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This paper is devoted to the multidisciplinary modelling of a pandemic initiated by an aggressive virus, specifically the so-called SARS–CoV–$2$ Severe Acute Respiratory Syndrome, corona virus n.$2$. The study is developed within a multiscale framework accounting for the interaction of different spatial scales, from the small scale of the virus itself and cells, to the large scale of individuals and further up to the collective behaviour of populations. An interdisciplinary vision is developed thanks to the contributions of epidemiologists, immunologists and economists as well as those of mathematical modellers. The first part of the contents is devoted to understanding the complex features of the system and to the design of a modelling rationale. The modelling approach is treated in the second part of the paper by showing both how the virus propagates into infected individuals, successfully and not successfully recovered, and also the spatial patterns, which are subsequently studied by kinetic and lattice models. The third part reports the contribution of research in the fields of virology, epidemiology, immune competition, and economy focussed also on social behaviours. Finally, a critical analysis is proposed looking ahead to research perspectives.

SARS-CoV-2 is a deadly virus that has affected human life since late 2019. Between all the countries that have reported the cases of patients with SARS-CoV-2 disease (COVID-19), the United States of America has the highest number of infected people and mortality rate. Since different states in the USA reported different numbers of patients and also death cases, analyzing the difference of SARS-CoV-2 between these states has great importance. Since the generated RNA walk from the SARS-CoV-2 genome includes complex random fluctuations that also contain information, in this study, we employ the complexity and information theories to investigate the variations of SARS-CoV-2 genome between different states in the USA for the first time. The results of our analysis showed that the fractal dimension and Shannon entropy of genome walk significantly change between different states. Based on these results, we can conclude that the SARS-CoV-2 genomic structure significantly changes between different states, which is resulted from the virus evolution. Therefore, developing a vaccine for SARS-CoV-2 is very challenging since it should be able to fight various structures of the virus in different states.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the most dangerous type of coronavirus and has infected over 25.3 million people around the world (including causing 848,000 deaths). In this study, we investigated the similarity between the genome walks of coronaviruses in various animals and those of human SARS-CoV-2. Based on the results, although bats show a similar pattern of coronavirus genome walks to that of SARS-CoV-2 in humans, decoding the complex structure of coronavirus genome walks using sample entropy and fractal theory showed that the complexity of the pangolin coronavirus genome walk has a 94% match with the complexity of the SARS-CoV-2 genome walk in humans. This is the first reported study that found a similarity between the hidden characteristics of pangolin coronavirus and human SARS-CoV-2 using complexity-based analysis. The results of this study have great importance for the analysis of the origin and transfer of the virus.

The current pandemic SARS-CoV-2 (also known as 2019-nCoV and COVID-19) viral infection is growing globally and has created a disastrous situation all over the world. One of the biggest challenges is that no drugs are available to treat this life-threatening disease. As no drugs are available for definitive treatment of this disease and the mortality rate is very high, there is an utmost need to cure the infection using novel technologies. This study will point out some new antimicrobial technologies that have great potentials for eradicating and preventing emerging infections. They can be considered as treatments of choice for viral infections in the future.

A Cu film with the ability to rapidly inactivate the COVID-19 virus was easily fabricated at approximately 23${}^{\circ }$C on a Na-free glass substrate. The well-adhered Cu films with thickness of approximately 16 $\mu$m and surface area of 8.71 10${}^{-3}$ m² g${}^{-1}$ were obtained by immersion of the glass substrate into an aqueous solution with dissolved Cu (II) complex of ammonia and ascorbic acid. The interface bonded between the film and glass substrate was very strong, such that the film did not peel off even when it was exposed to an ultrasonic wave of 100 mW (42 kHz) in water. The anti-COVID-19 activity in Dulbecco’s modified Eagle’s medium (DMEM) is effective within 2 h and is faster than that of commercial copper plates. The changes in the relative abundance of Cu₂O and CuO crystallines on the Cu film due to DMEM treatment and those in surface morphology were examined by X-ray diffraction peak analysis and field emission-scanning electron microscopy, respectively. The flame atomic absorption analyses of the recovered solutions after DMEM treatment indicated that the Cu ions from the Cu film with DMEM treatment for 1 hour at a concentration of 0.64 ± 0.03 ppm were eluted 2.3 times faster than those from the Cu plate. The rapid elution of Cu ions from Cu₂O crystallines on the film in the early stage is the primary factor in the inactivation of the COVID-19 virus, as elucidated from the time dependence of eluted Cu ions by DMEM treatment. Results from thermogravimetric and differential thermal analysis (TG-DTA) of the powder scratched from the Cu film suggested that a trace amount of organic residues remaining in the Cu film was important in the rapid activity.

