In this review, the potential of an emerging field of interdisciplinary climate research, that is the Coastal Boulder Deposits (CBDs) as natural archives for intense storms, is explored with particular reference to the Mediterranean region. First, the identification of the pertinent scientific articles was performed by using Web of Science (WoS) engine. Thus, the selected studies have been analysed to feature CBDs produced and/or activated during the last half century. Then, the meteorological events responsible to the literature reported cases were analysed in some details using the web archives of the Globo-Bolam-Moloch model cascade. The study of synoptical and local characteristics of the storms involved in the documented cases of boulder production/activation proved useful to assess the suitability of selected sites as geomorphological storm proxies. It is argued that a close and fruitful collaboration involving several scientific disciplines is required to develop this climate research field.

Portugal Mainland has hundreds of thousands of people living in the Atlantic coastal zone, with numerous high economic value activities and a high number of infrastructures that must be protected from natural coastal hazard, namely extreme storms and sea level rise (SLR). In the context of climate change adaptation strategies, a reliable and accurate assessment of the physical vulnerability to SLR is crucial. This study is a contribution to the implementation of flooding standards imposed by the European Directive 2007/60/EC, which requires each member state to assess the risk associated to SLR and floods caused by extreme events. Therefore, coastal hazard in the Continental Atlantic coast of Portugal Mainland was evaluated for 2025, 2050 and 2100 in the whole coastal extension with different sea level scenarios for different extreme event return periods and due to SLR. A coastal flooding probabilistic map was produced based on the developed methodology using Geographic Information Systems (GIS) technology. The Extreme Flood Hazard Index (EFHI) was determined on flood probabilistic bases through five probability intervals of 20% of amplitude. For a given SLR scenario, the EFHI is expressed, on the probabilistic flooding maps for an extreme tidal maximum level, by five hazard classes ranging from 1 (Very Low) to 5 (Extreme).

Dust storms and wildfires occur frequently in southeastern Australia. Their effects on ecology, environment and population exposure have been the focus of many studies recently. Dust storms do not emit ground-sequestered carbon but wildfires emit significant quantities of carbon into the atmosphere. However, both natural events promote phytoplankton growth in water bodies because carbon, and other trace elements such as iron, deposit on the surface water of oceans. Carbon dioxide is reabsorbed by phytoplankton via photosynthesis. The carbon balance cycle due to dust storms and wildfires are not well known. Recent studies on the carbon emission of the 2019-2020 summer wildfires in eastern Australia indicated that this megafire event emitted approximately 715 million tonnes of CO2 (195 Tg C) into the atmosphere from burned forest areas. The projected increase in the frequency of wildfires due to climate change alters what was a carbon neutral process of reabsorbing emitted carbon by the forests, and subsequently cannot be achieved. With the result of net loss of sequestered carbon to the atmosphere, subsequently further promotes a warming climate. This study focusses on the association of dust storms and wildfires in southeastern Australia with phytoplankton growth in the Tasman Sea due to the February 2019 dust storm event and the 2019-2020 Black Summer wildfires. Central Australia and western New South Wales were the sources of the dust storm emission (11 to 16 February 2019) and the Black Summer wildfires occured along the coast of New South Wales and Victoria (from early November 2019 to early Januaray 2020). The results show the similarities and differences in the deposition of particulate matter, phytoplankton growth and carbon reabsorption patterns in the Tasman Sea from these events. Using WRF-Chem model, during the 5 days dust storm event in February 2019, approximately ~1230 tons of total dust were predicted to be deposited in the Tasman Sea while ~132,000 tons of PM10 were deposited in the early stage of the wildfires from 1 to 8 November 2019.

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In each group, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/ml, p <0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p=0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p=0.013), RR = 0.50 (95% CI 0.25-0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients it contributed to reduced mortality.

Inflammation is an essential protective response against injury or infection. Physiological inflammation eliminates the pathogen, promotes tissue repair and healing. An exaggerated, out of control inflammation, however, can become pathological. Inflammation can generate secondary cell damage, inflame the vessels (endothelitis), activate coagulation processes. Among these pathogenetic factors (cell damage, inflammation, endothelitis, coagulopathies), self-amplification mechanisms can be created, spreading beyond the initial site, up to Multiple Organ Failure (MOF) and host death. If the inflammation does not resolve in a physiological way, the remodeling of the tissues can be maladaptive and lead to the onset of chronic inflammatory degenerative diseases. Diseases such as sepsis, burns, polytrauma, severe forms of influenza or COVID-19, are characterized by a condition of hyperinflammation, associated with a condition of immunosuppression. The initial events triggered by the pathogen (cell damage, interferon response in the case of viruses) ignite the inflammation by activating the inflammasome, the transcription factor NFkB, the release of pro-inflammatory eicosanoids (Prostaglandins, Leukotrienes, Thromboxanes) by neutrophils and macrophages. Hence, the cells of the innate immune system produce pro-inflammatory cytokines. Indeed, the ‘’eicosanoid storm’’ precedes the ‘’cytokine storm’’. Eicosanoids are a group of potent endogenous lipid mediators derived from omega-6 fatty acids Arachidonic Acid (AA). Eicosanoids include a group of molecules with pro-inflammatory (Prostaglandins, Leukotriens) and pro-coagulant (Thromboxanes) action. In addition, Arachidonic Acid (AA) is the source of Lipoxins (LXs). Lipoxins belong to a group of molecules collectively referred to as specialized pro-solving mediators (SPMs) which also include molecules derived from w-3 eicosapentaenoic acid (EPA): Resolvins (ReV-E sieres) and w-3 docohexanoic (DHA): Resolvins D-series (ReV D-series); Protectins (PTs); Maresins (MaRs). SPMs are important for the resolution phase of inflammation to take place properly. Their deficiency could be involved in both acute uncontrolled inflammation and chronic inflammation. The active regulation of the acute inflammatory process, integrating the precursors of Specialized Pro-resolving Mediators (SPMs), such as ⍵-6 and ⍵-3 in balanced ratio, or the SPMs themselves, could be a complementary therapeutic approach useful for taming the "storm of cytokines '' which characterizes exaggerated forms of inflammation. ⍵-3 and ⍵-6 are part of already widely used, readily available, inexpensive and safe supplements. Resolvins have already been included in clinical trials for various other inflammatory diseases (eye diseases, periodontal diseases).

