FDA's proposed rule and its regulatory impact on emerging and reemerging neglected tropical diseases in the United States.

Diagnosing infectious diseases significantly influences patient care, aiding in outbreak identification, response, and public health monitoring. However, the range of FDA-approved molecular tests remains notably limited, especially concerning neglected tropical diseases (NTDs). Drawing upon our experience as one of the largest healthcare networks in the greater New York metropolitan area, this viewpoint manuscript aims to spotlight the existing diagnostic landscape and unmet clinical needs for 4 emerging NTDs increasingly prevalent in the United States, additionally, it delves into the possible adverse effects of the FDA's Proposed Rule on Laboratory-Developed Tests for these clinical conditions and the broader spectrum of NTDs.

New daily persistent headache after SARS-CoV-2 infection in Latin America: a cross-sectional study.

BACKGROUND: Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes. METHODS: We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants' responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups. Participant data was summarized by descriptive statistics. Student's t and Mann-Whitney U tests were used according to the distribution of quantitative variables. For categorical variables, Pearson's chi-square and Fisher's exact tests were used according to the size of expected frequencies. Binomial logistic regression using the backward stepwise selection method was performed to identify factors associated with NDPH. RESULTS: Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the NDPH diagnostic criteria. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH. CONCLUSION: This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its associated factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.

Microbiome Alterations Driven by Trypanosoma cruzi Infection in Two Disjunctive Murine Models.

Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal tissues, including changes in anti-inflammatory (interleukin-4 [IL-4] and IL-10) and proinflammatory (gamma interferon, tumor necrosis factor alpha, and IL-6) cytokines. Bacterial species such as Bacteroides thetaiotaomicron, Faecalibaculum rodentium, and Lactobacillus johnsonii showed a decrease in relative abundance, while Akkermansia muciniphila and Staphylococcus xylosus increased. Likewise, as infection progressed, there was a decrease in gene abundances related to metabolic processes such as lipid synthesis (including short-chain fatty acids) and amino acid synthesis (including branched-chain amino acids). High-quality metagenomic assembled genomes of L. johnsonii and A. muciniphila among other species were reconstructed, confirming, functional changes associated with metabolic pathways that are directly affected by the loss of abundance of specific bacterial taxa. IMPORTANCE Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, presenting acute and chronic phases where cardiomyopathy, megaesophagus, and/or megacolon stand out. During the course of its life cycle, the parasite has an important gastrointestinal tract transit that leads to severe forms of CD. The intestinal microbiome plays an essential role in the immunological, physiological, and metabolic homeostasis of the host. Therefore, parasite-host-intestinal microbiome interactions may provide information on certain biological and pathophysiological aspects related to CD. The present study proposes a comprehensive evaluation of the potential effects of this interaction based on metagenomic and immunological data from two mice models with different genetic, immunological, and microbiome backgrounds. Our findings suggest that there are alterations in the immune and microbiome profiles that affect several metabolic pathways that can potentially promote the infection's establishment, progression, and persistence. In addition, this information may prove essential in the research of new prophylactic and therapeutic alternatives for CD.

Diversity and geographical distribution of Leishmania species and the emergence of Leishmania (Leishmania) infantum and L. (Viannia) panamensis in Central-Western Venezuela.

Transmission of cutaneous leishmaniasis in Venezuela reveals diverse and changing epidemiological landscapes, as well as a spectrum of clinical phenotypes presumed to be linked to a variety of Leishmania species. Central-western Venezuela constitutes one of the highest endemic epicenters in the country, and updated molecular epidemiological information is still lacking. Therefore, in this study we aimed to characterize the landscape of circulating Leishmania species across central-western Venezuela through the last two decades, performed comparisons of haplotype and nucleotide diversity, and built a geospatial map of parasite species distribution. A total of 120 clinical samples were collected from patients across the cutaneous disease spectrum, retrieving parasitic DNA, and further characterizing by PCR and sequencing of the HSP70 gene fragment. This data was later collated with further genetic, geospatial and epidemiological analyses. A peculiar pattern of species occurrence including Leishmania (Leishmania) amazonensis (77.63% N=59), Leishmania (Leishmania) infantum (14.47% N=11), Leishmania (Viannia) panamensis (5.26% N=4) and Leishmania (Viannia) braziliensis (2.63% N=2) was revealed, also highlighting a very low genetic diversity amongst all analyzed sequences. Geographical distribution showed that most cases are widely distributed across the greater urban-sub urban area of the Irribaren municipality. L.(L.) amazonensis appears to be widely dispersed throughout Lara state. Statistical analyses failed to reveal significance for any comparisons, leading to conclude a lack of association between the infective Leishmania species and clinical phenotypes. To the best of our knowledge, this is an unprecedented study which addresses comprehensively the geographical distribution of Leishmania species in central-western Venezuela throughout the last two decades, and the first to incriminate L. (L.) infantum as an etiologic agent of cutaneous leishmaniasis in this region. Our findings support that Leishmania endemism in central-western Venezuela is caused mainly by L.(L.) amazonensis. Future studies are needed to unveil additional details on the ecological intricacies and transmission aspects of leishmaniasis (i.e. sampling phlebotomines and mammals) and to adopt adequate public health prevention and control strategies and mitigate disease impact in this endemic region.