The inactivation ability of SARS-CoV-2 (COVID-19) was examined using two types of transparent Cu₂O thin films with different crystallinities on a Na-free glass substrate. The low-crystallinity Cu₂O thin film, which was fabricated by irradiating 254 nm ultraviolet (UV)-light with an intensity of 6.72 mW cm${}^{-2}$ onto a spin-coated precursor film involving Cu${}^{2+}$ complexes at room temperature, exhibited an outstanding COVID-19 inactivation ability to reduce 99.999% of the virus after 1 h of incubation. The X-ray diffraction results of the UV-irradiated thin film indicated a cubic Cu₂O lattice with a small crystallite size of 2 ± 1 nm. Conversely, the high-crystallinity Cu₂O thin film with a crystallite size of 16 ± 3 nm, obtained by heating a spin-coated precursor film containing another Cu${}^{2+}$ complex, showed a negligibly low inactivation activity at the same level as the Na-free glass substrate. The eluted concentrations of Cu ions from both Cu₂O thin films were analyzed after immersion in Dulbecco’s modified Eagle’s medium (DMEM) for 0.25–2 h. The eluted Cu–ion concentration of 1.16 ppm was observed for the UV-irradiated thin film by DMEM immersion after 1 h, but that of 0.04 ppm was observed for the heat-treated thin film. This indicated that an important factor of virus inactivation on Cu₂O thin films is highly related to the elution of Cu ions that occurred from the surface in the medium.

Millennia separate smallpox, the oldest pandemic, and COVID-19, the newest. Both calamities arose from an opportunistic virus amid human crowding. A vaccine for smallpox existed since the late 18th century, but it took worldwide public health strategy to eradicate it. COVID-19 proceeds against a hive of scientific collaboration, but succeeds, so far, from weak containment policies. COVID-19 was first identified in China, but it rose to become the American pandemic.

Viral respiratory infections have plagued mankind over its known history. Unfortunately, there has been a lack of meaningful progress in preventing the spread of viral respiratory infections globally. The central dogma appears to be that viruses are the villains. This framing focuses on a viral load balance (VLB) in the air. It follows that physical dilution through various means have been the primary focus of attempts to reduce the spread of infections. The problem of obesity provides a good example of how paradigm blindness can slow down progress in a field. Obesity has been framed as an energy balance disorder that blames overeating and lack of exercise for weight gain. Reframing obesity as a disorder of fat metabolism and storage caused by the quantity and quality of carbohydrates in the diet, referred to as the carbohydrate-insulin model (CIM), opened an alternative line of questioning with a testable hypothesis. Similarly, we postulate an alternative way to frame the spread of viral respiratory infections that would lead to new insights and potentially new ways to prevent infections.

It has long been recognized that viral respiratory infections show a pronounced seasonal variation, referred to as seasonal forging, such that they increase in the winter but decrease or virtually disappear in the summer. In temperate regions, people spend over 90% of their time indoors. This is, therefore, where most respiratory infections are expected to occur. Evidence has been accumulating for decades on the strong correlation between variations in indoor relative humidity (RH) and variations in infection rates. Within a RH Goldilocks zone of 40%-60%, encapsulated viruses like influenza and SARS are optimally inactivated outside the infected host. Below 40% and above 80%, viruses can survive for extended periods in the air or on surfaces. This may explain in part the seasonality of infections as the indoor level of RH in winter is typically about 20% and above 40% in summer in temperate regions. However, the mechanism for the inactivation at midrange RH (in summer) is not well understood. This paper offers a hypothesis that could explain these observations.

