Clinical Characterization and Outcomes of Patients with Hypercreatinemia Affected by COVID-19.

The present study evaluated the clinical presentation and outcome of COVID-19 patients with underlying hypercreatinemia at the time of hospitalization. A retrospective observational study was conducted from the 23rd of March 2020 to the 15th of April 2021 in 1668 patients confirmed positive for COVID-19 in the Chest Disease Hospital in Srinagar, India. The results of the present study revealed that out of 1668 patients, 339 with hypercreatinemia had significantly higher rates of admission to the intensive care unit (ICU), severe manifestations of the disease, need for mechanical ventilation, and all-cause mortality. Multivariable analysis revealed that age, elevated creatinine concentrations, IL-1, D-Dimer, and Hs-Crp were independent risk factors for in-hospital mortality. After adjusted analysis, the association of creatinine levels remained strongly predictive of all-cause, in-hospital mortality (HR-5.34; CI-4.89-8.17; p ≤ 0.001). The amelioration of kidney function may be an effective method for achieving creatinemic targets and, henceforth, might be beneficial for improving outcomes in patients with COVID-19.

The Impact of the COVID-19 Pandemic on Makkah City's Health Programs Performance

Background: Coronavirus (Covid-19) is a viral illness caused by a recently discovered coronavirus that began in the Chinese city of Wuhan in December 2019.(1). The impact of this global pandemic affects all social, psychological, and economic aspects of society, and health(1,2). The aim of the Saudi preventive health programs for Community health services was to increase awareness and decrease preventable diseases. This study aimed to assess the impact of the COVID-19 pandemic on key performance indicators of health programs at Makkah Al-Mukarramah City. Material and Methods: This comparative descriptive study was conducted to assess health programs' key performance indicators and statistics before COVID19 in 2019, in comparison with 2020 and 2021. KPI and statistics of health programs collected the data including that on chronic diseases Preventive programs, age categories and healthy life programs.

Insight into Oncogenic Viral Pathways as Drivers of Viral Cancers: Implication for Effective Therapy.

As per a recent study conducted by the WHO, 15.4% of all cancers are caused by infectious agents of various categories, and more than 10% of them are attributed to viruses. The emergence of COVID-19 has once again diverted the scientific community's attention toward viral diseases. Some researchers have postulated that SARS-CoV-2 will add its name to the growing list of oncogenic viruses in the long run. However, owing to the complexities in carcinogenesis of viral origin, researchers across the world are struggling to identify the common thread that runs across different oncogenic viruses. Classical pathways of viral oncogenesis have identified oncogenic mediators in oncogenic viruses, but these mediators have been reported to act on diverse cellular and multiple omics pathways. In addition to viral mediators of carcinogenesis, researchers have identified various host factors responsible for viral carcinogenesis. Henceforth owing to viral and host complexities in viral carcinogenesis, a singular mechanistic pathway remains yet to be established; hence there is an urgent need to integrate concepts from system biology, cancer microenvironment, evolutionary perspective, and thermodynamics to understand the role of viruses as drivers of cancer. In the present manuscript, we provide a holistic view of the pathogenic pathways involved in viral oncogenesis with special emphasis on alteration in the tumor microenvironment, genomic alteration, biological entropy, evolutionary selection, and host determinants involved in the pathogenesis of viral tumor genesis. These concepts can provide important insight into viral cancers, which can have an important implication for developing novel, effective, and personalized therapeutic options for treating viral cancers.

Evaluation of Convalescent Plasma in the Management of Critically Ill COVID-19 Patients (with No Detectable Neutralizing Antibodies Nab) in Kashmir, India.

