Clinical and molecular characterization of children and adults with respiratory bocavirus infection in Mexico: a cross-sectional nested study within the ILI002 prospective observational study.

Background: Human Bocaviruses (HBoV) can cause acute respiratory tract infections. High coinfection rates cloud its pathogenicity. This study sought to describe the clinical features of HBoV1 disease in children and adults with Influenza-like illness (ILI), exploring associations between viral load, clinical features, and seasonality. Methods: Patients who tested positive for HBoV1 by polymerase chain reaction, enrolled from April 2010 to March 2014 in the ILI002 prospective observational cohort study were included in this cross-sectional nested study. Participants were included in ILI002 if they presented with signs and/or symptoms suggestive of influenza-like illness. Samples were tested for viral load, and NP1 and VP1/VP2 phylogenetic analyses, except for the samples lacking suitable and viable clinical material for genotyping. Findings: We identified HBoV1 in 157 (2.8%) of participants. Prevalence was 4.5% in children and 1.8% in adults. Single HBoV1 detection occurred in 41.1% and 46.3% of children and adults, respectively. Children commonly experienced fever (83.3%), cough with sputum (74.4%), and shortness of breath (72.2%). In the multivariate analysis of children, significant positive associations were detected between viral loads and age (0.20 [95% CI: 0.07, 0.33]), and the presence of fever (2.64 [95% CI: 1.35, 3.94]), nasal congestion (1.03 [95% CI: 0.07, 1.99]), dry cough (1.32 [95% CI: 0.42, 2.22]), chest congestion (1.57 [95% CI: 0.33, 2.80]), red eyes (1.25 [95% CI: 0.35, 2.14]), cough with sputum (1.79 [95% CI: 0.80, 2.78]), and other signs and symptoms such as chills, dizziness, and diaphoresis (1.73 [95% CI: 0.19, 3.27]). In contrast, significant negative associations were found between viral loads and percent neutrophils on the blood count (-0.04 [95% CI: -0.06, -0.02]), fatigue (-1.60 [95% CI: -2.46, -0.74]) and the presence of other symptoms or signs, including adenopathy and rash (-1.26 [95% CI: -2.31, -0.21]). Adults commonly experienced sore throat (73.1%), fatigue (77.4%), and headache (73.1%). In the multivariate analysis of adults, significant positive associations were detected between viral load and body mass index (0.13 [95% CI: 0.04, 0.21]), and the presence of confusion (1.54 [95% CI: 0.55, 2.53]), and sore throat (1.03 [95% CI: 0.20, 1.85]), and significant negative associations were detected between viral load and chest congestion (-1.16 [95% CI: -2.07, -0.24]). HBoV1 was detected throughout the year irrespective of season, temperature, and humidity. Interpretation: This study demonstrated the importance of detecting HBoV1 in patients with influenza-like illness either as single infection or co-infection, in both adults and children, and improves the characterization of HBoV1 seasonality, clinical features, and viral load. Phylogenetic analyses show a high conservation. Funding: The Mexican Emerging Infectious Diseases Clinical Research Network (LaRed), CONACYT (Fondo Sectorial SSA/IMSS/ISSSTE, Projects No. 71260 and No. 127088), Fondos federales no. HIM/2015/006, NIAID, NIH through a contract with Westat, Inc. (HHSN2722009000031, HHSN27200002), NCI, NIH (75N91019D00024, 75N91019F00130). Additional information at the end of the manuscript.

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.

Predictors of Poor Outcomes in Young Non-Comorbid Patients with COVID-19.

Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objectives: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV. (Rev Invest Clin. 2022;74(5):268-75).

