Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico.

BACKGROUND: Drug-resistant tuberculosis (TB) is associated with higher mortality rates in patients with human immunodeficiency virus (HIV). In Mexico, the number of deaths due to TB among the HIV-positive population has tripled in recent years. METHODS: Ninety-three Mycobacterium tuberculosis strains isolated from the same number of HIV-infected patients treated in a public hospital in Mexico City were studied to determine the drug resistance to first- and second-line anti-TB drugs and to identify the mutations associated with the resistance. RESULTS: Of the 93 patients, 82.7% were new TB cases, 86% were male, and 73% had extrapulmonary TB. Most patients (94%) with a CD4 T-lymphocyte count <350 cells/mm3 were associated with extrapulmonary TB (p <0.0001), whilst most patients (78%) with a CD4 T-lymphocyte count >350 cells/mm3 were associated with pulmonary TB (p = 0.0011). Eighty-two strains were pan-susceptible, four mono-resistant, four poly-resistant, two multidrug-resistant, and one was extensively drug-resistant. In the rifampicin-resistant strains, rpoB S531L was the mutation most frequently identified, whereas the inhA C15T and katG S315T1 mutations were present in isoniazid-resistant strains. The extensively drug-resistant strain also contained the mutation gyrA D94A. CONCLUSIONS: These data highlight the need to promptly diagnose the drug resistance of M. tuberculosis among all HIV-infected patients by systematically offering access to first- and second-line drug susceptibility testing and to tailor the treatment regimen based on the resistance patterns to reduce the number of deaths in HIV-infected patients.

Clinical characteristics, bacterial coinfections and outcomes in COVID-19-associated pulmonary aspergillosis in a third-level Mexican hospital during the COVID-19 pre-vaccination era.

BACKGROUND: Damage due to respiratory viruses increases the risk of bacterial and fungal coinfections and superinfections. High rates of invasive aspergillosis are seen in severe influenza and COVID-19. This report describes CAPA cases diagnosed during the first wave in the biggest reference centre for severe COVID-19 in Mexico. OBJECTIVES: To describe the clinical, microbiological and radiological characteristics of patients with invasive pulmonary aspergillosis associated with critical COVID-19, as well as to describe the variables associated with mortality. METHODS: This retrospective study identified CAPA cases among individuals with COVID-19 and ARDS, hospitalised from 1 March 2020 to 31 March 2021. CAPA was defined according to ECMM/ISHAM consensus criteria. Prevalence was estimated. Clinical and microbiological characteristics including bacterial superinfections, antifungal susceptibility testing and outcomes were documented. RESULTS: Possible CAPA was diagnosed in 86 patients among 2080 individuals with severe COVID-19, representing 4.13% prevalence. All CAPA cases had a positive respiratory culture for Aspergillus species. Aspergillus fumigatus was the most frequent isolate (64%, n = 55/86). Seven isolates (9%, n = 7/80) were resistant to amphotericin B (A. fumigatus n = 5/55, 9%; A. niger, n = 2/7, 28%), two A. fumigatus isolates were resistant to itraconazole (3.6%, n = 2/55). Tracheal galactomannan values ranged between 1.2 and 4.05, while serum galactomannan was positive only in 11% (n = 3/26). Bacterial coinfection were documented in 46% (n = 40/86). Gram negatives were the most frequent cause (77%, n = 31/40 isolates), from which 13% (n = 4/31) were reported as multidrug-resistant bacteria. Mortality rate was 60% and worse prognosis was seen in older persons, high tracheal galactomannan index and high HbA1c level. CONCLUSIONS: One in 10 individuals with CAPA carry a resistant Aspergillus isolate and/or will be affected by a MDR bacteria. High mortality rates are seen in this population.

Giant Cell Tumor of the Thoracic Spine in a Young Female Patient in a México City Spine Center: A Case Report.

BACKGROUND Giant cell tumors of the bone (GCTB) are rare, locally aggressive benign neoplasms that primarily occur in the metaphyses of long bones. In less than 2% of cases, GCTBs arise in the spine, predominantly below the sacrum. We report the clinical manifestations, diagnostic approach, and successful surgical treatment of a patient with a GCTB of the thoracic spine. CASE REPORT A 21-year-old female patient presented to the Emergency Department with back pain and upper motor neuron syndrome. A thorough clinical and imaging examination revealed a tumor and pathological fracture of the T7 vertebra. Histopathological analysis confirmed the diagnosis of a GCTB. The tumor was successfully excised surgically via a posterior thoracic approach, including bilateral decompressive laminectomy, lateral costotransversectomy, and posterior corpectomy, followed by transpedicular instrumentation of the T5-T6 and T8-T9 vertebrae, and anterior arthrodesis with an autologous graft. The patient also received adjuvant radiotherapy. One year later, the patient had no signs of recurrence or physical limitations. CONCLUSIONS GCTBs located in the thoracic spine are uncommon and pose a significant challenge for healthcare professionals due to their non-specific clinical manifestations and the need for a multidisciplinary approach to their management. This case highlights the diagnostic and therapeutic implications of a GCTB of the thoracic spine and describes a successful surgical strategy resulting in complete recovery. The presented case adds to the limited published literature on GCTBs in this unusual location and further elaborates on their presentation and management.

