Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally. SOURCES OF DATA: Recent published literature. AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community. AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery. GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine. AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

Phantom Plague: How Tuberculosis Shaped History

The author highlights many challenges ahead that limit achieving the World Health Organization (WHO) End TB strategy without substantial additional investments and development of new tools to combat TB (the WHO End TB strategy targets a 90% reduction in TB cases and 95% reduction in TB-related deaths by 2035). [...]perhaps the book ends prematurely, because after it was written, new treatments were developed for highly drug-resistant TB that shifted to all oral regimens (WHO recommendation);a ≈90% favorable outcome was recently reported for the BPaL regimen used to treat highly drug-resistant TB (2). Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia, USA World Health Organization.

Ingestion of Illicit Substances by Young Children Before and During the COVID-19 Pandemic.

Importance: Information about the trend in illicit substance ingestions among young children during the pandemic is limited. Objectives: To assess immediate and sustained changes in overall illicit substance ingestion rates among children younger than 6 years before and during the COVID-19 pandemic and to examine changes by substance type (amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids) while controlling for differing statewide medicinal and recreational cannabis legalization policies. Design, Setting, and Participants: Retrospective cross-sectional study using an interrupted time series at 46 tertiary care children's hospitals within the Pediatric Health Information System (PHIS). Participants were children younger than 6 years who presented to a PHIS hospital for an illicit substance(s) ingestion between January 1, 2017, and December 31, 2021. Data were analyzed in February 2023. Exposure: Absence or presence of the COVID-19 pandemic. Main Outcome(s) and Measure(s): The primary outcome was the monthly rate of encounters for illicit substance ingestions among children younger than 6 years defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code(s) for poisoning by amphetamines, benzodiazepines, cannabis, cocaine, ethanol, and opioids. The secondary outcomes were the monthly rate of encounters for individual substances. Results: Among 7659 children presenting with ingestions, the mean (SD) age was 2.2 (1.3) years and 5825 (76.0%) were Medicaid insured/self-pay. There was a 25.6% (95% CI, 13.2%-39.4%) immediate increase in overall ingestions at the onset of the pandemic compared with the prepandemic period, which was attributed to cannabis, opioid, and ethanol ingestions. There was a 1.8% (95% CI, 1.1%-2.4%) sustained monthly relative increase compared with prepandemic trends in overall ingestions which was due to opioids. There was no association between medicinal or recreational cannabis legalization and the rate of cannabis ingestion encounters. Conclusions and Relevance: In this study of illicit substance ingestions in young children before and during the COVID-19 pandemic, there was an immediate and sustained increase in illicit substance ingestions during the pandemic. Additional studies are needed to contextualize these findings in the setting of pandemic-related stress and to identify interventions to prevent ingestions in face of such stress, such as improved parental mental health and substance treatment services, accessible childcare, and increased substance storage education.

Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M.

Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the ß-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.

Creative arts intervention to reduce burnout and decrease psychological distress in healthcare professionals: A qualitative analysis

Creative arts therapy (CAT) can potentially mitigate the unprecedented levels of healthcare professional (HCP) burnout that have been exacerbated by the COVID-19 pandemic. However, empirical evidence about the impact of CAT programs is lacking. We conducted focus groups with HCPs (N = 20) who participated in a 12-week CAT clinical trial to enhance the understanding of the effectiveness of the intervention. For HCPs experiencing burnout and psychological distress, our CAT program supported healing and resiliency through building a sense of community. Participants reported that several programmatic components contributed to this sense of community including: 1) diversity of participants' disciplines, roles, and geographic locations;2) physical separation between the conduct of the CAT program and their primary place of employment;3) facilitator skill;4) collectively contributing to a group project;and 5) being pushed out of their "comfort zone" through the creative activity. Although participants described the particular need for the CAT program in light of additional stressors induced by the COVID-19 pandemic, they believed that this program would have been beneficial pre-pandemic and in the future. To build long-term resiliency, participants suggested that CAT interventions should continue after the 12-week program.Copyright © 2023 Elsevier Ltd