Unlike the contiguous windthrows, the diffuse windthrows occurred as a result of wind gusts of lower speed (100-140 km/h) than in the first case (>140 km/h) are much more difficult to detect due to their much lower areas and due to their very large number, of several hundreds in the wooded mountain massifs. The objective of this research is to present a rapid procedure for the detection of the diffuse windthrows based on low cost, Landsat type images, knowing that certain sensors cannot be accessed without significant investments. Our application is based on the study of effects caused by the Xynthia storm in the Vosges Mountains in the North-East of France, on 28 February 2010. Thus, based on two sets of Landsat satellite images, we used the “dark object” approach and the Disturbance Index, as well as a classification of the images before and after the storm, resulting in a change map. Following the detection process, 257 scattered polygons were detected, totalling 229 ha. For validation purposes, high-resolution images and orthophotoplans taken before and after storm were used. The error matrix was calculated, achieving an overall accuracy of 86%, which confirms the quality of our analysis and supports this procedure for detecting diffuse windthrow based on low cost resources.

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in damage to the lungs and other organs. This remarkable increase in cytokines and other inflammatory molecules is primary caused by viral proteins, in particular ORF8, a unique accessory protein specific to SARS-CoV-2. In addition to its role in cytokine induction, ORF8 is attributed with various other functions, including its ability to evade type I interferon responses. Despite the evidence, the mechanisms through which ORF8 exerts these functions remains a subject of controversy. In this mini review, we discuss the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6. We also discuss data from our studies indicating that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs).

Sea surface wind forecasts in the Adriatic Sea often suffer for unadequate modelling, especially for the wind speed. This has detrimental effects on the accuracy of sea level and storm surge predictions. We present a numerical method to reduce the bias between the sea surface wind observed by the scatterometers and that supplied by the European Centre for Medium-Range Weather Forecasts (ECMWF) global atmospheric model, for storm surge forecasting applications. The method, called “wind bias mitigation”, relies on scatterometer observations to determine a multiplicative factor ∆ws which modulates the standard model wind in order to decrease the bias between scatterometer and model. We compare four different mathematical approaches to this method, for a total of eight different formulations of the multiplicative factor ∆ws. Four datasets are used for the assessment of the eight different bias mitigation methods: a collection of 29 Storm Surge Events (SEVs) cases in the years 2004-2014, a collection of 48 SEVs in the years 2013-2016, a collection of 364 cases of random sea level conditions in the same period, and a collection of the seven SEVs in 2012-2016 that were worst predicted by the Centro Previsioni e Segnalazioni Maree, Comune di Venezia (Tide Forecast and Early Warning Centre of the Venice Municipality - CPSM). The statistical analysis shows that the bias mitigation procedures supplies a mean wind speed more accurate than the standard forecast, when compared with scatterometer observations, in more than 70% of the analyzed cases.

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

Recently, the intensities of natural disasters have increased significantly owing to climate change and various other environmental factors, causing unprecedented damage. Measures must be established to reduce damage from large-scale natural disasters caused by the rapidly changing environment. The Japanese government published a hazard map manual in 2015 and obligates the creation of a hazard map as a measure to reduce high-scale storm surges. This manual presents a typhoon model based on a parametric model that is used to create a hazard map. The Myers model assuming concentric circles, which is primarily used in East Asia, is disadvantageous as it cannot consider geographic characteristics. Therefore, a new parametric model is necessary to calculate wind and pressure fields, which change according to geographic characteristics. To improve this limitation of the Myers model, we calculated the wind and pressure fields considering geographical effects by combining the Holland model, which can consider the size of a developing typhoon, and the Mascon model, which changes by geographic characteristics. To determine the gradient coefficient of the Holland model, the coefficient that changes every moment was calculated using grid point value data. The result indicated excellent reproducibility of storm surge height according to the geographic characteristics.

Some COVID-19 patients develop interstitial pneumonia that can evolve into Acute Respiratory Distress Syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia / reperfusion models and could also be exploited in acute lung injury, with hypoxia. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.

Hydroxychloroquine, a known antiviral metabolite of chloroquine, is increasingly used along with antibiotic azithromycin for the treatment of COVID-19 infection. In about one month India, the world’s largest manufacturer, delivered hydroxychloroquine for treating COVID-19 to over 50 countries. The therapy is being used across the world both for patients staying at home at the early phase of symptoms, as well as for patients hospitalized. We summarize achievements as of late April 2020, review possible modes of action and suggest avenues for the quick scale-up of production of hydroxychloroquine.

The ionospheric scintillation is a rapid phase and amplitude fluctuation of satellite signals due to the small-scale irregularity of electron density in the ionosphere. The characterization of the scintillation index in a proper way is a crucial aspect of the Global Positioning System (GPS) satellite signals for the purpose of space-based navigation, satellite communication, space weather as well as earth observation applications. In the current study, we analyzed the ionospheric scintillation index during the year of 2018 to 2019 over the Nepal region which locates itself almost being sandwiched between India and China and in the vicinity of low latitudes. The characteristic variations of scintillation occurrence are studied during the several geomagnetic storm and quiet days. The results show that the S4 indexes are varying from the 0.05 to 0.45 during the whole year. The S4 indexes behave higher variations during the whole day in the starting of the year and start to decrease at end of the day as well as at the ending months of the year 2019. The S4 values become completely less during the sunset time, while they have higher values during the sunrise. Especially, the S4 index during the storm days are larger than during the quiet days. It is worthy to note that the variations of S4 index studied in this current study do not follow the sunset property during the year of 2019. Consequently, the causes should be discovered and discussed additionally in the next research paper.

