Causes Coronavirus Disease 2019 Research Articles

Kawasaki-like disease in children with COVID-19

Sir, In late 2019, a new type of viral infection emerged in Wuhan, China, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) and which has become the most challenging pandemic of this century. COVID-19 has affected individuals of all ages worldwide. Epidemiological data from numerous countries show that children are a small minority of those who test positive. Most children with COVID-19 show mild symptoms or are asymptomatic, yet new concerns have emerged, with reports on hyperinflammatory states or Kawasaki-like disease [1,2]. Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that occurs mainly in children and rarely in adults [3]. Herein, we report a child with Kawasaki-like disease associated with COVID-19. A fifteen-year-old boy presented to our department with a four-day history of high fever, vomiting, diarrhea, abdomen pain, and erythematous rash. His previous medical history was unremarkable. A physical examination revealed diffuse, erythematous, maculopapular rash, bilateral conjunctivitis, erosive hyperemia of the oral mucosa, scrotal erythema, and a deepithelialized tongue (Figs. 1 and 2).

Antioxidant/anti-inflammatory effect of Mg2+ in coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi‐organ failure in severe cases. Magnesium (Mg2+) regulates many processes, including antioxidant and anti‐inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg2+ has an anti‐inflammatory response by reducing the levels of nuclear factor kappa B (NF‐κB), interleukin (IL) ‐6, and tumor necrosis factor alpha. Furthermore, Mg2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID‐19. This narrative review will address Mg2+ deficiency associated with a worse disease prognosis, Mg2+ supplementation as a potent antioxidant and anti‐inflammatory therapy during and after COVID‐19 disease, and suggest that randomised controlled trials are indicated.

Impact of Technological Developments on Infectious Disease Epidemiology: Lessons From the First 100 Years of the American Journal of Epidemiology.

Technological developments in laboratory and epidemiologic methods, combined with increasing computing power, have synergistically increased our understanding of the epidemiology of infectious disease. Using historical examples from the first 100 years of the American Journal of Epidemiology, we illustrate how these developments provided the foundation for the rapid detection of the agent causing coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from its transmission efficiency and modalities, risk factors, and natural history to the evaluation of new vaccines and treatments to control its spread and impact. Comparisons with timelines for elucidation of the epidemiology, natural history, and control of other infectious diseases, including viral hepatitis, humbly remind us of how much past discoveries have paved the way for more rapid discovery of and response to new pathogens. We close with some comments on a potential future role of the Journal in infectious disease epidemiology.

A systematic review of the variants of Sars-Cov-2

Before the end of December 2019, the epidemic was mainly localized in Wuhan, Hubei Province, China. Most of the cases in this stage were related to exposure to Huanan seafood market. "The virus is transmitted through human-to-human contact and rapidly spread across the world, and soon turned into a pandemic." Its symptoms can be divided to two main groups of majors (fever, cough, and dyspnea) and minors (anosmia, dysgeusia, headache, gastrointestinal symptoms, and skin lesions). Ever since, it has caused worldwide social and economic disruption, there are no universally recognized clinically useful antiviral drugs against COVID-19 so far (actually remdesivir showed good efficacy in many trials, but it needs to be further realized). Although there are several effective vaccines to prevent infection with SARS-CoV-2, efforts to develop medications and vaccines are continuing. Recently, a novel coronavirus, severe acute respiratory syndrome SARS-CoV-2, causing coronavirus disease 2019 (COVID-19), emerged in late 2019. During February 1-July 13, 2020, were identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 deaths in Italy by 5 March 2020. Currently, the following variants; Alpha, Beta, Gamma, Delta and Omicron were originated from United Kingdom, South Africa, Brazil/Japan, and India, respectively. The classification of SARS-CoV-2 variants is based on the mutations in the structure-based inclusions. Transmission varied not only by time and place but also by persons' sex and race. Younger adults (20–50 years of age) were involved in most transmission events.

The Effect of COVID-19 Infection on Male Fertility: A Narrative Review

The emergence of a new coronavirus, officially referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ), has challenged all healthcare workers and clinicians worldwide. The presence of the virus in biological fluids including the semen has raised some concerns about infertility treatment. There is evidence that SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), can damage the male reproductive system following the inflammatory process caused by the cytokine storm. However, the direct and long-term effects of SARS-CoV-2 on fertility and the reproductive capacity of the human testis are still open to controversy. The lasting presence of the virus, even after a complete recovery, can increase the risk of sexual transmission and adversely affect the male reproductive system, sexual function, and fertility. Therefore, there is a need for a careful assessment of reproductive organs and testicular function in male patients. This study aimed to evaluate the invasive effect of SARS-CoV-2 on the testis and male reproduction.

