A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8.

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing a role for an accessory protein in this context.

Community-level impacts of the coronavirus pandemic on malaria prevention and health-seeking behaviours in rural Benin: A mixed methods study.

Globally, negative impacts of the COVID-19 pandemic on malaria prevention and control efforts have been caused by delayed distributions of long-lasting insecticidal nets (LLIN), decreased outpatient attendance, and disruptions to malaria testing and treatment. Using a mixed methods approach, we aimed to evaluate the impact of COVID-19 on community-level malaria prevention and health-seeking practices in Benin more than one year after the start of the COVID-19 pandemic. We collected data through community-based cross-sectional surveys with 4200 households and ten focus group discussions (FGDs). Mixed effect logistic regression models accounting for a clustered sampling design were used to identify variables associated with main outcomes (good COVID-19 knowledge, LLIN usage and access, and avoidance of health centres). Consistent with the experiences of FGD participants, receiving information from radios or televisions was significantly associated with good COVID-19 knowledge and avoiding health centres because of the pandemic (p<0.001 for both). Qualitative findings also revealed varying and polarizing changes in health-seeking behaviours with participants noting that they either did not change their health-seeking behaviours or went to health centres less or more often because of the pandemic. LLIN usage and access did not decrease in the study area because of the pandemic (LLIN usage: 88% in 2019 to 99.9% in 2021; LLIN access: 62% in 2019 to 73% in 2021). An unexpected change and unintended challenge for sustained malaria prevention included families socially distancing in their homes, resulting in a shortage of LLINs. Our findings showed that there were minimal community-level impacts of the coronavirus pandemic on malaria prevention and health seeking behaviours in rural Benin, which highlights the importance of efforts to sustain malaria prevention and control interventions in the context of the COVID-19 pandemic.

An intelligent platform of services based on multimedia understanding and telehealth for supporting the management of SARS-CoV-2 multi-pathological patients

The combination of pervasive sensing and multimedia understanding with the advances in communications makes it possible to conceive platforms of services for providing telehealth solutions responding to the current needs of society. The recent outbreak has indeed posed several concerns on the management of patients at home, urging to devise complex pathways to address the Severe Acute Respiratory Syndrome (SARS) in combination with the usual diseases of an increasingly elder population. In this paper, we present TiAssisto, a project aiming to design, develop, and validate an innovative and intelligent platform of services, having as its main objective to assist both Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) multi-pathological patients and healthcare professionals. This is achieved by researching and validating new methods to improve their lives and reduce avoidable hospitalisations. TiAssisto features telehealth and telemedicine solutions to enable high-quality standards treatments based on Information and Communication Technologies (ICT), Artificial Intelligence (AI) and Machine Learning (ML). Three hundred patients are involved in our study: one half using our telehealth platform, while the other half participate as a control group for a correct validation. The developed AI models and the Decision Support System assist General Practitioners (GPs) and other healthcare professionals in order to help them in their diagnosis, by providing suggestions and pointing out possible presence or absence of signs that can be related to pathologies. Deep learning techniques are also used to detect the absence or presence of specific signs in lung ultrasound images. © 2022 IEEE.

evaluation of hematological abnormalities in subjects vaccinated with bnt162b2 in a longitudinal cohort of the coRe study

Background: Vaccination is considered the most effective preventive strategy to fight COVID-19. The aim of this study was to evaluate two critical concerns about: 1) the kinetic response of IgG and IgM, and: 2) the hematological abnormalities in a longitudinal cohort of health-care workers (HCW) who had received 2 doses of BNT162b2 mRNA-based vaccine. Method(s): Blood and nasopharyngeal swabs were collected from 46 volunteers' participants, previous written consensus, with presumable no symptoms of COVID-19. Anti-SARS-CoV-2 serum immunoglobulin G (IgG) and M (IgM) and hematological parameters were examined. Multivariable mixed-effects models for repeated measure analysis were adopted to evaluate time changes in IgG, IgM and hematological parameters, and to investigate associations with vaccination response. Result(s): Forty-six subjects (N.=46;31.8% men;68.2% women;mean age near 36 years-old) were enrolled among healthcare workers of IRCCS MultiMedica (Milan, Italy). Overall, increase in serological IgG concentration appeared mainly between 21-28 days after the 1st dose, whereas IgM did not reach positivity in all cases. Mean blood cells counts were in normal range but we observed a significant reduction of total white blood cells and absolute lymphocyte counts after the 1st dose, persisting until the day 28. The increase of monocytes and neutrophils the day after the 1st dose subsequently decayed significantly. Eosinophils concentration showed a tendency to increase over time. Peripheral blood smear showed a growing frequency of atypical lymphocytes (lympho-variants), and of plasmacytoid forms, whereas no difference was found in large granular lymphocytes (LGL), although a decay after the boost was evident. The stratification of subjects, relative to the timing of IgG increase, showed the occurrence of 3 different patterns after vaccination, namely early-responders (R+), late-responders (R-) and pauci-responders (PR) with a peculiar kinetics of hematological parameters. Lymphocytes were significantly associated with total IgG: lower in R+ and PR compared to R- (P=0.0193 and P=00054, respectively). Conclusion(s): In healthy subjects, anti SARS-CoV-2 vaccination induced a variety of non-pathologic abnormalities. The response to vaccination was not equal in the groups examined. In PR group a major difference occurred with respect to R- and R+. This work adds novel insight into the puzzle of changes induced by SARS-CoV-2 virus.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Analytical and qualitative investigation of COVID-19 mathematical model under fractional differential operator.