(1) Background: Cameron County, which is located in the Rio Grande Valley, holds historical records for storm surges with noticeable property damage, fatalities, and injuries; (2) Methods: using storm surge hazard datasets from the National Oceanic and Atlantic Agency (NOAA), and American Community Survey (ACS) 2019 datasets and Geographic Information System (GIS), the study estimates at-risk population and their socio-demographic attributes; (4) Conclusions: Estimated water levels of a storm surge could be reached up to 5 feet in category 1 event, 9 feet in category 2, 17 feet in category 3, and above 20 feet in category 4 and 5. In the category 5 event, there is an estimated 37% (159,659) of the total county’s population (434,294) will be under flooded water. Suggestions are made to better prepare and successfully evaluate.

This paper investigates the characteristics and impact of a major Saharan dust storm during June 14^th -19^th 2020 to atmospheric radiative and thermodynamics properties over the Atlantic Ocean. The event witnessed the highest ever aerosol optical depth (close to 2 during the peak of the storm) for June since 2002. The satellites and high-resolution model reanalysis products well captured the origin, spread and the effects of the dust storm. The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) profiles, lower angstrom exponent values (~ 0.12) and higher aerosol index value (> 4) tracked the presence of elevated dust. It was found that the dust AOD was as much as 250-300% higher than their climatology resulting in an atmospheric radiative forcing ~200% larger. As a result, elevated warming ( 8-16 %) was observed, followed by a drop in relative humidity(2-4%) in the atmospheric column, as evidenced by both in-situ and satellite measurements. Quantifications such as these for extreme dust events provide significant insights that may help in understanding their climate effects, including improvements to dust simulations using chemistry-climate models

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

Since the discovery of the first reported case with Zinc-deficiency in Iran¹ by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response ^2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency⁴. In the western world, Zinc deficiency is more prevalent among the geriatric population³, vegans/vegetarians, and people with certain underlying conditions⁴such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders^4,5. Zinc and Zinc deficiency has been associated with several infectious diseases ^2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21^st century^6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This ‘cytokine storm ‘produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1 and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

Background: Long-range transport of dust aerosol has intense impacts on the atmospheric environment over wide areas. Methods: The annual and seasonal changes in meteorological parameters associated with the occurrence of dust storms were studied. The features of an intense dust storm and its transport characteristics were studied during June 7th to June 9th 2010 in Ahvaz city. Temporal and spatial distribution of Middle Eastern dust storm event was analyzed by models of HYSPLIT and WRF/Chem, and in- situ observations. Results: A disagreement between the occurrences of dust storms, temperature, relative humidity and rainfall, show the major source of dust storms over Ahvaz city are neighboring countries. Using HYSPLIT results, the dust particles are mainly transported from north western region of Iraq and eastern Syria to downward areas including Ahvaz city. The arrived Dust aerosols mixed with local anthropogenic emissions, led to the highest PM10 concentration of 4200 ppm. The model results were found to well reproduce temporal and spatial distribution of mineral dust concentrations according to in-situ measurements. Conclusion: The performance of WRF/Chem was acceptable for simulation of temporal and spatial distributions of dust storm events. Therefore, it can be taken as a reference in daily air quality forecasting.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

Vagueira Beach on the Central Portuguese coast, is known as one of the places in Europe most affected by coastal erosion. The area has suffered more than 156 meters of coastline retreat over the period 1958 to 2001. With the aim to evaluate the influence of local factors on coastal erosion, this paper assesses the anthropogenic and natural factors that are related with the retreat of the coastline, by adopting statistical correlation and regression analyses. Through the Pearson's correlation coefficient (r) it was observed that local factors such as annual dredging at the Aveiro Port entrance (r = 0.93), the total length of groins in the Espinho-Vagueira section (r = 0.89), and storm events (r = 0.52) are directly related to coastline retreat in the area. A multiple linear regression model was developed in which coastline retreat is explained by these same factors over the period 1980 to 2006. With a coefficient of determination of R² = 0.91, it was observed that length of groins (significant at the 1% level), dredging of the port entrance (significant at the 5% level) and precipitation (as a proxy for storm events; significant at the 10% level) are significantly correlated with coastline retreat. Hence, it is shown that anthropogenic factors are the main drivers of coastline retreat in Vagueira Beach. This study provides an innovative approach for the assessment of coastal erosion, resulting in important information that can be used for decision-making related to coastal zone management as it allows to understand in greater detail the main drivers of coastal erosion.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

Seven human coronaviruses are known to infect humans. The most recent one, SARS-CoV-2, was isolated and identified in January 2020 from a patient presenting with severe respiratory illness in Wuhan, China. Even though viral coinfections have the potential to influence the resultant disease pattern in the host, very few studies have looked at the disease outcomes in patients infected with both HIV and hCoVs. Groups are now reporting that even though HIV-positive patients can be infected with hCoVs, the likelihood of developing severe CoV-related diseases in these patients is often similar to what is seen in the general population. This review aimed to summarize the current knowledge of coinfections reported for the HIV and hCoVs. Also, based on the available data, this review aimed to theorize why HIV-positive patients do not frequently develop severe CoV-related diseases.

The new pandemic coronavirus disease 2019 (COVID-19) is a worldwide threatening health issue. Early progression of this disease starts in the lung airways with an exaggerated inflammation, triggered by the viral infection and characterized by a “cytokine storm” that can lead to lethal lung injuries. In the absence of an effective anti-viral molecule and until the formulation of a successful vaccine, anti-inflammatory drugs might offer a complementary tool for controlling the associated complications and thus decreasing the subsequent fatalities. Drug repurposing for several molecules has emerged as a rapid temporary solution for COVID-19. Among these drugs, Thalidomide, a historically emblematic controversial molecule that harbors an FDA approval for treating Erythema Nodosum Leprosum (ENL) and multiple myeloma (MM). Based on only one-case report of positive outcomes in a patient treated amongst others with Thalidomide, two clinical trials on the efficacy and safety of Thalidomide in treating severe respiratory complications in COVID-19 patients were registered. Conversely, the absence of any substantial, promising evidence on Thalidomide usage in that context along with the discontinued studies on the efficiency of this drug in similar pulmonary diseases might cause a significant obstacle for carrying on clinical studies. In this review, we will discuss the theoretical effectiveness of this drug in attenuating inflammatory complications that are encountered in patients with COVID-19 while pinpointing the lack of evidence that is needed to move forward with this drug.