BACKGROUND: For centuries, convalescent plasma (CP) has been recommended to treat a diverse set of viral diseases. Therefore, the present study was undertaken to evaluate the effectiveness of CP in critically ill COVID-19 patients. METHODS AND MATERIALS: From 23 March 2021 to 29 December 2021, an open-label, prospective cohort, single-centre study was conducted at Chest Disease Hospital, Jammu and Kashmir, Srinagar. Patients with severe manifestation of coronavirus disease 2019 (COVID-19) under BST (best standard treatment) +CP were prospectively observed in order to evaluate effectiveness of CP therapy and historical control under BST were used as the control group Results: A total of 1667 patients were found positive for COVID-19. Of these, 873 (52.4%), 431 (28.8%), and 363 (21.8%) were moderately, severely, and critically ill, respectively. On 35th day post-infusion of CP, all-cause mortality was higher in the BST (best standard treatment) +CP group 12 (37.5%) compared to 127 (35%) in the BST group with an odds ratio (OR) of 1.4 and hazard ratio (HR) (95% CI: 1.08-1.79, p = 0.06). Similarly, 7 (21.9) patients in the BST+CP group and 121 (33.3) patients in the BST group showed the transition from critically ill to moderate disease with subhazard ratio (s-HR 1.37) (95% CI: 1.03-2.9). CONCLUSIONS: In the present study, we could not find any significant difference in the CP group and BST +CP in primary outcome of reducing all-cause mortality in critically ill patients with negligible Nabs levels. However, beneficial results were observed with use of CP in a limited number of secondary outcomes which includes days of hospitalization, negative conversion of SARS-CoV-2 on basis of RT-PCR on 7th day and 14th day, need for invasive mechanical ventilation on 14th day post-CP treatment, and resolution of shortness of breath.

Online surgical education adopted among urology residency programs in response to COVID-19: A pilot study.

OBJECTIVE: To understand the residents' perceptions of the, COVID-19 driven, newly implemented online learning systems adopted among accredited urology residency programs nationwide, and their sustainability following the pandemic era. MATERIALS AND METHODS: A survey was designed and dispersed to urology program coordinators and directors to distribute to their residents. In the survey, Online education models was the all-encompassing term to describe any form of resident education that occurred online. Anonymous surveys were exported from Survey Monkey and data was analyzed for statistical significance. RESULTS: Over 70% of urology residents agreed or were neutral to the statement that Online education models were equivalent to in-person learning. Only 13% of residents stated that online learning should not be continued following the pandemic. Several different parameters were assessed, and only 5 of them showed statistical significance. Stress, personal engagement, interpersonal communication efficiency and non-verbal cues were all lower with online education models. The only attribute that was scored higher by residents was network connectivity issues. CONCLUSIONS: An overwhelming majority of urology residents in the United States believe Online education models should continue to be adopted once the pandemic is over.

POSSIBLE IMPACTS OF COVID-19 PANDEMIC ON DOMESTIC WASTEWATER CHARACTERISTICS IN KUWAIT

The wastewater quality alterations due to the use of cleaning agents, sanitisers, and disinfectants, in addition to the accompanying use of water during COVID-19 have potential impacts on wastewater treatment operations. How the characteristics of wastewater could be altered by the COVID-19 pandemic was the concern of this investigation. Daily records of the Ardiya catchment in Kuwait City were examined for the period 2015–2020. Perhaps due to the excessive use of water during 2020 (446 compared to the five-year average of 436 l/c.d) and the corresponding wastewater generation increase (253 compared to the five-year average of 239 l/c.d), the effect of chemical usage on the wastewater quality has dampened. Nonetheless, an increase in the frequency of COD/BOD ratio > 3, TP in the range 6.5 to 8.5, TKN in the range 40 to 50 were observed in 2020, which was not observed during 2015–2019. These COVID-19 related alterations are important to take into consideration in wastewater treatment operations to achieve wastewater treatment targets. © 2022 The Author(s). Published by Vilnius Gediminas Technical University.