SARS-CoV-2 infection of kidney tissues from severe COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests diverse clinical pathologies involving multiple organs. While the respiratory tract is the primary SARS-CoV-2 target, acute kidney injury is common in COVID-19 patients, displaying as acute tubular necrosis (ATN) resulting from focal epithelial necrosis and eosinophilia, glomerulosclerosis, and autolysis of renal tubular cells. However, whether any renal cells are infected by SARS-CoV-2 and the mechanism involved in the COVID-19 kidney pathology remain unclear. METHODS: Kidney tissues obtained at autopsy from four severe COVID-19 patients and one healthy subject were examined by hematoxylin and eosin staining. Indirect immunofluorescent antibody assay was performed to detect SARS-CoV-2 spike protein S1 and nonstructural protein 8 (NSP8) together with markers of different kidney cell types and immune cells to identify the infected cells. RESULTS: Renal parenchyma showed tissue injury comprised of ATN and glomerulosclerosis. Positive staining of S1 protein was observed in renal parenchymal and tubular epithelial cells. Evidence of viral infection was also observed in innate monocytes/macrophages and NK cells. Positive staining of NSP8, which is essential for viral RNA synthesis and replication, was confirmed in renal parenchymal cells, indicating the presence of active viral replication in the kidney. CONCLUSIONS: In fatal COVID-19 kidneys, there are SARS-CoV-2 infection, minimally infiltrated innate immune cells, and evidence of viral replication, which could contribute to tissue damage in the form of ATN and glomerulosclerosis.

Development and characterization of a new monoclonal antibody against SARS-CoV-2 NSP12 (RdRp).

SARS-CoV-2 NSP12, the viral RNA-dependent RNA polymerase (RdRp), is required for viral replication and is a therapeutic target to treat COVID-19. To facilitate research on SARS-CoV-2 NSP12 protein, we developed a rat monoclonal antibody (CM12.1) against the NSP12 N-terminus that can facilitate functional studies. Immunoblotting and immunofluorescence assay (IFA) confirmed the specific detection of NSP12 protein by this antibody for cells overexpressing the protein. Although NSP12 is generated from the ORF1ab polyprotein, IFA of human autopsy COVID-19 lung samples revealed NSP12 expression in only a small fraction of lung cells including goblet, club-like, vascular endothelial cells, and a range of immune cells, despite wide-spread tissue expression of spike protein antigen. Similar studies using in vitro infection also generated scant protein detection in cells with established virus replication. These results suggest that NSP12 may have diminished steady-state expression or extensive posttranslation modifications that limit antibody reactivity during SARS-CoV-2 replication.

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case.

BACKGROUND: Cladophialophora bantiana is a dematiaceous, saprophytic fungus and a rare but reported cause of intracranial abscesses due to its strong neurotropism. Although it predominantly affects immunocompetent individuals with environmental exposure, more recently, its significance as a highly lethal opportunistic infection in transplant recipients has been recognized. Successful treatment requires timely but often challenging diagnosis, followed by complete surgical excision. Next-generation sequencing of microbial cell-free DNA (cfDNA) from plasma is a novel diagnostic method with the potential to identify invasive fungal infections more rapidly and less invasively than conventional microbiological testing, including brain biopsy. OBSERVATIONS: The authors described the case of a recipient of a liver transplant who presented with seizures and was found to have innumerable ring-enhancing intracranial lesions. The Karius Test, a commercially available method of next-generation sequencing of cfDNA, was used to determine the causative organism. Samples from the patient's plasma identified C. bantiana 6 days before culture results of the surgical specimen, allowing optimization of the empirical antifungal regimen, which led to a reduction in the size of the abscesses. LESSONS: The authors' findings suggest that microbial cfDNA sequencing may be particularly impactful in improving the management of brain abscesses in which the differential diagnosis is wide because of immunosuppression.