Predictors of poor outcomes in young non-comorbid patients with COVID-19

ABSTRACT Background: Prognostic factors in previously healthy young patients with COVID-19 remained understudied. Objective: The objective of the study was to identify factors associated with in-hospital death or need for invasive mechanical ventilation (IMV) in young (aged ≤ 65 years) and previously healthy patients with COVID-19. Methods: We conducted a prospective cohort study that included patients admitted with COVID-19. The primary outcome was in-hospital death/need for IMV. Secondary outcomes included need for IMV during follow-up, days on IMV, length of stay (LOS), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and pulmonary embolism (PE). Bivariate and multivariate analyses were performed. Results: Among 92 patients, primary outcome occurred in 16 (17%), death in 12 (13%), need for IMV in 16 (17%), HAP/VAP in 7 (8%), and PE in 2 (2%). Median LOS and IMV duration were 7 and 12 days, respectively. Independent associations were found between the primary outcome and male sex (Adjusted odds ratio [aOR] 7.1, 95%CI 1.1-46.0, p < 0.05), D-dimer levels > 1000ng/mL (aOR 9.0, 95%CI 1.6-49.1, p < 0.05), and RT-PCR Ct-value ≤ 24 on initial swab samples (aOR 14.3, 95%CI 2.0-101.5, p < 0.01). Conclusions: In young and non-comorbid COVID-19 patients, male sex, higher levels of D-dimer, and low SARS-CoV-2 RT-PCR Ct-value on an initial nasopharyngeal swab were independently associated with increased in-hospital mortality or need for IMV.

Significant Rise in SARS-CoV-2 Reinfection Rate in Vaccinated Hospital Workers during the Omicron Wave: A Prospective Cohort Study.

Background: Relatively low SARS-CoV-2 reinfection rates have been reported in vaccinated individuals, but updates considering the Omicron variant are lacking. Objectives: The objective of the study was to provide a current estimate of the SARS-CoV-2 reinfection rate in a highly immunized population. Methods: A prospective cohort of Mexican hospital workers was followed (March 2020-February 2022). Reinfection was defined as the occurrence of two or more episodes of COVID-19 separated by a period of ≥ 90 days without symptoms. The reinfection rate was calculated as the number of reinfection episodes per 100,000 persons per day. Results: A total of 3732 medical consultations were provided to 2700 workers, of whom 1388 (51.4%) were confirmed COVID-19 cases. A total of 73 reinfection cases were identified, of whom 71 (97.3%) had completed their primary vaccination series and 22 (30.1%) had had a booster dose before the second episode. The overall reinfection rate was 23.1 per 100,000 persons per day (as compared to a rate of 1.9 per 100,000 persons per day before the Omicron wave). Conclusions: The SARS-CoV-2 reinfection rate rose significantly during the Omicron wave despite a high primary vaccination coverage rate. Almost one-third of reinfected workers had a vaccine booster ≥ 14 days before the last COVID-19 episode.

Significant Rise in SARS-CoV-2 Reinfection Rate in Vaccinated Hospital Workers during the Omicron Wave: A Prospective Cohort Study

ABSTRACT Background: Relatively low SARS-CoV-2 reinfection rates have been reported in vaccinated individuals, but updates considering the Omicron variant are lacking. Objective: The objective of the study was to provide a current estimate of the SARS-CoV-2 reinfection rate in a highly immunized population. Methods: A prospective cohort of Mexican hospital workers was followed (March 2020-February 2022). Reinfection was defined as the occurrence of two or more episodes of COVID-19 separated by a period of ≥ 90 days without symptoms. The reinfection rate was calculated as the number of reinfection episodes per 100,000 persons per day. Results: A total of 3732 medical consultations were provided to 2700 workers, of whom 1388 (51.4%) were confirmed COVID-19 cases. A total of 73 reinfection cases were identified, of whom 71 (97.3%) had completed their primary vaccination series and 22 (30.1%) had had a booster dose before the second episode. The overall reinfection rate was 23.1 per 100,000 persons per day (as compared to a rate of 1.9 per 100,000 persons per day before the Omicron wave). Conclusions: The SARS-CoV-2 reinfection rate rose significantly during the Omicron wave despite a high primary vaccination coverage rate. Almost one-third of reinfected workers had a vaccine booster ≥ 14 days before the last COVID-19 episode.

