Effects of Regular Physical Activity on the Immune System, Vaccination and Risk of Community-Acquired Infectious Disease in the General Population: Systematic Review and Meta-Analysis.

BACKGROUND: Regular physical activity is the prime modality for the prevention of numerous non-communicable diseases and has also been advocated for resilience against COVID-19 and other infectious diseases. However, there is currently no systematic and quantitative evidence synthesis of the association between physical activity and the strength of the immune system. OBJECTIVE: To examine the association between habitual physical activity and (1) the risk of community-acquired infectious disease, (2) laboratory-assessed immune parameters, and (3) immune response to vaccination. METHODS: We conducted a systemic review and meta-analysis according to PRISMA guidelines. We searched seven databases (MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CINAHL, PsycINFO, and SportDiscus) up to April 2020 for randomised controlled trials and prospective observational studies were included if they compared groups of adults with different levels of physical activity and reported immune system cell count, the concentration of antibody, risk of clinically diagnosed infections, risk of hospitalisation and mortality due to infectious disease. Studies involving elite athletes were excluded. The quality of the selected studies was critically examined following the Cochrane guidelines using ROB2 and ROBINS_E. Data were pooled using an inverse variance random-effects model. RESULTS: Higher level of habitual physical activity is associated with a 31% risk reduction (hazard ratio 0.69, 95% CI 0.61-0.78, 6 studies, N = 557,487 individuals) of community-acquired infectious disease and 37% risk reduction (hazard ratio 0.64, 95% CI 0.59-0.70, 4 studies, N = 422,813 individuals) of infectious disease mortality. Physical activity interventions resulted in increased CD4 cell counts (32 cells/µL, 95% CI 7-56 cells/µL, 24 studies, N = 1112 individuals) and salivary immunoglobulin IgA concentration (standardised mean difference 0.756, 95% CI 0.146-1.365, 7 studies, N = 435 individuals) and decreased neutrophil counts (704 cells/µL, 95% CI 68-1340, 6 studies, N = 704 individuals) compared to controls. Antibody concentration after vaccination is higher with an adjunct physical activity programme (standardised mean difference 0.142, 95% CI 0.021-0.262, 6 studies, N = 497 individuals). CONCLUSION: Regular, moderate to vigorous physical activity is associated with reduced risk of community-acquired infectious diseases and infectious disease mortality, enhances the first line of defence of the immune system, and increases the potency of vaccination. PROTOCOL REGISTRATION: The original protocol was prospectively registered with PROSPERO (CRD42020178825).

An Updated Review on SARS-CoV-2 Main Proteinase (MPro): Protein Structure and Small-Molecule Inhibitors.

[Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses with spike (S) protein projections that allow the virus to enter and infect host cells. The S protein is a key virulence factor determining viral pathogenesis, host tropism, and disease pathogenesis. There are currently diverse corona viruses that are known to cause disease in humans. The occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), as fatal human CoV diseases, has induced significant interest in the medical field. The novel coronavirus disease (COVID-19) is an infectious disease caused by a novel strain of coronavirus (SAR-CoV-2). The SARS-CoV2 outbreak has been evolved in Wuhan, China, in December 2019, and identified as a pandemic in March 2020, resulting in 53.24 M cases and 1.20M deaths worldwide. SARS-CoV-2 main proteinase (MPro), a key protease of CoV-2, mediates viral replication and transcription. SARS-CoV-2 MPro has been emerged as an attractive target for SARS-CoV-2 drug design and development. Diverse scaffolds have been released targeting SARS-CoV-2 MPro. In this review, we culminate the latest published information about SARS-CoV-2 main proteinase (MPro) and reported inhibitors.

Potency of Mesenchymal Stem Cell and Its Secretome in Treating COVID-19.

