DateLife: Leveraging Databases and Analytical Tools to Reveal the Dated Tree of Life.

Chronograms-phylogenies with branch lengths proportional to time-represent key data on timing of evolutionary events, allowing us to study natural processes in many areas of biological research. Chronograms also provide valuable information that can be used for education, science communication, and conservation policy decisions. Yet, achieving a high-quality reconstruction of a chronogram is a difficult and resource-consuming task. Here we present DateLife, a phylogenetic software implemented as an R package and an R Shiny web application available at www.datelife.org, that provides services for efficient and easy discovery, summary, reuse, and reanalysis of node age data mined from a curated database of expert, peer-reviewed, and openly available chronograms. The main DateLife workflow starts with one or more scientific taxon names provided by a user. Names are processed and standardized to a unified taxonomy, allowing DateLife to run a name match across its local chronogram database that is curated from Open Tree of Life's phylogenetic repository, and extract all chronograms that contain at least two queried taxon names, along with their metadata. Finally, node ages from matching chronograms are mapped using the congruification algorithm to corresponding nodes on a tree topology, either extracted from Open Tree of Life's synthetic phylogeny or one provided by the user. Congruified node ages are used as secondary calibrations to date the chosen topology, with or without initial branch lengths, using different phylogenetic dating methods such as BLADJ, treePL, PATHd8, and MrBayes. We performed a cross-validation test to compare node ages resulting from a DateLife analysis (i.e, phylogenetic dating using secondary calibrations) to those from the original chronograms (i.e, obtained with primary calibrations), and found that DateLife's node age estimates are consistent with the age estimates from the original chronograms, with the largest variation in ages occurring around topologically deeper nodes. Because the results from any software for scientific analysis can only be as good as the data used as input, we highlight the importance of considering the results of a DateLife analysis in the context of the input chronograms. DateLife can help to increase awareness of the existing disparities among alternative hypotheses of dates for the same diversification events, and to support exploration of the effect of alternative chronogram hypotheses on downstream analyses, providing a framework for a more informed interpretation of evolutionary results.

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

Respiratory virus detection among healthcare professionals in Brazil: work-related contact and episode recurrence during the COVID-19 pandemic.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, changes in the circulation of respiratory viruses have been observed after measures to control the spread of SARS-CoV-2 were implemented. In this sense, we aimed to understand the circulation of the respiratory virus and its impact in a controlled healthy population of healthcare professional (HCP) volunteers in phase III of the clinical trial of the ChadOx nCoV1 conducted in São Paulo, Brazil. STUDY DESIGN: This was a nested observational cohort study within a clinical trial. METHODS: We performed RT-qPCR to detect SARS-CoV-2, influenza virus A and B (IVA and IVB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (hMPV), human coronaviruses (hCoVs: HKU-1, NL63, OC43, and 229-E), parainfluenza virus (PiV) I-IV, and q-PCR for adenovirus in nasopharyngeal and oropharyngeal samples obtained from HCP enrolled in the clinical trial to assess respiratory viruses infection among vaccinated and non-vaccinated. RESULTS: From July 2020 to January 2022, 876 samples were included from 737 volunteers (median age: 33 years, 62.9% female). New episodes were registered for 119 individuals. We observed an overall positivity of 37.7% for SARS-CoV-2 and 16.4% for other respiratory viruses; HRV was the second most detected virus (8%), followed by RSV (2.4%). Fully vaccinated individuals accounted for 53.3% of collected samples, and 52.9% presented at least one respiratory virus infection, with SARS-CoV-2 being the most predominant etiologic agent (62.3%). Influenza and hMPV were not detected among the tested samples. Among the subjects that presented more than one episode, SARS-CoV-2 and HRV infections were related to direct contact with patients (P < 0.002). CONCLUSIONS: Data show high infection rates among HCPs even under mask policies and contact precautions, highlighting the need for improvement in infection control measures in this population regardless of the vaccination program.

Why don't we share data and code? Perceived barriers and benefits to public archiving practices.

