RESUMO
MOTIVATION: The selection among substitution models of molecular evolution is fundamental for obtaining accurate phylogenetic inferences. At the protein level, evolutionary analyses are traditionally based on empirical substitution models but these models make unrealistic assumptions and are being surpassed by structurally constrained substitution (SCS) models. The SCS models often consider site-dependent evolution, a process that provides realism but complicates their implementation into likelihood functions that are commonly used for substitution model selection. RESULTS: We present a method to perform selection among site-dependent SCS models, also among empirical and site-dependent SCS models, based on the approximate Bayesian computation (ABC) approach and its implementation into the computational framework ProteinModelerABC. The framework implements ABC with and without regression adjustments and includes diverse empirical and site-dependent SCS models of protein evolution. Using extensive simulated data, we found that it provides selection among SCS and empirical models with acceptable accuracy. As illustrative examples, we applied the framework to analyze a variety of protein families observing that SCS models fit them better than the corresponding best-fitting empirical substitution models. AVAILABILITY AND IMPLEMENTATION: ProteinModelerABC is freely available from https://github.com/DavidFerreiro/ProteinModelerABC, can run in parallel and includes a graphical user interface. The framework is distributed with detailed documentation and ready-to-use examples.
Assuntos
Evolução Molecular , Proteínas , Filogenia , Teorema de Bayes , Funções Verossimilhança , Proteínas/genética , Modelos GenéticosRESUMO
Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity. Here, we present a substitution model of protein evolution with selection on both protein structure and enzymatic activity, and that can be applied to phylogenetics. In particular, the model considers the binding affinity of the enzyme-substrate complex as well as structural constraints that include the flexibility of structural flaps, hydrogen bonds, amino acids backbone radius of gyration, and solvent-accessible surface area that are quantified through molecular dynamics simulations. We applied the model to the HIV-1 protease and evaluated it by phylogenetic likelihood in comparison with the best-fitting empirical substitution model and a structurally constrained substitution model that ignores the enzymatic activity. We found that accounting for selection on the protein activity improves the fitting of the modeled functional regions with the real observations, especially in data with high molecular identity, which recommends considering constraints on the protein activity in the development of substitution models of evolution.
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Aminoácidos , Evolução Molecular , Filogenia , Probabilidade , Modelos Genéticos , Substituição de AminoácidosRESUMO
Streptococcus suis is a zoonotic pathogen that causes a major health problem in the pig production industry worldwide. Spain is one of the largest pig producers in the world. This work aimed to investigate the genetic and phenotypic features of invasive S. suis isolates recovered in Spain. A panel of 156 clinical isolates recovered from 13 Autonomous Communities, representing the major pig producers, were analysed. MLST and serotyping analysis revealed that most isolates (61.6%) were assigned to ST1 (26.3%), ST123 (18.6%), ST29 (9.6%), and ST3 (7.1%). Interestingly, 34 new STs were identified, indicating the emergence of novel genetic lineages. Serotypes 9 (27.6%) and 1 (21.8%) prevailed, followed by serotypes 7 (12.8%) and 2 (12.2%). Analysis of 13 virulence-associated genes showed significant associations between ST, serotype, virulence patterns, and clinical features, evidencing particular virulence traits associated with genetic clusters. The pangenome was generated, and the core genome was distributed in 7 Bayesian groups where each group included a variable set of over- and under-represented genes of different categories. The study provides comprehensive data and knowledge to improve the design of new vaccines, antimicrobial treatments, and bacterial typing approaches.