We have demonstrated that H₂O₂ and other reactive oxygen species (ROS) are formed spontaneously at the water-air interface of pure water microdroplets. Using only water and a nebulizing gas in the presence of oxygen, we have demonstrated the significant disinfectant potential of pure water microdroplets caused by the activity of H₂O₂ and other ROS. We postulate that spontaneous H₂O₂ and ROS formation in viruses containing exhaled microdroplets have a similar virucidal effect at mid-range RH. The droplet evaporation rate is sufficient to concentrate the solutes and provide enough time for reactions to occur at significantly higher rates than in bulk solutions. The concentration of H₂O₂ has also been shown to be positively correlated to RH. In addition, several other ROS/RNS may be present or formed through interactions with H₂O₂ that may act as even more effective virucide disinfectants to inactivate the virus. Below RH 40% evaporation happens too rapidly for these reactions to make an impact before the droplet is desiccated, and above RH 80% the solutes remain too diluted. Rapid inactivation of viruses at midrange RH may therefore play a greater role in preventing infections than physical dilution of virus load in the air through excessive mechanical ventilation. Similar to obesity, we suggest that a new paradigm that considers virus infectivity outside the host rather than the virus load balance in the air alone could greatly contribute to our understanding of respiratory infections. The proposed new “Relative Humidity Infectivity” RHI paradigm could explain the causal mechanisms underlying seasonal respiratory infections. This can point to better prevention strategies that avoid further distortion of our indoor environment and create conditions within which humans can thrive and be optimally protected. We need more focus on testing the various hypotheses and more data to determine which of the two paradigms will lead us in the right direction or how to use the best of both in an optimal combination. The stakes cannot be higher, and the potential for eradicating future viral respiratory pandemics with nature-based solutions may be right under our noses, literally.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became an established pandemic in 2020. The presence of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in male reproductive organ are considered as a potential for susceptibility of these organs to SARS-CoV-2 infection.

Review: Spermatogonia are the only cells that express ACE2 and TMPRSS2 in the testis, but the cells which co-express both genes are rare (0.05% of cells). Based on this co-expression, sperm are unlikely to be susceptible to infection by SARS-CoV-2. However, the co-expression of receptor basigin (BSG/CD147) and cathepsin L (CTSL) in primary spermatocytes, Leydig cells, myoid cells, endothelial cells, and spermatogonia might increase the testicular susceptibility to this viral infection. Testicular pain and discomfort have been reported in coronavirus disease 2019 (COVID-19) patients. Postmortem examination also reported seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation in COVID-19 patients. Compensated hypogonadism has been documented while the impact of COVID-19 on the semen quality is inconclusive. There is only one study that reported the presence of SARS-CoV-2 RNA in semen but, is not supported by other studies with better methods. The association between SARS-CoV-2 and assisted reproductive technology (ART) outcome is surrounded by some uncertainties. Recommendations have been made to reduce the risk of viral transmission to patients, staff, gametes, and embryos.

Summary: There is no definite correlation between SARS-CoV-2 infection and male reproductive system. However, a high level of vigilance is still required in services which involve the reproductive system.

Background: Asia Pacific Initiative on Reproduction (ASPIRE) aims to improve knowledge and awareness of Assisted Reproductive Technology (ART) and infertility-related services, with the aim of improving the quality of patient care.

Methods: A survey was developed and responded by a group of 10 ASPIRE board members to gather in-depth information about current practices, recommendations, and perceptions about SARS-CoV-2 and ART. The collected data were summarized and individual responses pooled among questions requiring voting. The overall rates were computed by response category. The group discussed the summary evidence, until a consensus was reached concerning a series of recommendation on how to make decisions concerning ART service provision during the current (and any future) pandemic. A two-tier recommendation was developed based on agreement rate and implementation priority. Tier 1 comprises recommendations in which the rate of “absolutely agree” responses were $\ge$60%, whereas tier 2 refers to recommendations in which the rate of “absolutely agree” plus “agree” was >60%, but the rate of “absolutely agree” was $\le$50%.

Results: The survey was responded by all participants between July 24 and July 30, 2020. Nine tier 1 and five tier 2 recommendations are provided concerning prevention, testing, personal protective equipment, informed consent, and quality management. The former indicates the situations in which most individuals should receive the intervention/procedure, whereas the latter relates to those that may be suitable for individual clinics and patients.

