HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.

AIDS-defining cancers declined after combined antiretroviral therapy (cART) introduction, but lymphomas are still elevated in HIV type 1 (HIV-1)-infected patients. In particular, non-Hodgkin's lymphomas (NHLs) represent the majority of all AIDS-defining cancers and are the most frequent cause of death in these patients. We have recently demonstrated that amino acid (aa) insertions at the HIV-1 matrix protein p17 COOH-terminal region cause protein destabilization, leading to conformational changes. Misfolded p17 variants (vp17s) strongly impact clonogenic B cell growth properties that may contribute to B cell lymphomagenesis as suggested by the significantly higher frequency of detection of vp17s with COOH-terminal aa insertions in plasma of HIV-1-infected patients with NHL. Here, we expand our previous observations by assessing the prevalence of vp17s in large retrospective cohorts of patients with and without lymphoma. We confirm the significantly higher prevalence of vp17s in lymphoma patients than in HIV-1-infected individuals without lymphoma. Analysis of 3,990 sequences deposited between 1985 and 2017 allowed us to highlight a worldwide increasing prevalence of HIV-1 mutants expressing vp17s over time. Since genomic surveillance uncovered a cluster of HIV-1 expressing a B cell clonogenic vp17 dated from 2011 to 2019, we conclude that aa insertions can be fixed in HIV-1 and that mutant viruses displaying B cell clonogenic vp17s are actively spreading.

Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) persistence in COVID-19 patients could play a key role in the emergence of variants of concern. The rapid intra-host evolution of SARS-CoV-2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID-19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID-19 patients with persistent SARS-CoV-2 infection, from January 2022 to March 2023, was conducted. To characterize the intra- and inter-host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS-CoV-2 intra-host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host-based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro-active genomic surveillance of persistent SARS-CoV-2 infected patients is recommended to identify genetically divergent lineages before their diffusion.

Changing and evolution of influenza virus: is it a trivial flu?

BACKGROUND: Influenza viruses are etiological agents which cause contagious respiratory, seasonal epidemics and, for Influenza A subtypes, pandemics. The clinical picture of Influenza has undergone continuous change over the years, due to intrinsic viral evolution as well as "reassortment" of its genomic segments. The history of Influenza highlights its ability to adapt and to rapidly evolve, without specific circumstances. This reflects the complexity of this pathology and poses the fundamental question about its assumption as a "common illness" and its impact on public health. SUMMARY: The global influenza epidemics and pandemics claimed millions of deaths, leaving an indelible mark on public health, and showing the need for a better comprehension of the influenza virus. The clear understanding of genetic variations during the Influenza seasonal epidemics is a crucial point for developing effective strategies for prevention, treatment, and vaccine design. The recent advance in Next Generation Sequencing approaches, model systems to virus culture and bioinformatics pipeline played a key role in the rapid characterization of circulating Influenza strains. In particular, the increase of computational power allowed to perform complex tasks in healthcare setting through Machine Learning (ML) algorithms, which analyze different variables, such as medical and laboratory outputs, to optimize medical research and to improve public health systems. The early detection of emerging and re-emerging pathogens is of matter importance to prevent next pandemics. KEY MESSAGES: The perception of influenza as a "trivial flu" or a more serious public health concern is a subject of ongoing debate, reflecting the multifaceted nature of this infectious disease. The variability in the severity of influenza shed the light on the unpredictability of the viral characteristics, coupled with the challenges in accurately predicting circulating strains. This adds complexity to the public health burden of Influenza and highlights the need of targeted interventions.

Estimating the undetected infections in the Monkeypox outbreak.

While the number of detected Monkeypox infections are widely available, an understanding of the extent of undetected cases is urgently needed for an effective tackling of its spread. The aim of this study is to estimate the true number of Monkeypox (detected and undetected) infections in most affected countries. The question being asked is: How many cases have actually occurred? We propose a lower bound estimator for the true number of Monkeypox cases. The estimator is data-driven and can be easily computed from the cumulative distributions of weekly cases. We focused on the ratio of the total estimated cases to the observed cases on July 31, 2022: The proportion of undetected cases was relevant in all countries, with countries whose estimated true number of infections could be more than three times the observed one. We provided a practical contribution to the understanding of the current Monkeypox wave and reliable estimates on how many undetected cases are going around in several countries, where the epidemic spreads differently.

Short-term forecasts of Monkeypox cases in multiple countries: keep calm and don't panic.