Assuntos
Streptococcus suis , Animais , Suínos , Streptococcus suis/genética , Espanha/epidemiologia , Teorema de Bayes , Tipagem de Sequências Multilocus/veterinária , Virulência , GenômicaRESUMO
Probabilistic phylogenetic tree reconstruction is traditionally performed under a best-fitting substitution model of molecular evolution previously selected according to diverse statistical criteria. Interestingly, some recent studies proposed that this procedure is unnecessary for phylogenetic tree reconstruction leading to a debate in the field. In contrast to DNA sequences, phylogenetic tree reconstruction from protein sequences is traditionally based on empirical exchangeability matrices that can differ among taxonomic groups and protein families. Considering this aspect, here we investigated the influence of selecting a substitution model of protein evolution on phylogenetic tree reconstruction by the analyses of real and simulated data. We found that phylogenetic tree reconstructions based on a selected best-fitting substitution model of protein evolution are the most accurate, in terms of topology and branch lengths, compared with those derived from substitution models with amino acid replacement matrices far from the selected best-fitting model, especially when the data has large genetic diversity. Indeed, we found that substitution models with similar amino acid replacement matrices produce similar reconstructed phylogenetic trees, suggesting the use of substitution models as similar as possible to a selected best-fitting model when the latter cannot be used. Therefore, we recommend the use of the traditional protocol of selection among substitution models of evolution for protein phylogenetic tree reconstruction.
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Aminoácidos , Evolução Molecular , Filogenia , Sequência de Bases , Modelos GenéticosRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and consequences of the observed SARS-CoV-2 molecular diversity, a variety of recent studies investigated the molecular evolution of this virus during its expansion in humans. In general, this virus evolves with a moderate rate of evolution, in the order of 10-3-10-4 substitutions per site and per year, which presents continuous fluctuations over time. Despite its origin being frequently associated with recombination events between related coronaviruses, little evidence of recombination was detected, and it was mostly located in the spike coding region. Molecular adaptation is heterogeneous among SARS-CoV-2 genes. Although most of the genes evolved under purifying selection, several genes showed genetic signatures of diversifying selection, including a number of positively selected sites that affect proteins relevant for the virus replication. Here, we review current knowledge about the molecular evolution of SARS-CoV-2 in humans, including the emergence and establishment of variants of concern. We also clarify relationships between the nomenclatures of SARS-CoV-2 lineages. We conclude that the molecular evolution of this virus should be monitored over time for predicting relevant phenotypic consequences and designing future efficient treatments.
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COVID-19 , Humanos , SARS-CoV-2/genética , Pandemias , Replicação Viral , Evolução MolecularRESUMO
Type IB topoisomerases relax the torsional stress associated with DNA metabolism in the nucleus and mitochondria and constitute important molecular targets of anticancer drugs. Vertebrates stand out among eukaryotes by having two Type IB topoisomerases acting specifically in the nucleus (TOP1) and mitochondria (TOP1MT). Despite their major importance, the origin and evolution of these paralogues remain unknown. Here, we examine the molecular evolutionary processes acting on both TOP1 and TOP1MT in Chordata, taking advantage of the increasing number of available genome sequences. We found that both TOP1 and TOP1MT evolved under strong purifying selection, as expected considering their essential biological functions. Critical active sites, including those associated with resistance to anticancer agents, were found particularly conserved. However, TOP1MT presented a higher rate of molecular evolution than TOP1, possibly related with its specialized activity on the mitochondrial genome and a less critical role in cells. We could place the duplication event that originated the TOP1 and TOP1MT paralogues early in the radiation of vertebrates, most likely associated with the first round of vertebrate tetraploidization (1R). Moreover, our data suggest that cyclostomes present a specialized mitochondrial Type IB topoisomerase. Interestingly, we identified two missense mutations replacing amino acids in the Linker region of TOP1MT in Neanderthals, which appears as a rare event when comparing the genome of both species. In conclusion, TOP1 and TOP1MT differ in their rates of evolution, and their evolutionary histories allowed us to better understand the evolution of chordates.
