Mental health and adherence to antiretroviral therapy among Mexican people living with HIV during the COVID-19 pandemic.

BACKGROUND: The mental health and medical follow-up of people living with HIV (PLWH) have been disrupted by the COVID-19 pandemic. The objectives of this study were to assess anxiety, depression and substance use in Mexican PLWH during the pandemic; to explore the association of these symptoms with adherence to antiretroviral therapy (ART), and to compare patients with and without vulnerability factors (low socioeconomic level, previous psychological and/or psychiatric treatment). METHODS: We studied 1259 participants in a cross-sectional study, PLWH receiving care at the HIV clinic in Mexico City were contacted by telephone and invited to participate in the study. We included PLWH were receiving ART; answered a structured interview on sociodemographic data and adherence to ART; and completed the psychological instruments to assess depressive and anxiety symptoms and substance use risk. Data collection was performed from June 2020 to October 2021. RESULTS: 84.7% were men, 8% had inadequate ART adherence, 11% had moderate-severe symptoms of depression, and 13% had moderate-severe symptoms of anxiety. Adherence was related to psychological symptoms (p < 0.001). Vulnerable patients were more likely to be women, with low educational level and unemployed (p < 0.001). CONCLUSIONS: It is important to address mental health of PLWH during the COVID-19 pandemic, with special attention to the most vulnerable individuals. Future studies are needed to understand the relationship between mental health and ART adherence.

SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients.

Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that in vitro exposure to SARS-CoV-2 activates the expression of the human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) in peripheral blood mononuclear cells from a subset of healthy donors, in ACE2 receptor and infection-independent manner. Plasma and/or sera of 221 COVID-19 patients from different cohorts, infected with successive SARS-CoV-2 variants including the Omicron, had detectable HERV-W ENV, which correlated with ENV expression in T lymphocytes and peaked with the disease severity. HERV-W ENV was also found in postmortem tissues of lungs, heart, gastrointestinal tract, brain olfactory bulb, and nasal mucosa from COVID-19 patients. Altogether, these results demonstrate that SARS-CoV-2 could induce HERV-W envelope protein expression and suggest its involvement in the immunopathogenesis of certain COVID-19-associated syndromes and thereby its relevance in the development of personalized treatment of patients.

Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury.

In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1ß were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.

Longitudinal Characterization of a Neutralizing and Total Antibody Response in Patients with Severe COVID-19 and Fatal Outcomes.

The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations in severe COVID-19 cases. Until now, the importance of developing a neutralizing antibody response in the acute phase and its relationship with progression to severe disease or fatal outcome among hospitalized patients remains unclear. In this study, we aim to characterize and compare longitudinally the primary humoral immune host response in the early stages of the disease, looking for an association between neutralization, antibody titers, infective viral lineage, and the clinical outcome in hospitalized and non-hospitalized patients. A total of 111 patients admitted at INER from November 2021 to June 2022 were included. We found that patients with negative or low neutralization showed a significant reduction in survival probability compared to patients with medium or high neutralization. We observed a significant decrease in the median of neutralization in patients infected with viral variants with changes in RBD of the spike protein. Our results suggest that developing an early and robust neutralizing response against SARS-CoV-2 may increase survival probability in critical patients.

The Alpha Variant (B.1.1.7) of SARS-CoV-2 Failed to Become Dominant in Mexico.

