Despite claims from prominent scientists that SARS‐CoV‐2 indubitably emerged naturally, the etiology of this novel coronavirus remains a pressing and open question: Without knowing the true nature of a disease, it is impossible for clinicians to appropriately shape their care, for policy‐makers to correctly gauge the nature and extent of the threat, and for the public to appropriately modify their behavior. Unless the intermediate host necessary for completing a natural zoonotic jump is identified, the dual‐use gain‐of‐function research practice of (...) viral serial passage should be considered a viable route by which the novel coronavirus arose. The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS‐CoV‐2's distinctive spike‐protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it. Additional molecular clues raise further questions, all of which warrant full investigation into the novel coronavirus's origins and a re‐examination of the risks and rewards of dual‐use gain‐of‐function research. (shrink)

COVID-19 poses an exceptional threat to global public health and well-being. Recognition of the need to develop effective vaccines at unprecedented speed has led to calls to accelerate research pathways ethically, including by conducting challenge studies ) with SARS-CoV-2. Such research is controversial, with concerns being raised about the social, legal, ethical and clinical implications of infecting healthy volunteers with SARS-CoV-2 for research purposes. Systematic risk evaluations are critical to inform assessments of the ethics of any proposed (...) class='Hi'>SARS-CoV-2 CHIs. Such evaluations will necessarily take place within a rapidly changing and at times contested epidemiological landscape, in which differing criteria for the ethical acceptability of research risks have been proposed. This paper critically reviews two such criteria and evaluates whether the use of effective treatment should be a necessary condition for the ethical acceptability of SARS-CoV-2 CHIs, and whether the choice of study sites should be influenced by COVID-19 incidence levels. The paper concludes that ethical evaluations of proposed SARS-CoV-2 CHIs should be informed by rigorous, consultative and holistic approaches to systematic risk assessment. (shrink)

Despite huge efforts towards understanding the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pathogenesis, little is known about the long‐term consequences of the disease. Here, we critically review existing literature about oncogenesis as a potential long‐term effect of SARS‐CoV‐2 infection. Like other viral infections, SARS‐CoV‐2 may promote cancer onset by inhibiting tumor suppressor genes. We conclude that, although unlikely, such hypothesis cannot be excluded a priori and we delineate an experimental approach to address it. Also see the (...) video abstract here: https://youtu.be/TBUTDSLR7vY. (shrink)

The world awaits a SARS-CoV-2 virus vaccine to keep the populace healthy, fully reopen their economies, and return their social and healthcare systems to “normal.” Vaccine safety and efficacy requires meticulous testing and oversight; this paper describes how despite grandiose public statements, the current vaccine development, testing, and production methods may prove to be ethically dubious, medically dangerous, and socially volatile. The basic moral concern is the potential danger to the health of human test subjects and, eventually, many vaccine (...) recipients. This is further complicated by economic and political pressures to reduce government oversight on rushed vaccine testing and production, nationalistic distribution goals, and failure to plan for the widespread immunization needed to produce global herd immunity. As this paper asserts, the public must be better informed to assess promises about the novel vaccines being produced and to tolerate delays and uncertainty. (shrink)

The pandemic of SARS-CoV-2 has led to unprecedented changes to society, causing unique problems that call for extraordinary solutions. We consider one such extraordinary proposal: ‘safer infection sites’ that would offer individuals the opportunity to be intentionally infected with SARS-CoV-2, isolate, and receive medical care until they are no longer infectious. Safer infection could have value for various groups of workers and students. Health professionals place themselves at risk of infection daily and extend this risk to their family (...) members and community. Similarly, other essential workers who face workplace exposure must continue their work, even if have high-risk household members and live in fear of infecting. When schools are kept closed because of the fear that they will be sites of significant transmission, children and their families are harmed in multiple ways and college students who are living on campus, whether or not they are attending classes in person, are contributing to high rates of transmission and experiencing high rates of exposure. We consider whether offering safer infection sites to these groups could be ethically defensible and identify the empirical unknowns that would need to resolve before reaching definitive conclusions. This article is not an endorsement of intentional infection with the coronavirus, but rather is meant to spark conversation on the ethics of out-of-the-box proposals. Perhaps most meaningfully, our paper explores the value of control and peace of mind for those among us most impacted by the pandemic: those essential workers risking the most to keep us safe. (shrink)

RaTG13, MP789, and RmYN02 are the strains closest to SARS‐CoV‐2, and their existence came to light only after the start of the pandemic. Their genomes have been used to support a natural origin of SARS‐CoV‐2 but after a close examination all of them exhibit several issues. We specifically address the presence in RmYN02 and closely related RacCSxxx strains of a claimed natural PAA/PVA amino acid insertion at the S1/S2 junction of their spike protein at the same position where (...) the PRRA insertion in SARS‐CoV‐2 has created a polybasic furin cleavage site. We show that RmYN02/RacCSxxx instead of the claimed insertion carry a 6‐nucleotide deletion in the region and that the 12‐nucleotide insertion in SARS‐CoV‐2 remains unique among Sarbecoviruses. Also, our analysis of RaTG13 and RmYN02's metagenomic datasets found unexpected reads which could indicate possible contamination. Because of their importance to inferring SARS‐CoV‐2′s origin, we call for a careful reevaluation of RaTG13, MP789 and RmYN02 sequencing records and assembly methods. (shrink)