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Cordados , DNA Mitocondrial , Animais , DNA Mitocondrial/genética , Cordados/genética , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/química , DNA Topoisomerases Tipo I/metabolismo , Mitocôndrias/genética , Núcleo Celular/genéticaRESUMO
Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several protein families, finding less detrimental effects than we previously expected. Although recombination can affect multiple protein sites, we found that the fraction of recombined proteins that are eliminated by negative selection because of insufficient stability is not significantly larger than the corresponding fraction of proteins produced by mutation events. Indeed, although recombination disrupts epistatic interactions, the mean stability of recombinant proteins is not lower than that of their parents. On the other hand, the difference of stability between recombined proteins is amplified with respect to the parents, promoting phenotypic diversity. As a result, at least one third of recombined proteins present stability between those of their parents, and a substantial fraction have higher or lower stability than those of both parents. As expected, we found that parents with similar sequences tend to produce recombined proteins with stability close to that of the parents. Finally, the simulation of protein evolution along the ancestral recombination graph with empirical substitution models commonly used in phylogenetics, which ignore constraints on protein folding stability, showed that recombination favors the decrease of folding stability, supporting the convenience of adopting structurally constrained models when possible for inferences of protein evolutionary histories with recombination.
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Dobramento de Proteína , Proteínas , Proteínas/genética , Simulação por Computador , Filogenia , Recombinação Genética/genética , Evolução Molecular , Estabilidade ProteicaRESUMO
The reconstruction of genetic material of ancestral organisms constitutes a powerful application of evolutionary biology. A fundamental step in this inference is the ancestral sequence reconstruction (ASR), which can be performed with diverse methodologies implemented in computer frameworks. However, most of these methodologies ignore evolutionary properties frequently observed in microbes, such as genetic recombination and complex selection processes, that can bias the traditional ASR. From a practical perspective, here I review methodologies for the reconstruction of ancestral DNA and protein sequences, with particular focus on microbes, and including biases, recommendations, and software implementations. I conclude that microbial ASR is a complex analysis that should be carefully performed and that there is a need for methods to infer more realistic ancestral microbial sequences.
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Evolução Biológica , Evolução Molecular , Sequência de Aminoácidos , Filogenia , SoftwareRESUMO
The selection of the best-fitting substitution model of molecular evolution is a traditional step for phylogenetic inferences, including ancestral sequence reconstruction (ASR). However, a few recent studies suggested that applying this procedure does not affect the accuracy of phylogenetic tree reconstruction. Here, we revisited this debate topic by analyzing the influence of selection among substitution models of protein evolution, with focus on exchangeability matrices, on the accuracy of ASR using simulated and real data. We found that the selected best-fitting substitution model produces the most accurate ancestral sequences, especially if the data present large genetic diversity. Indeed, ancestral sequences reconstructed under substitution models with similar exchangeability matrices were similar, suggesting that if the selected best-fitting model cannot be used for the reconstruction, applying a model similar to the selected one is preferred. We conclude that selecting among substitution models of protein evolution is recommended for reconstructing accurate ancestral sequences.
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Algoritmos , Evolução Molecular , Sequência de Aminoácidos , Mutação de Sentido Incorreto , Filogenia , Proteínas/genéticaRESUMO
RESUMEN Existe una variedad de tumores epiteliales, mesoteliales y de tejidos blandos que pueden desarrollarse en la red testicular y paratesticular. Se presenta el caso clínico de paciente con tumoración paratesticular derecha: Miofibroblastoma Mamario Paratesticular. Importante recalcar la variedad de origen embrionario para el desarrollo de estos tumores, así como el diagnóstico oportuno para el tratamiento y seguimiento resolutivo.
ABSTRACT There is a variety of epithelial, mesothelial, and soft tissue tumors that can develop in the testicular and paratesticular area. We present the case of a patient with a right paratesticular tumor that was diagnosed as paratesticular mammary myofibroblastoma. It is important to emphasize the embryonic origin variety for the development of these tumors, as well as having a timely diagnosis for treatment and decisive follow-up.