During the coronavirus disease 2019 (COVID-19) pandemic, the emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the United Kingdom in September 2020, was well documented in different areas of the world and became a global public health concern because of its increased transmissibility. The B.1.1.7 lineage was first detected in Mexico during December 2020, showing a slow progressive increase in its circulation frequency, which reached its maximum in May 2021 but never became predominant. In this work, we analyzed the patterns of diversity and distribution of this lineage in Mexico using phylogenetic and haplotype network analyses. Despite the reported increase in transmissibility of the B.1.1.7 lineage, in most Mexican states, it did not displace cocirculating lineages, such as B.1.1.519, which dominated the country from February to May 2021. Our results show that the states with the highest prevalence of B.1.1.7 were those at the Mexico-U.S. border. An apparent pattern of dispersion of this lineage from the northern states of Mexico toward the center or the southeast was observed in the largest transmission chains, indicating possible independent introduction events from the United States. However, other entry points cannot be excluded, as shown by multiple introduction events. Local transmission led to a few successful haplotypes with a localized distribution and specific mutations indicating sustained community transmission. IMPORTANCE The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021. In this work, we analyzed the distribution of B.1.1.7 in Mexico using phylogenetic and haplotype network analyses. Our results show that the states with the highest prevalence of B.1.1.7 (around 30%) were those at the Mexico-U.S. border, which also exhibited the highest lineage diversity, indicating possible introduction events from the United States. Also, several haplotypes were identified with a localized distribution and specific mutations, indicating that sustained community transmission occurred in the country.

Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease.

BACKGROUND: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. METHODS: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. RESULTS: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. CONCLUSIONS: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

POSTERIOR SEGMENT OCULAR FINDINGS IN CRITICALLY ILL PATIENTS WITH COVID-19.

PURPOSE: To describe ophthalmological fundoscopic findings in patients with COVID-19 admitted to the intensive care unit of the largest third-level referral center for COVID-19 in Mexico City. METHODS: In this cross-sectional single-center study, consecutive patients admitted to the intensive care unit with a diagnosis of COVID-19 underwent fundus examination with an indirect ophthalmoscope. Clinical photographs were taken using a posterior-pole camera. We explored the association between ocular manifestations and demographic characteristics, inflammatory markers, hemodynamic factors, and comorbidities. RESULTS: Of 117 patients examined, 74 were men; the median age was 54 years (range: 45-63 years). Forty-two patients had ophthalmological manifestations (unilateral in 23 and bilateral in 19), and 10 of these patients had more than one ophthalmological manifestation. Ocular findings were papillitis (n = 13), cotton wool spots (n = 12), retinal hemorrhages (n = 5), retinal nerve fiber layer edema (n = 8), macular whitening (n = 5), retinal vascular tortuosity (n = 4), papillophlebitis (n = 3), central retinal vein occlusion (n = 1), and branch retinal vein occlusion (n = 1). Ocular fundus manifestations were not associated with demographic characteristics, inflammatory markers, hemodynamic factors, or comorbidities. CONCLUSION: More than one-third of patients with severe COVID-19 had ophthalmological manifestations. The most frequent fundoscopic findings were optic nerve inflammation, microvasculature occlusion, and major vascular occlusions. We recommend long-term follow-up to prevent permanent ocular sequelae.

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.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

Antibody and Memory B-Cell Immunity in a Heterogeneously SARS-CoV-2-Infected and -Vaccinated Population.

Global population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accumulating through heterogeneous combinations of infection and vaccination. Vaccine distribution in low- and middle-income countries has been variable and reliant on diverse vaccine platforms. We studied B-cell immunity in Mexico, a middle-income country where five different vaccines have been deployed to populations with high SARS-CoV-2 incidences. Levels of antibodies that bound a stabilized prefusion spike trimer, neutralizing antibody titers, and memory B-cell expansion correlated with each other across vaccine platforms. Nevertheless, the vaccines elicited variable levels of B-cell immunity, and the majority of recipients had undetectable neutralizing activity against the recently emergent omicron variant. SARS-CoV-2 infection, experienced before or after vaccination, potentiated B-cell immune responses and enabled the generation of neutralizing activity against omicron and SARS-CoV for all vaccines in nearly all individuals. These findings suggest that broad population immunity to SARS-CoV-2 will eventually be achieved but by heterogeneous paths. IMPORTANCE The majority of studies on SARS-CoV-2 vaccine-elicited immunity and immune evasion have focused on single vaccines corresponding to those distributed in high-income countries. However, in low- and middle-income countries, vaccine deployment has been far less uniform. It is therefore important to determine the levels of immunity elicited by vaccines that have been deployed globally. Such data should help inform policy. Thus, this paper is very much a "real-world" study that focuses on a middle-income country, Mexico, in which five different vaccines based on mRNA, adenovirus, and inactivated-virus platforms have been extensively deployed, while (as documented in our study) SARS-CoV-2 variants with increasing degrees of immune evasiveness have propagated in the Mexican population, culminating in the recent emergence of B.1.1.529 (omicron).