The biological sciences community is increasingly recognizing the value of open, reproducible and transparent research practices for science and society at large. Despite this recognition, many researchers fail to share their data and code publicly. This pattern may arise from knowledge barriers about how to archive data and code, concerns about its reuse, and misaligned career incentives. Here, we define, categorize and discuss barriers to data and code sharing that are relevant to many research fields. We explore how real and perceived barriers might be overcome or reframed in the light of the benefits relative to costs. By elucidating these barriers and the contexts in which they arise, we can take steps to mitigate them and align our actions with the goals of open science, both as individual scientists and as a scientific community.

The Clash of Two Epidemics: the Relationship Between Opioids and Glucose Metabolism.

PURPOSE OF REVIEW: We are currently in the midst of a global opioid epidemic. Opioids affect many physiological processes, but one side effect that is not often taken into consideration is the opioid-induced alteration in blood glucose levels. RECENT FINDINGS: This review shows that the vast majority of studies report that opioid stimulation increases blood glucose levels. In addition, plasma levels of the endogenous opioid ß-endorphin rise in response to low blood glucose. In contrast, in hyperglycaemic baseline conditions such as in patients with type 2 diabetes mellitus (T2DM), opioid stimulation lowers blood glucose levels. Furthermore, obesity itself alters sensitivity to opioids, changes opioid receptor expression and increases plasma ß-endorphin levels. Thus, opioid stimulation can have various side effects on glycaemia that should be taken into consideration upon prescribing opioid-based medication, and more research is needed to unravel the interaction between obesity, glycaemia and opioid use.

Physcraper: a Python package for continually updated phylogenetic trees using the Open Tree of Life.

BACKGROUND: Phylogenies are a key part of research in many areas of biology. Tools that automate some parts of the process of phylogenetic reconstruction, mainly molecular character matrix assembly, have been developed for the advantage of both specialists in the field of phylogenetics and non-specialists. However, interpretation of results, comparison with previously available phylogenetic hypotheses, and selection of one phylogeny for downstream analyses and discussion still impose difficulties to one that is not a specialist either on phylogenetic methods or on a particular group of study. RESULTS: Physcraper is a command-line Python program that automates the update of published phylogenies by adding public DNA sequences to underlying alignments of previously published phylogenies. It also provides a framework for straightforward comparison of published phylogenies with their updated versions, by leveraging upon tools from the Open Tree of Life project to link taxonomic information across databases. The program can be used by the nonspecialist, as a tool to generate phylogenetic hypotheses based on publicly available expert phylogenetic knowledge. Phylogeneticists and taxonomic group specialists will find it useful as a tool to facilitate molecular dataset gathering and comparison of alternative phylogenetic hypotheses (topologies). CONCLUSION: The Physcraper workflow showcases the benefits of doing open science for phylogenetics, encouraging researchers to strive for better scientific sharing practices. Physcraper can be used with any OS and is released under an open-source license. Detailed instructions for installation and usage are available at https://physcraper.readthedocs.io.

MRI features of intra-axial histiocytic brain mass lesions.

AIM: To describe MRI features, including diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and perfusion-weighted imaging (PWI), of intra-axial tumour-like presentations of four different subtypes of histiocytosis. MATERIAL AND METHODS: The brain MRI findings of 23 patients with histologically proven histiocytosis were reviewed retrospectively (11 Langerhans cell histiocytosis [LCH], eight Erdheim-Chester disease [ECD], one overlap form LCH/ECD, two Rosai-Dorfman disease [RDD], and one haemophagocytic lymphohistiocytosis [HLH]) with single or multiple enhancing intraparenchymal brain lesions. RESULTS: Histiocytic brain mass lesions show some similar MRI features including Supra and/or infratentorial and/or paraventricular subcortical well-delineated masses, linear ependymal enhancement along the ventricles and brain stem lesions. Masses always present with mixed hyper- and hypointense signal on T2-weighted imaging (WI). Their enhancement is often homogeneous. Apparent diffusion coefficient (ADC) values are often normal or elevated. CONCLUSION: The presence of multiple periventricular and subcortical enhancing lesions with mixed signal intensity on T2WI and normal or high ADC values should lead radiologists to consider the diagnosis of histiocytic lesions and search for associated systemic lesions.