The COVID‐19 pandemic is responsible for millions of deaths worldwide yet its origin remains unclear. Two potential scenarios of how infection of humans initially occurred include zoonotic transfer from wild animals and a leak of the pathogen from a research laboratory. The Wuhan wet markets where wild animals are sold represent a strong scenario for zoonotic transfer. However, isolation of SARS‐CoV‐2 or its immediate predecessor from wild animals in their natural environment has yet to be documented. Due to incomplete (...) evidence for a zoonotic origin, a laboratory origin is plausible. The Wuhan Institute of Virology is at the epicenter of the pandemic and their work has included manipulation of wild‐type coronavirus to enable infection of human cells. Although stronger evidence supports the zoonotic transfer, inconclusive reports maintain the laboratory leak hypothesis alive. It is imperative to reach a factual conclusion to prevent future pandemics. (shrink)

El SARS-CoV-2 más conocido como COVID 19 ha evidenciado de forma radical como el sistema capitalista neoliberal, nos ha llevado a una serie de maquillajes de la realidad que no permitían ver la gravedad de su construcción de inequidad, pero lo que es peor, al convertir en una empresa rentable todo lo que toca, termino por desdibujar la democracia, la justicia, y el estado mismo. El presente texto que obedece al programa de investigación “proyecto 29-000029 Dinámicas urbano-regionales, economía solidaria (...) y construcción de paz territorial en Antioquia” de UNAULA, para demostrar lo inicialmente planteado se procederá primero mostrando como el sistema de salud al ser convertido en un negocio, no tuvo capacidad para enfrentar la pandemia en ninguna parte del mundo, ello tuvo como consecuencia la parálisis de la economía mundial, pero adicionalmente genero un escenario perfecto para el encumbramiento de dictadores disfrazados de mesías, bien sea por el temor de los parlamentos a enfermarse o su cierre simbólico por su ausencia, eliminando de tajo la escasa democracia representativa, sumado a la parálisis de la justicia, además de la pobreza, el racismo, desigualdad y la estigmatización, que se vio controlada por la represión armada y la vigilancia que reino en el mundo y especialmente en Colombia con diferentes facetas. (shrink)

The importance of the working document is that it allows the analysis of the information and the status of cases associated with (SARS-CoV-2) COVID-19 as open data at the municipal, state and national level, with a daily record of patients, according to a age, sex, comorbidities, for the condition of (SARS-CoV-2) COVID-19 according to the following characteristics: a) Positive, b) Negative, c) Suspicious. Likewise, it presents information related to the identification of an outpatient and / or hospitalized patient, (...) attending to their medical development, identifying: a) Recovered, b) Deaths and c) Active, in Phase 3 and Phase 4, in the five main population areas speaker of indigenous language in the State of Veracruz - Mexico. The data analysis is carried out through the application of a data mining algorithm, which provides the information, fast and timely, required for the estimation of Medical Care Scenarios of (SARS-CoV-2) COVID-19, as well as for know the impact on the indigenous language speaking population in Veracruz. For this purpose, the following study zones are presented: a) Totonacapan Zone, b) Huasteco from the Tantoyuca Zone, c) Otomi from the Inxhuatlan de Madero Zone, d) Nahuatl from the Zongolica Zone, e) Nahuatl from the Chicontepec Zone, f) Nahualt from the Pajapan Zone and g) Popoluca from the Soteapan Zone. This data article presents the information as of August 1, 2020 corresponding to the Otomi of the Ixhuatlan de Madero area. (shrink)

The importance of the working document is that it allows the analysis of the information and the status of cases associated with (SARS-CoV-2) COVID-19 as open data at the municipal, state and national level, with a daily record of patients, according to a age, sex, comorbidities, for the condition of (SARS-CoV-2) COVID-19 according to the following characteristics: a) Positive, b) Negative, c) Suspicious. Likewise, it presents information related to the identification of an outpatient and / or hospitalized patient, (...) attending to their medical development, identifying: a) Recovered, b) Deaths and c) Active, in Phase 3 and Phase 4, in the five main population areas speaker of indigenous language in the State of Veracruz - Mexico. The data analysis is carried out through the application of a data mining algorithm, which provides the information, fast and timely, required for the estimation of Medical Care Scenarios of (SARS-CoV-2) COVID-19, as well as for know the impact on the indigenous language speaking population in Veracruz. For this purpose, the following study zones are presented: a) Totonacapan Zone, b) Huasteco from the Tantoyuca Zone, c) Otomi from the Inxhuatlan de Madero Zone, d) Nahuatl from the Zongolica Zone, e) Nahuatl from the Chicontepec Zone, f) Nahualt from the Pajapan Zone and g) Popoluca from the Soteapan Zone. This data article presents the information as of August 1, 2020 corresponding to the Popoluca from the Soteapan Area. (shrink)

Severe acute respiratory syndrome‐coronavirus (SARS‐CoV)‐2′s origin is still controversial. Genomic analyses show SARS‐CoV‐2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS‐CoV‐2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in (...) other SARS‐like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat‐derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site‐directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS‐CoV‐2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS‐CoV‐2 origins. (shrink)

The importance of the working document is that it allows the analysis of the information and the status of cases associated with (SARS-CoV-2) COVID-19 as open data at the municipal, state and national level, with a daily record of patients, according to a age, sex, comorbidities, for the condition of (SARS-CoV-2) COVID-19 according to the following characteristics: a) Positive, b) Negative, c) Suspicious. Likewise, it presents information related to the identification of an outpatient and / or hospitalized patient, (...) attending to their medical development, identifying: a) Recovered, b) Deaths and c) Active, in Phase 3 and Phase 4, in the five main population areas speaker of indigenous language in the State of Veracruz - Mexico. The data analysis is carried out through the application of a data mining algorithm, which provides the information, fast and timely, required for the estimation of Medical Care Scenarios of (SARS-CoV-2) COVID-19, as well as for know the impact on the indigenous language speaking population in Veracruz. For this purpose, the following study zones are presented: a) Totonacapan Zone, b) Huasteco from the Tantoyuca Zone, c) Otomi from the Inxhuatlan de Madero Zone, d) Nahuatl from the Zongolica Zone, e) Nahuatl from the Chicontepec Zone, f) Nahualt from the Pajapan Zone and g) Popoluca from the Soteapan Zone. This data article presents the information as of August 1, 2020 corresponding to the Totonacapan Area. (shrink)