Mucormycosis an added burden to Covid-19 Patients: An in-depth Systematic Review

As of 25thJuly, 2022, global Disease burden of 575,430,244 confirmed cases and over 6,403,511 deaths have been attributed to coronavirus disease 2019 (COVID-19). Co-infections/secondary infections continue to plague patients around the world as result of the co-morbidities like diabetes mellitus, biochemical changes caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) especially significant elevation in free iron levels, immune suppression caused by SARS-CoV-2, and indiscriminate use of systemic corticosteroids for the treatment of severe COVID-19 disease. In such circumstances, opportunistic fungal infections pose significant challenge for COVID-19 disease therapy in patients with other co-morbidities. Although COVID-19-associated Mucormycosis (CAM) has been widely recognized, currently extensive research is being conducted on mucormycosis. It has been widely agreed that patients undergoing corticosteroid therapy are highly susceptible for CAM, henceforth high index of screening and intensive care and management is need of an hour in order to have favourable outcomes in these patients. Diagnosis in such cases is often delayed and eventually the disease progresses quickly which poses added burden to clinician and increases patient load in critical care units of hospitals. A vast perusal of literature indicated that patients with diabetes mellitus and those with other co-morbidities might be highly vulnerable to develop mucormycosis. In the present work, the case series of three patients presented at Chest Disease Hospital Srinagar, Jammu and Kashmir infected with CAM has been described with their epidemiological data in supplementary section. All these cases were found to be affected with co-morbidity of Diabetes Mellitus (DM) and were under corticosteroid therapy. Furthermore, given the significant death rate linked with mucormycosis and the growing understanding of the diseases significance, systematic review of the literature on CAM has been discussed and we have attempted to discuss emerging CAM and related aspects of the disease.

Comprehensive Highlights of the Universal Efforts towards the Development of COVID-19 Vaccine.

The world has taken proactive measures to combat the pandemic since the coronavirus disease 2019 (COVID-19) outbreak, which was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). These measures range from increasing the production of personal protective equipment (PPE) and highlighting the value of social distancing to the emergency use authorization (EUA) of therapeutic drugs or antibodies and their appropriate use; nonetheless, the disease is still spreading quickly and is ruining people's social lives, the economy, and public health. As a result, effective vaccines are critical for bringing the pandemic to an end and restoring normalcy in society. Several potential COVID-19 vaccines are now being researched, developed, tested, and reviewed. Since the end of June 2022, several vaccines have been provisionally approved, whereas others are about to be approved. In the upcoming years, a large number of new medications that are presently undergoing clinical testing are anticipated to hit the market. To illustrate the advantages and disadvantages of their technique, to emphasize the additives and delivery methods used in their creation, and to project potential future growth, this study explores these vaccines and the related research endeavors, including conventional and prospective approaches.

Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients.

RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences between the viruses are less well understood, especially whether RaTG13 spike can be efficiently neutralised by antibodies generated from infection with, or vaccination against, SARS-CoV-2. Using RaTG13 and SARS-CoV-2 pseudotypes we compared neutralisation using convalescent sera from previously infected patients or vaccinated healthcare workers. Surprisingly, our results revealed that RaTG13 was more efficiently neutralised than SARS-CoV-2. In addition, neutralisation assays using spike mutants harbouring single and combinatorial amino acid substitutions within the RBD demonstrated that both spike proteins can tolerate multiple changes without dramatically reducing neutralisation. Moreover, introducing the 484 K mutation into RaTG13 resulted in increased neutralisation, in contrast to the same mutation in SARS-CoV-2 (E484K). This is despite E484K having a well-documented role in immune evasion in variants of concern (VOC) such as B.1.351 (Beta). These results indicate that the future spill-over of RaTG13 and/or related sarbecoviruses could be mitigated using current SARS-CoV-2-based vaccination strategies.

D-dimer as a predictive and prognostic marker among COVID-19 patients.