Genomic imbalances in craniofacial microsomia.

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation-dependent probe amplification (MLPA) for all individuals. The CMA was performed only for individuals with additional major features. MLPA revealed pathogenic CNVs at the 22q11 region in 3/54 (5.6%) individuals. CMA revealed pathogenic CNVs in 4/17 (23.5%) individuals, including the three CNVs at the 22q11 region also detected by MLPA, and CNVs classified as variants of unknown significance (VOUS) in 4/17 (23.5%) individuals. Pathogenic alterations were found at the 2p12, 5p15, 13q13, and 22q11 regions. VOUS were found at 3q29, 5q22.2, 5q22.1, and 9p22 regions. All individuals with pathogenic alterations presented additional major features, including congenital heart disease (CHD). The literature review revealed pathogenic CNVs in 17/193 (8.8%) individuals and most of them also presented additional major features, such as CHD, renal anomalies, or developmental delay. In conclusion, CNVs should be investigated in patients with CFM and additional major features.

Thirty clues to the exceptional diversification of flowering plants.

BACKGROUND AND AIMS: As angiosperms became one of the megadiverse groups of macroscopic eukaryotes, they forged modern ecosystems and promoted the evolution of extant terrestrial biota. Unequal distribution of species among lineages suggests that diversification, the process that ultimately determines species richness, acted differentially through angiosperm evolution. METHODS: We investigate how angiosperms became megadiverse by identifying the phylogenetic and temporal placement of exceptional radiations, by combining the most densely fossil-calibrated molecular clock phylogeny with a Bayesian model that identifies diversification shifts among evolutionary lineages and through time. We evaluate the effect of the prior number of expected shifts in the phylogenetic tree. KEY RESULTS: Major diversification increases took place over 100 Ma, from the Early Cretaceous to the end of the Paleogene, and are distributed across the angiosperm phylogeny. The long-term diversification trajectory of angiosperms shows moderate rate variation, but is underlain by increasing speciation and extinction, and results from temporally overlapping, independent radiations and depletions in component lineages. CONCLUSIONS: The identified deep time diversification shifts are clues to the identification of ultimate drivers of angiosperm megadiversity, which probably involve multivariate interactions among intrinsic traits and extrinsic forces. An enhanced understanding of angiosperm diversification will involve a more precise phylogenetic location of diversification shifts, and integration of fossil information.

Recent radiation and dispersal of an ancient lineage: The case of Fouquieria (Fouquiericeae, Ericales) in North American deserts.

Arid biomes are particularly prominent in the Neotropics providing some of its most emblematic landscapes and a substantial part of its species diversity. To understand some of the evolutionary processes underlying the speciation of lineages in the Mexican Deserts, the diversification of Fouquieria is investigated, which includes eleven species, all endemic to the warm deserts and dry subtropical regions of North America. Using a phylogeny from plastid DNA sequences with samples of individuals from populations of all the species recognized in Fouquieria, we estimate divergence times, test for temporal diversification heterogeneity, test for geographical structure, and conduct ancestral area reconstruction. Fouquieria is an ancient lineage that diverged from Polemoniaceae ca. 75.54 Ma. A Mio-Pliocene diversification of Fouquieria with vicariance, associated with Neogene orogenesis underlying the early development of regional deserts is strongly supported. Test for temporal diversification heterogeneity indicates that during its evolutionary history, Fouquieria had a drastic diversification rate shift at ca.12.72 Ma, agreeing with hypotheses that some of the lineages in North American deserts diversified as early as the late Miocene to Pliocene, and not during the Pleistocene. Long-term diversification dynamics analyses suggest that extinction also played a significant role in Fouquieria's evolution, with a very high rate at the onset of the process. From the late Miocene onwards, Fouquieria underwent substantial diversification change, involving high speciation decreasing to the present and negligible extinction, which is congruent with its scant fossil record during this period. Geographic phylogenetic structure and the pattern of most sister species inhabiting different desert nucleus support that isolation by distance could be the main driver of speciation.