Road Development Risks and Challenges in the Philippines

The Philippines, as a fast-growing country, has had the highest road infrastructure investment to date for the past five years compared to the previous years. The infrastructure programs of the government as a solution to decongest Metro Manila and develop the countryside for economic growth are promising yet result in various risks and challenges. This research presents the road development issues from multiple sources;primary data from interviews of stakeholders of road development, secondary data from online news articles, social network services, government issuance, policies, and related literature. The Philippines is in a dire economic situation due to the Covid-19 outbreak that resulted in the country's worst economic performance since the Asian financial crisis in 1998. The country's economic managers pinned high hopes on the government infrastructure programs as a vital strategy to help pump-prime the economy towards recovery due to its job generation and multiplier effects. Hence, it implicates enormous risks and challenges such as low tax revenues, the trade-off with more urgent Covid-19 response measures, foreign and private companies support, unsolicited project proposals, inequitable distribution of infrastructures, and delays in construction activities. Various road development stakeholders also mentioned the need for strict road regulations, urban and regional planning, aesthetic improvement, urban renewal in aid of car-centric infrastructures, and routine maintenance on-road sections. The data are structured in various categories such as public involvement, environmental preservation, public policy, project planning, road design, road safety, economic recovery, and construction time. Lastly, the implications for future research directions are discussed. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Hospital-level care at home for patients with acute respiratory disease: A descriptive analysis.

BACKGROUND: Home hospital (HH) is hospital-level substitutive care delivered at home for acutely ill patients who would traditionally be cared for in the hospital. Despite HH programs operating successfully for years, and scientific evidence of similar or better outcomes compared to bricks and mortar care, HH outcomes in the US for respiratory disease have not been evaluated. RESEARCH QUESTION: Do outcomes differ between patients admitted to HH with acute respiratory illness vs other acute general medical conditions? STUDY DESIGN AND METHODS: Retrospective evaluation of prospectively collected data of patients admitted to HH (2017-21). We compared patients requiring admission with respiratory disease (asthma exacerbation (26%), acute exacerbation for COPD [AECOPD] (33%), and non-COVID-19 pneumonia [PNA] (41%)) to all other HH patients. During HH, patients received 2 nurse and 1 physician visit daily, intravenous medications, advanced respiratory therapies, and continuous heart and respiratory rate monitoring. MAIN OUTCOMES: acute and post-acute utilization and safety. RESULTS: We analyzed 1,031 patients; 24% were admitted for respiratory disease. Patients with and without respiratory disease were similar: mean age 68 (SD, 17), 62% female, and 48% White. Respiratory patients were more often active smokers (21% vs 9%; p<0.001). FEV1/FVC ≤70 in 80% of cases; 28% had severe or very severe obstructive pattern (n=118). During HH, respiratory patients had less utilization: length of stay (mean days, 3.4 vs 4.6), laboratory orders (median, 0 vs 2), intravenous medication (43% vs 73%) and specialist consultation (2% vs 7%) (p all <0.001). 96% of patients completed the full admission at home with no mortality in the respiratory group. Within 30-days of discharge, both groups had similar readmission, ED presentation and mortality rates. INTERPRETATION: HH is as safe and effective for patients with acute respiratory disease as for those with other acute general medical conditions. If scaled, it can generate significant high-value capacity for health systems and communities, with opportunities to advance the complexity of care delivered.

Road Development Risks and Challenges in the Philippines

The Philippines, as a fast-growing country, has had the highest road infrastructure investment to date for the past five years compared to the previous years. The infrastructure programs of the government as a solution to decongest Metro Manila and develop the countryside for economic growth are promising yet result in various risks and challenges. This research presents the road development issues from multiple sources;primary data from interviews of stakeholders of road development, secondary data from online news articles, social network services, government issuance, policies, and related literature. The Philippines is in a dire economic situation due to the Covid-19 outbreak that resulted in the country's worst economic performance since the Asian financial crisis in 1998. The country's economic managers pinned high hopes on the government infrastructure programs as a vital strategy to help pump-prime the economy towards recovery due to its job generation and multiplier effects. Hence, it implicates enormous risks and challenges such as low tax revenues, the trade-off with more urgent Covid-19 response measures, foreign and private companies support, unsolicited project proposals, inequitable distribution of infrastructures, and delays in construction activities. Various road development stakeholders also mentioned the need for strict road regulations, urban and regional planning, aesthetic improvement, urban renewal in aid of car-centric infrastructures, and routine maintenance on-road sections. The data are structured in various categories such as public involvement, environmental preservation, public policy, project planning, road design, road safety, economic recovery, and construction time. Lastly, the implications for future research directions are discussed. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Real world experience of single use flexible bronchoscopy over six months in a tertiary centre