We propose a parametric regression model for incidence indicators based on the use of the Richards' curve (a generalized logistic function) to analyse the current Monkeypox epidemic data for the most 10 affected countries worldwide. At present, results show that the outbreak is under control in most countries.

Traceability of SARS-CoV-2 transmission through quasispecies analysis.

During COVID-19 pandemic, consensus genomic sequences were used for rapidly monitor the spread of the virus worldwide. However, less attention was paid to intrahost genetic diversity. In fact, in the infected host, SARS-CoV-2 consists in an ensemble of replicating and closely related viral variants so-called quasispecies. Here we show that intrahost single nucleotide variants (iSNVs) represent a target for contact tracing analysis. Our data indicate that in the acute phase of infection, in highly likely transmission links, the number of viral particles transmitted from one host to another (bottleneck size) is large enough to propagate iSNVs among individuals. Furthermore, we demonstrate that, during SARS-CoV-2 outbreaks when the consensus sequences are identical, it is possible to reconstruct the transmission chains by genomic investigations of iSNVs. Specifically, we found that it is possible to identify transmission chains by limiting the analysis of iSNVs to only three well-conserved genes, namely nsp2, ORF3, and ORF7.

Genome-based survey of the SARS-CoV-2 BF.7 variant from Asia.

The SARS-CoV-2 BF.7 variant represents one of the most recent subvariant under monitoring. At the beginning of the 2023 it caused several concerns especially in Asia because of a resurge in COVID-19 cases. Here we perform a genome-based integrative approach on SARS-CoV-2 BF.7 to shed light on this emerging lineage and produce some consideration on its real dangerousness. Both genetic and structural data suggest that this new variant currently does not show evidence of an high expansion capability. It is very common in Asia, but it appears less virulent than other Omicron variants as proved by its relatively low evolutionary rate (5.62 × 10-4 subs/sites/years). The last plateau has been reached around December 14, 2022 and then the genetic variability, and thus the viral population size, no longer increased. As already seen for several previous variants, the features that may be theoretically related to advantages are due to genetic drift that allows to the virus a constant adaptability to the host, but is not strictly connected to a fitness advantage. These results have further pointed that the genome-based monitoring must continue uninterruptedly to be prepared and well documented on the real situation.

Genome-based comparison between the recombinant SARS-CoV-2 XBB and its parental lineages.

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability.

Genetic and structural analyses reveal the low potential of the SARS-CoV-2 EG.5 variant.

The severe acute respiratory syndrome coronavirus 2 EG.5 lineage is the latest variant under monitoring, and it is generating significant concern due to its recent upward trend in prevalence. Our aim was to gain insights into this emerging lineage and offer insights into its actual level of threat. Both genetic and structural data indicate that this novel variant presently lacks substantial evidence of having a high capacity for widespread transmission. Their viral population sizes expanded following a very mild curve and peaked several months after the earliest detected sample. Currently, neither the viral population size of EG.5 nor that of its first descendant is increasing. The genetic variability appear to be flattened, as evidenced by its relatively modest evolutionary rate (9.05 × 10-4 subs/site/year). As has been observed with numerous prior variants, attributes that might theoretically provide advantages seem to stem from genetic drift, enabling the virus to continually adjust to its host, albeit without a clear association with enhanced dangerousness. These findings further underscore the necessity for ongoing genome-based monitoring, ensuring preparedness and a well-documented understanding of the unfolding situation.

Epidemic history and evolution of an emerging threat of international concern, the severe acute respiratory syndrome coronavirus 2.

This comprehensive review focuses on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact as the cause of the COVID-19 pandemic. Its objective is to provide a cohesive overview of the epidemic history and evolutionary aspects of the virus, with a particular emphasis on its emergence, global spread, and implications for public health. The review delves into the timelines and key milestones of SARS-CoV-2's epidemiological progression, shedding light on the challenges encountered during early containment efforts and subsequent waves of transmission. Understanding the evolutionary dynamics of the virus is crucial in monitoring its potential for adaptation and future outbreaks. Genetic characterization of SARS-CoV-2 is discussed, with a focus on the emergence of new variants and their implications for transmissibility, severity, and immune evasion. The review highlights the important role of genomic surveillance in tracking viral mutations linked to establishing public health interventions. By analyzing the origins, global spread, and genetic evolution of SARS-CoV-2, valuable insights can be gained for the development of effective control measures, improvement of pandemic preparedness, and addressing future emerging infectious diseases of international concern.