Introduction: The COVID-19 pandemic is a global crisis, the number of cases and deaths are on a steep incline. This article reviews the possible immunological mechanisms which underlie the disease pathogenesis by looking at the behaviour of previous coronaviruses not only in humans but also other mammals which possibly act as reservoir hosts. Observations: A key aspect of this coronavirus as well as the previous SARS CoV seems to be the importance of host immune response in the pathology and clinical severity of illness caused by them. A hyperactive innate immune state in combination with an exhausted adaptive immune response are possible determinants of severe illness. Conclusion: There is a possibility that the current SARS CoV 2 has immune evasive tactics similar to SARS CoV in its repertoire, since they share a 76% homology. These might have been learnt behaviour from long periods of persistence in their reservoir hosts and they may be the reason behind the dysregulated immune response evoked in humans. That in turn is highly likely to be one of the factors which govern disease severity. With this in mind we want to bring the medical community’s attention to a ‘hit early, hit hard’ intervention as a possible strategy to modify the course of the disease and bring down the numbers of severe sufferers.

We present the AI-discovered aetiology of COVID-19, based on a precise disease model of COVID-19 built under five weeks that best matches the epidemiological characteristics, transmission dynamics, clinical features, and biological properties of COVID-19 and consistently explains the rapidly expanding COVID-19 literature. We present that SARS-CoV-2 implements a unique unbiased survival strategy of balancing viral replication with viral spread by increasing its dependence on (i) ACE2-expressing cells for viral entry and spread, (ii) PI3K signaling in ACE2-expressing cells for viral replication and egress, and (iii) viral-non-structural-and-accessory-protein-dependent immunomodulation to balance viral spread and viral replication. We further propose the combination of irinotecan (an in-market topoisomerase I inhibitor) and etoposide (an in-market topoisomerase IIinhibitor) could potentially be an exceptionally effective treatment to protect critically ill patients from death caused by COVID-19-specific cytokine storms triggered by sepsis, ARDS, and other fatal comorbidities.

The COVID-19 pandemic cost 7-8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the SARS-CoV2 virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in ARDS and lung injury. Anti-inflammatory intervention with anti-IL6 (anti-IL-6 receptor monoclonal antibodies (mAbs) (e.g., sarilumab, tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and /or steroid-based approach lead to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this short review, we summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus–host immune cross talks and presenting the possibilities of therapeutic intervention.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

The risks for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection are higher in obese individuals. Obesity is a state of chronic low-grade inflammation, with high leptin levels due to leptin resistance, high basal levels of other pro-inflammatory cytokines such as TNF-alpha, MCP-I and IL-6, and low adiponectin levels, thus contributing to a state of defective innate immunity as well as impaired B and T cell responses. Obesity is a risk factor for metabolic syndrome, diabetes, cardiovascular disease and hypertension. It has been observed that pre-existence of these diseases confers a higher risk of severe SARS CoV2 infection as well as the need for intensive care; even below the age of 60 years if their body mass index (BMI) is greater than 30 kg/m2, and even more so if it is > 35 kg/m2. The metabolic factors contributing to the changes in altering the immune mechanisms in obese individuals and how this enhances the susceptibility to infection and development of serious SARS-CoV2 infection have been the subject of many debates. Future development of targeted therapy and guidelines will be benefited by greater understanding into these metabolic pathways.

The ongoing COVID-19 pandemic is one of the biggest health and societal challenges of the recent decades. Among the causes of mortality triggered by SARS-CoV-2 infection, the presence of an inflammatory "cytokine storm" (CS) at later stages of the disease has been found to play a determinant role. Here, we used available transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients suffering from a CS to obtain gene-signatures associated to this pathological process. Using these signatures, we interrogated the Connectivity MAP (CMap) dataset that contains the effects of over 5,000 small molecules on the transcriptome of human cancer cell lines, and looked for molecules which effects on transcription mimic or oppose those associated to the CS. Consistent with their medical use, this analysis found a significant enrichment of glucocorticoids or inhibitors of the Janus Kinases (JAK) as drugs that could revert the CS. On the other hand, molecules that potentiate the immune response such as PKC activators are predicted to worsen the CS. Besides these expected findings, our analysis also reveals a potential effect of the antibiotic doxycycline or MAPK/RAF/MEK inhibitors in reverting the CS, or of topoisomerase inhibitors and the anti-alcohol abuse drug disulfiram in potentiating its effects. Finally, our analyses support that the gender-related differences in the severity of COVID-19 are related to the anti-inflammatory properties of female hormones. While acknowledging that this is an analysis based on limited available data, we decided to share it as a resource that might help others in the selection of drugs that could be tested in the context of experimental models of CS triggered by viral infections.

The Lower Rio Grande Valley, South Texas is considered one of the more vulnerable coastal areas to flooding related with abrupt climate changes. From 1980-2017, there were 7 flooding events, 57 severe storm events, and 8 tropical cyclone events with losses exceeding $1 billion in the State of Texas, according to NOAA NCEI. Coastal flooding is typically a result of storm surge and heavy rainfall produced by hurricanes and tropical storms. In this study, the two-dimensional hydrodynamic flow circulation model is developed to predict the Lower Rio Grande Valley coastal area inundation due to the hurricane storm surge, especially in the case of Hurricane Beulah, 1967. The tropical cyclone properties and tidal constituents were assigned to the updated watershed geographic information with the bottom bathymetric and roughness data. For model validation, the Hurricane Dolly 2008 storm surge due to Hurricane Beulah at the coast and the storm surge reaches up to approximately 40 kilometers west from the coast through a natural river channel. This model can be used for a reliable engineering tool for the coastal hazard emergency management and disaster mitigation.

COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-a. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IkBa was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF-a levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIkBa in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Given the documented wave-induced damage of elevated coastal decks during extreme natural hazards (e.g. hurricanes) in the last two decades, it is of utmost significance to decipher the wave-structure-interaction of complex deck geometries and quantify the associated loads. Therefore, this study focuses on the assessment of solitary wave impact on open-girder decks that allow the air to escape from the sides. To this end, an arbitrary Lagrangian-Eulerian (ALE) numerical method with a multi-phase compressible formulation is used for the development of three-dimensional hydrodynamic models, which are validated against a large-scale experimental dataset of a coastal deck. Using the validated model as a baseline, a parametric investigation of different deck geometries with a varying number of girders Ng and three different widths, was conducted. The results reveal that the Ng of a superstructure has a complex role and that for small wave heights the horizontal and uplift forces increase with the Ng, while for large waves the opposite happens. If the Ng is small the wave particles accelerate after the initial impact on the offshore girder leading to a more violent slamming on the onshore part of the deck and larger pressures and forces, however, if Ng is large then unsynchronized eddies are formed in each chamber, which dissipate energy and apply out-of-phase pressures that result in multiple but weaker impacts on the deck. The decomposition of the total loads into slamming and quasi-static components, reveals surprisingly consistent trends for all the simulated waves, which facilitates the development of predictive load equations. These new equations, which are a function of Ng and are limited by the ratio of the wavelength to the deck width, provide more accurate predictions than existing empirical methods, and are expected to be useful to both engineers and researchers working towards the development of resilient coastal infrastructure.

The coronavirus disease 2019 (COVID-19) is now a global pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unlike other known coronaviruses, such as the Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 reveals new clinical, immunological, and pathologic features. The lymphocyte depletion, macrophage and neutrophil hyperactivation, cytokine dysregulation, thrombophilia, delayed antiviral response, and immune exhaustion are key immunological findings linked to the clinical progression of this disease. Understanding and identifying the underlying immunological basis of COVID-19 is crucial to designing effective therapies. Here, we provide an overview of immunopathogenesis driven by SARS-CoV-2 after its interactions with the immune system.

Parametric cyclonic wind fields are widely used worldwide for insurance risk underwriting, coastal planning, or storm surge forecasts. They support high-stakes financial, development, and emergency decisions. Yet, there is still no consensus on the best parametric approach, or relevant guidance to choose among the great variety of published models. The aim of this paper is first and foremost to demonstrate that recent progresses on estimating extreme surface wind speeds from satellite remote sensing now makes it possible to select the best option with greater objectivity. In particular, we show that the Cyclone Global Navigation Satellite System (CYGNSS) mission of NASA is able to capture a substantial part of the tropical cyclones structure, and allows identifying systematic biases in a number of parametric models. Our results also suggest that none of the traditional empirical approaches can be considered as the best option in all cases. Rather, the choice of a parametric model depends on several criteria such as cyclone intensity and/or availability of wind radii information. The benefit of using satellite remote sensing data to better select a parametric model for a specific case study is tested here by simulating hurricane Maria (2017). The significant wave heights computed by a wave-current hydrodynamic coupled model are found to be in good accordance with the predictions given by the remote sensing data in terms of bias. The results and approach presented in this study should shed new light on how to handle parametric cyclonic wind models, and help the scientific community to conduct better wind, waves and surge analysis for tropical cyclones.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID’, emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review provides a summary of the primary effects of long COVID on the cardiovascular, nervous, and respiratory systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.

Urban trees are often more sun- and wind-exposed than their forest-grown counterparts. These environmental differences can impact how many species grow – impacting trunk taper, crown spread, branch architecture, and other aspects of tree form. Given these differences, windthrow models derived from traditional forest production data sources may not be appropriate for urban forest management. Additionally, visual abnormalities historically labeled as “defects” in timber production may not have a significant impact on tree failure potential. In this study, we look at urban tree failures associated with Hurricane Irma in Tampa, Florida, USA. We used spatial analysis to determine if patterns of failure existed among our inventoried trees. We also looked at risk assessment data to determine which visual defects were the most common and the most likely to be associated with branch or whole-tree failure. Results indicate that there was no spatial pattern associated with the observed tree failures – trees failed or withstood the storm as individuals. While some defects like decay and dead wood were associated with increased tree failure, other defects like weak branch unions and poor branch architecture were less problematic.

The energy potential of long-period oscillations is estimated by comparing it with watercourse power. The relaxation time of long-period waves is chosen for the estimation time interval, during which their amplitude decreases e (Euler's number) times from the initial one. According to calculations, the amount of energy produced during this time by the watercourse is 9.35–18.71 million kW×h, while the amount of energy of long-period oscillations is 3–6 times less – 1.60–5.48 million kW×h. The components of the economic factor of using long-period waves and currents for electricity production are the predictability of their magnitudes and location of maxima, long-term availability, concentration.