A Robust, Highly Multiplexed Mass Spectrometry Assay to Identify SARS-CoV-2 Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are characterized by differences in transmissibility and response to therapeutics. Therefore, discriminating among them is vital for surveillance, infection prevention, and patient care. While whole-genome sequencing (WGS) is the "gold standard" for variant identification, molecular variant panels have become increasingly available. Most, however, are based on limited targets and have not undergone comprehensive evaluation. We assessed the diagnostic performance of the highly multiplexed Agena MassARRAY SARS-CoV-2 Variant Panel v3 to identify variants in a diverse set of 391 SARS-CoV-2 clinical RNA specimens collected across our health systems in New York City, USA and Bogotá, Colombia (September 2, 2020 to March 2, 2022). We demonstrated almost perfect levels of interrater agreement between this assay and WGS for 9 of 11 variant calls (κ ≥ 0.856) and 25 of 30 targets (κ ≥ 0.820) tested on the panel. The assay had a high diagnostic sensitivity (≥93.67%) for contemporary variants (e.g., Iota, Alpha, Delta, and Omicron [BA.1 sublineage]) and a high diagnostic specificity for all 11 variants (≥96.15%) and all 30 targets (≥94.34%) tested. Moreover, we highlighted distinct target patterns that could be utilized to identify variants not yet defined on the panel, including the Omicron BA.2 and other sublineages. These findings exemplified the power of highly multiplexed diagnostic panels to accurately call variants and the potential for target result signatures to elucidate new ones. IMPORTANCE The continued circulation of SARS-CoV-2 amid limited surveillance efforts and inconsistent vaccination of populations has resulted in the emergence of variants that uniquely impact public health systems. Thus, in conjunction with functional and clinical studies, continuous detection and identification are quintessential to informing diagnostic and public health measures. Furthermore, until WGS becomes more accessible in the clinical microbiology laboratory, the ideal assay for identifying variants must be robust, provide high resolution, and be adaptable to the evolving nature of viruses like SARS-CoV-2. Here, we highlighted the diagnostic capabilities of a highly multiplexed commercial assay to identify diverse SARS-CoV-2 lineages that circulated from September 2, 2020 to March 2, 2022 among patients seeking care in our health systems. This assay demonstrated variant-specific signatures of nucleotide/amino acid polymorphisms and underscored its utility for the detection of contemporary and emerging SARS-CoV-2 variants of concern.

Tele-entomology and tele-parasitology: A citizen science-based approach for surveillance and control of Chagas disease in Venezuela.

Chagas Disease (CD), a chronic infection caused by the Trypanosoma cruzi parasite, is a Neglected Tropical Disease endemic to Latin America. With a re-emergence in Venezuela during the past two decades, the spread of CD has proved susceptible to, and inhibitable by a digital, real-time surveillance system effectuated by Citizen Scientists in communities throughout the country. The #TraeTuChipo (#BringYourKissingBug) campaign implemented in January 2020, has served as such a strategy counting on community engagement to define the current ecological distribution of CD vectors despite the absence of a functional national surveillance program. This pilot campaign collected data through online surveys, social media platforms, and/or telephone text messages. A total of 79 triatomine bugs were reported from eighteen Venezuelan states; 67 bugs were identified as Panstrongylus geniculatus, 1 as Rhodnius pictipes, 1 as Triatoma dimidiata, and 10 as Triatoma maculata. We analyzed 8 triatomine feces samples spotted from 4 Panstrongylus geniculatus which were confirmed positive by qPCR for T. cruzi . Further molecular characterization of discrete typing units (DTUs), revealed that all samples contained TcI, the most highly diverse and broadly distributed strain of T. cruzi. Moreover, analysis of the mitochondrial 12S gene revealed Myotis keaysi, Homo sapiens, and Gallus gallus as the main triatomine feeding sources. This study highlights a novel Citizen Science approach which may help improve the surveillance systems for CD in endemic countries.

