TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques.

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163+MRC1-, and TREM2+ populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection.

Predictors of Vaccine Uptake among Migrants in the United States: A Rapid Systematic Review.

Evaluating challenges to vaccine uptake in non-US-born individuals is necessary for increasing national vaccination rates. This rapid review was conducted to investigate predictors of vaccine utilization among US migrants. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist was utilized, along with the Rayyan webtool, to facilitate the process of identifying primary research articles. Data were independently extracted by using a piloted, customized form. This was tabulated and the results were reported. Of the 186 abstracts reviewed, nine articles were included. Populations included in this review were refugees (n = 1), undocumented migrants (n = 1), migrants crossing the US-Mexico border (n = 2), Blacks (n = 1), and US-born vs. non-US-born adults (n = 1). Three studies focused on "foreign-born" children. The vaccines included in the literature reviewed were both combined series and individual, with one study addressing immunization instead of specific vaccines. Detailed characteristics of these studies and their quality evaluations were also reported. This review identified gaps in research regarding immunization among different migrant groups. Multilevel interventions should be considered to leverage the existing facilitators and address the known modifiable barriers to creating an accessible and supportive environment for marginalized populations.

The Relationship Between Covid-19 Risk Perception and Vaccine Hesitancy in Cancer Patients: The Moderating Role of Externalizing Traits.

Objective: This mixed-methods study aimed to explore the role of externalizing traits in moderating the relationship between COVID-19 risk perception and vaccine hesitancy in patients diagnosed with cancer. A community-based participatory approach - comprising a preliminary qualitative inquiry and a subsequent cross-sectional research - was used to promote effective vaccination campaigns. Method: 12 people diagnosed with cancer and 7 cancer professionals were recruited for the qualitative inquiry, 356 people either under cancer treatment or in follow-up care for the cross-sectional research.A phenomenological analysis explored the transcripts of two focus groups. The cross-sectional research tested the hypothesis emerged during the previous qualitative inquiry through self-reported questionnaires and moderated regression. Results: Phenomenological analysis suggested a pivotal role of externalizing traits in vaccine hesitancy. Moderated regression revealed how the association between risk perception and vaccine hesitancy is moderated by externalizing traits, even when controlled for treatment adherence. Conclusions: In the present study we found a stronger relationship between risk perception and vaccine hesitancy for patients with higher levels of externalizing traits. We suggest that vaccination campaigns should be personality-informed to offer individualized and effective solutions. Patients with externalizing traits may cope dysfunctionally with vaccination campaigns.

To Boost or Not to Boost: Acceptability of a COVID-19 Booster Dose among Osteopathic Medical Students: A Cross-Sectional Study from a Medical School in New York.

The COVID-19 pandemic continues to evolve, with new variants emerging and vaccine-induced immunity waning. Protecting and retaining the healthcare force remains crucial in fighting this pandemic, as healthcare workers (HCWs) are a critical driver in increasing vaccine uptake among the public. This study explored the uptake of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) booster shots among medical students at the New York Institute of Technology College of Osteopathic Medicine (NYITCOM). Predictors for actual booster uptake were also examined. An electronic survey was distributed to Osteopathic Medical Students (OMS I-IV) in January 2022. The survey was distributed to 1762 students total, with 319 responses received (18%). Of those who responded, 70.2% (224/319) reported that they had already received a booster, while 29.5% (94/319) reported they had not yet received it. We identified that pharmaceutical mistrust, building long-lasting immunity via vaccines, and vaccines' adverse effects were the most significant predictors for how willing participants were to accept a booster dose. Vaccine hesitancy around the COVID-19 booster was prevalent during the surge of the highly transmissible variant Omicron. This finding necessitates some evidence-based approaches to enhance booster uptake among a population subgroup whose impact is critical.

The national COVID-19 vaccination campaign targeting the extremely vulnerable: the Florence Medical Oncology Unit experience in patients with cancer.