Adapting to the COVID-19 Pandemic: Recommendations for Cancer Centers

Starting in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) began a pandemic that has rapidly swept across the globe claiming many victims and forcibly changing the way of life for many.

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is modifying human activity all over the world with significant health and economic burden. The advent of the SARS-CoV-2 pandemic prompted the scientific community to learn the virus dynamics concerning transmissibility, epidemiology, and usefulness of vaccines in fighting emerging health hazards. Pieces of evidence suggest that the first and second doses of mRNA vaccines induce a significant antibody response in vaccinated subjects or patients who recovered from SARS-CoV-2 infection, demonstrating the importance of the previously formed memory. The aim of this work has been to investigate the effects of BNT162b2 Pfizer-BioNTech mRNA-based vaccine booster dose in a cohort of 11 uninfected immunocompetent (ICs), evaluating the humoral and cellular responses, with more carefulness on memory B and T cells. Our findings underscore the potential benefit of the third dose of mRNA vaccine on the lifespan of memory B and T cells, suggesting that booster doses could increase protection against SARS-CoV-2 infection.

Use of Circular Dichroism in the characterization of the fusion protein SARS-CoV-2 S protein (RBD)-hFc

Abstract From the receptor-binding domain (RBD) of the SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19), a RBD-hFc fusion protein was obtained at the Center of Molecular Immunology (Havana, Cuba). This fusion protein was used in the construction of a diagnostic device for COVID-19 called Ultramicroenzyme-Linked Immunosorbent Assay (UMELISA)-SARS-CoV-2-IgG and it is currently been used in the studies of biological activity of the Cuban vaccine Abdala (CIGB-66). In this work, Circular Dichroism (CD) is used to characterize this protein. Using Far Ultraviolet Circular Dichroism (FAR-UV CD), it was determined that the protein has a secondary structure in the form of a sheet-β fundamentally. Using this technique, a thermodynamic study was carried out and it was determined that the melting temperature (Tm) of the protein is 71.5 °C. Information about the tertiary structure of the protein was obtained using Near Ultraviolet Circular Dichroism (NEAR-UV CD) and Molecular Fluorescence; they indicates that the protein has a three-dimensional folding associated with the aromatic amino acids in its structure, where tryptophan (Trp) is located inside the folded structure of the protein while tyrosine (Tyr) is exposed to the solvent.

Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial.

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.

In Silico Multi-Target Approach Revealed Potential Lead Compounds as Scaffold for the Synthesis of Chemical Analogues Targeting SARS-CoV-2.

Simple SummaryCOVID-19 is an infectious disease caused by SARS-CoV-2. The virus has rapidly spread to humans, causing the ongoing coronavirus pandemic. Enormous progress in finding therapies has been made, but an effective therapy is still absent. In this study, we propose a computational strategy aimed at identifying novel multi-target scaffolds against the virus. The proposed study was performed using bioinformatics methods, such as homology modeling, virtual screening and classical molecular dynamics, where 3D structures of targets were reconstructed and compounds with potential inhibitory activity against different virus targets were identified. Furthermore, a potential mechanism of action was proposed. Our study could provide new insights and approaches for the rapid identification of novel multi-target inhibitors of SARS-CoV-2.Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an infectious disease that spreads rapidly in humans. In March 2020, the World Health Organization (WHO) declared a COVID-19 pandemic. Identifying a multi-target-directed ligand approach would open up new opportunities for drug discovery to combat COVID-19. The aim of this work was to perform a virtual screening of an exclusive chemical library of about 1700 molecules containing both pharmacologically active compounds and synthetic intermediates to propose potential protein inhibitors for use against SARS-CoV-2. In silico analysis showed that our compounds triggered an interaction network with key residues of the SARS-CoV-2 spike protein (S-protein), blocking trimer formation and interaction with the human receptor hACE2, as well as with the main 3C-like protease (3CLpro), inhibiting their biological function. Our data may represent a step forward in the search for potential new chemotherapeutic agents for the treatment of COVID-19.

Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for the prevention and treatment of SARS-CoV-2 infections. We evaluated the antiviral activity of sulforaphane (SFN), the principal biologically active phytochemical derived from glucoraphanin, the naturally occurring precursor present in high concentrations in cruciferous vegetables. SFN inhibited in vitro replication of six strains of SARS-CoV-2, including Delta and Omicron, as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN should be explored as a potential agent for the prevention or treatment of coronavirus infections.