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BACKGROUND: Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8 + T-cell responses restricted by protective HLA-B alleles. Individuals carrying HLA-B*14:02 control HIV-1 infection is related to an immunodominant Env-CD8 + T-cell response. Limited data are available on the contribution of HLA-B*14:02 CD8 + T -cells in LTNPs. RESULTS: In this study, we performed a virological and immunological detailed analysis of an HLA-B*14:02 LNTP individual that lost viral control (LVC) 27 years after HIV-1 diagnosis. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8 + T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. By IFN-γ ELISpot and immune phenotype, we characterized HLA- B*14:02 HIV-1 CD8 + T cell responses targeting, Gag-DA9 and Env-EL9 epitopes before and after LVC. We observed an immunodominant response against the Env-EL9 epitope and a decreased of the CD8 T + cell response over time with LVC. Loss of Env-EL9 responses was concomitant with selecting K588R + L592R mutations at Env-EL9. Finally, we evaluated the impact of Env-EL9 escape mutations on HIV-1 infectivity and Env protein structure. The K588R + L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC. CONCLUSIONS: These findings support the contribution of immunodominant Env-EL9 CD8 + T-cell responses and the imposition of immune escape variants with higher replicative capacity associated with LVC in this LNTP. These data highlight the importance of Env-EL9 specific-CD8 + T-cell responses restricted by the HLA-B*14:02 and brings new insights into understanding long-term HIV-1 control mediated by Env mediated CD8 + T-cell responses.
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Linfócitos T CD8-Positivos , Infecções por HIV , HIV-1 , Antígenos HLA-B , Infecções por HIV/imunologia , HIV-1/fisiologia , Antígenos HLA-B/genética , Humanos , Evasão da Resposta Imune , Carga ViralRESUMO
The last glacial period (LGP) promoted a loss of genetic diversity in Paleolithic populations of modern humans from diverse regions of the world by range contractions and habitat fragmentation. However, this period also provided some currently submersed lands, such as the Sunda shelf in Southeast Asia (SEA), that could have favored the expansion of our species. Concerning the latter, still little is known about the influence of the lowering sea level on the genetic diversity of current SEA populations. Here, we applied approximate Bayesian computation, based on extensive spatially explicit computer simulations, to evaluate the fitting of mtDNA data from diverse SEA populations with alternative evolutionary scenarios that consider and ignore the LGP and migration through long-distance dispersal (LDD). We found that both the LGP and migration through LDD should be taken into consideration to explain the currently observed genetic diversity in these populations and supported a rapid expansion of first populations throughout SEA. We also found that temporarily available lands caused by the low sea level of the LGP provided additional resources and migration corridors that favored genetic diversity. We conclude that migration through LDD and temporarily available lands during the LGP should be considered to properly understand and model the first expansions of modern humans.
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Evolução Biológica , DNA Mitocondrial , Povo Asiático/genética , Teorema de Bayes , DNA Mitocondrial/genética , Variação Genética/genética , HumanosRESUMO
TOPIIA topoisomerases are required for the regulation of DNA topology by DNA cleavage and re-ligation and are important targets of antibiotic and anticancer agents. Humans possess two TOPIIA paralogue genes (TOP2A and TOP2B) with high sequence and structural similarity but distinct cellular functions. Despite their functional and clinical relevance, the evolutionary history of TOPIIA is still poorly understood. Here we show that TOPIIA is highly conserved in Metazoa. We also found that TOPIIA paralogues from jawed and jawless vertebrates had different origins related with tetraploidization events. After duplication, TOP2B evolved under a stronger purifying selection than TOP2A, perhaps promoted by the more specialized role of TOP2B in postmitotic cells. We also detected genetic signatures of positive selection in the highly variable C-terminal domain (CTD), possibly associated with adaptation to cellular interactions. By comparing TOPIIA from modern and archaic humans, we found two amino acid substitutions in the TOP2A CTD, suggesting that TOP2A may have contributed to the evolution of present-day humans, as proposed for other cell cycle-related genes. Finally, we identified six residues conferring resistance to chemotherapy differing between TOP2A and TOP2B. These six residues could be targets for the development of TOP2A-specific inhibitors that would avoid the side effects caused by inhibiting TOP2B. Altogether, our findings clarify the origin, diversification and selection pressures governing the evolution of animal TOPIIA.