A robust, highly multiplexed mass spectrometry assay to identify SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are characterized by differences in transmissibility and response to therapeutics. Therefore, discriminating among them is vital for surveillance, infection prevention, and patient care. While whole viral genome sequencing (WGS) is the "gold standard" for variant identification, molecular variant panels have become increasingly available. Most, however, are based on limited targets and have not undergone comprehensive evaluation. We assessed the diagnostic performance of the highly multiplexed Agena MassARRAY ® SARS-CoV-2 Variant Panel v3 to identify variants in a diverse set of 391 SARS-CoV-2 clinical RNA specimens collected across our health systems in New York City, USA as well as in Bogotá, Colombia (September 2, 2020 - March 2, 2022). We demonstrate almost perfect levels of interrater agreement between this assay and WGS for 9 of 11 variant calls (κ ≥ 0.856) and 25 of 30 targets (κ ≥ 0.820) tested on the panel. The assay had a high diagnostic sensitivity (≥93.67%) for contemporary variants (e.g., Iota, Alpha, Delta, Omicron [BA.1 sublineage]) and a high diagnostic specificity for all 11 variants (≥96.15%) and all 30 targets (≥94.34%) tested. Moreover, we highlight distinct target patterns that can be utilized to identify variants not yet defined on the panel including the Omicron BA.2 and other sublineages. These findings exemplify the power of highly multiplexed diagnostic panels to accurately call variants and the potential for target result signatures to elucidate new ones. Importance: The continued circulation of SARS-CoV-2 amidst limited surveillance efforts and inconsistent vaccination of populations has resulted in emergence of variants that uniquely impact public health systems. Thus, in conjunction with functional and clinical studies, continuous detection and identification are quintessential to inform diagnostic and public health measures. Furthermore, until WGS becomes more accessible in the clinical microbiology laboratory, the ideal assay for identifying variants must be robust, provide high resolution, and be adaptable to the evolving nature of viruses like SARS-CoV-2. Here, we highlight the diagnostic capabilities of a highly multiplexed commercial assay to identify diverse SARS-CoV-2 lineages that circulated at over September 2, 2020 - March 2, 2022 among patients seeking care at our health systems. This assay demonstrates variant-specific signatures of nucleotide/amino acid polymorphisms and underscores its utility for detection of contemporary and emerging SARS-CoV-2 variants of concern.

Cutaneous leishmaniosis due to Leishmania mexicana in a cat treated with cryotherapy.

We report the novel use of cryosurgery to treat cutaneous feline leishmaniosis (FeL) in a domestic cat from mid-western Venezuela. Amastigotes, evident by microscopy in aspirates from the nodular, erythematous nose lesions, were identified as Leishmania mexicana by cytochrome b gene sequence analysis. Lesions resolved completely without relapse after 14 months.

Nous décrivons une nouvelle utilisation de la cryochirurgie pour traiter la leishmaniose féline cutanée (FeL) chez un chat domestique du centre-ouest du Venezuela. Les amastigotes, observés par microscopie dans les cytoponctions des lésions nodulaires et érythémateuses du nez, ont été identifiés comme Leishmania mexicana par analyse de la séquence du gène du cytochrome b. Les lésions ont complètement disparu sans rechute après 14 mois.

Describimos el uso novedoso de la criocirugía para tratar la leishmaniosis cutánea felina (FeL) en un gato doméstico del medio oeste de Venezuela. Los amastigotes, evidentes por microscopía en los aspirados de las lesiones nasales nodulares eritematosas, se identificaron como Leishmania mexicana mediante el análisis de la secuencia del gen del citocromo b. Las lesiones se resolvieron completamente sin recidiva tras 14 meses.

Neste estudo, relatamos a utilização inédita de criocirurgia para tratar leishmaniose felina cutânea (FeL) em um gato doméstico no centro-oeste da Venezuela. Amastigotas, evidentes à microscopia de aspirados da lesão nodular e eritematosa na região nasal, foram identificadas como Leishmania Mexicana por sequenciamento do gene do citocromo b. As lesões se resolveram completamente sem recidiva após 14 meses.