The development of single use flexible bronchoscopes (SUFBs) has accelerated in recent years, with the reduced risk of infectious transmission and reduced need for endoscopy staff particularly advantageous in the COVID-19 era. Despite complex cleaning systems for reusable flexible bronchoscopes (RFBs), disinfection is often inadequate with the consequent risk of cross infection. We trialled the routine use of The Surgical Company Bronchoflex © SUFB in a tertiary bronchoscopy service. 139 procedures were performed by five consultants from January to July 2021, with the main indications being infection (45%) and malignancy (32%). Most were performed in the endoscopy suite;eight procedures took place in the Intensive Care Unit, six at ward level and three in theatre as an adjunct to rigid bronchoscopy. SUFBs were used across a range of procedures including bronchoalveolar lavage, brushings, endobronchial biopsy, transbronchial needle aspiration, argon plasma coagulation, cryobiopsy and stent placement. 85% of procedures had no complications related to the use of a SUFB with a user satisfaction score of above 4/5 in 89% of cases (Figure 1). Issues with image quality (6%) or suction (5%) meant the reversion to reusable bronchoscope in some cases. Overall, the use of SUFBs has significant benefits in patient care with the ability to use the SUFB across a range of indications and procedures with high user satisfaction.

SARS-CoV-2 Vaccine Immunogenicity in Patients with Gastrointestinal Cancer Receiving Systemic Anti-Cancer Therapy.

INTRODUCTION: Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination. MATERIALS AND METHODS: Between September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine. RESULTS: All 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39. CONCLUSION: Despite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients' ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses. CLINICAL TRIAL REGISTRATION NUMBER: NCT04427280.

St-Elevation Myocardial Infarction With Complete Heart Block in the Setting of Vagally Mediated Coronary Vasospasm

Introduction: This case identifies vagal tone as a paradoxical cause of coronary artery spasm, coinciding with complete heart block. It will additionally identify proper management in these cases. Clinical Presentation: A 53 year old male with a medical history of HIV not of ART, acute, infectious COVID-19 and late, latent syphilis admitted for malaise, found to have DLBCL. Following a routine blood draw the patient experienced acute chest and abdominal pain. Minutes later, while having a bowel movement he experienced syncope with heart rates in the 30s. EKG showed ST elevations in leads II, III, and aVF. Troponin-T was elevated to 0.15. Echocardiogram showed inferior wall hypokinesis. Coronary angiography showed non-obstructive right coronary disease. Cardiac MRI demonstrated no evidence of infiltrative disease or myocarditis. The patient experienced a similar episode the following morning, during blood draw, EKG and telemetry demonstrated complete heart block with ST elevations (image). This suggested vagal mediated AV block with coronary artery spasm (CAS). He was started on the anticholinergic hyoscyamine and amlodipine for vasodilation. Following initiation of therapy, the patient had no further episodes of chest pain or bradycardia. Discussion(s): While acetylcholine causes vasodilation via endothelial NO, interestingly, it can also lead to CAS. In the setting of vascular smooth muscle cell (VSMC) hyper-reactivity or high vagal tone, VSMC muscarinic receptors are activated leading to vasoconstriction. Vagal tone can cause both CAS with resulting STEMI as well as AV blockade resulting in high degree heart block (image). When ischemic symptoms are accompanied by AV block in the setting of high vagal tone, consider vagal mediated CAS. Calcium channel blockers such as amlodipine are used to manage CAS. When the suspected mechanism is vagal tone, management includes avoidance of precipitating factors and or anticholinergic premedication.

Unique Variants of Avian Coronaviruses from Indigenous Chickens in Kenya.