The World Health Organisation declared COVID-19 a global pandemic on 11th March 2020, recognising that the underlying SARS-CoV-2 has caused the greatest global crisis since World War II. In this chapter, we present a framework to evaluate whether and to what extent the use of digital systems that track and/or trace potentially infected individuals is not only legal but also ethical.

In December 2019, the city of Wuhan in Hubei became the epicenter of an unprecedented health crisis. SARS-CoV-2 is marking a watershed moment for sapiens. On the one hand, we are facing the most serious health emergency of the 21st century, on the other hand we are beginning to experience the negative effects of our development models that do not take into account the welfare of non-human animals and the systemic effect that our actions have on the balance of (...) the biosphere. In the contributions hosted in this Dossier, the plurality of issues raised by SARS-CoV-2 comes to light clearly and distinctly. From bioethical questions to biopolitical issues, including an in-depth examination of the effects that the pandemic is having on society and on the capacity for self-perception of sapiens, we try to shed light on the countless consequences that this pandemic is bringing with it. (shrink)

Celem przeprowadzonych badań jest próba oceny sposobu funkcjonowania Uniwersytetu Trzeciego Wieku działającego na Uniwersytecie Rolniczym w Krakowie w latach 2019–2022 w kontekście wykorzystania w procesie kształcenia narzędzi cyfrowych. Na podstawie zebranych danych i przeprowadzonej analizy podjęto próbę uzyskania odpowiedzi na następujące pytania badawcze: Jaka formuła została wówczas przyjęta, jeśli chodzi o sposób prowadzenia wykładów, organizowania uroczystości akademickich i innych wydarzeń naukowych oraz kulturalnych w okresie obowiązujących restrykcji sanitarnych spowodowanych pandemią SARS-CoV-2? Jaka była aktywność słuchaczy podczas zastosowania nowych metod i (...) technik kształcenia? Czy narzędzia cyfrowe, wdrożone wówczas w celu realizacji zadań, znalazły zastosowanie po zniesieniu obowiązkowych restrykcji sanitarnych? (shrink)

In times of crisis, one of the areas heavily affected has been food, as a direct consequence of the damage caused to family farming and therefore to Food and Nutrition Security (SAN). Climate change, in turn, causes widespread crises, which, due to their impact on humanity, and above all, on SAN, provide complex humanitarian crises, worsening hunger. The military conflict imposes difficulties in access to food and production. This study aimed to critically describe the panorama of climate change and armed (...) conflicts in Africa, relating them to the pandemic of COVID-19 as a factor of aggravating the situation of food insecurity in African countries. A literature review study was carried out in various databases, journals and portals for this purpose, with emphasis on Google Scholar, CAPES and governmental portals. The results point to climate change, as being multicausal, and constitute a risk factor for agriculture and SAN, in African countries, characterized by the destruction of crops and the reduction of food availability. Armed conflicts makes difficult to produce and distribute food, especially for people who’s affected. (shrink)

Viruses are the simplest of pathogens, but possess sophisticated molecular mechanisms to manipulate host behavior, frequently utilizing molecular mimicry. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to bind to the host receptor neuropilin-1 in order to gain entry into the cell. To do this, the virus utilizes its spike protein polybasic cleavage site (PCS), which mimics the CendR motif of neuropilin-1’s endogenous ligands. In addition to facilitating cell entry, binding to neuropilin-1 has analgesic effects. We discuss (...) the potential impact of neuropilin-1 binding by SARS-CoV-2 in ameliorating sickness behavior of the host, and identify a convergent evolutionary strategy of PCS cleavage and subsequent neuropilin binding in other human viruses. In addition, we discuss the evolutionary leap of the ancestor of SARS-COV-2, which involved acquisition of the PCS thus faciliting binding to the neuropilin-1 receptor. Acquisition of the PCS by the ancestor of SARS-CoV-2 appears to have led to pleiotropic beneficial effects including enhancement of cell entry via binding to ACE2, facilitation of cell entry via binding to neuropilin-1, promotion of analgesia, and potentially the formation of decoy epitopes via enhanced shedding of the S1 subunit. Lastly, other potential neuromanipulation strategies employed by SARS-CoV-2 are discussed, including interferon suppression and the resulting reduction in sickness behavior, enhanced transmission through neurally mediated cough induction, and reduction in sense of smell. (shrink)

The occurrence of a new strain of SARS-CoV-2 cannot be ruled out. Therefore, this study seeks to investigate the possible effects of a hypothetical imperfect anti-COVID-19 vaccine on the control of not only the first variant of SARS-CoV-2 but also the second variant of SARS-CoV-2. We further examine the rates and a, escape of quarantined infectious individuals from isolation centers. The control R c and basic reproduction numbers R 0 are computed which gives assess to obtain asymptotic (...) stability of disease-free equilibrium point globally and the existence of a unique persistent equilibrium solution. Numerical results reveal that people infected with the second strain who are vaccinated with an imperfect vaccine are under control but the prevalence of the second variant enhances the prevalence of the first variant. Thus, discovering a vaccine that is effective for the prevention of variant 2 is necessary for the control of COVID-19. Numerical results also reveal that increase in the rate at which individuals infected with the first variant escape the isolation center gives rise to the population infected with the first variant and lowers the peak of the population infected with the second variant. This is probably because individuals infected with the second variant appear to be more careful with their lives and get vaccinated more than individuals infected with the first variant. (shrink)