RT-PCR/MALDI-TOF Diagnostic Target Performance Reflects Circulating SARS-CoV-2 Variant Diversity in New York City.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern have emerged. New variants pose challenges for diagnostic platforms because sequence diversity can alter primer/probe-binding sites (PBSs), causing false-negative results. The MassARRAY SARS-CoV-2 Panel (Agena Bioscience) uses RT-PCR and mass spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we use a data set of 256 SARS-CoV-2-positive specimens collected between April 11, 2021, and August 28, 2021, to evaluate target performance with paired sequencing data. During this time frame, two targets in the N gene (N2 and N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3'-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk, 20.02; 95% CI, 11.36 to 35.72; P < 0.0001). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3'-mismatch to the N2 probe PBS and increases target dropout risk (relative risk, 11.92; 95% CI, 8.17 to 14.06; P < 0.0001). These findings highlight the robust capability of MassARRAY SARS-CoV-2 Panel target results to reveal circulating virus diversity, and they underscore the power of multitarget design to capture variants of concern.

Epidemiological Dynamics of SARS-CoV-2 Variants During Social Protests in Cali, Colombia.

Background: The third wave of the global health crisis attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus reached Colombia in March 2021. Over the following 6 months, it was interpolated by manifestations of popular disapproval to the actual political regime-with multiple protests sprouting throughout the country. Large social gatherings seeded novel coronavirus disease 2019 (COVID-19) variants in big cities and propagated their facile spread, leading to increased rates of hospitalizations and deaths. Methods: In this article, we evaluate the effective reproduction number (Rt) dynamics of SARS-CoV-2 in Cali, Colombia, between 4 April 2021 and 31 July 2021 based on the analysis of 228 genomes. Results: Our results showed clear contrast in Rt values between the period of frequent protests (Rt > 1), and the preceding and following months (Rt < 1). Genomic analyses revealed 16 circulating SARS-CoV-2 lineages during the initial period-including variants of concern (VOCs) (Alpha, Gamma, and Delta) and variants of interest (VOIs) (Lambda and Mu). Furthermore, we noticed the Mu variant dominating the COVID-19 distribution schema as the months progressed. We identified four principal clusters through phylogenomic analyses-each one of potentially independent introduction to the city. Two of these were associated with the Mu variant, one associated with the Gamma variant, and one with the Lambda variant. Conclusion: Our results chronicle the impact of large group assemblies on the epidemiology of COVID-19 during this intersection of political turmoil and sanitary crisis in Cali, Colombia. We emphasize upon the effects of limited biosecurity strategies (which had characterized this time period), on the spread of highly virulent strains throughout Cali and greater Colombia.

Impact of SARS-CoV-2 Mu variant on vaccine effectiveness: A comparative genomics study at the peak of the third wave in Bogota, Colombia.

We assessed the circulation of severe acute respiratory syndrome coronavirus-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above is possibly associated with specific mutations that confer it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g., Omicron) and their impact on vaccination efforts worldwide.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

Hotspots for SARS-CoV-2 Omicron variant spread: Lessons from New York City.

The coronavirus disease-2019 (COVID-19) pandemic is still challenging public health systems worldwide, particularly with the emergence of novel SARS-CoV-2 variants with mutations that increase their transmissibility and immune escape. This is the case of the variant of concern Omicron that rapidly spread globally. Here, using epidemiological and genomic data we compared the situations in South Africa as the epicenter of emergence, United Kingdom, and with particular interest New York City. This rapid global dispersal from the place of first report reemphasizes the high transmissibility of Omicron, which needed only two weeks to become dominant in the United Kingdom and New York City. Our analyses suggest that as SARS-CoV-2 continues to evolve, global authorities must prioritize equity in vaccine access and continued genomic surveillance. Future studies are still needed to fully unveil the biological properties of Omicron, but what is certain is that vaccination, large-scale testing, and infection prevention efforts are the greatest arsenal against the COVID-19 pandemic.

Correlation between Identification of ß-Lactamase Resistance Genes and Antimicrobial Susceptibility Profiles in Gram-Negative Bacteria: a Laboratory Data Analysis.