Different Clinical Presentations of Human Rhinovirus Species Infection in Children and Adults in Mexico.

Background: Human rhinoviruses (HRVs) are a common cause of influenza-like illness, with the ability to infect the upper and lower respiratory tracts. In this study we aim to describe the clinical and molecular features of HRV infection in Mexican children and adults. Methods: We performed a hospital-based, 4-year multicenter prospective observational cohort study of patients with influenza-like illness. Participants who tested positive for HRV were included. We described demographic, clinical, and laboratory characteristics and the association between HRV types, illness severity, and clinical outcomes. Results: Of the 5662 subjects recruited, 1473 (26%) had HRV; of those, 988 (67.1%) were adults (≥18 years) and 485 (32.9%) were children. One hundred sixty-seven (11.33%) samples were sequenced; 101 (60.5%) were rhinovirus species A (HRV-A), 22 (13.2%) were rhinovirus species B (HRV-B), and 44 (26.3%) were rhinovirus species C (HRV-C). Among children and adults, 30.5% and 23.5%, respectively, were hospitalized (non-intensive care unit [ICU]). The odds of HRV-C are higher than HRV-A for participants in the ICU (compared to outpatient) and when platelets, lymphocytes, white blood cells, and lactate dehydrogenase are increased. The odds of HRV-C are higher than HRV-A and HRV-B with shortness of breath. The odds of HRV-A are higher than HRV-B, and the odds of HRV-B are higher than HRV-C, when mild symptoms like muscle ache and headache occur. Conclusions: Rhinoviruses are a common cause of influenza-like illness. It is necessary to improve the surveillance, testing, and species identification for these viruses to understand different clinical presentations and risk factors associated with worse outcomes. Clinical Trials Registration. NCT01418287.

Large-scale screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among healthcare workers: Prevalence and risk factors for asymptomatic and pauci-symptomatic carriers, with emphasis on the use of personal protective equipment (PPE).

Healthcare workers (HCWs) not fulfilling the coronavirus disease 2019 (COVID-19) case definition underwent severe acute respiratory coronavirus virus 2 (SARS-CoV-2) screening. Risk of exposure, adherence to personal protective equipment (PPE), and symptoms were assessed. In total, 2,000 HCWs were screened: 5.5% were positive for SARS-CoV-2 by polymerase chain reaction (PCR). There were no differences in PPE use between SARS-CoV-2-positive and -negative HCWs (adherence, >90%). Nursing and kitchen staff were independently associated with positive SARS-CoV-2 results.

Factors Associated with COVID-19 and Asymptomatic Carriage in Healthcare Workers of a COVID-19 Hospital

ABSTRACT Background: Risk factors for coronavirus disease (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic carriage (AC) in healthcare workers (HCWs) have been scarcely characterized. Objective: The objective of the study was to study factors associated with COVID-19 and AC in HCWs of a COVID-19 academic medical center. Methods: This is a case-control study. Cases were either symptomatic or asymptomatic HCWs with a positive SARS-CoV-2 polymerase chain reaction (PCR) test result between March 16 and May 21 of 2020. Adjusted odds ratios (aOR) were calculated by means of multivariable logistic regression. In addition, each subject was followed for 14 days to inform outcomes. Results: One hundred thirty of 249 (52.2%) symptomatic HCWs had COVID-19; 10 were hospitalized but none died. Of 987 asymptomatic HCWs, 37 (3.7%) were AC; 6 of the remaining 950 asymptomatic HCWs with a negative PCR test result were found to be presymptomatic COVID-19 cases the following 14 days. Nurses were more frequently present in the COVID-19 group (51.5% vs. 37.0%), but multivariable analysis rendered non-significant results. After adjustment for age, comorbidities, and working place, factors found to be associated with AC were: working in wards as a nurse (aOR = 9.19, 95% confidence interval [CI] = 1.05-80.22, p = 0.045), kitchen personnel (aOR = 4.09, 95% CI = 1.55-10.83, p = 0.005), and being a physician (aOR = 0.12, 95% CI = 0.03-0.54, p = 0.006). Conclusions: HCW category was the predominant factor associated with AC of SARS-CoV-2 in this study.