The crosstalk between gut barrier impairment, mitochondrial dysfunction, and microbiota alterations in people living with HIV.

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH.

Viral metagenomics unveils MW (Malawi) polyomavirus infection in Brazilian pediatric patients with acute respiratory disease.

Viral metagenomics has been extensively applied for the identification of emerging or poorly characterized viruses. In this study, we applied metagenomics for the identification of viral infections among pediatric patients with acute respiratory disease, but who tested negative for SARS-CoV-2. Twelve pools composed of eight nasopharyngeal specimens were submitted to viral metagenomics. Surprisingly, in two of the pools, we identified reads belonging to the poorly characterized Malawi polyomavirus (MWPyV). Then, the samples composing the positive pools were individually tested using quantitative polymerase chain reaction for identification of the MWPyV index cases. MWPyV-positive samples were also submitted to respiratory virus panel testing due to the metagenomic identification of different clinically important viruses. Of note, MWPyV-positive samples tested also positive for respiratory syncytial virus types A and B. In this study, we retrieved two complete MWPyV genome sequences from the index samples that were submitted to phylogenetic inference to investigate their viral origin. Our study represents the first molecular and genomic characterization of MWPyV obtained from pediatric patients in South America. The detection of MWPyV in acutely infected infants suggests that this virus might participate (coparticipate) in cases of respiratory symptoms. Nevertheless, future studies based on testing of a larger number of clinical samples and MWPyV complete genomes appear to be necessary to elucidate if this emerging polyomavirus might be clinically important.

Molecular identification of the emerging Human Gemykibivirus-2 (HuGkV-2) among Brazilian blood donors.

Human gemykibivirus-2 (HuGkV-2) belonging to the Gemykibivirus genus (Genomoviridae family) is an emerging DNA virus which has been described as a component of the virome of a wide variety of samples including clinical ones. So far, the HuGkV-2 DNA prevalence in the human population as well as its clinical impact are completely unknown. The objective of this study was to investigate the HuGkV-2 DNA prevalence among Brazilian healthy blood donors from three different geographic regions. A total of 450 blood samples were screened for HuGkV-2 DNA (150 samples were from the Brazilian Amazon, 150 from Midwest Brazil and 150 from South Brazil). The overall HuGkV-2 DNA prevalence was 7.8 %. Considering the examined regions, the highest prevalence was observed in the Brazilian Amazon (city of Macapa, state of Amapa), 15.3 %, followed by the Midwest Brazil (city of Brasilia, Federal District) (6.0 %) and South Brazil (city of Santa Maria, Rio Grande do Sul State) (2.0 %). This study gives preliminary insights on the molecular prevalence of HuGkV-2 DNA among Brazilian blood donors, highlighting that the highest HuGkV-2 prevalence was recorded in the Brazilian Amazon. However, more studies regarding the prevalence, transmission routes and any possible clinical effects appear to be crucial in order to understand the impact of this emerging viral agent.

Associated effects of clinical characteristics, risk factors, and comorbidity on disease severity and mortality among patients with COVID-19 in Sulaimani City/ Kurdistan Region of Iraq.

The effects of clinical symptoms, laboratory indicators, and comorbidity status of SARS-CoV-2-infected patients on the severity of disease and the risk of death were investigated. Questionnaires and electronic medical records of 371 hospitalized COVID-19 patients were used for data collection (demographics, clinical manifestation, comorbidities, laboratory data). Association among categorical variables was determined using Kolmogorov-Smirnov test (P-value ≤0.05). Median age of study population (249 males, 122 females) was 65 years. Roc curves analysis found that age ≥64 years and age ≥67 years are significant cut-offs identifying patients with more severe disease and mortality at 30 days. CRP values at cut-off ≥80.7 and ≥95.8 significantly identify patients with more severe disease and mortality. Patients with more severe disease and risk of death were significantly identified with platelet value at the cut-off ≤160,000, hemoglobin value at the cut-off ≤11.7, D-Dimer values ≥1383 and ≥1270, and with values of neutrophil granulocytes (≥8.2 and ≤2) and lymphocytes (≤2 and ≤2.4). Detailed clinical investigation suggests granulocytes together with lymphopenia may be a potential indicator for diagnosis. Older age, several comorbidities (cancer, cardiovascular diseases, hypertension) and more laboratory abnormalities (CRP, D-Dimer, platelets, hemoglobin) were associated with development of more severity and mortality among COVID-19 patients.