Uncovering Higher-Taxon Diversification Dynamics from Clade Age and Species-Richness Data.

The relationship between clade age and species richness has been increasingly used in macroevolutionary studies as evidence for ecologically versus time-dependent diversification processes. However, theory suggests that phylogenetic structure, age type (crown or stem age), and taxonomic delimitation can affect estimates of the age-richness correlation (ARC) considerably. We currently lack an integrative understanding of how these different factors affect ARCs, which in turn, obscures further interpretations. To assess its informative breadth, we characterize ARC behavior with simulated and empirical phylogenies, considering phylogenetic structure and both crown and stem ages. First, we develop a two-state birth-death model to simulate phylogenies including the origin of higher taxa and a hierarchical taxonomy to determine ARC expectations under ecologically and time-dependent diversification processes. Then, we estimate ARCs across various taxonomic ranks of extant amphibians, squamate reptiles, mammals, birds, and flowering plants. We find that our model reproduces the general ARC trends of a wide range of biological systems despite the particularities of taxonomic practice within each, suggesting that the model is adequate to establish a framework of ARC null expectations for different diversification processes when taxa are defined with a hierarchical taxonomy. ARCs estimated with crown ages were positive in all the scenarios we studied, including ecologically dependent processes. Negative ARCs were only found at less inclusive taxonomic ranks, when considering stem age, and when rates varied among clades. This was the case both in ecologically and time-dependent processes. Together, our results warn against direct interpretations of single ARC estimates and advocate for a more integrative use of ARCs across age types and taxonomic ranks in diversification studies. [Birth-Death models; crown age; diversity dependence; extinction; phylogenetic structure; speciation; stem age; taxonomy; time dependence; tree simulations.].

Case­control study of Epstein­Barr virus and Helicobacter pylori serology in Latin American patients with gastric disease.

BACKGROUND: Chronic tissue damage induced by Helicobacter pylori (HP)-driven inflammation is considered the main risk of gastric carcinoma (GC). Epstein­Barr virus (EBV) infection has also been associated with GC. In this study, we aim to address the role of EBV in inflammatory GC precursor lesions and its added risk to HP infection. METHODS: Antibodies against EBV, HP and the bacterial virulence factor CagA were measured in sera from 525 Mexican and Paraguayan patients with gastric disease. Gastric samples were characterised according to the updated Sydney classification and associations were estimated between antibody responses and severity of both tissue damage and inflammation. RESULTS: We found significant associations (odd ratios and trends) between EBV and HP copositivity and premalignant lesions and intestinal-type GC. The EBV and HP coinfection was also significantly associated with increased infiltration of immune cells. No association was found between EBV and the less inflammation-driven diffuse-type GC. CONCLUSIONS: Our study suggests that EBV co-participates with HP to induce severe inflammation, increasing the risk of progression to intestinal-type GC.

A metacalibrated time-tree documents the early rise of flowering plant phylogenetic diversity.

The establishment of modern terrestrial life is indissociable from angiosperm evolution. While available molecular clock estimates of angiosperm age range from the Paleozoic to the Late Cretaceous, the fossil record is consistent with angiosperm diversification in the Early Cretaceous. The time-frame of angiosperm evolution is here estimated using a sample representing 87% of families and sequences of five plastid and nuclear markers, implementing penalized likelihood and Bayesian relaxed clocks. A literature-based review of the palaeontological record yielded calibrations for 137 phylogenetic nodes. The angiosperm crown age was bound within a confidence interval calculated with a method that considers the fossil record of the group. An Early Cretaceous crown angiosperm age was estimated with high confidence. Magnoliidae, Monocotyledoneae and Eudicotyledoneae diversified synchronously 135-130 million yr ago (Ma); Pentapetalae is 126-121 Ma; and Rosidae (123-115 Ma) preceded Asteridae (119-110 Ma). Family stem ages are continuously distributed between c. 140 and 20 Ma. This time-frame documents an early phylogenetic proliferation that led to the establishment of major angiosperm lineages, and the origin of over half of extant families, in the Cretaceous. While substantial amounts of angiosperm morphological and functional diversity have deep evolutionary roots, extant species richness was probably acquired later.

