Developments and Trends in Energy Poverty Research - Literature Visualization Analysis Based on CiteSpace

The purpose of this paper is to help better understand the problem of energy poverty;to grasp the research context, evolution trends and research hotspots of energy poverty;and to find clues from research on energy poverty. In this paper, we use the scientific quantitative knowledge graph method and CiteSpace software to analyze 814 studies in the WOS (Web of Science) and CNKI (China National Knowledge Infrastructure) databases, such as a literature characteristic analysis, a core author and research institution network analysis, a research hotspot analysis, research trends and a frontier analysis. The results show that the specific connotations of energy poverty are different between developed countries and developing countries. In developed countries, energy poverty is mainly manifested in the affordability of energy consumption, while in developing countries, energy poverty is manifested in the availability of energy. The causes, impacts and solutions of energy poverty are the focus of CNKI and WOS literature, and their perspectives of the impacts and solutions are relatively consistent. However, in terms of the causes, scholars of WOS discuss the energy supply side and the demand side, while scholars of CNKI mainly analyze the energy demand side. The quantitative evaluation system of energy poverty has not been unified, which restricts the depth and breadth of energy poverty research. Topics such as the expanding scope of research objects;the interaction among energy poverty, the 'two-carbon';target and other macro factors;the complex and severe energy poverty situation following the COVID-19 pandemic and the outbreak of the war in Ukraine;and the ways to solve the energy poverty problem in the context of China may become the focus of research in the future. This study provides an overview for researchers who are not familiar with the field of energy poverty, and provides reference and inspiration for future research of scholars in the field of energy poverty research.

Shortening the Biologics Clinical Timeline with a Novel Method for Generating Stable, High Producing Cell Pools and Clones (preprint)

Reducing drug development timelines is an industry-wide goal to bring medicines to patients in need more quickly. This was exemplified in the COVID-19 pandemic where reducing development timelines had a direct impact on the number of lives lost to the disease. The use of drug substance produced using cell pools, as opposed to clones, has the potential to shorten development timelines. Toward this goal, we have developed a novel technology, GPEx® Lightning, that allows for rapid, reproducible, targeted recombination of transgenes into more than 200 Dock sites in the CHO genome. This allows for rapid production of high expressing stable cell pools and clones that reach titers of 4 to 12 g/L in generic fed-batch production. These pools and clones are highly stable in both titer and glycosylation, showing strong similarity in glycosylation profiles.

Cytokine nanosponges suppressing overactive macrophages and dampening systematic cytokine storm for the treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction. Inspired by macrophage membranes harbor the receptors with special high affinity for proinflammation cytokines, lipopolysaccharide (LPS)-stimulated macrophage membrane-coated nanoparticles (LMNP) were developed to show strong sponge ability to both IFN-γ and IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo. Besides, LMNP also efficiently alleviated HLH-related symptoms including cytopenia, hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models. Furthermore, its sponge effect also worked well for five human HLH samples in vitro. Altogether, it's firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation, which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants (preprint)

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

Phase separation-mediated condensation of N protein-deaminase complex promotes SARS-CoV-2 mutagenesis (preprint)

The emergence of SARS-CoV-2 variants poses enormous challenges to the prevention and control of COVID-19 with alterations in antigenicity, transmissibility and pathogenicity. The rapid evolution of RNA viruses could be caused by high mutation frequencies during replication, arising by replication errors, intergenomic recombination or even host deaminases. We sought to understand whether host deaminases are involved in SARS-CoV-2 mutation, and how they orchestrate host deaminases to trigger this process. Herein, we provided the experimental evidence that APOBEC and ADAR deaminases act as the driving forces for SARS-CoV-2 mutagenesis. Mechanistically, SARS-CoV-2 nucleocapsid (N) protein, which is responsible for packaging viral genomic RNA, complexes with host deaminases to facilitate viral RNA mutation. Moreover, N protein employs deaminases-involved condensates to further promote viral RNA mutation. Mutant N protein with F17A substitution, defective in entry of deaminases-involved RNA granules, leads to the decreased mutation of viral RNA, confirming the function of N protein-deaminase condensates on RNA editing. Our study sheds light on the novel mechanism of SARS-CoV-2 mutation during host-virus arms race.

Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.1 and BA.2 variants and their mouse origins (preprint)

The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies reveal that the BA.2 spike trimer have 11-fold and 2-fold higher potency to human ACE2 than the spike trimer from the wildtype and Omicron BA.1 strains. The structure of the BA.2 spike timer reveals that all three receptor-binding domains (RBD) in the spike trimer are in open conformation, ready for high affinity binding to human ACE2, providing the basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to have efficient inhibition of Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to the mouse ACE2 with high potency. In contrast, the wildtype spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants from human-cat-mouse-human circle, which could have important implications in establishing an effective strategy in combating viral infection.

Impact of COVID-19 on Astronomy: Two Years In (preprint)

We study the impact of the COVID-19 pandemic on astronomy using public records of astronomical publications. We show that COVID-19 has had both positive and negative impacts on research in astronomy. We find that the overall output of the field, measured by the yearly paper count, has increased. This is mainly driven by boosted individual productivity seen across most countries, possibly the result of cultural and technological changes in the scientific community during COVID. However, a decreasing number of incoming new researchers is seen in most of the countries we studied, indicating larger barriers for new researchers to enter the field or for junior researchers to complete their first project during COVID. Unfortunately, the overall improvement in productivity seen in the field is not equally shared by female astronomers. By fraction, fewer papers are written by women and fewer women are among incoming new researchers in most countries. Even though female astronomers also became more productive during COVID, the level of improvement is smaller than for men. Pre-COVID, female astronomers in the Netherlands, Australia, Switzerland were equally as or even more productive than their male colleagues. During COVID, no single country's female astronomers were able to be more productive than their male colleagues on average.

Alveolar regeneration following viral infection is independent of tuft cells (preprint)

Severe injuries following viral infection cause lung epithelial destruction with the presence of ectopic basal progenitor cells (EBCs), although the exact function of EBCs remains controversial. We and others previously showed the presence of ectopic tuft cells in the disrupted alveolar region following severe influenza infection. Here, we further revealed that the ectopic tuft cells are derived from EBCs. This process is amplified by Wnt signaling inhibition but suppressed by Notch inhibition. Further analysis revealed that p63-CreER labeled population de novo arising during regeneration includes alveolar epithelial cells when Tamoxifen was administrated after viral infection. The generation of the p63-CreER labeled alveolar cells is independent of tuft cells, demonstrating segregated differentiation paths of EBCs in lung repair. EBCs and ectopic tuft cells can also be found in the lung parenchyma post SARS-CoV-2 infection, suggesting a similar response to severe injuries in humans.

Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody: mechanisms for the high infectivity, immune evasion and antibody drug discovery (preprint)

The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7°C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.

Occurrence of COVID-19 symptoms during SARS-CoV-2 infection defines waning of humoral immunity (preprint)

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections. One-Sentence SummaryPrevalence and durability of SARS-CoV-2-specific IgG responses and neutralizing capacities correlate with COVID-19 symptoms.

Chinese medicine (Q-14) in the Treatment of Patients with Coronavirus Disease 2019 (COVID-19): A Single-center, Open label, Randomised Controlled Trial (preprint)