Dust storms originating from Central Australia and western New South Wales frequently cause high particles concentration at many sites across New South Wales, both inland and along the coast. This study focussed on a dust storm event in February 2019 which affect air quality across the state as detected at many ambient monitoring stations in the Department of Planning, Industry and Environment (DPIE) air quality monitoring network. The WRF-Chem (Weather Research and Forecast Model – Chemistry) model is used to study the formation, dispersion and transport of dust across the state of New South Wales (NSW, Australia). Wildfires also happened in northern NSW at the same time of the dust storm in February 2019, and their emissions are taken into account in WRF-Chem model by using Fire Inventory from NCAR (FINN) as emission input. The model performance is evaluated and is shown to predict fairly accurate the PM2.5 and PM10 concentration as compared to observation. The predicted PM2.5 concentration over New South Wales during 5 days from 11 to 15 February 2019 is then used to estimate the impact of the February 2019 dust storm event on three health endpoints namely mortality, respiratory and cardiac diseases hospitalisation rates. The results show that even though as the daily average of PM2.5 over some parts of the state, especially in western and north western NSW near the centre of the dust storm and wild fires, are very high (over 900 µg/m3), the population exposure is low due to the sparse population. The top five Statistical Area Level 4 regions with the most impact in term of mortality, respiratory diseases hospitalisation and cardiac disease hospitalisation are Far West and Orana, Newcastle and Lake Macquarie, New England and North West, Sydney – Inner South West and either Central Coast (mortality) or Sydney – Parramatta (respiratory diseases hospitalisation) or Sydney – Inner West (cardiac diseases hospitalisation). Generally, the health impact is similar in order of magnitude to that caused by biomass burnings events from wildfires or from hazardous reduction burnings (HRBs) near populous centres such as in Sydney in May 2016. One notable difference is the higher respiratory diseases hospitalisation for this dust event (161) compared to fire event (24).

COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.

The traditional approach of considering the probability distribution of rain attenuation leads to overdesign the power margin of data channels. We have first recalled a method, proposed in 2016, which with a small power margin, bandwidth expansion and variable symbol rate avoids overdesign and can transfer the same data volume as if the link were in clear–sky conditions. It is charaterized only by the link mean efficiency 0≤η≤1, suitably defined. It is usefull only if: (a) data must be downloaded also when it is raining; (b) real–time communication is not strictly required. We have applied it to the links of GeoSurf satellite constellations by simulating rain attenuation time series at 80 GHz (mm–wave) with the Synthetic Storm Technique, from rain-rate time series recorded on–site, at sites located in different climatic regions. The power margin to be implemented ranges from 2.0 dB to 7.4 dB – well within the current technology – regardless the instantaneous rain attenuation. The clear–sky bandwidth is expanded 1.75 to 2.80 times, not large per se, but it may challenge current technology if the clear–sky bandwidth is already large.

Landward displacement of coastal boulders is a morphodynamic signature of inundation and erosion processes. The study of these movements can provide useful elements for coastal hazards assessment. In this note, using open-access remote sensing resources, the 2017 to 2021 annual mobility of medium, coarse, and very coarse boulders spread over about 100 km of the eastern coast of the Gulf of Taranto (Italy) is detected. A large interannual variability was found. As established by multi-temporal object-based image analysis, one hundred and ten boulders changed position between July 2019 and June 2020, no boulder was displaced between July 2017 and July 2018, and few boulders were displaced between July 2018 and July 2019, and June 2020 and September 2021. A hydrodynamic analysis of the investigated boulder displacement led to the estimation of the energy of nearshore waves that hit the coast. The storm Detlef, that crossed over the Mediterranean Sea during 11-13 November 2019, is presumed to be the main cause of the massive displacement phenomenon.

Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.

The main goal of the paper is to compare the effects of the wave spectrum, computed using the Discrete Interaction Approximation (DIA) and the Webb–Resio–Tracy (WRT) methods, on statistical wave properties such as skewness and kurtosis. The statistical properties are obtained by integrating the three-dimensional free-surface Euler equations with a high-order spectral method combined with a phenomenological filter to account for the energy dissipation due to breaking waves. In addition, we investigate the minimum spatial domain size required to obtain meaningful statistical wave properties. The numerical simulations are performed over a physical domain of size 4.13 km × 4.13 km. The results indicate that statistical properties must be computed over an area of at least 4 km2. The results also suggest that selecting a more computationally expensive WRT method does not affect the statistical values to a great extent. The most noticeable effect is due to the energy dissipation filter that is applied. It is concluded that selecting the WRT or the DIA algorithm for computing the wave spectrum needed for the numerical simulations does not lead to major differences in the statistical wave properties. However, more accurate energy dissipation mechanisms due to wave breaking are needed.

Evidence was brought forward in England and the USA that Black, Asian, Latino and Minority Ethnic people exhibit higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the Interferon-induced transmembrane protein 3 (IFITM3) gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. IFITM3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up to these two developments in the ongoing SARS-CoV-2 pandemic, the present study investigates a possible association between the differences in mortality of ethnic groups in England and the combined haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for 26 populations from 1000 Genomes Project and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A significant correlation (r=0.9687, p= 0.0003) was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles, suggesting that the combination of reference alleles of the specific SNPs may be implicated in more severe outcomes of COVID-19. This study calls for further focus on the role of IFITM3 variants in the mechanism of cellular invasion of SARS-CoV-2, their impact in COVID-19 severity and their possible implications in vaccination efficacy.

Traditional flood hazard analyses often rely on univariate probability distributions; however, in many coastal catchments, flooding is the result of complex hydrodynamic interactions between multiple drivers. For example, synoptic meteorological conditions can produce considerable rainfall-runoff, while also generating wind-driven elevated sea levels. When these drivers interact in space and time, they can exacerbate flood impacts; this phenomenon is known as compound flooding. In this paper, we build a Bayesian Network based on Gaussian copulas to generate the equivalent of 500 years of daily stochastic boundary conditions for a coastal watershed in Southeast Texas. In doing so, we overcome many of the limitations of conventional univariate approaches and are able to probabilistically represent compound floods caused by riverine and coastal interactions. We calculate the resulting water levels using a 1D steady-state hydraulic model and find that flood stages in the catchment are strongly affected by backwater effects from tributary inflows and downstream water levels. By comparing with a bathtub modeling approach, we show that simplifying the multivariate dependence between flood drivers can lead to an underestimation of flood impacts, highlighting that accounting for multivariate dependence is critical for the accurate representation of flood risk in coastal catchments prone to compound events.