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS‐CoV‐2 infection studies and analysis of COVID‐19 patient samples, we found that SARS‐CoV‐2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class (...) I genes. In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID‐19. (shrink)

Immunity against SARS‐CoV‐2 that is acquired by convalescent COVID‐19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue‐resident memory T (TRM) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL‐17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site by CCL20 and expand in the (...) presence of IL‐23. These nTh17 cells are converted to TRM cells upon encounter with SARS‐CoV‐2 and continue to exist as ex‐Th17 cells, which exert Th1‐like immunity during a memory response. G‐CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G‐CSF may be effective against COVID‐19. Administration of G‐CSF to patients infected with SARS‐CoV‐2 is worth a clinical trial. (shrink)

We explore the ethics of deliberately exposing consenting adults to SARS-CoV-2 to induce immunity to the virus (“DEI” for short). We explain what a responsible DEI program might look like. We explore a consequentialist argument for DEI according to which DEI is a viable harm-reduction strategy. Then we consider a non-consequentialist argument for DEI that draws on the moral significance of consent. Additionally, we consider arguments for the view that DEI is unethical on the grounds that, given that large-scale (...) DEI would be highly likely to result in some severe illnesses and deaths, DEI amounts to a form of killing. Our thesis is that incorporating a DEI program alongside the status-quo “calibrate-the-curve” responses could have significant advantages at the early stages of pandemics. These potential advantages mean that, at a minimum, research into DEI would have been justified early in the COVID-19 pandemic, and that DEI programs should be explored as potential additions to our overall approach to emerging pandemics in the future. (shrink)

Since its emergence, the novel coronavirus disease of 2019 has had enormous physical, social, and psychological impacts worldwide. The aim of this article was to identify elements of our knowledge on asbestos exposure and malignant mesothelioma that can provide insight into the psychological impact of the COVID-19 pandemic and be used to develop adequate interventions. Although the etiology of Covid-19 and MM differs, their psychological impacts have common characteristics: in both diseases, there is a feeling of being exposed through aerial (...) contagion to an “invisible killer” without boundaries that can strike even the strongest individuals. In both cases, affected persons can experience personality dysfunction, anxiety, depression, and posttraumatic symptoms; helplessness, hopelessness, and projection of destructive thoughts onto external forces often emerge, while defense mechanisms such as denial, splitting, repression, and reduced emotional expression are used by individuals to contain their overwhelming anxieties. We believe that in both diseases, an integrated multidimensional intervention offered by hospitals and other public health services is the most effective approach to alleviating patients’ and caregivers’ psychological distress. In particular, we emphasize that in the context of both MM and COVID-19, Brief Psychoanalytic Group therapy can help patients and caregivers attribute meaning to the significant changes in their lives related to the experience of the disease and identify adaptive strategies and more realistic relational modalities to deal with what has happened to them. We also highlight the importance of developing a surveillance system that includes individual anamnestic evaluation of occupational risk factors for COVID-19 disease. (shrink)

A number of papers have appeared recently arguing for the conclusion that it is ethically acceptable to infect healthy volunteers with severe acute respiratory syndrome coronavirus 2 as part of research projects aimed at developing COVID-19 vaccines or treatments. This position has also been endorsed in a statement by a working group for the WHO. The papers generally argue that controlled human infection is ethically acceptable if the risks to participants are low and therefore acceptable, the scientific quality of the (...) research is high, the research has high social value, participants give full informed consent, and there is fair selection of participants. All five conditions are necessary premises in the overall argument that such research is ethically acceptable. The arguments concerning risk and informed consent have already been critically discussed in the literature. This paper therefore looks specifically at the arguments relating to condition 3 ‘high social value’ and condition 5 ‘fair selection of participants’ and shows that whereas they may be valid, they are not sound. It is highly unlikely that the conditions that are necessary for ethical CHI trials to take place will be fulfilled. Most, if not all, CHI trials will thus be well intentioned but unethical. (shrink)

The SARS‐CoV‐2 virus is responsible for the COVID‐19 pandemic the world experience since 2019. The protein responsible for the first steps of cell invasion, the spike protein, has probably received the most attention in light of its central role during infection. Computational approaches are among the tools employed by the scientific community in the enormous effort to study this new affliction. One of these methods, namely molecular dynamics (MD), has been used to characterize the function of the spike protein (...) at the atomic level and unveil its structural features from a dynamic perspective. In this review, we focus on these main findings, including spike protein flexibility, rare S protein conformational changes, cryptic epitopes, the role of glycans, drug repurposing, and the effect of spike protein variants. (shrink)

Tyshkovskiy and Panchin have recently published a commentary on our paper in which they outline several “points of disagreement with the Segreto/Deigin hypothesis.” As our paper is titled “The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin,” points of disagreement should provide evidence that rules out a laboratory origin. However, Tyshkovskiy and Panchin provide no such evidence and instead attempt to criticize our arguments that highlight aspects of SARS‐CoV‐2 that could be consistent with the lab (...) leak hypothesis. Strikingly, Tyshkovskiy and Panchin's main point of criticism is based on a false premise that we have claimed RaTG13 to be a direct progenitor of SARS‐CoV‐2, and their other points of criticism are either not valid, based on flawed mathematical analysis, or are unrelated to our hypotheses. Thus, the genetic structure of SARS‐CoV‐2 remains consistent with both natural or laboratory origin, which means that both the zoonotic and the lab leak hypothesis need to be investigated equally thoroughly. (shrink)