The avian gamma-coronavirus infectious bronchitis virus (AvCoV, IBV; Coronaviridae family) causes upper respiratory disease associated with severe economic losses in the poultry industry worldwide. Here, we report for the first time in Kenya and the Eastern African region two novel AvCoVs, designated IBV/ck/KE/1920/A374/2017 (A374/17) and AvCoV/ck/KE/1922/A376/2017 (A376/17), inadvertently discovered using random nontargeted next-generation sequencing (NGS) of cloacal swabs collected from indigenous chickens. Despite having genome organization (5'UTR-[Rep1a/1ab-S-3a-3b-E-M-4b-4c-5a-5b-N-6b]-3'UTR), canonical conservation of essential genes and size (~27.6 kb) typical of IBVs, the Kenyan isolates do not phylogenetically cluster with any genotypes of the 37 IBV lineages and 26 unique variants (UVs). Excluding the spike gene, genome sequences of A374/17 and A376/17 are only 93.1% similar to each other and 86.7-91.4% identical to genomes of other AvCoVs. All five non-spike genes of the two isolates phylogenetically cluster together and distinctly from other IBVs and turkey coronaviruses (TCoVs), including the indigenous African GI-26 viruses, suggesting a common origin of the genome backbone of the Kenyan isolates. However, isolate A376/17 contains a TCoV-like spike (S) protein coding sequence and is most similar to Asian TCoVs (84.5-85.1%) compared to other TCoVs (75.6-78.5%), whereas isolate A374/17 contains an S1 gene sequence most similar to the globally distributed lineage GI-16 (78.4-79.5%) and the Middle Eastern lineage GI-23 (79.8-80.2%) viruses. Unanswered questions include the actual origin of the Kenyan AvCoVs, the potential pathobiological significance of their genetic variations, whether they have indeed established themselves as independent variants and subsequently spread within Kenya and to the neighboring east/central African countries that have porous live poultry trade borders, and whether the live-attenuated Mass-type (lineage GI-1)-based vaccines currently used in Kenya and most of the African countries provide protection against these genetically divergent field variants.

Socio-economic and demographic factors influencing the spatial spread of COVID-19 in the USA

As the COVID-19 pandemic progressed in the USA, ‘hotspots' shifted geographically over time to suburban and rural counties showing a high prevalence of the disease. We analyse population-adjusted confirmed case rates based on daily US county-level variations in COVID-19 confirmed case counts during the first several months of the pandemic (1 March 2020 through 23 May 2020) to evaluate the spatial dependence between neighbouring counties and quantify the overall spatial effect of socio-economic and demographic factors on the prevalence of COVID-19. We indeed find strong evidence of county-level socio-economic and demographic factors influencing the spatial spread such as sex, race, ethnicity, population density, pollution, health conditions, and income. The relevance of the spatial factors suggests that neighbouring counties have a significant and positive effect on the prevalence of COVID-19. Copyright © 2022 Inderscience Enterprises Ltd.

Socio-economic and demographic factors influencing the spatial spread of COVID-19 in the USA

As the COVID-19 pandemic progressed in the USA, 'hotspots' shifted geographically over time to suburban and rural counties showing a high prevalence of the disease. We analyse population-adjusted confirmed case rates based on daily US county-level variations in COVID-19 confirmed case counts during the first several months of the pandemic (1 March 2020 through 23 May 2020) to evaluate the spatial dependence between neighbouring counties and quantify the overall spatial effect of socio-economic and demographic factors on the prevalence of COVID-19. We indeed find strong evidence of county-level socio-economic and demographic factors influencing the spatial spread such as sex, race, ethnicity, population density, pollution, health conditions, and income. The relevance of the spatial factors suggests that neighbouring counties have a significant and positive effect on the prevalence of COVID-19.

Critical literature review and pooled analysis of diagnostic accuracy of Ortho VITROS SARS-CoV-2 antigen test for diagnosing acute SARS-CoV-2 infections.

Background: The present study is aimed at reviewing and meta-analyzing the currently published data on the diagnostic accuracy of Ortho VITROS SARS-CoV-2 antigen test for diagnosing acute SARS-CoV-2 infections. Methods: An electronic search was conducted in Scopus and Medline with the keywords "VITROS" AND "antigen" AND "COVID-19" OR "SARS-CoV-2" AND "immunoassay" within the search fields "TITLE" AND "ABSTRACT" AND "KEYWORDS", without no date (i.e., up to January 23, 2022) or language restrictions, aimed at detecting documents reporting the diagnostic accuracy of this SARSCoV-2 immunoassay compared with reference molecular diagnostic methods. Results: Overall, 5 studies (n=2734 samples) were finally included in our pooled analysis, four of which also provided diagnostic sensitivity in oro-and nasopharyngeal samples with high viral load. The pooled cumulative diagnostic sensitivity and specificity were 0.82 (95%CI, 0.78-0.86) and 1.00 (95%CI, 1.00-1.00), respectively, whilst the area under the curve was 0.995 (95%CI, 0.993-0.997), the cumulative agreement 97.2% (95%CI, 96.5-97.8%), with 0.89 (95%CI, 0.86-0.91) kappa statistics, thus reflecting an almost perfect concordance with reference molecular biology techniques. The pooled diagnostic sensitivity in samples with high viral load was as high as 0.98 (95%CI, 0.96-0.99). Conclusions: These results confirm that the automated and high-throughput Ortho VITROS SARS-CoV-2 antigen test may represent a valuable surrogate of molecular testing for diagnosing acute SARS-CoV-2 infections, especially in subjects with high viral load.