Diagnostic performance of the Qiaprep amp Viral RNA UM kit for the detection of COVID-19 compared to RT-PCR.

Background: RT-PCR is the currently recommended laboratory method for diagnosing acute SARS-CoV-2 infection. Nevertheless, to carry out this assay, numerous manual steps are necessary, but they are long lasting and error-prone. A new sample preparation solution was launched, the Qiaprep & amp Viral RNA UM kit, that combines a short, liquid-based sample preparation with one-step RT-PCR amplification and detection of SARS-CoV-2. Such alternative allows reducing the handling of samples and obtaining a result in a shorter period of time. The objective of the study was to compare the performance of the kit with RT-PCR. Methods: A prospective trial was carried out in the clinical microbiology laboratory of a tertiary care hospital. The pharyngeal and nasopharyngeal swabs included in the study were taken from patients who underwent medical consultation because compatible COVID-19 symptoms. Samples were processed simultaneously for the reference RT-PCR and by the QIA P&A kit. Results: 190 samples were included in the clinical trial. The reference RT-PCR method indicated that 125 (66%) samples, out of the 190, were positive. The QIA P&A kit showed 112 positive samples for SARS-CoV-2. The QIA P&A kit has a sensitivity of 86% to detect SARS-CoV-2 and a 100% specificity, the positive predictive value was of 96%, the negative predictive value 78%, and the obtained Kappa value was 0,76. QIA P&A kit showed a lower mean cycle threshold compared with the diagnostic standard, with a statistically significant difference (p < 0.05). Conclusion: The QIA P&A kit has an acceptable, yet not optimal performance for sample preparation and amplification of SARS-CoV-2 and further studying is required for it to be validated as a cost-effective, rapid diagnostic method for detecting infections.

Low sensitivity of the COVID-19 antigen test (PANBIO™ COVID-19 Ag rapid test) to detect asymptomatic infections in health personnel of the National Institute of Respiratory Diseases.

Background: COVID-19 requires an early diagnosis to optimize management and limit transmission. SARS-CoV-2 is able to spread effectively. Infected asymptomatic individuals have been found to be contagious. RT-qPCR is the currently recommended laboratory method for diagnosing acute infection. However, rapid antigen detection (RAD) tests are not only fast, but require less specialized training. The possibility of using RAD tests to identify asymptomatic patients is attractive, as it could effectively contribute to minimizing the hospital spread of SARS-CoV-2. The objective of the study was to determine the performance of RAD vs. RT-qPCR for the detection of asymptomatic cases in INER health personnel. Methods: In order to follow WHO guidelines, generalized tests, a test station for health care workers was implemented on demand. A rapid test was carried out and a second sample was taken to be processed by RT-qPCR. With the results of both tests we conducted a retrospective study. Sensitivity, specificity, positive predictive value, negative predictive value and negative likelihood ratios were calculated. Results: A total of 1640 RAD tests were performed in health care workers (mean age was 39, 69, 47% with a self-reported comorbidity). Participants provided 1,640 valid RAD/RT-qPCR test pairs with 2% testing positive via RT-qPCR. 12 RAD samples were positive for SARS-CoV-2. Overall sensitivity of the PANBIO ™ COVID-19 Ag Rapid Test test was 35.2%. Conclusions: RADs are not recommended for the detection of asymptomatic cases due to low performance.

Clinical and Virological Features of Patients Hospitalized with Different Types of COVID-19 Vaccination in Mexico City.

Coronavirus disease 2019 (COVID-19) vaccines effectively protect against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity remain poorly understood. This work aimed to compare COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in Mexico City. From March to September 2021, clinical, demographic characteristics, and viral variants were obtained from 1014 individuals with a documented SARS-CoV-2 infection. We compared unvaccinated, partially vaccinated, and fully vaccinated patients, stratifying by age groups. We also fitted multivariate statistical models to evaluate the impact of vaccination status, SARS-CoV-2 lineages, vaccine types, and clinical parameters. Most hospitalized patients were unvaccinated. In patients over 61 years old, mortality was significantly higher in unvaccinated compared to fully vaccinated individuals. In patients aged 31 to 60 years, vaccinated patients were more likely to be outpatients (46%) than unvaccinated individuals (6.1%). We found immune disease and age above 61 years old to be risk factors, while full vaccination was found to be the most protective factor against in-hospital death. This study suggests that vaccination is essential to reduce mortality in a comorbid population such as that of Mexico.