Abstract: The COVID-19 disease, which is caused by the novel coronavirus, SARS-CoV-2, has affected the world by increasing the mortality rate in 2020. Currently, there is no definite treatment for COVID-19 patients. Several clinical trials have been proposed to overcome this disease and many are still under investigation. In this review, we will be focusing on the potency of mesenchymal stem cells (MSCs) and MSC-derived secretome for treating COVID-19 patients. Fever, cough, headache, dizziness, and fatigue are the common clinical manifestations in COVID-19 patients. In mild and severe cases, cytokines are released hyper-actively which causes a cytokine storm leading to acute respiratory distress syndrome (ARDS). In order to maintain the lung microenvironment in COVID-19 patients, MSCs are used as cell-based therapy approaches as they can act as cell managers which accelerate the immune system to prevent the cytokine storm and promote endogenous repair. Besides, MSCs have shown minimal expression of ACE2 or TMPRSS2, and hence, MSCs are free from SARS-CoV-2 infection. Numerous clinical studies have started worldwide and demonstrated that MSCs have great potential for ARDS treatment in COVID-19 patients. Preliminary data have shown that MSCs and MSC-derived secretome appear to be promising in the treatment of COVID-19. Lay Summary: The COVID-19 disease is an infection disease which affects the world in 2020. Currently, there is no definite treatment for COVID-19 patients. However, several clinical trials have been proposed to overcome this disease and one of them is using mesenchymal stem cells (MSCs) and MSC-derived secretome for treating COVID-19 patients. During the infection, cytokines are released hyper-actively which causes a cytokine storm. MSCs play an important role in maintaining the lung microenvironment in COVID-19 patients. They can act as cell managers which accelerate the immune system to prevent the cytokine storm and promote the endogenous repair. Therefore, it is important to explore the clinical trial in the world for treating the COVID-19 disease using MSCs and MSC-derived secretome.

Distance Management of Spinal Disorders During the COVID-19 Pandemic and Beyond: Evidence-Based Patient and Clinician Guides From the Global Spine Care Initiative.

BACKGROUND: The COVID-19 pandemic has greatly limited patients' access to care for spine-related symptoms and disorders. However, physical distancing between clinicians and patients with spine-related symptoms is not solely limited to restrictions imposed by pandemic-related lockdowns. In most low- and middle-income countries, as well as many underserved marginalized communities in high-income countries, there is little to no access to clinicians trained in evidence-based care for people experiencing spinal pain. OBJECTIVE: The aim of this study is to describe the development and present the components of evidence-based patient and clinician guides for the management of spinal disorders where in-person care is not available. METHODS: Ultimately, two sets of guides were developed (one for patients and one for clinicians) by extracting information from the published Global Spine Care Initiative (GSCI) papers. An international, interprofessional team of 29 participants from 10 countries on 4 continents participated. The team included practitioners in family medicine, neurology, physiatry, rheumatology, psychology, chiropractic, physical therapy, and yoga, as well as epidemiologists, research methodologists, and laypeople. The participants were invited to review, edit, and comment on the guides in an open iterative consensus process. RESULTS: The Patient Guide is a simple 2-step process. The first step describes the nature of the symptoms or concerns. The second step provides information that a patient can use when considering self-care, determining whether to contact a clinician, or considering seeking emergency care. The Clinician Guide is a 5-step process: (1) Obtain and document patient demographics, location of primary clinical symptoms, and psychosocial information. (2) Review the symptoms noted in the patient guide. (3) Determine the GSCI classification of the patient's spine-related complaints. (4) Ask additional questions to determine the GSCI subclassification of the symptom pattern. (5) Consider appropriate treatment interventions. CONCLUSIONS: The Patient and Clinician Guides are designed to be sufficiently clear to be useful to all patients and clinicians, irrespective of their location, education, professional qualifications, and experience. However, they are comprehensive enough to provide guidance on the management of all spine-related symptoms or disorders, including triage for serious and specific diseases. They are consistent with widely accepted evidence-based clinical practice guidelines. They also allow for adequate documentation and medical record keeping. These guides should be of value during periods of government-mandated physical or social distancing due to infectious diseases, such as during the COVID-19 pandemic. They should also be of value in underserved communities in high-, middle-, and low-income countries where there is a dearth of accessible trained spine care clinicians. These guides have the potential to reduce the overutilization of unnecessary and expensive interventions while empowering patients to self-manage uncomplicated spinal pain with the assistance of their clinician, either through direct in-person consultation or via telehealth communication.

Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases.

The immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic.

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: "hemophagocytic syndrome" OR "macrophage activation syndrome" OR "hemophagocytic lymphohistiocytosis", OR "cytokine storm". Finally, AND "COVID-19" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of "Hemophagocytic syndrome" OR "Macrophage activation syndrome" OR "Hemophagocytic lymphohistiocytosis" OR "Cytokine storm" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND "COVID-19") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

Inorganic and Polymeric Nanoparticles for Human Viral and Bacterial Infections Prevention and Treatment.