The origin of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the subject of many hypotheses. One of them, proposed by Segreto and Deigin, assumes artificial chimeric construction of SARS‐CoV‐2 from a backbone of RaTG13‐like CoV and receptor binding domain (RBD) of a pangolin MP789‐like CoV, followed by serial cell or animal passage. Here we show that this hypothesis relies on incorrect or weak assumptions, and does not agree with the results of comparative genomics analysis. The genetic divergence (...) between SARS‐CoV‐2 and both its proposed ancestors is too high to have accumulated in a lab, given the timeframe of several years. Furthermore, comparative analysis of S‐protein gene sequences suggests that the RBD of SARS‐CoV‐2 probably represents an ancestral non‐recombinant variant. These and other arguments significantly weaken the hypothesis of a laboratory origin for SARS‐CoV‐2, while the hypothesis of a natural origin is consistent with all available genetic and experimental data. (shrink)

The world’s first COVID-19 human challenge trial using the D614G strain of SARS-CoV-2 is underway in the United Kingdom. The Wellcome Trust is funding challenge stock preparation of the Beta variant (B.1.351) for a follow-up human challenge trial, and researchers at Imperial College London are considering conducting that trial. However, little has been written thus far about the ethical justifiability of human challenge trials with SARS-CoV-2 variants of concern. While vaccine resistance as such does not increase risks for (...) volunteers in COVID-19 challenge trials, we explore two specific characteristics of some variants that may initially be thought to make such trials unethical and conclude that SARS-CoV-2 variant challenge trials can remain ethical. (shrink)

In response to the COVID‐19 pandemic, some authors have advocated a program of controlled voluntary infection (CVI) with SARS‐CoV‐2. Under CVI, during periods where the medical system is under capacity, volunteers from low‐risk groups would be intentionally infected after giving informed consent, and then quarantined until they have developed immunity. Proponents claim that this could have benefits for society, such as building herd immunity and ensuring that critical workers won’t be incapacitated during the peak of the infection. They also (...) claim that this could have benefits for individuals, such as being safely exempted from lockdown measures and (for individuals who are likely to be infected anyway) ensuring that the infection happens under relatively less dangerous conditions. Some respond that CVI would unethical. Here, I argue that, while CVI may or may not be ill‐advised for empirical reasons, there are no in‐principle ethical objections to it (i.e., if CVI would work as well as its proponents think, it would be ethical to implement it). I present three arguments for this conclusion. The first is an argument from informed consent: informed consent to relevantly similar medical procedures renders performing these procedures permissible, so informed consent to CVI would render it permissible. The second is an argument from reasonable beneficence: it draws on recent work by Caspar Hare on relevantly similar choices to argue that CVI is permissible. The third is an argument from precedent: smallpox variolation was permissible, and CVI is relevantly similar to that, so CVI is permissible. (shrink)

Sovereign is he who provides the exception.…The exception is more interesting than the rule. The rule proves nothing; the exception proves everything. In the exception the power of real life breaks through the crust of a mechanism that has become torpid by repetition.In spring 2020, in response to the COVID-19 crisis, world leaders imposed severe restrictions on citizens’ civil, political, and economic liberties. These restrictions went beyond less controversial and less demanding social distancing measures seen in past epidemics. Many states (...) and countries imposed universal lockdowns. Lockdowns, as we define them here, require people to stay home; in some countries and places, citizens must have ad hoc licenses to... (shrink)

Sitting on the fine line between pathogen ‘transmissibility’ and ‘severity’, the Behavioural Immune System (BIS) is responsible for activating behaviours that minimise infection risks and maximise fitness. To achieve self-preservation, the BIS also fuels social and political attitudes. We aim to explain societal changes that may be sparked by COVID-19 by highlighting links between human evolutionary history and our psychological faculties mediated by the BIS.

Emergence of the novel pathogenic coronavirus SARS‐CoV‐2 and its rapid pandemic spread presents challenges that demand immediate attention. Here, we describe the development of a semi‐quantitative high‐content microscopy‐based assay for detection of three major classes (IgG, IgA, and IgM) of SARS‐CoV‐2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi‐automated image analysis workflow resulted in specific, sensitive and unbiased assay that complements the portfolio of SARS‐CoV‐2 serological (...) assays. Sensitive, specific and quantitative serological assays are urgently needed for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high‐throughput microscopy to rapidly develop serological assays for emerging virus infections. (shrink)

The SARS-CoV-2 pandemic constituted a crisis situation in which science was very far from Kitcher’s ideal of well-ordered science. I suggest that this could and should have been different. Kitcher’s ideal should play a role in assessing the allocation of research resources in future crisis situations, as it provides a way to balance highly divergent interests and incorporate the common good into decision-making processes on research.