OBJECTIVES: To examine D-dimer, coagulation profile, and platelet count among patients hospitalized with coronavirus disease-19 (COVID-19) and compare them to findings from non-COVID-19 subjects. METHODS: The participants in this retrospective hospital-based observational study design included 112 confirmed diagnosed with COVID-19 who were admitted to King Khaled Hospital, Najran, Saudi Arabia, and another 112 non-COVID-19 subjects as a comparative group. Laboratory investigations, demographic and clinical records were obtained from participants' electronic indexed medical records. Coronavirus disease-19 diagnosis was confirmed according to positive real time polymerase chain reaction assay carried out at the hospital's central laboratory, where samples were extracted from a nasopharyngeal swab. Pneumonia related to COVID-19 is classified as critical, severe, moderate, mild, and asymptomatic whereas thrombocytopenia was marked when the platelet count was <150.00×109/L. Suitable statistical analysis was applied to determine possible differences between the findings from the 2 groups. RESULTS: The D-dimer and activated partial thromboplastin clotting time mean values were significantly elevated (p<0.001). The international normalized ratio and platelet count mean values confirmed a significant decrease (p<0.001). Thrombocytopenia was found 9 times in COVID-19 higher than in the non-COVID-19. D-dimer and prothrombin time mean values increased significantly among the COVID-19 patients with all patterns of symptoms on admission (p<0.001). CONCLUSION: D-dimer mean values increased significantly in deceased COVID-19 and in hospitalized intensive care unit (ICU) wards patients (p<0.001), indicating a potential predictive and prognostic severity marker, particularly among COVID-19 patients in the ICU.

Neutralizing antibody activity against 21 SARS-CoV-2 variants in older adults vaccinated with BNT162b2.

SARS-CoV-2 variants may threaten the effectiveness of vaccines and antivirals to mitigate serious COVID-19 disease. This is of most concern in clinically vulnerable groups such as older adults. We analysed 72 sera samples from 37 individuals, aged 70-89 years, vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) 3 weeks apart, for neutralizing antibody responses to wildtype SARS-CoV-2. Between 3 and 20 weeks after the second vaccine dose, neutralizing antibody titres fell 4.9-fold to a median titre of 21.3 (neutralization dose 80%), with 21.6% of individuals having no detectable neutralizing antibodies at the later time point. Next, we examined neutralization of 21 distinct SARS-CoV-2 variant spike proteins with these sera, and confirmed substantial antigenic escape, especially for the Omicron (B.1.1.529, BA.1/BA.2), Beta (B.1.351), Delta (B.1.617.2), Theta (P.3), C.1.2 and B.1.638 spike variants. By combining pseudotype neutralization with specific receptor-binding domain (RBD) enzyme-linked immunosorbent assays, we showed that changes to position 484 in the spike RBD were mainly responsible for SARS-CoV-2 neutralizing antibody escape. Nineteen sera from the same individuals boosted with a third dose of BNT162b2 contained higher neutralizing antibody titres, providing cross-protection against Omicron BA.1 and BA.2. Despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines can elicit broad neutralizing antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

[Online surgical education adopted among urology residency programs in response to COVID-19: A pilot study]. / La educación quirúrgica en línea implementada en los programas de residencia urológica como respuesta a la COVID-19: estudio piloto.

Objective: To understand the residents' perceptions of the, COVID-19 driven, newly implemented online learning systems adopted among accredited urology residency programs nationwide, and their sustainability following the pandemic era. Materials and methods: A survey was designed and dispersed to urology program coordinators and directors to distribute to their residents.In the survey, online education models was the all-encompassing term to describe any form of resident education that occurred online. Anonymous surveys were exported from Survey Monkey and data was analyzed for statistical significance. Results: Over 70% of urology residents agreed or were neutral to the statement that online education models were equivalent to in-person learning. Only 13% of residents stated that online learning should not be continued following the pandemic. Several different parameters were assessed, and only 5 of them showed statistical significance. Stress, personal engagement, interpersonal communication efficiency and non-verbal cues were all lower with online education models. The only attribute that was scored higher by residents was network connectivity issues. Conclusions: An overwhelming majority of urology residents in the United States believe online education models should continue to be adopted once the pandemic is over.