BACKGROUND: International and national oncology societies had released recommendations in favor of COVID-19 vaccination in cancer patients. In the context of the national vaccination campaign targeting the so called extremely vulnerable, we aimed to assess the safety and efficacy of the mRNA vaccines in a cohort of 623 patients. METHODS: Between March 26 and April 04, 2021, the Pfizer and BioNTech BNT162b2 mRNA and the Moderna mRNA-1273 vaccines were given as a two-dose prime-boost regimen. Starting on September 25th 2021 a third dose was offered to patients in whom a suboptimal immunogenicity with COVID-19 vaccination could be expected. Safety assessments were performed by phone call 7 days after each dose. Electronic health records were accessed to review demographic information, disease history, treatment detail, and outcome events of participants patients'. FINDINGS: No toxicities were reported in 63.7%, 54%, and in 48.7% patients with cancer after each dose. Mild-to-moderate pain at the injection site was the most commonly adverse event. After the second dose, 46% of the 610 patients reported toxicity, with more systemic side-effects observed. Fever was reported in 45% of patients, with a temperature ≥ 38 °C in 21.4% of them. Of the 335 patients receiving a third vaccine dose, 51% reported toxicity, with 13% of patients reporting more than one effect. Logistic regression analysis reported mixed results, with limited variables or categories reporting a significant odd ratio. The type of vaccine reported a significant value at first dose (OR = 0.12; CI 0.52, 0.26; p = 0.00). Thirty-four cases of COVID-19 infection were reported with only one patient requiring a short-term hospitalization for monitoring. INTERPRETATION: The safety profile of the mRNA vaccines does not raise any specific concerns and support prioritization of vaccination for cancer patients.

Predictors for Actual COVID-19 Vaccine Uptake and Intended Booster Dosage among Medical Students of an Osteopathic Medical School in New York.

Exploring future physicians' attitudes toward vaccination is crucial as physicians' recommendation is the top predictor for individuals to receive vaccines. This study explored the uptake of COVID-19 vaccines and the intention for future booster dose uptake among students at the New York Institute of Technology College of Osteopathic Medicine (NYITCOM). Predictors for actual vaccine and intended booster uptake were also examined. An electronic survey was distributed to Osteopathic Medical Students (OMS I-IV) in the Spring of 2021. A total of 1331 students received the survey, with 316 responses received (24%). In total, 95.3% (301/316) of the respondents reported that they already received vaccines, while 3.1% (13/316) reported that they had not yet received a vaccine. Moreover, 88.9% of the respondents (281/316) were in favor of a booster dose, which was a strong predictor for actual vaccine uptake. We identified that the Asian race, pharmaceutical mistrust, building immunity via vaccines, adequate vaccine testing, and willingness to get non-U.S. manufactured vaccines are the most significant predictors for willingness to accept a booster dose. A very high COVID-19 vaccine uptake among NYITCOM OMS was found in our study. The study also observed a high acceptance of an additional dose of the COVID-19 vaccine in the future.

Perceptions of COVID-19 vaccines among osteopathic medical students (OMS).

BACKGROUND: Research has shown that physicians' recommendations are one of the top predictors for individuals to receive vaccines. This study examined the perceptions of new COVID-19 vaccines among the medical students at the X and the factors that influenced their opinions. OBJECTIVE: To measure X students' perception of a new COVID-19 vaccine and the factors which drive their opinions. METHODS: An electronic survey of 37 questions was distributed to Osteopathic Medical Students (OMS I-IV) of X in October of 2020. RESULTS: 1770 total students received the survey, and 197 responded (11%). 45% (88/197) of the respondents reported that they would receive new COVID-19 vaccines if they were available at the time of the survey, while 19% (37/197) reported that they had not yet decided. Confidence in the US healthcare system, pharmaceutical trust, the United States Food and Drug Administration's (FDA)'s minimum effectiveness level, adequate vaccine testing, additional vaccine dose, and antivaccine acquaintances were significant predictors of intended vaccine uptake. CONCLUSIONS: Our findings confirmed a low acceptance of the new COVID-19 vaccine among OMS students, which mirrored the general public's low acceptance rate. Better education of OMS about vaccination benefits and the vaccine development process may increase future immunization rates.