Genetic Analysis of SARS-CoV-2 Variants in Mexico during the First Year of the COVID-19 Pandemic.

During the first year of the SARS-CoV-2 pandemic in Mexico, more than two million people were infected. In this study, we analyzed full genome sequences from 27 February 2020 to 28 February 2021 to characterize the geographical and temporal distribution of SARS-CoV-2 lineages and identify the most common circulating lineages during this period. We defined six different geographical regions with particular dynamics of lineage circulation. The Northeast and Northwest regions were the ones that exhibited the highest lineage diversity, while the Central south and South/Southeast regions presented less diversity with predominance of a certain lineage. Additionally, by late February 2021, lineage B.1.1.519 represented more than 89% of all circulating lineages in the country.

Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes.

The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.

Emergence and spread of the potential variant of interest (VOI) B.1.1.519 of SARS-CoV-2 predominantly present in Mexico.

SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report the identification of a potential variant of interest, harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B.1.1.519, that rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

Low Incidence and Mortality by SARS-CoV-2 Infection Among Healthcare Workers in a Health National Center in Mexico: Successful Establishment of an Occupational Medicine Program.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthcare workers (HCWs) constitute a population which is significantly affected by SARS-CoV-2 infection worldwide. In Mexico, the Instituto Nacional de Enfermedades Respiratorias (INER) is the principal national reference of respiratory diseases. Aim: To evaluate the efficiency of the INER-POL-TRAB-COVID19 program to mitigate the SARS-CoV-2 infection risk among the INER-healthcare workers (INER-HCW). Methods: Currently, the INER has 250 beds and 200 respiratory ventilators to support COVID-19 patients in critical condition. On March 1st, 2020, the INER-POL-TRAB-COVID19 program was launched to mitigate the SARS-CoV-2 infection risk among the INER-HCW. Findings: From March 1st to October 1st, 2020, 71.5% of INER-HCWs were tested for SARS-CoV-2 infection, and 77% of them were frontline workers. Among the tested INER-HCWs, 10.4% were positive for SARS-CoV-2 infection. Nonetheless, nosocomial infection represented only 3.8% of the cases and the mortality was null. Fifty-three of INER-HCWs positive to SARS-CoV-2 had a negative test 42-56 days post-diagnosis and were returned to service. Finally, although a change in the PPE implemented on May 11th, 2020, the incidence of SARS-CoV-2 infection was not affected. Conclusion: INER has a lower incidence of HCWs infected with SARS-CoV-2 as compared to the mean of the national report. The implementation of the INER-POL-TRAB-COVID19 program is efficient to decrease the risk of infection among the HCWs. Our findings suggest that the implementation of a similar program at a national level can be helpful to provide a safe environment to HCWs and to prevent the collapse of health institutions.

A 34-Year-Old Woman with a Diamniotic Dichorionic Twin Pregnancy Presenting with an Erythematous and Papular Skin Rash Associated with SARS-CoV-2 Infection.

BACKGROUND The damage caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has been extensive. Pregnant women are a group requiring special attention in medicine given the anatomical and physiological changes that occur during pregnancy. Skin rash is commonly associated with pregnancy, with the most common form of an erythematous maculopapular rash being pruritic urticarial papules and plaques of pregnancy. Skin rash is also an increasingly reported initial presentation in patients with coronavirus disease 2019 (COVID-19), due to infection with SARS-CoV-2. CASE REPORT A 34-year-old woman with a diamniotic dichorionic twin pregnancy presented with clinical picture characterized by dermatological manifestations, namely an erythematous and papular skin rash associated with SARS-CoV-2 infection. A real-time reverse transcription-polymerase chain reaction (GeneFinder) test was positive for SARS-CoV-2 detection. CONCLUSIONS Ten months after the onset of this pandemic, there is no conclusive evidence indicating that pregnant women represent a sector more or less vulnerable to severe forms of COVID-19 than the general population. This report has highlighted the importance of performing a reliable diagnostic test for SARS-CoV-2 infection in patients who present with a skin rash, particularly pregnant women.

COVID-19 and Tuberculosis Coinfection in a 51-Year-Old Taxi Driver in Mexico City.