OBJECTIVE To evaluate the efficacy and safety of Chinese medicine (Q-14) plus standard care compared with standard care alone in adult with coronavirus disease 2019 (COVID-19). Study DESIGN Single-center, open label, randomised controlled trial. SETTING Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS 204 patients with laboratory confirmed COVID-19 were randomised in to treatment group and control group, which was 102 patients each group. INTERVENTIONS In treatment group, Q-14 was administrated at 10g (granules), twice daily for 14 days and plus standard care. In control group, patients were given standard care alone for 14 days. MAIN OUTCOME MEASURE The primary outcome was conversion time of SARS-CoV-2 viral assay. Adverse events were analyzed in the safety population. RESULTS Among 204 patients, 195 were analyzed according to the intention to treat principle. There were 149 patients (71 vs. 78 in treatment group and control group respectively) turning to negative via SARS-CoV-2 viral assay. No statistically significance showed in conversion time between treatment group and control group (FAS: Median (IQR): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); Mean rank: 67.92 vs. 81.44; P=0.051.). Time to recovery of fever was shorter in treatment group as compared in control group. The disappearance rate of symptom in cough, fatigue, chest discomfort was significantly higher in treatment group. In chest computed tomography (Chest CT) examinations, overall evaluation of chest CT examination after treatment compared with baseline showed more patients improved in treatment group .There were no significant differences in the other outcomes. CONCLUSION Administration of Q-14 on standard care for COVID-19 was useful for improvement of symptoms (such as fever, cough, fatigue and chest discomfort), while did not result in a significantly higher probability of negative conversion of SARS-CoV-2 viral assay. No serious adverse events were reported. TRIAL REGISTRATION ChiCTR2000030288

Longitudinal Trajectories of Pneumonia Lesions and Lymphocyte counts Associated with Disease Severity among Convalescent COVID-19 Patients: A Group-based Multi-trajectory Analysis (preprint)

BackgroundTo explore the long-term trajectories considering pneumonia volumes and lymphocyte counts with individual data in COVID-19. MethodsA cohort of 257 convalescent COVID-19 patients (131 male and 126 females) were included. Group-based multi-trajectory modelling was applied to identify different trajectories in terms of pneumonia lesion percentage and lymphocyte counts covering the time from onset to post-discharge follow-ups. We studied the basic characteristics and disease severity associated with the trajectories.ResultsWe characterised four distinct trajectory subgroups. (1) Group 1 (13.9%), pneumonia increased until a peak lesion percentage of 1.9% (IQR 0.7~4.4) before absorption. The slightly decreased lymphocyte rapidly recovered to the top half of the normal range. (2) Group 2 (44.7%), the peak lesion percentage was 7.2% (IQR 3.2~12.7). The abnormal lymphocyte count restored to normal soon. (3) Group 3 (26.0%), the peak lesion percentage reached 14.2% (IQR 8.5~19.8). The lymphocytes continuously dropped to 0.75 × 109/L after one day post-onset before slowly recovering. (4) Group 4 (15.4%), the peak lesion percentage reached 41.4% (IQR 34.8~47.9), much higher than other groups. Lymphopenia was aggravated until the lymphocytes declined to 0.80 × 109/L on the fourth day and slowly recovered later. Patients in the higher order groups were older and more likely to have hypertension and diabetes (all P values < 0.05), and have more severe disease.ConclusionsOur findings provide new insights to understand the heterogeneous natural courses of COVID-19 patients and the associations of distinct trajectories with disease severity, which is essential to improve the early risk assessment, patient monitoring, and follow-up schedule.

Voxel-level forecast system for lesion development in patients with COVID-19 (preprint)

The global spread of COVID-19 seriously endangers human health and even lives. By predicting patients' individualized disease development and further performing intervention in time, we may rationalize scarce medical resources and reduce mortality. Based on 1337 multi- stage ([≥]3) high-resolution chest computed tomography (CT) images of 417 infected patients from three centers in the epidemic area, we proposed a random forest + cellular automata (RF+CA) model to forecast voxel-level lesion development of patients with COVID-19. The model showed a promising prediction performance (Dice similarity coefficient [DSC] = 71.1%, Kappa coefficient = 0.612, Figure of Merit [FoM] = 0.257, positional accuracy [PA] = 3.63) on the multicenter dataset. Using this model, multiple driving factors for the development of lesions were determined, such as distance to various interstitials in the lung, distance to the pleura, etc. The driving processes of these driving factors were further dissected and explained in depth from the perspective of pathophysiology, to explore the mechanism of individualized development of COVID-19 disease. The complete codes of the forecast system are available at https://github.com/keyunj/VVForecast_covid19.