Severe COVID-19 Is Characterized by an Impaired Type I Interferon Response and Elevated Levels of Arginase Producing Granulocytic Myeloid Derived Suppressor Cells.

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.

A yeast expressed RBD-based SARS-CoV-2 vaccine formulated with 3M-052-alum adjuvant promotes protective efficacy in non-human primates.

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.

Myeloid-derived suppressor cells (MDSC): When good intentions go awry.

MDSC are a heterogeneous population of immature myeloid cells that are released by biological stress such as tissue damage and inflammation. Conventionally, MDSC are known for their detrimental role in chronic inflammation and neoplastic conditions. However, their intrinsic functions in immunoregulation, wound healing, and angiogenesis are intended to protect from over-reactive immune responses, maintenance of immunotolerance, tissue repair, and homeostasis. Paradoxically, under certain conditions, MDSC can impair protective immune responses and exacerbate the disease. The transition from protective to harmful MDSC is most likely driven by environmental and epigenetic mechanisms induced by prolonged exposure to unresolved inflammatory triggers. Here, we review several examples of the dual impact of MDSC in conditions such as maternal-fetal tolerance, self-antigens immunotolerance, obesity-associated cancer, sepsis and trauma. Moreover, we also highlighted the evidence indicating that MDSC have a role in COVID-19 pathophysiology. Finally, we have summarized the evidence indicating epigenetic mechanisms associated with MDSC function.

Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe.

The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19-attributable mortality was calculated using propensity score-matched historic control data and after 28 days of follow-up was 20.0% (95% confidence interval 18.7%-21.4%) in 3285 patients receiving dialysis and 19.9% (17.5%-22.5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44.3% (35.7%-53.9%) did not survive COVID-19. Mortality risk was 1.28 (1.02-1.60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity.

Impact of COVID-19 pandemic in Spanish Nephrology Servicesservices impact of the pandemic on COVID-19 Spanish Nephrology Services

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has required a rapid and drastic transformation of hospitals, and consequently also of Spanish Nephrology Units, to respond to the critical situation. The Spanish Society of Nephrology conducted a survey directed to the Heads of Nephrology Departments in Spain that addressed the reorganisation of Nephrology departments and activity during the peak of COVID-19 pandemic. The survey focused on the integration of nephrologists in COVID-19 teams, nephrology inpatient care activities (elective admissions, kidney biopsies), the performance of elective surgeries such as vascular accesses or implantation of peritoneal catheters, the suspension of kidney transplantation programmes and the transformation of nephrology outpatient clinics. This work details the adaptation and transformation of nephrology services during the COVID-19 pandemic in Spain. During this period, elective admissions to Nephrology Services, elective surgeries and biopsies were suspended, and the kidney transplant programme was scaled back by more than 75%. It is worth noting that outpatient nephrology consultations were carried out largely by telephone. In conclusion, the pandemic has clearly impacted clinical activity in Spanish Nephrology departments, reducing elective activity and kidney transplants, and modifying activity in outpatient clinics. A restructuring and implementation plan in Nephrology focused on telemedicine and/or virtual medicine would seem to be both necessary and very useful in the near future. Resumen La pandemia de la infección por el coronavirus tipo 2 del síndrome respiratorio agudo grave o SARS-CoV-2 causante de la enfermedad por coronavirus de 2019 (COVID-19) ha precisado de una transformación drástica de los hospitales y por consiguiente de los servicios de Nefrología de España. Desde la Sociedad Española de Nefrología se ha realizado una encuesta a los Jefes de Servicios de Nefrología de España abordando la reorganización de los servicios de Nefrología y actividad en la época de mayor afectación por COVID-19. Hemos preguntado por la integración de los nefrólogos en equipos COVID-19, la actividad asistencial de hospitalización de Nefrología (ingresos programados, biopsias renales), la realización de cirugías programadas como los accesos vasculares o implantación de catéteres peritoneales, la suspensión o no del programa de trasplante renal y la transformación de las consultas externas de nefrología. En el trabajo actual se detalla la adaptación y transformación de los servicios de nefrología en la pandemia COVID-19 en España. Durante dicho periodo se han suspendido los ingresos programados en los Servicios de Nefrología, la realización de cirugías/biopsias programadas y ha disminuido en más de un 75% el programa de trasplante renal. Es de interés mencionar que las consultas externas de nefrología se han realizado mayoritariamente telefónicamente. En conclusión, la pandemia ha impactado claramente en la actividad clínica en los servicios de Nefrología españoles disminuyendo la actividad programada y los trasplantes renales y modificando la actividad en consultas externas. Un plan de transformación asistencial e implementación de telemedicina en Nefrología parece necesario y de gran utilidad en un futuro próximo.

