Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Ozone: A Novel Sterilizer for Personal Protective Equipment.

OBJECTIVE: Personal protective equipment (PPE) is urgently sought during public health crises. It is necessary for the safety of both the patient and the healthcare professional. Yet during the recent COVID-19 pandemic, PPE scarcity in many countries, including the United States, has impacted the level of care for patients and the safety of healthcare personnel. Additionally, the implementation of mandatory mask mandates for the general public in many countries forced individuals to either reuse PPE, which can contribute to poor hygiene, or buy PPE in bulk and thereby contribute to the scarcity of PPE. In this study, we investigate the possibility of using a cost-effective ozone sterilization unit on contaminated N95 masks as an alternative to current sterilization methods. METHOD: This protocol examined ozone's ability to decontaminate N95 mask fabric that was exposed to a surrogate virus (Escherichia coli bacteriophage MS2). Once the sterilization unit achieves an ozone concentration of ~30 ppm, a 60-minute or 120-minute sterilization cycle commences. Following the sterilization cycle, we investigated the amount of viable virus on the slide using a viral plaque assay and compared it to a non-sterilized, control slide. Furthermore, we carried out trials to investigate the safety of an ozone sterilization device, by measuring the levels of ozone exposure that individuals may experience when operating the sterilization unit post-cycle. RESULTS: We showed that a 120-minute sterilization cycle at ~30 ppm achieves a 3-log reduction in viral activity, thereby complying with industry and U.S. Food and Drug Administration (FDA) standards. Further, we demonstrated that when following our protocol, the ozone exposure levels for a simple sterilization unit to be used at home complied with federal and industry standards. CONCLUSION: Ozone may have the potential to decontaminate masks and other PPE.

Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity.

PURPOSE OF REVIEW: While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT FINDINGS: Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.

Fact vs Fallacy: The Anti-Vaccine Discussion Reloaded.

In the light of the COVID-19 pandemic, anti-vaccine sentiments have been on the rise, with a recent seminal study on the development of anti-vaccine views in social media even making its way into Nature Communications. Yet, with the current scientific consensus being in overwhelming agreement over the safety and efficacy of vaccines, many scientists lose their grasp on the fears, concerns, and arguments that the opposition may hold. This paper discusses and evaluates vaccine-hesitant individuals on a socioeconomic, historical, and philosophical landscape. It also provides an analysis of common argumentative patterns and the psychological impact that these arguments may have on undecided individuals. The discussion also explores why anti-vaccine sentiments are on the rise, and how members of the scientific and medical community require a more structured approach to communicating key arguments. This is particularly important if vaccination rates and herd immunity are to be sustained. No longer is it sufficient to win arguments based on a factual and scientific basis, but rather scientists and medical practitioners have to focus on conveying confidence and reassurance on both an informative and emotional level to those with doubts and fears.