Design and Development of Nanoscale Aptasensors for Viral Diagnostics

Viral infection may be a serious threat for human beings. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly transmissible virus causing coronavirus disease 2019 (COVID-19) in humans and creating a universal pandemic outbreak. The current methods for detection of SARS-CoV-2 include real-time reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and loop-mediated isothermal amplification (LAMP). Though the methods are widely used for the diagnosis of COVID-19, they too have their limitations such as time-consuming process, sophisticated instrumental setup, which requires highly skilled personnel for operation, and prevalence of false positive/negative reports. Therefore, there is a pressing need to develop alternative tools such as point-of-care testing (POCT) devices to detect SARS-CoV-2 rapidly, accurately, and user-friendly. Here, the authors propose a one-step diagnostic method using aptamer-based sensing technology. The intended design of aptamer-based biosensors (also known as aptasensors) utilizes the optical properties of gold nanoparticles (AuNP) conjugated with angiotensin-converting enzyme-2 (ACE-2) aptamers targeting SARS-CoV-2 using lateral flow assay (LFA). This study leads to the development of portable nanoscale aptasensors for viral diagnostics.

Restarting spirometry testing: considering and minimising the risks posed by COVID-19

Spirometry is a pulmonary function test normally performed in primary and secondary care as part of the diagnosis and assessment of patients with respiratory conditions, notably chronic obstructive pulmonary disease. Spirometry involves three main risks of transmitting the virus that causes coronavirus disease 2019 (COVID-19): aerosols, droplets and direct contact with contaminated surfaces. The COVID-19 pandemic therefore negatively affected spirometry testing, which had to be drastically reduced or interrupted. Services are being gradually restarted but concerns and challenges remain. This article describes the challenges posed by COVID-19 to spirometry testing and outlines the recommendations of professional organisations, including the Association for Respiratory Technology and Physiology and the Primary Care Respiratory Society, for restarting spirometry testing while ensuring patient and staff safety. The article also discusses innovative devices and new models of service delivery that could assist in ensuring that spirometry testing can be performed more safely.

Prescribing errors in post - COVID-19 patients: prevalence, severity, and risk factors in patients visiting a post - COVID-19 outpatient clinic

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has necessitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identified as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescribing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post–COVID-19 patients, hospitalized during the first wave of COVID-19 in the Netherlands, 3 months after discharge.MethodsThis prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3 months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs.ResultsNinety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identified PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identified ICU admission (OR 6.08, 95% CI 2.16–17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34–21.5) as independent risk factors for PEs.ConclusionsPEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID-19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.

SARS-CoV-2 vaccines are well tolerated in patients with mastocytosis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) initially emerged in December 2019 in Wuhan, People's Republic of China, and its rapid spread led to a global pandemic. Vaccines are the single, most effective method of stopping the pandemic and concerns about vaccine safety have necessitated updates to the knowledge, especially in terms of allergic diseases. Patients with mastocytosis, who frequently experience recurrent anaphylaxis, constitute an important group that needs to be investigated as to whether the COVID-19 vaccines can be administered safely.

Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells via angiotensin-converting enzyme 2 (ACE2) and causes coronavirus disease 2019 (COVID-19). Here, through a genome-wide association study, we identify a variant (rs190509934, minor allele frequency 0.2–2%) that downregulates ACE2 expression by 37% (P = 2.7 × 10−8) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10−13), providing human genetic evidence that ACE2 expression levels influence COVID-19 risk. We also replicate the associations of six previously reported risk variants, of which four were further associated with worse outcomes in individuals infected with the virus (in/near LZTFL1, MHC, DPP9 and IFNAR2). Lastly, we show that common variants define a risk score that is strongly associated with severe disease among cases and modestly improves the prediction of disease severity relative to demographic and clinical factors alone.

Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which was classified as a pandemic in March 2020. As of 22 January 2022, globally more than 347 million cases of COVID-19 have been diagnosed, with 5.6 million deaths, making it the deadliest pandemic since the influenza pandemic in 1918. The clinical presentation of COVID-19-related illness spans from asymptomatic to mild respiratory symptoms akin to influenza infection to acute symptoms, including pneumonia necessitating hospitalisation and admission to intensive care units. COVID-19 starts in the upper respiratory tract and lungs but in severe cases can also involve the heart, blood vessels, brain, liver, kidneys and intestine. The increasing global health and economic burden of COVID-19 necessitates an urgent and global response. Understanding the functional characteristics and cellular tropism of SARS-CoV-2, and the pathogenesis that leads to multi-organ failure and death, has prompted an unprecedented adoption of organoid models. Successful drug discovery and vaccine development rely on pre-clinical models that faithfully recapitulate the viral life cycle and the host cell response to infection. Human stem cell-derived organoids fulfill these criteria. Here we highlight the role of organoids in the study of SARS-CoV-2 infection and modelling of COVID-19 pathogenesis.