Infectious diseases hold third place in the top 10 causes of death worldwide and were responsible for more than 6.7 million deaths in 2016. Nanomedicine is a multidisciplinary field which is based on the application of nanotechnology for medical purposes and can be defined as the use of nanomaterials for diagnosis, monitoring, control, prevention, and treatment of diseases, including infectious diseases. One of the most used nanomaterials in nanomedicine are nanoparticles, particles with a nano-scale size that show highly tunable physical and optical properties, and the capacity to a wide library of compounds. This manuscript is intended to be a comprehensive review of the available recent literature on nanoparticles used for the prevention and treatment of human infectious diseases caused by different viruses, and bacteria from a clinical point of view by basing on original articles which talk about what has been made to date and excluding commercial products, but also by highlighting what has not been still made and some clinical concepts that must be considered for futures nanoparticles-based technologies applications.

SARS-CoV-2: A critical review of its history, pathogenesis, transmission, diagnosis and treatment.

The outbreak of the deadly virus (novel coronavirus or Severe Acute Respiratory Syndrome Coronavirus-2) that emerged in December 2019, remained a controversial subject of intense speculations regarding its origin, became a worldwide health problem resulting in serious coronavirus disease 2019 (acronym COVID-19). The concern regarding this new viral strain "Severe Acute Respiratory Syndrome Coronavirus-2" (acronym SARS-CoV-2) and diseases it causes (COVID-19) is well deserved at all levels. The incidence of COVID-19 infection and infectious patients are increasing at a high rate. Coronaviruses (CoVs), enclosed positive-sense RNA viruses, are distinguished by club-like spikes extending from their surface, an exceptionally large genome of RNA, and a special mechanism for replication. Coronaviruses are associated with a broad variety of human and other animal diseases spanning from enteritis in cattle and pigs and upper chicken respiratory disease to extremely lethal human respiratory infections. With World Health Organization (WHO) declaring COVID-19 as pandemic, we deemed it necessary to provide a detailed review of coronaviruses discussing their history, current situation, coronavirus classification, pathogenesis, structure, mode of action, diagnosis and treatment, the effect of environmental factors, risk reduction and guidelines to understand the virus and develop ways to control it.

Experience of percutaneous tracheostomy in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious disease that causes respiratory failure. Tracheostomy is an essential procedure in critically ill COVID-19 patients; however, it is an aerosol-generating technique and thus carries the risk of infection transmission. We report our experience with percutaneous tracheostomy and its safety in a real medical setting. METHODS: During the COVID-19 outbreak, 13 critically ill patients were admitted to the intensive care unit (ICU) at Daegu Catholic University Medical Center between February 24 and April 30, 2020. Seven of these patients underwent percutaneous tracheostomy using Ciaglia Blue Rhino. The medical environment, percutaneous tracheostomy method, and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results were retrospectively reviewed. After treatment, the COVID-19 infection status of healthcare personnel was investigated by RT-PCR. RESULTS: The ICU contained negative pressure cohort areas and isolation rooms, and healthcare personnel wore a powered air-purifying respirator system. We performed seven cases of percutaneous tracheostomy in the same way as in patients without COVID-19. Five patients (71.4%) tested positive for COVID-19 by RT-PCR at the time of tracheostomy. The median cycle threshold value for the RNA-dependent RNA polymerase was 30.60 (interquartile range [IQR], 25.50-36.56) in the upper respiratory tract and 35.04 (IQR, 28.40-36.74) in the lower respiratory tract. All healthcare personnel tested negative for COVID-19 by RT-PCR. CONCLUSIONS: Percutaneous tracheostomy was performed with conventional methods in the negative pressure cohort area. It was safe to perform percutaneous tracheostomy in an environment of COVID-19 infection.

Nutraceutical Targeting of Inflammation-Modulating microRNAs in Severe Forms of COVID-19: A Novel Approach to Prevent the Cytokine Storm.