Dominance of Three Sublineages of the SARS-CoV-2 Delta Variant in Mexico.

In this study, we analyzed the sequences of SARS-CoV-2 isolates of the Delta variant in Mexico, which has completely replaced other previously circulating variants in the country due to its transmission advantage. Among all the Delta sublineages that were detected, 81.5 % were classified as AY.20, AY.26, and AY.100. According to publicly available data, these only reached a world prevalence of less than 1%, suggesting a possible Mexican origin. The signature mutations of these sublineages are described herein, and phylogenetic analyses and haplotype networks are used to track their spread across the country. Other frequently detected sublineages include AY.3, AY.62, AY.103, and AY.113. Over time, the main sublineages showed different geographical distributions, with AY.20 predominant in Central Mexico, AY.26 in the North, and AY.100 in the Northwest and South/Southeast. This work describes the circulation, from May to November 2021, of the primary sublineages of the Delta variant associated with the third wave of the COVID-19 pandemic in Mexico and highlights the importance of SARS-CoV-2 genomic surveillance for the timely identification of emerging variants that may impact public health.

Development and Testing of a Low-Cost Inactivation Buffer That Allows for Direct SARS-CoV-2 Detection in Saliva.

Massive testing is a cornerstone in efforts to effectively track infections and stop COVID-19 transmission, including places with good vaccination coverage. However, SARS-CoV-2 testing by RT-qPCR requires specialized personnel, protection equipment, commercial kits, and dedicated facilities, which represent significant challenges for massive testing in resource-limited settings. It is therefore important to develop testing protocols that are inexpensive, fast, and sufficiently sensitive. Here, we optimized the composition of a buffer (PKTP), containing a protease, a detergent, and an RNase inhibitor, which is compatible with the RT-qPCR chemistry, allowing for direct SARS-CoV-2 detection from saliva without extracting RNA. PKTP is compatible with heat inactivation, reducing the biohazard risk of handling samples. We assessed the PKTP buffer performance in comparison to the RNA-extraction-based protocol of the US Centers for Disease Control and Prevention in saliva samples from 70 COVID-19 patients finding a good sensitivity (85.7% for the N1 and 87.1% for the N2 target) and correlations (R = 0.77, p < 0.001 for N1, and R = 0.78, p < 0.001 for N2). We also propose an auto-collection protocol for saliva samples and a multiplex reaction to minimize the PCR reaction number per patient and further reduce costs and processing time of several samples, while maintaining diagnostic standards in favor of massive testing.

Seroepidemiology of SARS-CoV-2 in healthcare personnel working at the largest tertiary COVID-19 referral hospitals in Mexico City.

INTRODUCTION: We performed a longitudinal SARS-CoV-2 seroepidemiological study in healthcare personnel of the two largest tertiary COVID-19 referral hospitals in Mexico City. METHODS: All healthcare personnel, including staff physicians, physicians in training, nurses, laboratory technicians, researchers, students, housekeeping, maintenance, security, and administrative staff were invited to voluntarily participate, after written informed consent. Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. RESULTS: A total of 883 participants (out of 3639 registered employees) contributed with at least one blood sample. The median age was 36 years (interquartile range: 28-46) and 70% were women. The most common occupations were nurse (28%), physician (24%), and administrative staff (22%). Two hundred and ninety participants (32.8%) had a positive-test result in any of the visits, yielding an overall adjusted prevalence of 33.5% for the whole study-period. Two hundred and thirty-five positive tests were identified at the baseline visit (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.54-3.25; laboratory technician vs. physician: aOR = 4.38, 95% CI: 1.75-10.93) and community (municipality of residence Xochimilco vs. Tlalpan: aOR = 2.03, 95% CI: 1.09-3.79) risk-factors. The incidence rate was 3.0 cases per 100 person-months. Incident cases were associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR = 2.45, 95% CI: 1.21-5.00). CONCLUSIONS: We observed that between October 2020 and June 2021, healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City had similar level of exposure to SARS-CoV-2 than the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk. Our observations are consistent with successful occupational medicine programs for SARS-CoV-2 infection control in the participating institutions but suggest the need to strengthen mitigation strategies in the community.