Moral Decision-Making, Stress, and Social Cognition in Frontline Workers vs. Population Groups During the COVID-19 Pandemic: An Explorative Study.

On March 9, 2020, Italy has gone into "lockdown" because of COVID-19 pandemic, with a national quarantine. All non-essential working activities and schools of all levels have been temporarily closed: consequently, the entire population have been forced to dramatically change their daily habits. The pandemic raised important psychological, moral, social, and economic issues. Our research focused on the moral decision-making of people during an emergency. This paper reports two studies. The aim of Study 1 was to evaluate moral decision-making, level of perceived stress, ability of mentalizing and empathy in university students and Italian workers. 224 front-line workers (FLW), 413 second-line workers (SLW), and 663 university students (US), during Italian Phase 1 of lockdown, completed an online questionnaire. The results of Study 1 showed that participants in the FLW group are more likely to choose utilitarian solutions and judge as morally acceptable actions finalized to saving lives of more people if this requires sacrificing a low number of individuals. At the same time, decision-making was experienced as less unpleasant and less arousing with respect to the other two groups, demonstrating a greater ability to keep emotional control under pressure. In Study 2, we compared the same variables used in Study 1, selecting two professional categories from the FLW group engaged in emergency during COVID-19, namely healthcare providers (n = 82) and public safety personnel (n = 117). Our results showed that healthcare providers were more stressed and emotionally involved than public safety personnel, with higher empathic concern and arousal in moral decision-making. We suggest it is essential providing immediate psychological support and monitoring physical and emotional well-being for workers in the front-line during emergencies like the COVID-19 pandemic, in order to prevent experiences of moral distress or mental health problems.

Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques.

SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection.

[Impact of the COVID-19 pandemic on Spanish Nephrology Services]. / Impacto de la pandemia COVID-19 en los servicios de Nefrología españoles.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has required a rapid and drastic transformation of hospitals, and consequently also of Spanish Nephrology Units, to respond to the critical situation. The Spanish Society of Nephrology conducted a survey directed to the Heads of Nephrology Departments in Spain that addressed the reorganisation of Nephrology departments and activity during the peak of COVID-19 pandemic. The survey has been focused on the integration of nephrologists in COVID-19 teams, nephrology inpatient care activities (elective admissions, kidney biopsies), the performance of elective surgeries such as vascular accesses or implantation of peritoneal catheters, the suspension of kidney transplantation programmes and the transformation of nephrology outpatient clinics. This work details the adaptation and transformation of nephrology services during the COVID-19 pandemic in Spain. During this period, elective admissions to Nephrology Services, elective surgeries and biopsies were suspended, and the kidney transplant programme was scaled back by more than 75%. It is worth noting that outpatient nephrology consultations were carried out largely by telephone. In conclusion, the pandemic has clearly impacted clinical activity in Spanish Nephrology departments, reducing elective activity and kidney transplants, and modifying activity in outpatient clinics. A restructuring and implementation plan in Nephrology focused on telemedicine and/or virtual medicine would seem to be both necessary and very useful in the near future.

Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.

Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques.

Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.