We reported the frequency of resistance gene detection in Gram-negative blood culture isolates and correlated these findings with corresponding antibiograms. Data were obtained from 1045 isolates tested on the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panels at the Mount Sinai Hospital Clinical Microbiology Laboratory in New York from March 2019 to February 2021. Susceptibilities were performed using Vitek 2 (bioMérieux Clinical Diagnostics) or Microscan (Beckman Coulter Inc.). blaCTX-M was detected in 26.4% Klebsiella pneumoniae, 23.5% Escherichia coli, and 16.4% Proteus mirabilis isolates. As would be expected, both blaCTX-M and blaCTX-M negative isolates were likely to be susceptible to newer agents while blaCTX-M positive isolates were more likely to be resistant to earlier generations of beta-lactam antibiotics. 3/204 blaCTX-M-positive isolates were found to be ceftriaxone-susceptible. Conversely, 2.8% ceftriaxone nonsusceptible strains were negative for all ß-lactamase genes on the ePlex BCID-GN panel, including blaCTX-M. The prevalence of CTX-M-producing Enterobacterales remains high in the United States. A small number of blaCTX-M-positive isolates were susceptible to ceftriaxone, and a small number of ceftriaxone nonsusceptible isolates were negative for blaCTX-M. Further studies are needed to determine the optimal management when an isolate is phenotypically susceptible to ceftriaxone, but blaCTX-M is detected. IMPORTANCE There is limited literature on corresponding results obtained from rapid molecular diagnostics with the antibiotic susceptibility profile. We reported a correlation between the results obtained from ePlex and the antibiograms against a large collection of Gram-negative bacteria. We reported that there can be a discrepancy in a small number of cases, but the clinical significance of that is unknown.

Food for thought: Eating before saliva collection and interference with SARS-CoV-2 detection.

Saliva is a promising specimen for the detection of viruses that cause upper respiratory infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its cost-effectiveness and noninvasive collection. However, together with intrinsic enzymes and oral microbiota, children's unique dietary habits may introduce substances that interfere with diagnostic testing. To determine whether children's dietary choices impact SARS-CoV-2 molecular detection in saliva, we performed a diagnostic study that simulates testing of real-life specimens provided from healthy children (n = 5) who self-collected saliva at home before and at 0, 20, and 60 min after eating 20 foods they selected. Each of 72 specimens was split into two volumes and spiked with SARS-CoV-2-negative or SARS-CoV-2-positive clinical standards before side-by-side testing by reverse-transcription polymerase chain reaction matrix-assisted laser desorption ionization time-of-flight (RT-PCR/MALDI-TOF) assay. Detection of internal extraction control and SARS-CoV-2 nucleic acids was reduced in replicates of saliva collected at 0 min after eating 11 of 20 foods. Interference resolved at 20 and 60 min after eating all foods except hot dogs in one participant. This represented a significant improvement in the detection of nucleic acids compared to saliva collected at 0 min after eating (p = 0.0005). We demonstrate successful detection of viral nucleic acids in saliva self-collected by children before and after eating a variety of foods. Fasting is not required before saliva collection for SARS-CoV-2 testing by RT-PCR/MALDI-TOF, but waiting for 20 min after eating is sufficient for accurate testing. These findings should be considered for SARS-CoV-2 testing and broader viral diagnostics in saliva specimens.

First wave of COVID-19 in Venezuela: Epidemiological, clinical, and paraclinical characteristics of first cases.

The coronavirus disease 2019 (COVID-19) pandemic has particularly affected countries with weakened health services in Latin America, where proper patient management could be a critical step to address the epidemic. In this study, we aimed to characterize and identify which epidemiological, clinical, and paraclinical risk factors defined COVID-19 infection from the first confirmed cases through the first epidemic wave in Venezuela. A retrospective analysis of consecutive suspected cases of COVID-19 admitted to a sentinel hospital was carried out, including 576 patient cases subsequently confirmed for severe acute respiratory syndrome coronavirus 2 infection. Of these, 162 (28.1%) patients met the definition criteria for severe/critical disease, and 414 (71.2%) were classified as mild/moderate disease. The mean age was 47 (SD 16) years, the majority of which were men (59.5%), and the most frequent comorbidity was arterial hypertension (23.3%). The most common symptoms included fever (88.7%), headache (65.6%), and dry cough (63.9%). Severe/critical disease affected mostly older males with low schooling (p < 0.001). Similarly, higher levels of glycemia, urea, aminotransferases, total bilirubin, lactate dehydrogenase, and erythrocyte sedimentation rate were observed in severe/critical disease patients compared to those with mild/moderate disease. Overall mortality was 7.6% (44/576), with 41.7% (28/68) dying in hospital. We identified risk factors related to COVID-19 infection, which could help healthcare providers take appropriate measures and prevent severe clinical outcomes. Our results suggest that the mortality registered by this disease in Venezuela during the first epidemic wave was underestimated. An increase in fatalities is expected to occur in the coming months unless measures that are more effective are implemented to mitigate the epidemic while the vaccination process is ongoing.