The coronavirus disease 2019 (COVID-19) pandemic has become the number one health problem worldwide. As of August 2020, it has affected more than 18 million humans and caused over 700,000 deaths worldwide. COVID-19 is an infectious disease that can lead to severe acute respiratory syndrome. Under certain circumstances, the viral infection leads to excessive and uncontrolled inflammatory response, which is associated with the massive release of inflammatory cytokines in pulmonary alveolar structures. This phenomenon has been referred to as the "cytokine storm," and it is closely linked to lung injury, acute respiratory syndrome and mortality. Unfortunately, there is currently no vaccine available to prevent the infection, and no effective treatment is available to reduce the mortality associated with the severe form of the disease. The cytokine storm associate with COVID-19 shows similarities with those observed in other pathologies such as sepsis, acute respiratory distress syndrome, acute lung injury and other viral infection including severe cases of influenza. However, the specific mechanisms that cause and modulate the cytokine storm in the different conditions remain to be determined. micro-RNAs are important regulators of gene expression, including key inflammatory cytokines involved in the massive recruitment of immune cells to the lungs such as IL1ß, IL6, and TNFα. In recent years, it has been shown that nutraceutical agents can modulate the expression of miRs involved in the regulation of cytokines in various inflammatory diseases. Here we review the potential role of inflammatory-regulating-miRs in the cytokine storm associated with COVID-19, and propose that nutraceutical agents may represent a supportive therapeutic approach to modulate dysregulated miRs in this condition, providing benefits in severe respiratory diseases.

Emerging coronavirus diseases and future perspectives.

Coronavirus related infectious diseases seems to be biggest challenge of 21 century that have been constantly emerging and threating public health around the globe. Coronavirus disease-19 (COVID-19) that was detected as cause of respiratory tract infection in China by end the December 2019 impelled World Health Organization to declare in January 2020 public health emergency of international concern and consequently pandemic in March 2020. Over a past six months COVID-19 pandemic has wrapped up all continents except Antarctica. Scientists around the globe are finding way to tackle and reduce the ultimate risk and size of pandemic with lower morbidity and mortality rates. In this context, technologies such as sequencing, Crispr and artificial intelligence are playing vital role in diagnosis and management of infectious disease in contrast to conventional methods. Despite of this, there is a need to have rapid and early diagnostic tools and systems that recognize infectious disease in asymptotic condition. Here we provide an overview on the recent CoV outbreak and contribution of technologies with the emphasis on the future management for detection of such infectious diseases.

Tea Bioactive Modulate Innate Immunity: In Perception to COVID-19 Pandemic.

Innate immunity impairment led to disruption in cascade of signaling pathways upregulating pro-inflammatory cytokines, diminish interferons, depleted natural killer cells and activate reactive oxygen species production. These conditions severely affected body's ability to fight against infectious diseases and also plays a pivotal role in disease progression. Here, in emphasis is on nutritional immunity for regulating effective innate immune response for combating against infectious diseases like novel coronavirus disease (COVID 19). Drawing from discoveries on in-vitro experiments, animal models and human trials, tea polyphenols, micronutrients, and vitamins has the potential to modulate and enhance innate immune response. This article provides a comprehensive review on tea (Camellia sinensis L) infusion (a hot water extract of dried processed tea leaves prepared from young shoots of tea plant) as an innate immunity modulator. Tea infusion is rich in polyphenols; epigallocatechin gallate (EGCG) and theaflavin (TF), major green and black tea polyphenols, respectively. Studies showed their immunomodulatory competence. Tea infusions are also rich in alkaloids; caffeine and its intermediates, theophylline and theobromine, which have anti-inflammatory properties. Tea plant being an acidophilic perennial crop can accumulate different micronutrients, viz., copper (Cu), iron (Fe), manganese (Mn), selenium (Se), and zinc (Zn) from growing medium, i.e., from soil, which led to their considerable presence in tea infusion. Micronutrients are integral part of innate immune response. Overall, this review presents tea infusion as an important source of nutritional immunity which can enhance innate immune response in order to mitigate the unprecedented COVID-19 pandemic.

Efficacy of Traditional Chinese Medicine on COVID-19: Two Case Reports.