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Antígenos de Neoplasias , Proteínas de Ligação a DNA , Animais , Antígenos de Neoplasias/genética , DNA , Proteínas de Ligação a DNA/genéticaRESUMO
The evolution of structural proteins is generally constrained by the folding stability. However, little is known about the particular capacity of viral proteins to accommodate mutations that can potentially affect the protein stability and, in general, the evolution of the protein stability over time. As an illustrative model case, here, we investigated the evolution of the stability of the human immunodeficiency virus (HIV-1) protease (PR), which is a common HIV-1 drug target, under diverse evolutionary scenarios that include (1) intra-host virus evolution in a cohort of seventy-five patients sampled over time, (2) intra-host virus evolution sampled before and after specific PR-based treatments, and (3) inter-host evolution considering extant and ancestral (reconstructed) PR sequences from diverse HIV-1 subtypes. We also investigated the specific influence of currently known HIV-1 PR resistance mutations on the PR folding stability. We found that the HIV-1 PR stability fluctuated over time within a constant and wide range in any studied evolutionary scenario, accommodating multiple mutations that partially affected the stability while maintaining activity. We did not identify relationships between change of PR stability and diverse clinical parameters such as viral load, CD4+ T-cell counts, and a surrogate of time from infection. Counterintuitively, we predicted that nearly half of the studied HIV-1 PR resistance mutations do not significantly decrease stability, which, together with compensatory mutations, would allow the protein to adapt without requiring dramatic stability changes. We conclude that the HIV-1 PR presents a wide structural plasticity to acquire molecular adaptations without affecting the overall evolution of stability.
RESUMO
MOTIVATION: The evolutionary processes of mutation and recombination, upon which selection operates, are fundamental to understand the observed molecular diversity. Unlike nucleotide sequences, the estimation of the recombination rate in protein sequences has been little explored, neither implemented in evolutionary frameworks, despite protein sequencing methods are largely used. RESULTS: In order to accommodate this need, here I present a computational framework, called ProteinEvolverABC, to jointly estimate recombination and substitution rates from alignments of protein sequences. The framework implements the approximate Bayesian computation approach, with and without regression adjustments and includes a variety of substitution models of protein evolution, demographics and longitudinal sampling. It also implements several nuisance parameters such as heterogeneous amino acid frequencies and rate of change among sites and, proportion of invariable sites. The framework produces accurate coestimation of recombination and substitution rates under diverse evolutionary scenarios. As illustrative examples of usage, I applied it to several viral protein families, including coronaviruses, showing heterogeneous substitution and recombination rates. AVAILABILITY AND IMPLEMENTATION: ProteinEvolverABC is freely available from https://github.com/miguelarenas/proteinevolverabc, includes a graphical user interface for helping the specification of the input settings, extensive documentation and ready-to-use examples. Conveniently, the simulations can run in parallel on multicore machines. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Evolução Molecular , Software , Simulação por Computador , Teorema de Bayes , Recombinação GenéticaRESUMO
The COVID-19 pandemic is promoting online education. In this concern, not only online teaching of wet laboratory practices is being challenging, but also online teaching of practices in bioinformatics. Here, I discuss the problematic of online teaching practices in bioinformatics and provide fundamental guidelines, especially oriented for beginner educators, that can help in the time of the pandemic.
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COVID-19/epidemiologia , Biologia Computacional/educação , Educação a Distância , Pandemias , SARS-CoV-2 , COVID-19/prevenção & controle , HumanosRESUMO
DNA topoisomerase III beta (TOP3B) is unique by operating on both DNA and RNA substrates to regulate gene expression and genomic stability. Mutations in human TOP3B are linked to neurodevelopmental and cognitive disorders, highlighting its relevance for human health. Despite the emerging importance of TOP3B, its precise cellular functions and evolutionary history remain poorly understood. Here, we show that TOP3B is conserved across main metazoan groups and evolved under strong purifying selection. Subdomain IV was identified as the most conserved TOP3B region, in agreement with its role in providing the structural foundation of the protein. On the contrary, subdomain II is the less conserved, possibly because it is the most structurally flexible region of all TOP3B regions. Interestingly, TOP3B residue at position 472, previously associated with schizophrenia, is highly variable across animals, suggesting a more specific role in humans and related species. Finally, we show that all TOP3B CXXC zinc finger motifs previously identified at the protein C-terminal region are retained across metazoans. We also found that the two major methylation sites known to regulate TOP3B activity are located in the most conserved region of the C-terminal arginine-glycine-glycine (RGG) box, suggesting that a similar regulatory mechanism may operate throughout animals. Overall, our results provide a better understanding of the evolution and functional roles of TOP3B.