Boulder dynamics may provide essential data for the coastal evolution and hazards assessment and can be focused as a proxy for the onshore effect of intense storm waves. In this work, detailed observations of currently available satellite imagery of the Earth surface allowed to identify several coastal boulders displacements in the Southern Apulia coast (Italy), in a period between July 2018 and June 2020. Field surveys confirmed the displacements of several dozens of boulders up to several meters in size, also allowing the determination of the initial position for many of them. Archive weather analyses identified two possible causative storms during the same period, and calculations based on analytical equations are found in agreement with the displacement by storm waves for most of the observed boulders. The results help to give insights about the onshore effect of high storm waves on the coastal hydrodynamics and the possible future flooding hazard in the studied coast.

The storm of November 12th-13th, 2019 provoked the displacements of boulders in a central Mediterranean rocky coast; with reference to a selected area, prone to the boulder production and geomorphologically monitored for years, a field-oriented study approach was applied for the phenomenon, by collating data concerning pre-storm locations and kinematics of these boulders. The number of displaced boulders is 11, that is, in terms of morphological imprint of a specific storm, one of the major study cases for the Mediterranean. In addition, based on widely used hydrodynamic equations, the minimum wave height required to displace the boulders is assessed. The values conform with the expected values for the wave climate dominating during the causative meteorological event and give a measure of the energy of the storm slamming the coast. Boulder dislodgements usually have plays a key role in determining the rate of the coastal recession, likely also in the investigated area. In view of an adverse climate evolution with a possible increase of energy and frequency of severe storms, the results deriving from the study of this morphodynamics should be considered for the hazard assessment and coastal management.

Stormwater management is a key urban issue in the world, in line with the global issues of urban sprawl and climate change. It is urgent to investigate the effectiveness in managing stormwater with different strategies for maintain urban resilience. A method based on a storm water management model (SWMM) was developed for assessing the control of stormwater runoff volume and the percentage removal of suspended solids by implementing a Sponge City strategy. An interdisciplinary approach was adopted incorporating Low Impact Development (LID) with urban Green Infrastructure and Gray Infrastructure paradigms in a typical old residential community in Suzhou, China. Four types of sponge facilities for reducing stormwater runoff were bio-retention cells, permeable pavements, grassed pitches, and stormwater gardens. The simulation results indicate that the stormwater pipe system can meet the management standard for storms with a five-year recurrence interval. The volume capture ratio of annual runoff is 91% and the reduction rate of suspended solids is 56%. This study demonstrates that Sponge City strategy is an effective approach for managing stormwater, particularly in old and densely populated urban areas. Implementing spongy facilities with a LID strategy for stormwater management can significantly enhance urban water resilience and increase ecosystem services.

The premise regarding COVID-19 disease is that it is a spectrum which begins with infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The individual response to it depends on many factors including co-morbid conditions. An important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops after the infection. The immuno-chemical chaos created in this cytokine storm is to the benefit of the virus. In this meta analysis the authors explore ways to let the cytokine storm die down by looking into the role of histamine. Histamine is a metabolic product of the essential aminoacid histidine. Histamine has 4 known receptors: H1, H2, H3 and H4. The immunoglobulines IgE and IgM are indicative for a COVID-19 infection. This immune response is related to inflammation. Inflammation, in turn, runs mainly via histamine after e.g. virus inoculation. The goal of the meta-study is to gather evidence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the cytokine overproduction in the $\approx$ 30\% of the patients suffering from gastrointestinal problems caused by SARS-CoV-2. Our concept is as follows. If we can strike a careful balance between hampering the gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine storm, then the natural immunity can later on come on line again and attack the virus without being led astray by cytokine chaos. We will concentrate on H4R but also look at H1R and H2R related effects. The proposed substances in our systemic approach can be balanced for an effective early treatment. The nature of our work is by its method and results theoretical. In that respect we also may note the structural chemistry indol skeleton resemblance among a number of different drugs.

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

Severe COVID-19 alters the biochemical and morphological characteristics of blood cells in a wide variety of ways. To date, however, the vast majority of research has been devoted to the study of leukocytes, while erythrocyte morphological changes have received significantly less attention. The purpose of this research was to identify erythrocyte types that were unique to COVID-19, compare the number of different poikilocyte types, and measure erythrocyte sizes to provide data on size dispersion. Red blood cells obtained from 6 control donors (800-2200 cells for each donor) and 5 COVID-19 patients (800-1900 cells for each patient) were examined using low voltage scanning electron microscopy. We did not discover any forms of poikilocytes that would be unique to COVID-19. Among COVID-19 patients, we observed an increase in the number of acanthocytes (p=0.01) and a decrease in the number of spherocytes (p=0.03). In addition, our research demonstrates that COVID-19 causes an increase in the median (p=0.004) and interquartile range (p=0.009) when assessing erythrocyte size.

Combined sewer overflow (CSO) is a significant environmental concern and public health (e.g., water contamination, eutrophication, and beach closure). The Environmental Protection Agency (EPA) has introduced the National Pollutant Discharge Elimination System (NPDES) permitting program to regulate and address this matter. This program mandates the control of CSOs for more than 700 municipalities obligated to devise Long-term Control Plans (LTCPs) to curb combined sewer overflows and bring them down to safe levels. LTCP involves diverse strategies, including sewer separation, green infrastructure improvements, and conventional gray infrastructure upgrades. This study investigates several municipalities’ solutions for CSO problems in conventional methods and wireless sensor technology as real-time control. The investigation mainly focuses on a comparative analysis of two cities, Richmond, Virginia, and South Bend, Indiana, such as average rainfall, the frequency of overflows, and the capacity of treatment plants. The findings indicate that integrating sensor technology could significantly enhance modeling endeavors, bolster the capacity of existing structures, and substantially enhance preparedness for storm events. The EPA’s Storm Water Management Modeling (SWMM) software is utilized. Through an analysis of SWMM data, the study suggests the potential for leveraging wireless sensor technology to achieve more robust control over CSOs as a part of LTCPs.