Betacoronavirus 1 in alpacas (Vicugna pacos) in the High Peruvian Andes.

Genetic sequences highly related to Bovine coronavirus (BCoV) were detected in fecal samples from Peruvian 1-3 week old alpaca crias located on six farms in Puno department, some of which shared pastures with cattle. A total of 60 samples were screened for coronavirus using a nested PCR amplification of a fragment of the RNA-dependent RNA polymerase (RdRp) gene. Sequences from 11 positive samples were highly similar to the Kakegawa, Quebec and Mebus BCoV strains (99.5-100.0%) and 99.2% identical to an alpaca Coronavirus (CoV) previously detected in the USA. The detection of genetic sequences related to BCoV from Peruvian alpaca crias suggests possible role of this virus on enteric disorders etiology in the High Andes.

Three decades after the publication of the Lamendin method for adult age-at-death estimation: Methodological evolution of the procedure and interpretations.

More than three decades have passed since the publication of Lamendin et al.'s proposal in 1992. Over this time, numerous investigations have been conducted to assess the applicability of the technique in different populations with acceptable results in terms of estimation errors. The proposal by Lamendin and colleagues remains relevant today, and has made a significant contribution to adult age-at-death estimation due to its simplicity, repeatability, replicability, and high performance. Indeed, significant progress towards systematizing and strengthening the procedure has been reported in the published literature. One noteworthy advancement is the development of an international database that supports the use of Bayesian statistics for age-at-death estimation. This resource plays a crucial role in standardizing the methodology and improving the reliability for obtaining more reliable results on a global scale. The aim of this study is to investigate the historical evolution of the technique, to assess the accuracy of the results obtained by different analytic procedures, and to explore its impact in forensic applications through a systematic analysis of the specialized literature on this field. The current state of research indicates that this type of methodological research is an ongoing process, far from being completed. Many questions and challenges that require further attention to address effectively these issues remain unanswered, such as the development of non-linear regressions and probabilistic approaches, the deepening of procedures that improve global approximations, and the intensification of research focused on achieving more accurate estimations among individuals over 70 years-old. However, studies generally agree that the Lamendin technique works well for individuals between the ages of 30-60 years. It is still in force today, although the method has been significantly perfected. Despite the degree of research development in this area, further efforts are needed to improve the understanding and performance of these kinds of procedures. This will ultimately lead to an improvement in the accuracy and reliability of forensic investigation results worldwide.

Theories on the Link Between Autism Spectrum Conditions and Trans Gender Modality: a Systematic Review.

While research on the prevalence of co-occurring autism spectrum conditions (ASC) and trans gender modality (TGM) is available, less is known about the underlying mechanism of this association. Insight is needed to improve treatment of trans autistic people. This review provides an overview of theories on the ASC-TGM link and the available evidence for/against them published between January 2016 and October 2020. A systematic search was performed in PubMed, PsycINFO, Web of Science, and Scopus. This resulted in 36 studies, in which 15 theories were identified. Results indicate all theories lack substantial empirical support. Unlikely and promising theories were identified. The most promising theories were those on resistance to social norms and weakened sex differences. Future directions are provided.

Post-surgical endophthalmitis with secondary meningitis. About a case.