La educación quirúrgica en línea implementada en los programas de residencia urológica como respuesta a la COVID-19: estudio piloto Online surgical education adopted among urology residency programs in response to COVID-19: A pilot study

Objetivo Comprender la percepción de los residentes respecto a los sistemas de aprendizaje en línea, los cuales, impulsados por la pandemia de la COVID-19, han sido recientemente implementados a nivel nacional en los programas de residencia urológica acreditados. Adicionalmente, nos proponemos analizar su sostenibilidad tras la era de la pandemia. Material y métodos Se diseñó una encuesta para, a través de los coordinadores y directores de programas de urología, difundirla a los residentes de urología. En la encuesta, los modelos de educación en línea englobaron cualquier forma de educación recibida por los residentes que se diera en línea. Las encuestas anónimas se exportaron de Survey Monkey y se analizaron los datos para determinar la significación estadística. Resultados Más del 70% de los residentes de urología estuvieron de acuerdo, o mostraron una actitud neutral, ante la afirmación de que los modelos de educación en línea eran equivalentes al aprendizaje presencial. Solo el 13% de los residentes afirmaron que el aprendizaje en línea no debería continuar tras la pandemia. Se evaluaron diversos parámetros, y solo 5 de ellos mostraron significación estadística. El estrés, el compromiso personal, la eficacia de la comunicación interpersonal y las señales no verbales fueron más bajos para los modelos de educación en línea. El único aspecto al que los residentes dieron mayor puntuación fue el de los problemas de conectividad a una red. Conclusiones La gran mayoría de los residentes de urología en Estados Unidos cree que los modelos de educación en línea deben mantenerse una vez terminada la pandemia.

Hematological Findings among COVID-19 Patients Attending King Khalid Hospital at Najran, Kingdom of Saudi Arabia.

COVID-19 is a global pandemic viral infection that has affected millions worldwide. Limited data is available on the effect of COVID-19 on hematological parameters in Saudi Arabia. This study is aimed at examining the role of hematological parameters among COVID-19 patients admitted to King Khalid Hospital in Najran, Saudi Arabia. This is a retrospective, hospital-based study of 514 cases who were recruited during August to October 2020. 257 COVID-19 patients formed the study group, and a further 257 negative subjects formed the control group. Anemia was significantly elevated in positive subjects over controls (respectively, 64.2% and 35.8%), with patients 2.5 times more likely to be anemic (p < 0.01). Thrombocytopenia was higher in patients over controls (respectively, 62% and 38%), with patients ~1.7 times more likely to be thrombocytopenic (p < 0.01). Moreover, leukopenia was significantly higher in patients over controls (respectively, 71% and 29%), with positive subjects ~2.6 times more likely to be leukopenic. Our study results indicate that mild anemia associated with leukopenia may have diagnostic value for COVID-19. Careful assessment of hematological parameters, at baseline and throughout the disease path, will assist physicians in formulating personalized approaches to treatment and promptly offer intensive care to those in greater need.

Complete Blood Count Alterations of COVID-19 Patients in Riyadh, Kingdom of Saudi Arabia

This study is aimed at evaluating the association between Coronavirus disease 19 (COVID-19) and the primary complete blood count (CBC) parameters in confirmed positive patients. In a retrospective cross-sectional study, 384 files of patients with confirmed COVID-19 diagnosis hospitalized at King Saud Medical City, Riyadh, were chosen randomly as a study group for hematological parameters, with another 384 non-COVID-19 files of patients without history of any disease which could influence the hematological profile were selected as a control group. The gender, age, and nationality of the control group were matched with those of the study group. Anemia and thrombocytopenia prevalence was significantly higher in COVID-19 positive patients compared with negative. However, the positive cases were 3.4 times more likely to be anemic and approximately 5.3 times as likely to be thrombocytopenic, while the prevalence of leukopenia showed no statistical significance between the two groups. However, the Mean Cell Volume (MCV), Total White Blood Cell (WBC) count, lymphocyte count, and basophil count median values showed a nonsignificant difference between the two groups. Anemia and thrombocytopenia may be highly developed in severe positive cases, and therefore, further studies are recommended to validate these findings.

Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway.

SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs, and farmed mink. Since the start of the 2019 pandemic, several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all three mink adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.

Production of Recombinant Replication-defective Lentiviruses Bearing the SARS-CoV or SARS-CoV-2 Attachment Spike Glycoprotein and Their Application in Receptor Tropism and Neutralisation Assays.

For enveloped viruses, such as SARS-CoV-2, transmission relies on the binding of viral glycoproteins to cellular receptors. Conventionally, this process is recapitulated in the lab by infection of cells with isolated live virus. However, such studies can be restricted due to the availability of high quantities of replication-competent virus, biosafety precautions and associated trained staff. Here, we present a protocol based on pseudotyping to produce recombinant replication-defective lentiviruses bearing the SARS-CoV or SARS-CoV-2 attachment Spike glycoprotein, allowing the investigation of viral entry in a lower-containment facility. Pseudoparticles are produced by cells transiently transfected with plasmids encoding retroviral RNA packaging signals and Gag-Pol proteins, for the reconstitution of lentiviral particles, and a plasmid coding for the viral attachment protein of interest. This approach allows the investigation of different aspects of viral entry, such as the identification of receptor tropism, the prediction of virus host range, and zoonotic transmission potential, as well as the characterisation of antibodies (sera or monoclonal antibodies) and pharmacological inhibitors that can block entry. Graphic abstract: SARS-CoV and SARS-CoV-2 pseudoparticle generation and applications.

A survey of urology residency program directors assessing criteria to interview applicants during the COVID-19 pandemic

INTRODUCTION AND OBJECTIVE: To determine criteria of interest to Urology residency program directors (PDs) when selecting applicants for residency interviews during the COVID-19 pandemic. METHODS: An anonymous survey was sent via email to all Urology residency PDs across the United States. PDs were asked to assign the degree of importance (1-5, with 5 being very important) of selected factors in deciding which applicants to interview. Surveys were distributed and study data was managed using REDCap. Descriptive statistical analyses were performed. RESULTS: In total, 130 urology residency PDs were contacted and 64 (49.3%) responded to the survey. Urology letter(s) of recommendation (LOR) based on non-virtual rotation(s), Urology clerkship grades, research experience, and Visa status of the applicant were cited as the most important factors in selecting applicants for interview with median importance ratings of 5, 4, 4, and 5, respectively. Urology LOR based on virtual rotation(s), virtual subinternship( s), and participation in social media activities were the least important in selecting applicants for interviews with median importance ratings of 2 for each. Notably, Urology LOR(s) based on non-virtual rotation(s) and Visa status were consistently ranked as the most important factors by over 50% of PDs. CONCLUSIONS: Urology PDs value urology LOR(s) from nonvirtual rotation(s), Urology clerkship grades, research experience, and applicant Visa status as the most important factors in selecting applicants for interviews during the COVID-19 pandemic. Virtual rotation(s) and social media activity were ranked the lowest among criteria that influence the selection process for interviews.

COVID-19 Pandemic Diagnosis and Analysis Using Clinical Decision Support Systems

Since the pandemic began, the attention of the entire world has turned to the digital health environment to provide potential health options to minimize the effects of this pandemic in this moment of unparalleled medical crisis. Paper presents the survey on the role of Artificial Intelligence in decision support systems to diagnose COVID-19 and we are presenting the Artificial Intelligence (AI) model for Decision Support System (DSS), Challenges faced during earlier pandemic due to lack of faster and efficient methods of diagnosis and Opportunities and Challenges of Clinical Decision Support System (CDSS). A three-dimensional deep learning system, called COVID-19 Neural Network detection (COVNet), is developed to detect COVID-19 based on CT images of the chest. We have seen that Decision support system using AI in Healthcare that is termed as Clinical decision support system is a very helpful, fast and advanced technique because during pandemics like COVID-19 the cases are increasing exponentially day by day so it’s not possible to diagnose each patient manually. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway. (preprint)

SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.