Geriatric rehabilitation during COVID-19: a lesson learned

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus that causes coronavirus disease 2019 (COVID-19) infection and is responsible for a deadly pandemic. The elderly population have a high risk to be infected by COVID-19 and tend to have worse outcomes compared to adult population. Elderly patients also have higher comorbidity than the whole population. Therefore, management of COVID-19 in the elderly needs special attention in terms of regarding drug doses, drug interactions, and side effects of the drugs given. Approach from Physical Medicine and Rehabilitation (PM&R) in elderly population known as Geriatric Rehabilitation is required for COVID-19 because PM&R will go through all phases of treatment during the acute, sub-acute, and long-term care phases. The targets are relieving symptoms, assisting in the mechanical ventilation weaning process, preventing decondition of the airway and other organ systems, and managing psychosocial aspects, especially in the vulnerable and high-risk elderly population. The geriatric rehabilitation approach to COVID-19 patients resulted in improved functional prognosis, optimized role of function, and improved Quality of Life.

Inactivation of Pathogens in Air Using Ultraviolet Direct Irradiation Below Exposure Limits.

A method is described for inactivation of pathogens, especially airborne pathogens, using ultraviolet (UV) radiation emitted directly into occupied spaces and exposing occupants to a dose below the accepted actinic exposure limit (EL). This method is referred to as direct irradiation below exposure limits, or DIBEL. It is demonstrated herein that low-intensity UV radiation below exposure limits can achieve high levels of equivalent air changes per hour (ACHeq) and can be an effective component of efforts to combat airborne pathogens such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). An ACHeq of 4 h-¹ is presently achievable over a continuous 8 h period for the SARS-CoV-2 virus with UV-C light-emitting diodes (LEDs) having peak wavelength at 275 nm, and future improvements in LED technology and optics are anticipated to enable improvements up to 150 h-¹ in the coming decade. For example, the actinic EL is 60 J/m² at 254 nm, and human coronaviruses, including SARS-CoV-2, have a UV dose required for 90 % inactivation of about 5 J/m² at 254 nm. Irradiation by 254 nm UV-C at the EL is expected to provide 90 % inactivation of these organisms in air in about 40 min when the UV-C is delivered at a constant irradiance over 8 h, or in about 5 min if the UV-C is delivered at a constant irradiance over 1 h. Since the irradiation is continuous, the inactivation of initial contaminants accumulates to 99 % and then 99.9 %, and it also immediately begins inactivating any newly introduced (e.g., exhaled) pathogens at the same rate throughout the 8 h period. The efficacy for inactivating airborne pathogens with DIBEL may be expressed in terms of ACHeq, which may be compared with conventional ventilation-based methods for air disinfection. DIBEL may be applied in addition to other disinfection methods, such as upper room UV germicidal irradiation, and mechanical ventilation and filtration. The ACHeq of the separate methods is additive, providing enhanced cumulative disinfection rates. Conventional air disinfection technologies have typical ACHeq values of about 1 h-¹ to 5 h-¹ and maximum practical values of about 20 h-¹. UV-C DIBEL currently provides ACHeq values that are typically about 1 h-¹ to 10 h-¹, thus either complementing, or potentially substituting for, conventional technologies. UV-C DIBEL protocols are forecast herein to evolve to >100 ACHeq in a few years, potentially surpassing conventional technologies. UV-A (315 nm to 400 nm) and/or UV-C (100 nm to 280 nm) DIBEL is also efficacious at inactivating pathogens on surfaces. The relatively simple installation, low acquisition and operating costs, and unobtrusive aesthetic of DIBEL using UV LEDs contribute value in a layered, multi-agent disinfection strategy.

Omicron the New COVID-19 Variant, a Review

SARS-CoV-2 virus(COVID-19), the cause of coronavirus disease, has several variations.Some are thought to be particularly important or have been said to be so, because of their potential for greater transmissibility, Virus pathogenicity has grown, or vaccinations against them have become less effective. These mutations have a role in the COVID-19 pandemic's persistence. The B.1.1.529-Omicron variant, found in many coronavirus cases reported in South Africa discovered late 2021, having a surprisingly great number of mutations which raise a concern toward the spreadablity of this variant and severity of illness in comparison to other corona virus variants as well as the effectivity of the available vaccinations. This review summarizes of the most recent information and the answers to most of the world's questions about Omicron.