Conclusions: This document provides the ASPIRE viewpoint on better managing infertile patients seeking ART during the COVID-19 pandemic. This expert opinion guide aims to help both competent authorities and healthcare providers to deliver quality and safe ART.

On March 12, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic. The rapidly increasing number of cases and deaths have overwhelmed the health care system worldwide. We aimed to provide a narrative review on some practical issues of COVID-19 and rheumatic diseases with the limited data to the date of April 26, 2020.

Coronavirus disease 2019 (COVID-19) was one of the most important infections in the past few years. Although most cases of COVID-19 are mild, serious complications may arise. The multisystem inflammatory syndrome (MIS) is a rare but severe, yet poorly understood complication of COVID-19. It was first described in childhood patients with COVID-19 (MIS-C) but is increasingly reported in adults. MIS-A may lead to diagnostic and therapeutic dilemma as its manifestations may mimic a flare of the underlying disease and the use of immunosuppressive therapy may further increase the risk of other infective complications in these patients. However, MIS-A has rarely been reported in patients with pre-existing autoimmune conditions. We hereby present a patient with systemic lupus erythematosus who developed severe MIS-A 6 weeks after a recent SARS-CoV-2 infection.

Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) epidemic has become a once-in-a-century pandemic sweeping across the whole world. While countries around the world are working together to combat the pandemic, the world still faces serious threats. Current experience shows that prevention is more important than treatment, especially for healthcare workers (HCWs), the infection of whom is tantamount to in-hospital secondary transmission to other HCWs and inpatients. Anesthesia providers, emergency physicians, and healthcare workers in the ICU are at an enhanced risk of contamination; hence, we give some advice derived from clinical practice and other guidance on how to protect HCWs from SARS-CoV-2 infection. Despite high-quality evidence regarding the association between transmission of COVID-19 among the HCWs and aerosol-generating procedures, such as endotracheal intubation, being inadequate, HCWs should raise their vigilance in these procedures and more evidence should be generated.

SARS-CoV-2 Main protease (M^pro) is pivotal in viral replication and transcription. M^pro mediates proteolysis of translated products of replicase genes ORF1a and ORF1ab. Surveying pre-clinical trial M^pro inhibitors suggests potential enhanced efficacy for some moieties. Concordant with promising in vitro and in silico data, the protease inhibitor GC376 was chosen as a lead. Modification of GC376 analogues yielded a series of promising M^pro inhibitors. Design optimization identified compound G59i as lead candidate, displaying a binding energy of $-$10.54 kcal/mol for the complex. Robust interactivity was noted between G59i and M^pro. With commendable ADMET characteristics and enhanced potency, further G59i analysis may be advantageous; moreover, identified key M^pro residues could contribute to the design of neotenic inhibitors.

Viruses such as the novel coronavirus, SARS-CoV-2, that is wreaking havoc on the world, depend on interactions of its own proteins with those of the human host cells. Relatively small changes in sequence such as between SARS-CoV and SARS-CoV-2 can dramatically change clinical phenotypes of the virus, including transmission rates and severity of the disease. On the other hand, highly dissimilar virus families such as Coronaviridae, Ebola, and HIV have overlap in functions. In this work we aim to analyze the role of protein sequence in the binding of SARS-CoV-2 virus proteins towards human proteins and compare it to that of the above other viruses. We build supervised machine learning models, using Generalized Additive Models to predict interactions based on sequence features and find that our models perform well with an AUC-PR of 0.65 in a class-skew of 1:10. Analysis of the novel predictions using an independent dataset showed statistically significant enrichment. We further map the importance of specific amino-acid sequence features in predicting binding and summarize what combinations of sequences from the virus and the host is correlated with an interaction. By analyzing the sequence-based embeddings of the interactomes from different viruses and clustering them together we find some functionally similar proteins from different viruses. For example, vif protein from HIV-1, vp24 from Ebola and orf3b from SARS-CoV all function as interferon antagonists. Furthermore, we can differentiate the functions of similar viruses, for example orf3a’s interactions are more diverged than orf7b interactions when comparing SARS-CoV and SARS-CoV-2.