Severe acute respiratory syndrome coronavirus 2-infected pneumonia (novel coronavirus-infected pneumonia [NCIP]) is a new viral illness initially identified in the central Chinese city of Wuhan in December 2019. According to the daily report on the epidemic situation of coronavirus disease (COVID-19) issued by the National Health and Family Planning Commission of the People's Republic of China on March 23, 2020: COVID-19 is highly infectious, causing extremely high incidence of NCIP throughout Wuhan and has spread swiftly to 34 provinces within China and >100 other countries around the world between January and March 2020. Up to August 11, 2020, there have been 89,383 cases diagnosed as coronavirus-infected pneumonia; and 4,696 deaths in China (mortality rate of 5.25%) and worldwide reports have confirmed 19,936,210 cases and 732,499 deaths. These figures have been increasing daily. The treatment of viral conditions is well established within the context of Chinese Medicine. We report 2 successful cases in this study showing the patient's chest computed tomography scans and temperature charts made on before, during, and after treatment to demonstrate proof of the positive benefits achieved. Traditional Chinese Medicine (TCM) demonstrates a positive effect in the treatment for COVID-19. It is highly recommended that TCM be incorporated early on in the treatment schedule for COVID-19.

COVID-19: Look to the Future, Learn from the Past.

There is a current pandemic of a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of confirmed infected cases has been rapidly increasing. This paper analyzes the characteristics of SARS-CoV-2 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. COVID-19 is similar to the diseases caused by SARS-CoV and MERS-CoV virologically and etiologically, but closer to influenza in epidemiology and virulence. The comparison provides a new perspective for the future of the disease control, and offers some ideas in the prevention and control management strategy. The large number of infectious people from the origin, and the highly infectious and occult nature have been two major problems, making the virus difficult to eradicate. We thus need to contemplate the possibility of long-term co-existence with COVID-19.

From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo.

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

Potential Effect of COVID-19 on Maternal and Infant Outcome: Lesson From SARS.

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is highly infectious and its ongoing outbreak has been declared a global pandemic by the WHO. Pregnant women are susceptible to respiratory pathogens and the development of severe pneumonia, suggesting the urgent need to assess the potential maternal and infant outcome of pregnancy with COVID-19. The intrauterine vertical transmission potential of SARS-CoV-2 also remains controversial. Herein, we discuss the potential effect of COVID-19 on maternal and infant outcomes based on current studies, including those published in Chinese, in a total of 80 mothers with COVID-19 and 80 infants. We also comprehensively explored the mother-to-child transmission routes of SARS-CoV-2, in particular the route of intrauterine vertical transmission. Given SARS-CoV-2 is a sister to SARS-CoV, of the SARS-related coronavirus species, we made a comprehensive comparison between them to learn from experiences with SARS. Although there is no evidence supporting the intrauterine vertical transmission of SARS-CoV-2, our comprehensive analysis suggests that the adverse maternal and infant outcomes caused by COVID-19 cannot be underestimated. Further, we speculated that the inconsistency between nucleic acids and serological characteristics IgM to SARS-CoV-2 of infants' specimens may be caused by the disruption of the amniotic barrier by the inflammatory factors induced by SARS-CoV-2 infection. Our review is beneficial to understand the effect of SARS-CoV-2 on maternal and infant outcomes.

Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review.

INTRODUCTION: Corona virus is a group of viruses that cause diseases in mammals and birds. In humans, these families of viruses can cause respiratory infections from a mild form to fatal. It is preferably called coronavirus. Formally, it is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) and this disease is called coronavirus disease 2019 (COVID-19). SARS-CoV-2 is infectious in humans and the world health organization has announced COVID-19 as pandemic disease. Tocilizumab is a biological agent that inhibits the cytokine, interleukin 6 (IL-6 inhibitor). As SARS-CoV-2 infection leads to the development of cytokine storm syndrome, the drug, tocilizumab, seems to have a positive effect on patients with COVID-19. AIM: To analyze and review the possible effects and efficacy of the tocilizumab (monoclonal antibody against IL-6 receptors) in SARS-CoV-2 patients. MATERIALS AND METHODS: A search was carried out for all recent review articles, which were used to study the SARS-CoV-2 disease and their characteristics. Furthermore, we have analyzed the most recent research articles on monoclonal antibody against IL-6 receptors (tocilizumab) and their possible clinical effects in COVID-19 and its' clinical trials. RESULTS: COVID-19 is a disease caused by SARS-CoV-2 infection. It is a life threatening condition, which can give rise to fatal outcomes if left untreated. However, there are no approved treatments for COVID-19 globally. Furthermore, we can conclude that SARS-CoV-2 is associated with the worsening of lung conditions, characterized by interstitial pneumonia with acute respiratory distress syndrome as a result of cytokine storm syndrome. According to available research data, tocilizumab, a recombinant humanized anti-human monoclonal antibody of IgG1τ (gamma 1, kappa), can improve patient's condition from cytokine storm syndrome by inhibiting the IL-6 (Interleukin 6) receptors. CONCLUSION: The rational use of the tocilizumab in severe and critically ill COVID-19 patients can prevent the development of irreversible lung injury and death of the patient. Three retrospective studies of Xiaoling Xu et al., Pan luo et al., and Paola Tonaiti et al. have shown the efficacy of tocilizumab in severe and critically ill COVID-19 patients. However, we need more randomized research studies with a significant number of patients which can confirm the promising results on tocilizumab treatment in COVID-19 patients. Moreover, ongoing clinical trails such as TOSCA, COVACTA results have not been published yet which are expected to give better and more significant results on tocilizumab's effectiveness and safety.