In the current article, we aim to study in detail a novel coronavirus (2019-nCoV or COVID-19) mathematical model for different aspects under Caputo fractional derivative. First, from analysis point of view, existence is necessary to be investigated for any applied problem. Therefore, we used fixed point theorem's due to Banach's and Schaefer's to establish some sufficient results regarding existence and uniqueness of the solution to the proposed model. On the other hand, stability is important in respect of approximate solution, so we have developed condition sufficient for the stability of Ulam-Hyers and their different types for the considered system. In addition, the model has also been considered for semianalytical solution via Laplace Adomian decomposition method (LADM). On Matlab, by taking some real data about Pakistan, we graph the obtained results. In the last of the manuscript, a detail discussion and brief conclusion are provided.

Evaluation of changes in antimicrobial susceptibility in bacteria infecting children and their mothers in pediatric, neonatal-intensive care unit, and gynecology/obstetrics wards of a quaternary referral hospital during the COVID-19 pandemic.

The World Health Organization released a statement warning of increased risk for the incidence of multidrug resistant microorganisms and the absence of new drugs to control such infections soon. Since the beginning of the COVID-19 pandemic, the prescription of antimicrobial agents has increased and may have accelerated the emergence of multidrug resistant (MDR) bacteria. This study aimed to evaluate maternal and pediatric infections within a hospital from January 2019 to December 2021. An observational retrospective cohort study was performed at a quaternary referral hospital in a metropolitan area of Niteroi city, Rio de Janeiro state, Brazil. A total of 196 patients' medical records were analyzed. The data from 90 (45.9%) patients were collected before the SARS-CoV-2 pandemic, 29 (14.8%) from the 2020 pandemic period, and 77 (39.3%) from the 2021 pandemic period. A total of 256 microorganisms were identified during this period. Out of those, 101 (39.5%) were isolated in 2019, 51 (19.9%) in 2020, and 104 (40.6%) in 2021. Antimicrobial susceptibility tests were performed on 196 (76.6%) clinical isolates. The exact binomial test showed that the distribution of Gram-negative bacteria was predominant. The most common microorganism was Escherichia coli (23%; n = 45), followed by Staphylococcus aureus (17.9%, n = 35), Klebsiella pneumoniae (12.8%, n = 25), Enterococcus faecalis (7.7%, n = 15), Staphylococcus epidermidis (6.6%, n = 13) and Pseudomonas aeruginosa (5.6%, n = 11). Staphylococcus aureus was the predominant species among resistant bacteria. Among the antimicrobial agents tested, the following were resistant, presented on a descending scale: penicillin (72.7%, p = 0.001, Binomial test), oxacillin (68.3%, p = 0.006, Binomial test), ampicillin (64.3%, p = 0.003, Binomial test), and ampicillin/sulbactam (54.9%, p = 0.57, Binomial test). Infections with S. aureus were 3.1 times greater in pediatrics and maternal units than in other hospital wards. Despite the global reduction in the incidence of MRSA, we observed an increase in MDR S. aureus in this study. No changes were observed in the frequency of resistance profiles of the clinical isolates after the establishment of the global SARS-CoV-2 pandemic. More comprehensive studies are needed to understand the impact of the global SARS-CoV-2 pandemic on the resistance levels of bacteria associated with neonate and pediatric patients.

DACov: A Deeper Analysis of Data Augmentation on the Computed Tomography Segmentation Problem (preprint)

Due to the COVID-19 global pandemic, computer-assisted diagnoses of medical images have gained much attention, and robust methods of semantic segmentation of Computed Tomography (CT) images have become highly desirable. In this work, we present a deeper analysis of how data augmentation techniques improve segmentation performance on this problem. We evaluate 20 traditional augmentation techniques on five public datasets. Six different probabilities of applying each augmentation technique on an image were evaluated. We also assess a different training methodology where the training subsets are combined into a single larger set. All networks were evaluated through a 5-fold cross-validation strategy, resulting in over 4,600 experiments. We also propose a novel data augmentation technique based on Generative Adversarial Networks (GANs) to create new healthy and unhealthy lung CT images, evaluating four variations of our approach with the same six probabilities of the traditional methods. Our findings show that GAN-based techniques and spatial-level transformations are the most promising for improving the learning of deep models on this problem, with the StarGANv2 + F with a probability of 0.3 achieving the highest F-score value on the Ricord1a dataset in the unified training strategy. Our code is publicly available at https://github.com/VRI-UFPR/DACov2022