Several coastal barriers experienced significant erosion and change in shape throughout the Mediterranean coasts over the past decades, and the issue has become of increasing concern for scientists and policymakers. With reference to a case study and by meteorological and geomorphological investigations, this note aims to infer recent shoreline dynamics and define coastal phenomena shaping the beach-dune barrier of Cesine Lagoon (South Italy), to finally point out the weather-driven processes. A challenge for this research was to obtain significant results from publicly available sources and simple and inexpensive methods. The retreat of the dune toe, the accretion of washover fans, and the formation of gravel beaches have been related to the analyzed wind-wave conditions. Net longshore transport was found in accordance with the direction of the more intense winds. The role of extreme events in the shaping of coastal landforms is yet to be established even if they greatly increase the vulnerability to flooding of the study area. The results achieved so far are starting points for further data collection and analysis in the perspective of assessing the impact of climate changes on the lagoon barrier.

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. The anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of lead compounds was confirmed using lipopolysaccharide (LPS) treated blood to mimic conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disorder which is characterized by fibrofatty degeneration of cardiac muscles mainly in the right ventricular myocardium. It may cause tachyarrhythmias or right-heart failure or may cause sudden death, especially in young athletes. In our case report, we present a case of young age male patient who presented at a local community hospital with the complaint of atypical chest pain, palpitations, and vomiting and sustained ventricular tachycardia (VT) on electrocardiograph (ECG) showing sustained ventricular tachycardia, left bundle branch morphology with the superior axis. The normal sinus rhythm was achieved after multiple DC cardioversion attempts and he was referred to our tertiary care hospital. Later ECG demonstrated epsilon waves and T wave inversion in v1 to v4 and RBBB morphology. The echocardiography showed a severely dilated right ventricle with dysfunction and right ventricle ventricular apical aneurysm. The definitive diagnosis of ARVC was made as per Revised Task Force Criteria 2010 and the electrophysiology review suggested implantable cardiac defibrillator (ICD) device placement. The patient successfully received a dual-chamber ICD device and he remained asymptomatic.

This study reports the first example of major erosion from hurricanes degrading a rocky coastline anywhere around the Gulf of California, although other sources of evidence are well known regarding the effect of inland erosion due to catastrophic rainfall in the Southern Cape Region of the Baja California peninsula and farther north. The uplifted, 12-meter terrace on the eastern shore of Isla del Carmen is the site of an unconsolidated coastal boulder deposit (CBD) consisting of large limestone blocks and boulders eroded from underlying Pliocene strata. The CBD stretches approximately 1.5 km in length, mostly set back 25 m from the lip of the terrace. The largest blocks of upturned limestone near the terrace edge are estimated to weigh between 5.8 and 28 metric tons. Waves impacting the rocky coast that peeled back slabs of horizontally layered limestone at this spot are calculated to have been between 11.5 and 14 m in height. Analysis of sampled boulders from the CBD set back from the terrace edge by 25 m suggest that the average wave height responsible for moving those boulders was on the order of 4.3 m. Additional localities with exposed limestone shores, as well as other more common rock types of igneous origin, have yet to be surveyed for this phenomenon elsewhere around the Gulf of California.

A typhoon-induced storm surge is considered one of the most severe coastal disasters in Taiwan. However, the combination of the storm surge and the astronomical tide called the storm tide can actually cause extreme flooding in coastal areas. This study implemented a two-dimensional hydrodynamic model to account for the interaction between tides and storm surges on the coast of Taiwan. The model was validated with observed water levels at Sauo Fish Port, Hualien Port, and Chenggong Fish Port under different historical typhoon events. The model results are in reasonable agreement with the measured data. The validated model was then used to evaluate the effects of the typhoon's intensity, bathymetric change, and the combination of the typhoon’s intensity and bathymetric change on the maximum storm tide and its distribution along the east coast of Taiwan. The results indicated that the maximum storm tide rises to 1.92 m under a typhoon with an intensity of a 100-year return period. The maximum storm tide increased from a baseline of 1.26 m to 2.63 m for a 90% bathymetric rise at Sauo Fish Port under the conditions of Typhoon Jangmi (2008). The combination of the intensity of a typhoon with a 100-year return period and a 90% bathymetric rise will result in a maximum storm tide exceeding 4 m, 2 m, and 3 m at Sauo Fish Port, Hualien Port, and Chenggong Fish Port, respectively. We also found that the distribution of the maximum storm tide on the east coast of Taiwan can expand significantly subject to the bathymetric rise.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.

A better understanding of the expected future cyclonic activity, especially in the Mediterranean Basin in winter, is essential for developing scientifically based adaptation and mitigation methods to extreme precipitation and wind anomalies. The aim of this study is to analyze the change of winter cyclonic activity in the Mediterranean-Black Sea region, within the Atlantic–European region, at the beginning (as the recent historical period), middle and end of the 21st century. The projections are based on an ensemble of seven CMIP6 models, which showed the best consistency with NCEP/NCAR and ERA5 reanalysis, under the intermediate SSP2-4.5 and highest-emission SSP5-8.5 scenarios. The results show a consistent increase of the frequency of cyclones over Central Europe and the British Isles associated with the shift of cyclone tracks: norward from the Western Mediterranean region and southward from the Iceland Low. The latter leads to a decrease of the frequency in the north of the Atlantic–European region. At the same time, there is a reduction of the frequency of cyclones over the east of the Mediterranean Sea consistent with the decrease of cyclogenesis events. Area-averaged cyclone numbers in the Western and Eastern Mediterranean and the Black Sea subregions reduce to the end of the century under the highest-emission scenario, but not constantly and with a raise in the middle of the 21st century under both scenarios, which may be linked to the long-term multidecadal variability or regional features. In general, our study shows that the future winter cyclonic activity in the Mediterranean-Black Sea region responds unevenly to global climate changes, because regional and monthly features are important, as well as accounting for the long-term quasiperiodic variability.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

Electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 hours. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1-V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On the day 8 of hospitalization, patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.

Keywords: Baseband, GeoSurf Constellation, Interference, Linear Distortions, Passband, Time Delay, Rain attenuation, Synthetic Storm Technique, ultra–wideband.

With an estimated 3 to 5 million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society [1] and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are shedding new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.