EventScore: An Automated Real-time Early Warning Score for Clinical Events

Early prediction of patients at risk of clinical deterioration can help physicians intervene and alter their clinical course towards better outcomes. In addition to the accuracy requirement, early warning systems must make the predictions early enough to give physicians enough time to intervene. Interpretability is also one of the challenges when building such systems since being able to justify the reasoning behind model decisions is desirable in clinical practice. In this work, we built an interpretable model for the early prediction of various adverse clinical events indicative of clinical deterioration. The model is evaluated on two datasets and four clinical events. The first dataset is collected in a predominantly COVID-19 positive population at Stony Brook Hospital. The second dataset is the MIMIC III dataset. The model was trained to provide early warning scores for ventilation, ICU transfer, and mortality prediction tasks on the Stony Brook Hospital dataset and to predict mortality and the need for vasopressors on the MIMIC III dataset. Our model first separates each feature into multiple ranges and then uses logistic regression with lasso penalization to select the subset of ranges for each feature. The model training is completely automated and doesn't require expert knowledge like other early warning scores. We compare our model to the Modified Early Warning Score (MEWS) and quick SOFA (qSOFA), commonly used in hospitals. We show that our model outperforms these models in the area under the receiver operating characteristic curve (AUROC) while having a similar or better median detection time on all clinical events, even when using fewer features. Unlike MEWS and qSOFA, our model can be entirely automated without requiring any manually recorded features. We also show that discretization improves model performance by comparing our model to a baseline logistic regression model. © 2022 IEEE.

Genome Sequence Variations of Infectious Bronchitis Virus Serotypes From Commercial Chickens in Mexico.

New variants of infectious bronchitis viruses (IBVs; Coronaviridae) continuously emerge despite routine vaccinations. Here, we report genome sequence variations of IBVs identified by random non-targeted next generation sequencing (NGS) of vaccine and field samples collected on FTA cards from commercial flocks in Mexico in 2019-2021. Paired-ended sequencing libraries prepared from rRNA-depleted RNAs were sequenced using Illumina MiSeq. IBV RNA was detected in 60.07% (n = 167) of the analyzed samples, from which 33 complete genome sequences were de novo assembled. The genomes are organized as 5'UTR-[Rep1a-Rep1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b]-3'UTR, except in eight sequences lacking non-structural protein genes (accessory genes) 4b, 4c, and 6b. Seventeen sequences have auxiliary S2' cleavage site located 153 residues downstream the canonically conserved primary furin-specific S1/S2 cleavage site. The sequences distinctly cluster into lineages GI-1 (Mass-type; n = 8), GI-3 (Holte/Iowa-97; n = 2), GI-9 (Arkansas-like; n = 8), GI-13 (793B; n = 14), and GI-17 (California variant; CAV; n = 1), with regional distribution in Mexico; this is the first report of the presence of 793B- and CAV-like strains in the country. Various point mutations, substitutions, insertions and deletions are present in the S1 hypervariable regions (HVRs I-III) across all 5 lineages, including in residues 38, 43, 56, 63, 66, and 69 that are critical in viral attachment to respiratory tract tissues. Nine intra-/inter-lineage recombination events are present in the S proteins of three Mass-type sequences, two each of Holte/Iowa-97 and Ark-like sequence, and one each of 793B-like and CAV-like sequences. This study demonstrates the feasibility of FTA cards as an attractive, adoptable low-cost sampling option for untargeted discovery of avian viral agents in field-collected clinical samples. Collectively, our data points to co-circulation of multiple distinct IBVs in Mexican commercial flocks, underscoring the need for active surveillance and a review of IBV vaccines currently used in Mexico and the larger Latin America region.