Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico

The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In Mexico, this subvariant began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in the country. Unlike previous SARS-CoV-2 variants, BA.1 did not acquire local substitutions nor exhibited a geographically distinct circulation pattern in Mexico. However, a regional difference in the speed of the replacement of the Delta variant was observed, as some northern states showed persistence of Delta lineages well into February 2022. Mexican states were divided into four regions (North, Central North, Central South, and Southeast) based on the lineage circulation before the dominance of BA.1 to study possible causes for this difference. For each region, the time to fixation of BA.1, the diversity of Delta sublineages in the weeks preceding BA.1 entry, the population density, and the level of virus circulation during the inter-wave interval were determined. An association between a faster Omicron spread and lower Delta diversity, as well as fewer COVID-19 cases during the Delta-BA.1.x inter-wave period, was observed. For example, the North region exhibited the slowest spread but had the highest diversity of Delta sublineages and the greatest number of inter-wave cases relative to the maximum amount of the virus circulating in the region, whereas the Southeast region showed the opposite. Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics. Nonetheless, if there is a significant difference in the fitness of the variants or the time allowed for the competition is sufficient, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico. Impact statementThe surveillance of lineage circulation of SARS-CoV-2 has helped identify variants that have a transmission advantage and are of concern to public health and to track the virus dispersion accurately. However, many factors contributing to differences in lineage spread dynamics beyond the acquisition of specific mutations remain poorly understood. In this work, a description of BA.1 entry and dispersion within Mexico is presented, and which factors potentially affected the spread rates of the Omicron variant BA.1 among geographical regions in the country are analyzed, underlining the importance of population density, the proportion of active cases, and viral lineage diversity and identity before the entry of BA.1. Data summaryThis work was carried out using data shared through the GISAID initiative. All sequences and metadate are available through GISAID with the accession EPI_SET_220927gw, accession numbers and metadata are also reported in the supplemental material of this article. Epidemiological data was obtained though the Secretaria de Salud website (https://www.gob.mx/salud/documentos/datos-abiertos-152127),

Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in Vaccinated and Unvaccinated Patients in Mexico City

Coronavirus disease 2019 (COVID-19) vaccines are very effective at protecting against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity remain poorly understood. Here we compared COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in Mexico City. From March to September 2021, clinical and demographic characteristics were obtained from 1,014 individuals with a documented SARS-CoV-2 infection, and viral variants were identified in a subset of 386 patients. We compared unvaccinated, partially vaccinated, and fully vaccinated patients, stratifying by age groups. We 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 as risk factors. While fully vaccination was found as 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.

EVALUATION OF A RAPID ANTIGEN TEST FOR SARS-COV-2 IN SYMPTOMATIC PATIENTS AND THEIR CONTACTS: A MULTICENTER STUDY

BACKGROUNDPoint-of-care rapid tests to identify SARS-CoV-2 can be of great help because, in principle, they allow decisions to be made at the site of care for treatment, or for the separation of cohorts avoiding cross-infection, especially in emergency situations. METHODSA cross sectional study in adults requesting care in Emergency Rooms (ER), or the outpatient clinics of referral hospitals for COVID-19, to define the diagnostic characteristics of a rapid antigen test for SARS-CoV-2 (the Abbott Panbio) having as a gold standard the RT-PCR for SARS-CoV-2. Health personnel in a routine situation within an active pandemic in several cities of Mexico performed the tests. RESULTSA total of 1,069 participants with a mean age of 47 years (SD 16 years), 47% with a self-reported comorbidity, and an overall prevalence of a positive RT-PCR test of 45%, were recruited from eight hospitals in Mexico. Overall sensitivity of the Panbio test was 54.4% (95%CI 51-57) with a positive likelihood ratio of 35.7, a negative likelihood ratio of 0.46 and a Receiver-Operating Characteristics curve area of 0.77. Positivity for the rapid test depended strongly on an estimate of the viral load (Cycle threshold of RT-PCR, Ct), and the days of symptoms. With a Ct[≤]25, sensitivity of the rapid test was 0.82 (95%CI, 0.76-0.87). For patients during the first week of symptoms sensitivity was 69.6% (95%CI 66-73). On the other hand, specificity of the rapid test was above 97.8% in all groups. CONCLUSIONSThe Panbio rapid antigen test for SARS-CoV-2 has a good specificity, but due to low and heterogeneous sensitivity in real life, a negative test in a person with suggestive symptoms at a time of community transmission of SARS-CoV-2 requires confirmation with RT-PCR, and after the first week of symptoms, sensitivity decreases considerably.

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

COVID-19 outbreak has caused over 3 million deaths worldwide. Understanding disease pathology 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 particularly important since its known that the respiratory microbiota interacts 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 with healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure across study groups and correlated the results with clinical data. We found differences in diversity and abundance of bacteria between groups, higher levels of dysbiosis in the respiratory microbiota of COVID-19 patients (regardless of severity level), differences in diversity structure among mild, severe, and fatal COVID-19, and the presence of specific bacteria that correlated with clinical variables associated with increased mortality risk. Our data suggest that host-related and environmental factors could be affecting the respiratory microbiota before SARS-CoV-2 infection, potentially compromising the immunological response of the host against disease and promoting secondary bacterial infections. For instance, the high levels of dysbiosis coupled with low microbial structural complexity in the respiratory microbiota of COVID-19 patients, possibly resulted from antibiotic uptake and comorbidities, could have consequences for the host and microbial community level. Altogether, our findings identify the respiratory microbiota as a potential factor associated with COVID-19 severity.