Factors Associated with COVID-19 and Asymptomatic Carriage in Healthcare Workers of a COVID-19 Hospital.

BACKGROUND: Risk factors for coronavirus disease (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic carriage (AC) in healthcare workers (HCWs) have been scarcely characterized. OBJECTIVE: The objective of the study was to study factors associated with COVID-19 and AC in HCWs of a COVID-19 academic medical center. METHODS: This is a case-control study. Cases were either symptomatic or asymptomatic HCWs with a positive SARS-CoV-2 polymerase chain reaction (PCR) test result between March 16 and May 21 of 2020. Adjusted odds ratios (aOR) were calculated by means of multivariable logistic regression. In addition, each subject was followed for 14 days to inform outcomes. RESULTS: One hundred thirty of 249 (52.2%) symptomatic HCWs had COVID-19; 10 were hospitalized but none died. Of 987 asymptomatic HCWs,37 (3.7%) were AC; 6 of the remaining 950 asymptomatic HCWs with a negative PCR test result were found to be presymptomatic COVID-19 cases the following 14 days. Nurses were more frequently present in the COVID-19 group (51.5% vs. 37.0%), but multivariable analysis rendered non-significant results. After adjustment for age, comorbidities, and working place, factors found to be associated with AC were: working in wards as a nurse (aOR = 9.19, 95% confidence interval [CI] = 1.05-80.22, p = 0.045), kitchen personnel (aOR = 4.09, 95% CI = 1.55-10.83, p = 0.005), and being a physician (aOR = 0.12, 95% CI = 0.03-0.54, p = 0.006). CONCLUSIONS: HCW category was the predominant factor associated with AC of SARS-CoV-2 in this study.

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.

High HPgV replication is associated with improved surrogate markers of HIV progression.

BACKGROUND: Human Pegivirus (HPgV) may have a beneficial effect on HIV disease progression in co-infected patients; however, the virologic characteristics of this infection are not well defined. In this study, we determined HPgV viremia prevalence in Mexico and provide new insights to understand HPgV infection and HPgV/HIV co-infection. METHODS: We analyzed and quantified 7,890 serum samples for HPgV viremia by One-Step RT-Real-Time PCR, 6,484 from healthy blood donors and 1,406 from HIV-infected patients. Data on HIV progression were obtained from patients' records. HPgV genotyping was performed in 445 samples by nested PCR of the 5'URT region. Finite Mixture Models were used to identify clustering patterns of HPgV viremia in blood donors and co-infected antiretroviral (ART)-naïve patients. RESULTS: HPgV was detected in 2.98% of blood donors and 33% of HIV patients, with a wide range of viral loads. The most prevalent genotypes were 3 (58.6%)and 2 (33.7%). HPgV viral loads from healthy blood donors and HPgV/HIV+ ART-naïve co-infected patients were clustered into two component distributions, low and high, with a cut-off point of 5.07log10 and 5.06log10, respectively. High HPgV viremia was associated with improved surrogate markers of HIV infection, independent of the estimated duration of HIV infection or HIV treatment. CONCLUSIONS: HPgV prevalence in Mexico was similar to that reported for other countries. The prevalent genotypes could be related to Mexico's geographic location and ethnicity, since genotype 2 is frequent in the United States and Europe and genotype 3 in Asia and Amerindian populations. HPgV viral load demonstrated two patterns of replication, low and high. The more pronounced beneficial response observed in co-infected patients with high HPgV viremia may explain discrepancies found between other studies. Mechanisms explaining high and low HPgV replication should be explored to determine whether the persistently elevated replication depends on host or viral factors.