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DNA Topoisomerases Tipo I , Evolução Molecular , Animais , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , Humanos , Mutação , Proteínas/metabolismoRESUMO
The history of modern humans in the Iberian Peninsula includes a variety of population arrivals sometimes presenting admixture with resident populations. Genetic data from current Iberian populations revealed an overall east-west genetic gradient that some authors interpreted as a direct consequence of the Reconquista, where Catholic Kingdoms expanded their territories toward the south while displacing Muslims. However, this interpretation has not been formally evaluated. Here, we present a qualitative analysis of the causes of the current genetic gradient observed in the Iberian Peninsula using extensive spatially explicit computer simulations based on a variety of evolutionary scenarios. Our results indicate that the Neolithic range expansion clearly produces the orientation of the observed genetic gradient. Concerning the Reconquista (including political borders among Catholic Kingdoms and regions with different languages), if modeled upon a previous Neolithic expansion, it effectively favored the orientation of the observed genetic gradient and shows local isolation of certain regions (i.e., Basques and Galicia). Despite additional evolutionary scenarios could be evaluated to more accurately decipher the causes of the Iberian genetic gradient, here we show that this gradient has a more complex explanation than that previously hypothesized.
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Genética Populacional , Simulação por Computador , Europa (Continente) , Evolução Molecular , Variação Genética , HumanosRESUMO
Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2. Comparisons were performed through allele diversities, linkage disequilibrium status and recombination frequencies within and between X and Y chromosomes. In agreement with previous studies, we confirmed the role of PAR1 as a male-specific recombination hotspot, but also observed similar characteristic patterns of diversity in both regions although male recombination occurs at PAR2 to a much lower extent (at least one recombination event at PAR1 and in ≈1% in normal male meioses at PAR2). Furthermore, we demonstrate that both PARs harbor significantly different allele frequencies between X and Y chromosomes, which could support that recombination is not sufficient to homogenize the pseudoautosomal gene pool or is counterbalanced by other evolutionary forces. Nevertheless, the observed patterns of diversity are not entirely explainable by sexually antagonistic selection. A better understanding of such processes requires new data from intergenerational transmission studies of PARs, which would be decisive on the elucidation of PARs evolution and their role in male-driven heterosomal aneuploidies.
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Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Regiões Pseudoautossômicas/genética , Recombinação Genética/genética , Mapeamento Cromossômico/métodos , Troca Genética/genética , Feminino , Frequência do Gene/genética , Ligação Genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Meiose/genéticaRESUMO
The aim of this study was to determine the relationship between COVID-19 severity and androgenic alopecia in patients hospitalized in the Surgery Service of Honorio Delgado Espinoza Hospital in Arequipa, Peru. A cross-sectional study was performed in male patients with a diagnosis of COVID-19. Alopecia, clinical characteristics, treatment, and evolution were collected. In all, 98 patients were included; median age was 55 years old (range 18-89), 32.7% with comorbidities, and 45.9% with androgenic alopecia. The severity of COVID-19 infection was moderate to severe in 13.2% of patients without alopecia, and in 88.9% of patients with alopecia (p>0.001). In the logistic regression model analysis, patients with alopecia had a higher risk of presenting moderate to severe symptoms due to SARS-CoV-2 infection (OR: 80.2; 95% CI 16.2-397.7). In conclusion, the severity of infection was statistically significant in patients over 60 years old and those with alopecia.