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

SARS-CoV-2 variants have emerged in late 2020 and there are at least three variants of concern (B.1.1.7, B.1.351, P1) reported by WHO. These variants have several substitutions in the Spike protein that affect receptor binding; they present increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we are reporting 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, which rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial.

Health care workers are at high risk of being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Our aim is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) for prophylaxis of COVID19 in health personnel exposed to patients infected by SARS-COV-2. MethodsDouble-blind randomized, placebo-controlled single center clinical trial. Included subjects were health care workers caring for severe COVD19 patients. Main outcome was time to symptomatic SARS-CoV2 infection. Results127 subjects with a confirmed baseline negative RT-PCR SARS-CoV2 test were included in the trial, 62 assigned to HCQ and 65 to placebo. One subject (1.6%) in the HCQ group and 6 (9,2%) subjects in the placebo group developed COVID-19. (Log Rank test p = 0.09). No severe COVID19 cases were observed. The study was suspended because of a refusal to participate and losses to follow up after several trials reported lack of effectiveness of hydroxychloroquine in hospitalized patients with COVID-19. CONCLUSIONAlthough the number of symptomatic infections in health personnel was lower in the HCQ group, the difference was not statistically significant. The trial is underpowered due to the failure to complete the estimated sample size.

Comparison of the clinical characteristics and mortality in ARDS due to COVID-19 versus ARDS due to Influenza A-H1N1pdm09

ImportanceInfection with the SARS-Cov-2 and Influenza A-H1N1 viruses is responsible for the first pandemics of the 21st century. Both of these viruses can cause severe pneumonia and acute respiratory distress syndrome (ARDS). The clinical differences and mortality associated with these two pandemic pneumonias in patients with ARDS are not well established ObjectiveTo compare case-fatality between ARDS-Covid-19 and ARDS-Influenza A (H1N1), adjusting for known prognostic risk factors. Design, Setting and ParticipantsOne hundred forty-seven patients with COVID-19 were compared with 94 with Influenza A-H1N1, all of these were admitted to the intensive care unit of the Referral Center for Respiratory Diseases and COVID-19 in Mexico City and fulfilled the criteria of ARDS. ResultsPatients arrived at the hospital after 9 days of symptoms. Influenza patients had more obesity, more use of Norepinephrine, and higher levels of lactic dehydrogenase and glucose, and fewer platelets and lower PaO2/FIO2. Crude mortality was higher in COVID than in influenza (39% vs. 22%; p = 0.005). In a Cox proportional hazard model, patients with a diagnosis of COVID-19 had a hazard ratio (HR) = 3.7; 95% Confidence Interval [CI] = 1.9-7.4, adjusted for age, gender, sequential organ failure assessment (SOFA) score, ventilatory ratio, and prone ventilation. In the fully adjusted model, the ventilatory ratio and the absence of prone-position ventilation were also predictors of mortality. CONCLUSIONCOVID-19 patients treated in an intensive care unit (ICU) had a 3.7 times higher risk of death than similar patients with Influenza A-H1N1, after adjusting for SOFA score and other relevant risk factors for mortality. QuestionIs the mortality of ARDS associated with Covid-19 greater than that of ARDS associated to influenza H1N1? FindingsIn a Cox proportional hazard model, patients with a diagnosis of COVID-19 had a hazard ratio (HR) = 3.7; 95% Confidence Interval [CI] = 1.9-7.4, adjusted for age, gender, sequential organ failure assessment (SOFA) score. MeaningCOVID-19 patients treated in an intensive care unit (ICU) had a 3.7 times higher risk of death than similar patients with Influenza A-H1N1