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

The geography of COVID-19 spread in Italy and implications for the relaxation of confinement measures.

The pressing need to restart socioeconomic activities locked-down to control the spread of SARS-CoV-2 in Italy must be coupled with effective methodologies to selectively relax containment measures. Here we employ a spatially explicit model, properly attentive to the role of inapparent infections, capable of: estimating the expected unfolding of the outbreak under continuous lockdown (baseline trajectory); assessing deviations from the baseline, should lockdown relaxations result in increased disease transmission; calculating the isolation effort required to prevent a resurgence of the outbreak. A 40% increase in effective transmission would yield a rebound of infections. A control effort capable of isolating daily  ~5.5% of the exposed and highly infectious individuals proves necessary to maintain the epidemic curve onto the decreasing baseline trajectory. We finally provide an ex-post assessment based on the epidemiological data that became available after the initial analysis and estimate the actual disease transmission that occurred after weakening the lockdown.

The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has led to a declaration of a Public Health Emergency of International Concern by the World Health Organization. As of May 18, 2020, there have been more than 4.7 million cases and over 316,000 deaths worldwide. COVID-19 is caused by a highly infectious novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to an acute infectious disease with mild-to-severe clinical symptoms such as flu-like symptoms, fever, headache, dry cough, muscle pain, loss of smell and taste, increased shortness of breath, bilateral viral pneumonia, conjunctivitis, acute respiratory distress syndromes, respiratory failure, cytokine release syndrome (CRS), sepsis, etc. While physicians and scientists have yet to discover a treatment, it is imperative that we urgently address 2 questions: how to prevent infection in immunologically naive individuals and how to treat severe symptoms such as CRS, acute respiratory failure, and the loss of somatosensation. Previous studies from the 1918 influenza pandemic have suggested vitamin D's non-classical role in reducing lethal pneumonia and case fatality rates. Recent clinical trials also reported that vitamin D supplementation can reduce incidence of acute respiratory infection and the severity of respiratory tract diseases in adults and children. According to our literature search, there are no similar findings of clinical trials that have been published as of July 1st, 2020, in relation to the supplementation of vitamin D in the potential prevention and treatment for COVID-19. In this review, we summarize the potential role of vitamin D extra-renal metabolism in the prevention and treatment of the SARS-CoV-2 infection, helping to bring us slightly closer to fulfilling that goal. We will focus on 3 major topics here: 1. Vitamin D might aid in preventing SARS-CoV-2 infection: Vitamin D: Overview of Renal and Extra-renal metabolism and regulation. Vitamin D: Overview of molecular mechanism and multifaceted functions beyond skeletal homeostasis. Vitamin D: Overview of local immunomodulation in human infectious diseases. Anti-viral infection. Anti-malaria and anti-systemic lupus erythematosus (SLE). 2. Vitamin D might act as a strong immunosuppressant inhibiting cytokine release syndrome in COVID-19: Vitamin D: Suppression of key pro-inflammatory pathways including nuclear factor kappa B (NF-kB), interleukin-6 (IL-6), and tumor necrosis factor (TNF). 3. Vitamin D might prevent loss of neural sensation in COVID-19 by stimulating expression of neurotrophins like Nerve Growth Factor (NGF): Vitamin D: Induction of key neurotrophic factors. .