The recent changes in COVID-19 symptoms suggest convergent evolution of respiratory diseases. This process is analogous to the emergence of animal mimetic complexes and complements previously identified types of mimicry. A novel pathogen might go unnoticed or insufficiently counteracted if it resembles a disease that the host already faced on multiple occasions, which creates a selective pressure towards a typical symptomic phonotype. In short, the reason why so many unrelated pathogens cause similar symptoms may correspond to the reasons that drove (...) the evolution of the ‘warning’ wasp-like colouration in various insect species. (shrink)

The current SARS-CoV-2 crisis raises questions about the challenges faced by nation states and international organisations in offering a coordinated international response to the pandemic, and reveals the great vulnerability of European countries, which are implementing lockdown measures and imposing restrictions on international travel, for the most part on a unilateral basis. Such measures run counter to the prevailing approach of the previous two centuries that developed an international public health space. This article examines the measures adopted by European (...) states in order to contain 19th-century cholera pandemics, which took shape through the development of an international maritime quarantine system, based primarily on the implementation of national regulations and local decision-making. This regime was quickly viewed as ineffective and out of step with liberal ideas that urged a “laissez-faire” approach to public health matters. In its stead, a long-term trend developed towards easing quarantine measures. Nation states supported the internationalisation of the fight against pandemics, which chiefly consisted of externalising quarantine measures to the East in order to eliminate them in Europe. This process was based on a subtle dialectical relationship between the construction of an international public health space and the affirmation of state sovereignty, and continued into the 20th century with the progressive creation of international institutions responsible for advancing global health. (shrink)

The current SARS-CoV-2 crisis raises questions about the challenges faced by nation states and international organisations in offering a coordinated international response to the pandemic, and reveals the great vulnerability of European countries, which are implementing lockdown measures and imposing restrictions on international travel, for the most part on a unilateral basis. Such measures run counter to the prevailing approach of the previous two centuries that developed an international public health space. This article examines the measures adopted by European (...) states in order to contain 19th-century cholera pandemics, which took shape through the development of an international maritime quarantine system, based primarily on the implementation of national regulations and local decision-making. This regime was quickly viewed as ineffective and out of step with liberal ideas that urged a “laissez-faire” approach to public health matters. In its stead, a long-term trend developed towards easing quarantine measures. Nation states supported the internationalisation of the fight against pandemics, which chiefly consisted of externalising quarantine measures to the East in order to eliminate them in Europe. This process was based on a subtle dialectical relationship between the construction of an international public health space and the affirmation of state sovereignty, and continued into the 20th century with the progressive creation of international institutions responsible for advancing global health. (shrink)

The aim of this paper is to explore the connections between semiotics and biology by examining the behaviors of both humans and non-cognizant agents, using Bayesian and heuristic inference. The argument is that higher-level organisms use complex predictive reasoning to deal with uncertainty, while non-cognizant species, such as SARS-CoV-2, rely on an economy-driven heuristic to enter host cells. From this viewpoint, the current pandemic is characterized as a clash of representations resulting from the anthropocentric construction of the self, which (...) neglects the complexities of the natural world. (shrink)

This paper describes the UK Research Ethics Committee’s (REC) preparations and review of the global first SARS-CoV-2 human infection challenge studies. To frame our review, we used the WHO guidance and our UK Health Research Authority ethical review framework. The WHO criteria covered most issues we were concerned about, but we would recommend one further criterion directing RECs to consider alternative research designs. Could research questions be equally well answered by less intrusive studies? The committee met virtually, ensuring broad (...) representation across the UK nations and also ensuring applicants could attend easily. We worked in collaboration with the applicants but while we recognise that such proximity might raise the accusation of ‘collusion’, we made every effort to maintain ‘moral distance’ and all decisions were made by the committee alone. Prior existing processes and policy facilitated training and review but even with this preparation, review took time and this could have hindered a rapid response to the emergency. Review for the various follow-on studies will now be speedier and once the pandemic has subsided, our group could be reconvened in future emergencies. In conclusion, we have tried to make decisions in good faith. We know there is controversy and disagreement and reasonable people may feel we have made the wrong decision. A more detailed analysis, built on the WHO guidance, is provided in online supplemental material. (shrink)

Incarcerated persons have suffered a disproportionate burden of SARS-CoV-2 infection compared to the general population, with heightened risk for adverse...

The causative agent of COVID‐19 SARS‐CoV‐2 has led to over 4 million deaths worldwide. Understanding the origin of this coronavirus is important for the prevention of future outbreaks. The dominant point of view that the virus transferred to humans either directly from bats or through an intermediate mammalian host has been challenged by Segreto and Deigin, who claim that the genome of SARS‐CoV‐2 has certain features suggestive of its artificial creation. Following their response to our commentary, here we (...) continue the discussion of the proposed arguments for this hypothesis. We show that neither the existence of a furin cleavage site in SARS‐CoV‐2, nor the presence of specific sequences within the nucleotide insertion encoding that site are evidence for intelligent design. We also explain why existing genetic data, viral diversity and past human history suggest that a natural origin of the virus is the most likely scenario. Genetic evidence suggesting otherwise is yet to be presented. (shrink)

PurposeThis study aims to describe the adverse events following immunization of SARS-CoV-2 vaccination in cancer patients/survivors associated with their psychological distress.MethodsA cross-sectional study was conducted to assess AEFIs after the receipt of SARS-CoV-2 vaccines in cancer patients/survivors attending a university hospital in Malaysia. Psychological distress was measured using the Hospital Anxiety and Depression Scale before and after the first and second doses of COVID-19 vaccine.ResultsA total of 217 complete responses were received. Compared with before vaccination, both HADS Anxiety (...) and HADS Depression scores were significantly reduced after the first and second dose of the SARS-CoV-2 vaccine. Most of the participants had mild-or-moderate systemic and local AEFIs, with the most common being pain at the injection site, tiredness, and headache for both the first and second doses of the vaccine. Positive correlations between the total AEFI score and HADS-A and HADS-D scores were observed after the first dose of the SARS-CoV-2 vaccine. Similarly, positive associations were observed between the total AEFI score and HADS-A and HADS-D scores after the second dose of the SARS-CoV-2 vaccine.ConclusionMild-to-moderate AEFIs found in this study help address vaccine hesitancy in cancer patients/survivors. Receiving the SARS-CoV-2 vaccine had a positive effect on decreasing psychological distress in cancer patients/survivors. High severity of an AEFI was associated with higher anxiety and depressive symptoms. (shrink)