A Curated Web Tracker of Global Development of Treatments and Vaccines for COVID-19 (preprint)

The response to the global pandemic of SARS-CoV-2 that causes COVID-19 disease has been an unprecedented mobilization of global scientific and medical effort in an unusual race for effective treatments and vaccines. Such a sense of urgency and intensity could however be potentially undermined without a general bigger picture of the whole landscape. In order to provide such an overall landscape, we set out to build a comprehensive tracker of global treatment and vaccine development on an interactive web application that presents a dynamic and up-to-date inventory of treatments and vaccines in various stages of clinical development. An additional layer of expert curation is applied to the raw data to categorize and curate treatments and vaccines to reveal intrinsic similarities and patterns. The combination of these features on the web application makes it a unique curated tracker that provides insights to a broad range of audiences from institutional organizers, research investigators, to general public.Availability: This curated web tracker is available at https://racetoacure.stanford.eduConflict of Interest: The authors declare no competing interests.Funding: Funding support for this project came from internal funds, no external funds were received or requested.

SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalsecent COVID-19 individuals (preprint)

An unaddressed key question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T cell responses against SARS-CoV-2 in COVID-19 convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory CD4 and CD8 T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 and CD8 T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 and CD8 T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 T cells in the first 6-month post COVID-19 disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory CD4 and CD8 T cell responses were quite heterogenous between patients. Loss of memory CD4 T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.

Gene Expression Meta-Analysis Identifies Molecular Changes Associated with SARS-CoV Infection in Lungs (preprint)

Background: Severe Acute Respiratory Syndrome (SARS) corona virus (SARS-CoV) infections are a serious public health threat because of their pandemic-causing potential. This work uses mRNA expression data to predict genes associated with SARS-CoV infection through an innovative meta-analysis examining gene signatures (i.e., gene lists ranked by differential gene expression between SARS and mock infection). Methods: This work defines 29 gene signatures representing SARS infection across seven strains with established mutations that vary virulence (infectious clone SARS (icSARS), Urbani, MA15, {Delta}ORF6, BAT-SRBD, {Delta}NSP16, and ExoNI) and host (human lung cultures and/or mouse lung samples) and examines them through Gene Set Enrichment Analysis (GSEA). To do this, first positive and negative icSARS gene panels were defined from GSEA-identified leading-edge genes between 500 genes from positive or negative tails of the GSE47960-derived icSARSvsmock signature and the GSE47961-derived icSARSvsmock signature, both from human cultures. GSEA then was used to assess enrichment and identify leading-edge icSARS panel genes in the other 27 signatures. Genes associated with SARS-CoV infection are predicted by examining membership in GSEA-identified leading-edges across signatures. Results: Significant enrichment (GSEA p<0.001) was observed between GSE47960-derived and GSE47961-derived signatures, and those leading-edges defined the positive (233 genes) and negative (114 genes) icSARS panels. Non-random (null distribution p<0.001) significant enrichment (p<0.001) was observed between icSARS panels and all verification icSARSvsmock signatures derived from human cultures, from which 51 over- and 22 under-expressed genes were shared across leading-edges with 10 over-expressed genes already being associated with icSARS infection. For the icSARSvsmock mouse signature, significant, non-random enrichment (both p<0.001) held for only the positive icSARS panel, from which nine genes were shared with icSARS infection in human cultures. Considering other SARS strains, significant (p<0.01), non-random (p<0.002) enrichment was observed across signatures derived from other SARS strains for the positive icSARS panel. Five positive icSARS panel genes, CXCL10, OAS3, OASL, IFIT3, and XAF1, were found in mice and human signatures. Conclusion: The GSEA-based meta-analysis approach used here identified genes with and without reported associations with SARS-CoV infections, highlighting this approachs predictability and usefulness in identifying genes that have potential as therapeutic targets to preclude or overcome SARS infections.