A 61-year-old man presented hyperacute endophthalmitis due to Proteus mirabilis after a pars plana vitrectomy. In the first examination (24 h after surgery), visual acuity (VA) was of hand movement, biomicroscopy showed edematous cornea, Tyndall ++++ and fibrin membrane, with vitritis and impossibility of visualizing retina details. Treatment with intravitreal injections was performed. Despite the treatment, the patient's symptoms worsened, and he began with poor general condition, fever, and leukocytosis, requiring hospitalization and intravenous treatment because of a diagnosis of secondary meningitis due to post-surgical endophthalmitis. The patient required enucleation of the affected eye without prosthesis placement. Even though post-surgical bacterial endophthalmitis is usually an infection confined to the eye, this clinical case demonstrates the possibility of the infection spreading to the rest of the body, potentially endangering the patient's life.

The utility of serologic tests as biomarkers for Helicobacter pylori-associated precancerous lesions and gastric cancer varies between Latin American countries.

PURPOSE: Currently, studies on serologic diagnosis of Helicobacter pylori-associated gastric cancer (GC) in Latin America are scarce. The aim of the present study was to evaluate the association between H. pylori serology tests in patients with early precancerous lesions or GC, when compared with non-atrophic gastritis in Colombia, Paraguay, and Mexico, three countries in Latin America with a high prevalence of H. pylori infection but contrasting rates of GC mortality. METHODS: Gastric biopsies and blood samples were obtained from patients attending the gastroenterology or oncology services of hospitals in the three participating countries. IgG antibodies against H. pylori whole-cell antigens and CagA were tested in 1,117 sera using an enzyme-linked immunoabsorbent assay. RESULTS: Positive and significant associations were shown for H. pylori seropositivity and preneoplastic lesions in Mexico (OR 2.0; 95 % CI 1.1-3.4) but not in Colombia (OR 1.2; 95 % CI 0.6-2.1) or Paraguay (OR 1.5; 95 % CI 0.6-3.2); no significant associations were shown for GC in any country. CagA seropositivity was associated with preneoplasic lesions in all three countries (ORs = 2.1, 3.0, and 3.1 for Mexico, Colombia, and Paraguay, respectively), and with GC only in Colombia (OR 4.3; 95 % CI 2.1-9.2). CONCLUSIONS: In countries of Latin America, the IgG CagA test might be a useful biomarker for patients with gastric preneoplastic lesions and for those at risk of developing gastric cancer.

Post-COVID-19 Brain [18F] FDG-PET Findings: A Retrospective Single-Center Study in the United States.

BACKGROUND AND PURPOSE: The pathophysiology of neurologic manifestations of postacute sequelae of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is not clearly understood. Our aim was to investigate brain metabolic activity on [18F] FDG-PET/CT scans in patients with a history of coronavirus disease 2019 (COVID-19) infection before imaging. MATERIALS AND METHODS: This retrospective study included 45 patients who underwent [18F] FDG-PET/CT imaging for any reason and had, at least once, tested positive for COVID-19 at any time before imaging. Fifteen patients had available [18F] FDG-PET scans obtained under identical conditions before the infection. A group of 52 patients with melanoma or multiple myeloma who underwent [18F] FDG-PET/CT were used as controls. Whole-brain 2-sample t test analysis was performed using SPM software to identify clusters of hypo- and hypermetabolism and compare brain metabolic activity between patients with COVID-19 and controls. Paired sample t test comparison was also performed for 15 patients, and correlations between metabolic values of clusters and clinical data were measured. RESULTS: Compared with the control group, patients with a history of COVID-19 infection exhibited focal areas of hypometabolism in the bilateral frontal, parietal, occipital, and posterior temporal lobes and cerebellum (P = .05 uncorrected at the voxel level, family-wise error-corrected at the cluster level) that peaked during the first 2 months, improved to near-complete recovery around 6 months, and disappeared at 12 months. Hypermetabolism involving the brainstem, cerebellum, limbic structures, frontal cortex, and periventricular white matter was observed only at 2-6 months after infection. Older age, neurologic symptoms, and worse disease severity scores positively correlated with the metabolic changes. CONCLUSIONS: This study demonstrates a profile of time-dependent brain PET hypo- and hypermetabolism in patients with confirmed SARS-CoV-2 infection.