The SARS-CoV-2 pandemic has highlighted the interdependency of healthcare systems and research organizations on manufacturers and suppliers of personnel protective equipment and the need for well-trained personnel who can react quickly to changing working conditions. Reports on challenges faced by research laboratory workers are rare in contrast to the lived experience of hospital health care workers. We report on experiences gained by RLWs who significantly contributed to combating the pandemic under particularly challenging conditions due to increased workload, sickness and (...) interrupted PPE supply chains. RLWs perform a broad spectrum of work with SARS-CoV-2 such as autopsies, establishment of virus cultures and infection models, development and verification of diagnostics, performance of virus inactivation assays to investigate various antiviral agents including vaccines and evaluation of decontamination technologies in high containment biological laboratories. Performance of autopsies and laboratory work increased substantially during the pandemic and thus led to highly demanding working conditions with working shifts of more than eight hours working in PPE that stressed individual limits and also the ergonomic and safety limits of PPE. We provide detailed insights into the challenges of the stressful daily laboratory routine since the pandemic began, lessons learned, and suggest solutions for better safety based on a case study of a newly established HCBL designed for autopsies and research laboratory work. Reduced personal risk, increased resilience, and stress resistance can be achieved by improved PPE components, better training, redundant safety measures, inculcating a culture of safety, and excellent teamwork. (shrink)

ObjectiveThe study is an explorative investigation aimed to assess the differences in acute stress response patterns of health workers facing coronavirus disease 2019 (COVID-19) during Italy’s first lockdown.MethodsA cross-sectional investigation using convenience sampling method was conducted in Italy during April 2020. Eight hundred fifty-eight health workers participated in the research filling out self-report measures including Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), and Impact of Event Scale–Revised (IES-R).ResultsModerate/severe depression was found in 28.9% (95% CI, 25.8–32.04), (...) moderate/severe anxiety in 55.4% (95% CI, 51.9–58.8), insomnia in 15% (95% CI, 12.5–17.5), and distress in 52.5% (95% CI, 48.5%–56.6) of participants. The 3% of health workers reported frequent suicidal thoughts. Female sex, working for >15 h/week in a COVID-19 unit, and living apart from family were associated with a significantly higher risk of distress, anxiety, insomnia, depression, and functional impairment. Four profiles were identified on the basis of psychopathological measures: Profile_0 included 44% (N= 270); Profile_1, 25.6% (N= 157); Profile_2, 19.1% (N= 117); and Profile_3, 11.3% (N= 69) of participants. Results showed a significant effect for Profiles X IES-R (η2= 0.079;f= 0.29), indicating that in all profiles, except for Profile_0, avoidance scale is lower than hyperarousal and intrusion symptoms scales of the IES-R. This characteristic could be a probable index of the control exerted by the responders to not fly away from their job.ConclusionThe identification of specific profiles could help psychiatrists and emergency psychologists to build specific interventions in terms of both primary and secondary prevention to face future waves of the COVID-19 outbreak. (shrink)

ZusammenfassungDieser Beitrag ist Teil des Forums COVID-19: Perspektiven in den Geistes- und Sozialwissenschaften. Das neuartige Coronavirus (Sars-CoV-2) stellt die Weltgemeinschaft vor eine große Herausforderung. Das Wissen über das Virus und seine Eigenschaften ist lückenhaft, aber der Bedarf, politische und medizinische Entscheidungen an wissenschaftlicher Erkenntnis auszurichten ist groß. Diese Lage führt zu einer Dynamisierung der Forschung. Ein prominentes Beispiel ist die WHO-Studie SOLIDARITY. Die epistemologischen Besonderheiten und die daraus resultierenden ethischen Implikationen werden in diesem Beitrag näher beleuchtet.

We investigate the epistemological consequences of a positive polymerase chain reaction SARS-CoV test for two relevant hypotheses: V is the hypothesis that an individual has been infected with SARS-CoV-2; C is the hypothesis that SARS-CoV-2 is the cause of flu-like symptoms in a given patient. We ask two fundamental epistemological questions regarding each hypothesis: First, how much confirmation does a positive test lend to each hypothesis? Second, how much evidence does a positive test provide for each hypothesis (...) against its negation? We respond to each question within a formal Bayesian framework. We construe degree of confirmation as the difference between the posterior probability of the hypothesis and its prior, and the strength of evidence for a hypothesis against its alternative in terms of their likelihood ratio. We find that test specificity—and coinfection probabilities when making inferences about C—were key determinants of confirmation and evidence. Tests with 8) for V against ¬V regardless of sensitivity. Accordingly, low specificity tests could not provide strong evidence in favor of C in all plausible scenarios modeled. We also show how a positive influenza A test disconfirms C and provides weak evidence against C in dependence on the probability that the patient is influenza A infected given that his/her symptoms are not caused by SARS-CoV-2. Our analysis points out some caveats that should be considered when attributing symptoms or death of a positively tested patient to SARS-CoV-2. (shrink)