Analysis of SARS-CoV-2 spike glycosylation reveals shedding of a vaccine candidate (preprint)

Severe acute respiratory syndrome coronavirus 2 is the causative pathogen of the COVID-19 pandemic which as of Nov 15, 2020 has claimed 1,319,946 lives worldwide. Vaccine development focuses on the viral trimeric spike glycoprotein as the main target of the humoral immune response. Viral spikes carry glycans that facilitate immune evasion by shielding specific protein epitopes from antibody neutralisation. Immunogen integrity is therefore important for glycoprotein-based vaccine candidates. Here we show how site-specific glycosylation differs between virus-derived spikes and spike proteins derived from a viral vectored SARS-CoV-2 vaccine candidate. We show that their cellular secretion pathways are unique, resulting in different protein glycosylation and secretion, which may have implications for the resulting immune response and future vaccine design.

Intranasal Administration of ACIS KEPTIDE™ Prevents SARS-CoV2-Induced Acute Toxicity in K18-hACE2 Humanized Mouse Model of COVID-19: A Mechanistic Insight for the Prophylactic Role of KEPTIDE™ in COVID-19 (preprint)

Abstract: Previously, we have demonstrated that ACIS KEPTIDE, a chemically modified peptide, selectively binds to ACE-2 receptor and prevents the entry of SARS-CoV2 virions in vitro in primate kidney Cells. However, it is not known if ACIS KEPTIDE attenuates the entry of SARS-CoV2 virus in vivo in lung and kidney tissues, protects health, and prevent death once applied through intranasal route. In our current manuscript, we demonstrated that the intranasal administration of SARS-CoV2 (1*106) strongly induced the expression of ACE-2, promoted the entry of virions into the lung and kidney cells, caused acute histopathological toxicities, and mortality (28%). Interestingly, thirty-minutes of pre-treatment with 50 g/Kg Body weight ACIS normalized the expression of ACE-2 via receptor internalization, strongly mitigated that viral entry, and prevented mortality suggesting its prospect as a prophylactic therapy in the treatment of COVID-19. On the contrary, the peptide backbone of ACIS was unable to normalize the expression of ACE-2, failed to improve the health vital signs and histopathological abnormalities. In summary, our results suggest that ACIS is a potential vaccine-alternative, prophylactic agent that prevents entry of SARS-CoV2 in vivo, significantly improves respiratory health and also dramatically prevents acute mortality in K18-hACE2 humanized mice.

Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation (preprint)

Severe acute respiratory coronavirus 2 (SARS-CoV-2), the agent of the ongoing COVID-19 pandemic, jumped into humans from an unknown animal reservoir in late 2019. In line with other coronaviruses, SARS-CoV-2 has the potential to infect a broad range of hosts. SARS-CoV-2 genomes have now been isolated from cats, dogs, lions, tigers and minks. SARS-CoV-2 seems to transmit particularly well in mink farms with outbreaks reported in Spain, Sweden, the Netherlands, Italy, the USA and Denmark. Genomic data from SARS-CoV-2 isolated from infected minks provides a natural case study of a secondary host jump of the virus, in this case from humans to animals, and occasionally back again. We screened published SARS-CoV-2 genomes isolated from minks for the presence of recurrent mutations common in mink but infrequent in SARS-CoV-2 genomes from human infections. We identify 23 recurrent mutations including three nonsynonymous mutations in the Receptor Binding Domain of the SARS-CoV-2 spike protein that independently emerged at least four times but are only very rarely observed in strains circulating in humans. The repeat emergence of mutations across phylogenetically distinct lineages of the virus isolated from minks points to ongoing adaptation of SARS-CoV-2 to a new host. The rapid acquisition and spread of SARS-CoV-2 mutations in minks suggests that if a similar phenomenon of host adaptation had occurred upon its jump into humans, those human-specific mutations would likely have reached fixation already before the first SARS-CoV-2 genomes were generated.