Clinical Follow-Up in People Living with HIV During the COVID-19 Pandemic in Mexico.

Clinical follow-up in people living with HIV (PLWH) has individual and public health implications. The objectives of this study were to measure variables related to follow-up failures, identify self-reported reasons to maintain adequate follow-up or for having follow-up failures, and know how the pandemic influenced patients' clinical follow-up. Participants were PLWH receiving HIV-health care at a hospital-based clinic in Mexico City which became an exclusive COVID-19 health service. Participants completed a telephone semi-structured interview and online psychological questionnaires. Lower educational and socioeconomic level, longer times of transportation to the clinic, being attended by different doctors, detectable viral load, having previous dropouts, inadequate antiretroviral adherence, and less HIV knowledge were related to follow-up failures. COVID-19 had a significant negative impact, but it also had positive repercussions for patients with adequate follow-up. These results could help develop effective psychosocial programs and improve healthcare in institutions to facilitate patient retention.

RESUMEN: El seguimiento clínico en las personas que viven con VIH (PVV) tiene implicaciones individuales y de salud pública. Los objetivos de este estudio fueron medir las variables relacionadas con las fallas en el seguimiento, identificar las razones reportadas para mantener un seguimiento adecuado o para tener fallas en el seguimiento, y conocer cómo la pandemia influyó en el seguimiento clínico de los individuos. Los participantes eran PVV que recibían atención médica para el VIH en una clínica hospitalaria de Ciudad de México que se convirtió en un servicio exclusivo para COVID-19. Los participantes completaron una entrevista semiestructurada por teléfono y cuestionarios psicológicos en línea. El nivel educativo y socioeconómico más bajo, mayor tiempo de transporte a la clínica, falta de continuidad del médico, carga viral detectable, tener abandonos previos, inadecuada adherencia al tratamiento antirretroviral y menor conocimiento del VIH se relacionaron con las fallas en el seguimiento. La pandemia demostró tener un importante impacto negativo, pero también tuvo repercusiones positivas para los pacientes con un seguimiento adecuado. Estos resultados son importantes para desarrollar programas psicosociales eficaces y mejorar la atención sanitaria en las instituciones para facilitar la retención de los pacientes.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Genomic Characterization of SARS-CoV-2 Isolated from Patients with Distinct Disease Outcomes in Mexico.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has shown a wide spectrum of clinical manifestations ranging from asymptomatic infections to severe disease and death. Pre-existing medical conditions and age have been mainly linked to the development of severe disease; however, the potential association of viral genetic characteristics with different clinical conditions remains unclear. SARS-CoV-2 variants with increased transmissibility were detected early in the pandemics, and several variants with potential relevance for public health are currently circulating around the world. In this study, we characterized 57 complete SARS-CoV-2 genomes during the exponential growth phase of the early epidemiological curve in Mexico, in April 2020. Patients were categorized under distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors, the patients were less than 60 years old and with no diagnosed comorbidities A trait-association phylogenomic approach was used to explore genotype-phenotype associations, represented by the co-occurrence of mutations, disease severity outcome categories, and clusters of Mexican sequences. Phylogenetic results revealed a higher genomic diversity compared to the initial viruses detected during the early stage of the local epidemic. We identified a total of 90 single nucleotide variants compared to the Wuhan-Hu-1 genome, including 54 nonsynonymous mutations. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors. IMPORTANCE The genetic association of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with different clinical conditions remains unclear and needs further investigation. In this study, we characterized 57 complete SARS-CoV-2 genomes from patients in Mexico with distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors the patients were less than 60 years old and with no diagnosed comorbidities. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors.

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.

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.

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.