BACKGROUND Coinfection with severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) and Mycobacterium tuberculosis (MBT) has been reported, albeit rarely, in various parts of the world and has received attention from health systems because up to one-third of the world's population has been infected with SARS-CoV-2. Mexico was not included in the first-ever report on a global cohort of patients with this coinfection. We report on a case of SARS-CoV-2/MBT coinfection in a 51-year-old taxi driver from Mexico City that underscores the importance of rapid and accurate laboratory testing, diagnosis, and treatment. CASE REPORT We present the case of a man in the sixth decade of life who was admitted to the National Institute of Respiratory Diseases (INER) with a diagnosis of COVID-19 pneumonia, which was confirmed by nasopharyngeal exudate using real-time polymerase chain reaction (RT-PCR) for the identification of SARS-CoV-2. Findings from imaging studies suggested that the patient might be coinfected with MBT. That suspicion was confirmed with light microscopy of a sputum sample after Ziehl-Neelsen staining and when a Cepheid Xpert MTB/RIF assay, an automated semi-quantitative RT-PCR assay, failed to detect rifampicin resistance. The patient was discharged from the hospital 10 days later. CONCLUSIONS The present report underscores the importance of using validated molecular diagnostic tests to identify coinfections in areas where there is a high prevalence of other causes of pneumonia, such as MBT, as a way to improve clinical outcomes in patients during the COVID-19 pandemic. While it is imperative to control the COVID-19 pandemic, the medical community must not forget about the other pandemics to which populations are still prey, and tuberculosis is one of them. We must remain alert to any clinical subtleties so as to ensure timely and accurate diagnosis and stay one step ahead of COVID-19.

Immunological Evaluation for Personalized Interventions in Children with Tuberculosis: Should It Be Routinely Performed?

Childhood tuberculosis (TB) is a significant public health problem and the ninth leading cause of death worldwide. Progression of Mycobacterium tuberculosis infection to active disease depends on mycobacterial virulence, environmental diversity, and host susceptibility and immune response. In children, malnutrition and immaturity of the immune system contribute to an inadequate immune response. Coinfections, though rarely described in TB, might be associated with host immune deficiencies. Here, we describe the immunological evaluation of eight pediatric patients infected with a member of the M. tuberculosis complex, most of them with concomitant pulmonary infections (bacteria, viruses, or fungi). We assessed the functionality of several innate immunity receptors, IL-12 receptor, and IFN-γ receptor, as well as the antioxidant levels (glutathione), which are essential mechanisms for fighting intracellular pathogens such as M. tuberculosis. This study is aimed at developing a thorough immunological evaluation of patients with TB and a coinfection.

A 65-Year-Old Woman with a History of Type 2 Diabetes Mellitus and Hypertension and a 15-Day History of Dry Cough and Fever Who Presented with Acute Renal Failure Due to Infection with SARS-Cov-2.

BACKGROUND Acute kidney injury is one of the most common complications in patients infected with SARS-CoV-2, occurring in up to 7% of cases and increasing to 23% in patients treated in the Intensive Care Unit (ICU). The objective of this report was to describe the clinical case of a patient infected by SARS-CoV-2 who developed acute renal injury, probably secondary to this infection. CASE REPORT On 1 April 2020, a 65-year-old woman presented to the emergency service of the National Institute of Respiratory Diseases, Mexico City, with a 15-day history of dry cough and subjective fever. Finally, the following diagnoses were integrated: Acute renal injury of etiology to be determined (acute chronic kidney disease secondary to T2DM vs. acute renal injury by SARS-CoV-2) and COVID-19. The patient had a typical presentation of severe COVID-19, evidencing all the risk and severity factors for this disease. However, after being admitted to the hospital, she showed evidence of acute renal injury. Although the renal injury may have been due to microangiopathic damage caused by chronic hypertension and diabetes, it is imperative to consider the possibility that such exacerbation contributes to SARS-CoV-2 infection or synergy of multiple factors. CONCLUSIONS Every aspect of this pandemic remains unclear. The formulation of hypotheses to explain the physiopathological mechanisms by which this new virus can cause mortality in infected patients may help reduce mortality rates and control the pandemic itself.

Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.

Full genome sequence of the first SARS-CoV-2 detected in Mexico.

SARS-CoV-2 was first detected in the city of Wuhan, Hubei Province, China. In this report, we describe the complete genome sequence of the first imported SARS-CoV-2, detected in a Mexican patient who had traveled to Bergamo, Italy. Phylogenetic analysis showed that this isolate belongs to subclade A2a (lineage G) and is closely related to isolates from Finland, Germany and Brazil, all of which were from patients with a history of travel to Italy. This is the first report of the complete genome sequence of this virus in Mexico.

High performance of rapid influenza diagnostic test and variable effectiveness of influenza vaccines in Mexico.

OBJECTIVES: To evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines' effectiveness (VE) during an outbreak setting. METHODS: We compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses. RESULTS: We enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0-54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza. CONCLUSIONS: The RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.