

COVID-19, an Opportunity for Developing Countries?

The COVID-19 outbreak was declared by the World Health Organization (WHO) as global pandemic in March 2020. Considering the necessity to implement rapid response to control the pandemic and the fragility and the state of need of low income countries, it will be mandatory to develop a global approach in order to reduce the spread of infection and the creation of community viral reservoirs. So far, we could hypothesize a worst case scenario in which when the COVID-19 outbreak hits a peak in Africa and in low-income countries, the majority of such countries will be unprepared, with low resources allocated for affording the viral emergency and the consequences will be catastrophic with no lesson learnt. In the best case scenario, the COVID-19 will not affect Africa or South America on a large scale and, if the prevention measures will be implemented, we could register a lower incidence of hygiene linked diseases that still represent leading causes of death.

Viewpoint: Origin of SARS-CoV-2.

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational "hot spot" as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required.

Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features.

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

The structural basis of accelerated host cell entry by SARS-CoV-2†.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other human coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium, and this, in turn, allows faster viral 'surfing' of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2.

Viewpoint: Origin of SARS-CoV-2

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational “hot spot”as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required

Malaria and COVID-19: Common and Different Findings.

Malaria and COVID-19 may have similar aspects and seem to have a strong potential for mutual influence. They have already caused millions of deaths, and the regions where malaria is endemic are at risk of further suffering from the consequences of COVID-19 due to mutual side effects, such as less access to treatment for patients with malaria due to the fear of access to healthcare centers leading to diagnostic delays and worse outcomes. Moreover, the similar and generic symptoms make it harder to achieve an immediate diagnosis. Healthcare systems and professionals will face a great challenge in the case of a COVID-19 and malaria syndemic. Here, we present an overview of common and different findings for both diseases with possible mutual influences of one on the other, especially in countries with limited resources.

Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature.

The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.