HYDROXYCHLOROQUINE FOR THE TREATMENT OF SEVERE RESPIRATORY INFECTION BY COVID-19: A RANDOMIZED CONTROLLED TRIAL

The novel coronavirus pandemic (COVID-19) represents a major public health problem due to its rapid spread and its ability to generate severe pneumonia. Thus, it is essential to find a treatment that reduces mortality. Our objective was to estimate whether treatment with 400 mg/day of Hydroxychloroquine for 10 days reduces in-hospital mortality in subjects with severe respiratory disease due to COVID-19 compared with placebo. Material and methodsA double-blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of Hydroxychloroquine for the treatment of severe disease by COVID-19 through an intention-to-treat analysis. Eligible for the study were adults aged more than 18 years with COVID-19 confirmed by RT-PCR and lung injury requiring hospitalization with or without mechanical ventilation. Primary outcome was 30-day mortality. Secondary outcomes: days of mechanical ventilation, days of hospitalization and cumulative incidence of serious adverse events. ResultsA total of 214 patients with COVID-19 were recruited, randomized and analyzed. They were hypoxemic with a mean SpO2 of 65% {+/-} 20, tachycardic (pulse rate 108{+/-}17 min-1) and tachypneic (32 {+/-}10 min-1); 162 were under mechanical ventilation at randomization. Thirty-day mortality was similar in both groups (38% in Hydroxychloroquine vs. 41% in placebo, hazard ratio [HR] 0.88, 95% Confidence Interval [95%CI] 0.51-1.53). In the surviving participants, no significant difference was found in secondary outcomes. ConclusionNo beneficial effect or significant harm could be demonstrated in our randomized controlled trial including 214 patients, using relatively low doses of Hydroxychloroquine compared with placebo in hospitalized patients with severe COVID-19. CONSORT GUIDELINES O_TBL View this table: org.highwire.dtl.DTLVardef@c46418org.highwire.dtl.DTLVardef@1877269org.highwire.dtl.DTLVardef@1685cb1org.highwire.dtl.DTLVardef@9d8b09org.highwire.dtl.DTLVardef@11339bc_HPS_FORMAT_FIGEXP M_TBL C_TBL

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Genomic analysis of early SARS-CoV-2 strains introduced in Mexico

The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement 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, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCEUnderstanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.

[Plethysmographic and radiologic measurement of the total lung capacity during acute attack of bronchial asthma]. / Medición pletismográfica y radiológica de la capacidad pulmonar total durante un ataque agudo de asma bronquial.

There is controversy on the behavior of total lung capacity (TLC) during an acute asthma attack because the severe airflow obstruction causes an overestimation of the intrathoracic gas measured by plethysmography. We measured plethysmographic and radiologic TLC (TLCpl, TLCrx) in 17 patients with acute asthma, at admission and 3-5 days later when clinical and spirometric improvement was seen. TLCrx was measured planimetrically from routine chest X-rays in postero-anterior and lateral projection. Patients had a mean age of 32 +/- 15 years (ranging from 8-53) and six were males. FEV1 and FVC increased significantly in the second evaluation (1.36 +/- 0.7 vs 1.99 +/- 0.7 L, and 1.97 +/- 0.9 vs 2.6 +/- 1 L respectively, p less than 0.05), whereas airway resistance decreased (13.4 +/- 5.3 vs 9.8 +/- 3.4 cm H2O/L/s, p less than 0.05). On the other hand, we did not find a significant change in TLCpl (4.4 +/- 1.1 vs 4.6 +/- 1.2 L) nor in TLCrx (4.2 +/- 0.9 vs 4.1 +/- 0.8 L). We found no significant difference between TLCpl and TLCrx.

[Radiographic measurement of the total pulmonary capacity: comparison of 2 planimetric methods]. / Medición radiográfica de la capacidad pulmonar total: comparación de dos métodos planimétricos.

We analyzed accuracy and reproducibility of a radiographic method for calculation of total lung capacity (TLC) from the sum of pulmonary area. Pulmonary area from a routine postero-anterior and lateral chest radiography was measured by two methods: using a planimeter (standard) and with a virgin radiographic plaque with lines separating squares of 1cm per side. Plethismographic TLC was obtained adding the functional residual capacity to inspiratory capacity. We studied 13 healthy subjects (mean age of 30 years, eight males), 13 with interstitial lung disease (mean age of 45 years, two males) and 12 with chronic bronchitis or emphysema (mean age of 63 years, three males). Measured TLC varied from 1.9 to 7.2 liters. The linear regression equation found was: TLC = 0.007 total lung area (cm2) 0.572, R = 0.906, P less than 0.001 which is very similar to that reported by Harris et al.8 Interobserver variability in the measurement was very small taking into account that no efforts were made to uniformize the observers. Main interobserver differences were in the tracing of the lung limits, and not in the actual measurement of the lung area. We found no differences between the two methods for measuring lung area except that the planimeter is faster and more reproducible. Radiographic method for measuring TLC is accurate and available in most places.

[Iatrogenic trends as indicator of clinical competence in courses of specialization in medicine]. / Tendencias iatrogénicas como indicador de competencia clínica en los cursos de especialización en medicina.

Iatrogenesis, understood here as an unfavourable effect to the health of patients provoked by the medical institution, has risen little interest in the researchers of the health area in spite of its growing presence. The present study had the aim of exploring the iatrogenic behavior of 659 recently graduated physicians by a questionnaire composed by clinical cases which described diagnostic and/or therapeutic situations that required the making of decisions. The questionnaire consisted of 600 general medical knowledge questions of which 112 explored commission of iatrogenic behavior. The group showed a iatrogenicity index of 39.5% ranging between 15.2% and 74.1%. When this iatrogenicity index was compared to that of global medical knowledge (600 questions) no correlation was found. It is concluded that the "iatrogenicity" index of this group is high and lacks correlation with the global medical knowledge. This suggests that the individualized and careful use of the diagnostic and therapeutic resources suitable for specific situations in patients does not receive sufficient emphasis during the teaching-learning process nor does it play a prominent role within the priorities of knowledge that are learned in the school of medicine. The need to deepen our understanding of the iatrogenic behavior of the physicians at different levels of their professional training is emphasized.