HIV-1-Host Interaction in Gut-Associated Lymphoid Tissue (GALT): Effects on Local Environment and Comorbidities.

HIV-1 replication in the gastrointestinal (GI) tract causes severe CD4+ T-cell depletion and disruption of the protective epithelial barrier in the intestinal mucosa, causing microbial translocation, the main driver of inflammation and immune activation, even in people living with HIV (PLWH) taking antiretroviral drug therapy. The higher levels of HIV DNA in the gut compared to the blood highlight the importance of the gut as a viral reservoir. CD4+ T-cell subsets in the gut differ in phenotypic characteristics and differentiation status from the ones in other tissues or in peripheral blood, and little is still known about the mechanisms by which the persistence of HIV is maintained at this anatomical site. This review aims to describe the interaction with key subsets of CD4+ T cells in the intestinal mucosa targeted by HIV-1 and the role of gut microbiome and its metabolites in HIV-associated systemic inflammation and immune activation that are crucial in the pathogenesis of HIV infection and related comorbidities.

Integrative Genome-Based Survey of the SARS-CoV-2 Omicron XBB.1.16 Variant.

The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10-4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages.

The COVID-19 pandemic: viral variants and vaccine efficacy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has prompted the scientific community and the pharmaceutical companies to put maximum efforts into developing vaccines to contain the spread of this disease. Presently, many vaccines have been developed and authorized for use in human beings in different countries. In particular, in Europe to date, the Pfizer-BioNTech, Moderna, AstraZeneca and Janssen COVID-19 vaccines have been authorized. All of them are based on a version of the spike (S) glycoprotein characterized at the beginning of the pandemic. However, they differ by their level of efficacy against COVID-19. SARS-COV-2, like other RNA viruses, mutates continually. Genome sequencing analysis shows a nucleotide substitution rate of about 1 × 10-3 substitutions per year that leads to the emergence of variants through point mutations, insertions, deletions and recombination. There is concern about the ability of the current vaccines to protect against emerging viral variants. Mutations in the S-glycoprotein may affect transmission dynamics and the risk of immune escape. In this review, we address the different technological platforms in use for developing COVID-19 vaccines, the impact of emerging viral variants on virus transmission, hospitalization, and response to current vaccines, as well as rare but important adverse reactions to them. Finally, different methods for measuring antibody response to the vaccines, including the importance of using the WHO International Standard to calibrate immunoassays accurately to an arbitrary unit, to reduce interlaboratory variation and to create a common language for reporting results, are reported.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

The first Italian outbreak of SARS-CoV-2 B.1.1.7 lineage in Corzano, Lombardy.

In December 2020, Italy experienced the first case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) B.1.1.7 lineage. In January 2021, we identified 21 cases of this variant in Corzano, defining the first outbreak of SARS-CoV-2 B.1.1.7 lineage in Italy. The high transmissibility of the B.1.1.7 variant represented an important benefit for the virus, which became rapidly dominant on the territory. Containment measures induced the epidemic curve onto a decreasing trajectory underlining the importance of appropriate control and surveillance for restraint of virus spread. Highlights The first Italian outbreak of SARS-CoV-2 B.1.1.7 lineage occurred in Lombardy in January 2021. The outbreak originated by a single introduction of the B.1.1.7 lineage. The genomic sequencing revealed, for the first time, the presence of the V551F mutation in the B.1.1.7 lineage in Italy. Surveillance, prompt sequencing and tracing efforts were fundamental to identify and to quickly contain the outbreak.

The SARS-CoV-2 Mu variant should not be left aside: It warrants attention for its immuno-escaping ability.

The COVID-19 pandemic continues to have a threatening impact on a global scale, largely due to the emergence of newly SARS-CoV-2 variants. The Mu (PANGO lineage B.1.621), was first identified in Colombia in January 2021 and was classified as a variant of interest (VOI) in August 2021, due to a constellation of mutations that likely-mediate an unexpectedly enhanced immune resistance to inactivated vaccine-elicited antibodies. Despite recent studies suggesting that the Mu variant appears to have less infectivity than the Delta variant, here we examined the structural effect of the Mu spike protein mutations and predicted the potential impact on infectivity of the Mu variant compared with the Delta and Delta plus spike protein.