The epidemiological situation resulting from the SARS-CoV-2 pandemic caused the Polish universities to fully switch to distance education in March 2020. Medical e-learning has not yet been broadly implemented into the education process. Therefore, examples of successful e-learning implementations or the organization of the process of medical e-learning offer a valuable source of knowledge today, which is needed immediately. The article presents e-learning practices at the Polish medical universities during the SARS-CoV-2 epidemic during the period from March to (...) September 2020, covering seven universities in Poland that offer medical and health studies. The organization and implementation of e-learning classes is presented, including knowledge evaluation practices, providing example decisions issued by university rectors, on which the teaching process was based. A detailed presentation of the schools’ organizational units or workgroups that played an important role in the process of coordination of measures supporting e-education is also included. The article also presents a description of the software applications, utilities, and services used at the schools in the course of the process of online education. Below are some examples of specific such implementations in selected university courses. (shrink)

IntroductionThe world pandemic of the virus SARS-CoV-2, which causes COVID-19 infection was announced by the World Health Organization on March 11, 2020. Due to the restrictions that were introduced in order to minimize the spread of the virus, people more often suffer from stress, depression, anxiety, and sleep disorders. The aim of this study was evaluation of the stress levels and sleep disorders among nursing students during the pandemic SARS-CoV-2.Materials and Study MethodsThis is a cross-sectional study conducted among (...) 397 nursing students on March 2020. The research tools used were original questionnaires, Perceived Stress Scale, and the Athenian Insomnia Scale, as well as Coping with Stress Inventory.ResultsRespondents felt a high level of stress, which occurred in 68.8% of interviewees regarding whether there was a danger of contracting COVID-19. Respondents experienced 84% stress levels when a family member suffered from COVID-19. Sleep disorders were determined mainly by the fear of infection and contact with someone who might be infected with the virus. Nursing students who felt a high level of stress often suffered from sleep disorders more frequently than students who felt a low or average stress level. The respondents decided to cope with stress by denial, taking psychoactive substances, ceasing action, or blaming themselves. The greater the intensity of stress experienced by students, the more often they undertook avoidance behaviors or showed helplessness.ConclusionDuring the pandemic, students experienced severe stress, which resulted in sleep disorders and avoidance behaviors. (shrink)

The first clinical symptoms focused on the presentation of coronavirus disease 2019 have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins.Methods: Available 11 of the 29 SARS-CoV-2 proteins’ structures have been extracted from Protein Data (...) Bank. HMI-PRED, a recently developed web server for structural PREDiction of protein-protein interactions between host and any microbial species, was used to find the “interface mimicry” through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System.Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control.Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations. (shrink)

The coronavirus pandemic has necessitated extraordinary human resilience in order to preserve and prolong life and social order. Risks to health and even life are being confronted by workers in health and social care, as well as those in roles previously never defined as “frontline,” such as individuals working in community supply chain sectors. The strategy adopted by the United Kingdom government in facing the challenges of the pandemic was markedly different from other countries. The present study set out to (...) examine what variables were associated with resilience, burnout, and wellbeing in all sectors of frontline workers, and whether or not these differed between the UK and Republic of Ireland. Individuals were eligible if they were a frontline worker in the UK or RoI during the pandemic. Part of a larger, longitudinal study, the participants completed an online survey to assess various aspects of their daily and working lives, along with their attitudes toward their government’s handling of the crisis, and measurement of psychological variables associated with heroism. A total of 1,305 participants provided sufficient data for analysis. UK-based workers reported lower wellbeing than the RoI-based participants. In multivariate models, both psychological and pandemic-related variables were associated with levels of resilience, burnout, and wellbeing in these workers, but which pandemic-related variables were associated with outcomes differed depending on the country. The judgment of lower timeliness in their government’s response to the pandemic appeared to be a key driver of each outcome for the UK-based frontline workers. These findings provide initial evidence that the different strategies adopted by each country may be associated with the overall wellbeing of frontline workers, with higher detriment observed in the UK. The judgment of the relatively slow response of the UK government to instigate their pandemic measures appears to be associated with lower resilience, higher burnout, and lower wellbeing in frontline workers in the UK. (shrink)

Public health strategies recommend isolating patients with SARS-CoV-2 infection. But compassionate care in the intensive care unit (ICU) is an ethical obligation of modern medicine that cannot be justified by the risk of infection or the lack of personal protective equipment. This article describes the experiences of clinicians in ICUs in the south of Spain promoted by the Andalusian Society of Intensive Care SAMIUC, in the hope it will serve to improve the conditions in which these patients die, and (...) to help their families who suffer when they cannot say good-bye to their loved ones.In the south of Spain, healthcare professionals use daily videoconferencing to improve communication between clinicians, patients, and their relatives who cannot visit them in the ICU. This close communication allows families to see their loved ones and extends communication between healthcare professionals, patients, and their relatives. To allow family members to accompany patients at the end of life, it is possible to adapt public health rules to the epidemic situation. (shrink)

Biocidal agents such as formaldehyde and glutaraldehyde are able to inactivate several coronaviruses including SARS‐CoV‐2. In this article, an insight into one mechanism for the inactivation of these viruses by those two agents is presented, based on analysis of previous observations during electron microscopic examination of several members of the orthocoronavirinae subfamily, including the new virus SARS‐CoV‐2. This inactivation is proposed to occur through Schiff base reaction‐induced conformational changes in the spike glycoprotein leading to its disruption or breakage, (...) which can prevent binding of the virus to cellular receptors. Also, a new prophylactic and therapeutic measure against SARS‐CoV‐2 using acetoacetate is proposed, suggesting that it could similarly break the viral spike through Schiff base reaction with lysines of the spike protein. This measure needs to be confirmed experimentally before consideration. In addition, a new line of research is proposed to help find a broad‐spectrum antivirus against several members of this subfamily. (shrink)