Monitoring the effects of BNT162B2 vaccine on platelet activation and immunephenotyping by multidisciplinary approaches: The longitudinal CORE study

Background: Vaccination is an effective strategy to prevent symptomatic COVID-19 but rare adverse effects have been reported, including cerebral venous thrombosis. Aim of this study was: 1) to monitor platelet abnormalities after vaccination in subjects receiving two doses of RNA-based BNT162B2;2) to analyze the link between platelet alpha-granules and the open canalicular system (OCS);and 3) to measure concentrations of 3 miRNAs known to be associated with platelet activation. Material(s) and Method(s): Healthy subjects were enrolled among healthcare workers of IRCCS MultiMedica (CORE study). Blood and nasopharyngeal swabs were collected before immunization (T0), and after 24 hours (T1-1st dose), 7 (T2), 14 (T3), 21 (T4-2nd dose) and 28 (T5) days, obtaining plasma, fresh platelets and PBMCs. Hematological parameters were measured by Sysmex analyser (XN 9000), morphology by Cellavision DM 96, and serological tests for the detection of immunoglobulin G (IgG) and M (IgM) by TGS COVID-19 kit (Technogenetisc). The cut-off values to assess immunopositivity after vaccination were in accordance with WHO International Standard 20/136. RNA extraction from nasopharyngeal swab was performed using Janus G3 and Chemagic 360. Real-time RT-PCR Assay was used to detect SARS-CoV-2 virus (Perkin Elmer). qPCR (QuantStudio 6 flex, Applied Biosystems) was used to detect miR-21, miR-125b and miR-185 in plasma. Washed platelets were analyzed by Transmission Electron Microscopy (TEM). Kruskal-Wallis test were performed for comparisons. Flux cytofluorimetry on PBMCs were used in a subgroup of subjects after a 3rd dose, as pilot study. Result(s): Forty-six subjects (31.8% men;68.2% women;mean age 36 years-old) were enrolled. Overall, anti-Sars-Cov-2 IgG concentration peaked between 21-28 days after the 1st dose, whereas IgM did not reach positivity in all cases. Mean hematological counts were in the normal range, with significant decrease of neutrophils over time, relative to T0. Peripheral blood smear showed at T5 13,64% increase of giant platelets, and 39,47% increase in thrombocyte aggregation (ANOVA, p=0.02). Morphological TEM analysis showed that the number of platelet alpha granules decreased at T2 and T3, but increased at T4 and T5. Conversely, OCS determined using canalicular/platelet area (um2) ratio, increased at T2 and T3, then returned to baseline values. Plasma miR-125b expression values increased at T1 (p<0.0001 vs T0), whereas miR-185 slightly increased. No significant differences were found for miR-21. Correlation between these 3 miRNAs were significant (miR-21 vs miR-125b, r=0.74, p<0.0001;miR-21 vs miR-185, r=0.9, p<0.0001;miR-185 vs miR-125b, r=0.76, p<0.0001). All miRNAs returned to baseline values after 28 day. In a subgroup where PBMC were processed the day after the 3rd dose, we observed increased mean frequencies of CD4+producing IFN-g, CD8+, CD8+producing IFN-g, and NK cells-producing IFN-g (54%, 63%, 672%, 665%, respectively). Conclusion(s): In healthy subjects, BNT162B2 vaccination transiently induced a variety of abnormalities of platelet activation and expression of miRNAs, that subsided 1 weeks after 2nd dose. This could contribute to explain the mechanism of early prothrombotic abnormalities observed in vaccinated subjects. In addition, 3rd dose could improve the response to SARS-CoV2, inducing increased CD4+-, CD8+-and NK-cells producing IFN-g. The CORE study was approved by Local Ethical Committee. All participants provided written informed consent.

Personality Traits Prediction from Text via Machine Learning

Social media platforms have been expanding their user bases. For example, LinkedIn counts 917 million monthly visitors, while Twitter has 3.62 billion monthly visitors. YouTube has 22.77 billion monthly visitors, and Instagram has 2.86 billion monthly visitors. Reports confirm data size increase of the social media networks above by 20-30% every day. With the spread of COVID-19, the same platforms have been broadly used by the worldwide collectiveness to socialize and stay amongst people. Analyzing text from Social Networking sites helps recognize individuals' personality traits automatically. A person's personality refers to their unique characteristics that shape their habits, behaviour, attitude, and cognitive tendencies. In this work, several machine learning techniques are surveyed to estimate personality traits from input text using the Myers-Briggs Type Indicator (MBTI) model. Experiments are run over a freely accessible dataset from Kaggle. In addition, techniques such as tokenization, word stemming, stop word elimination, and feature selection, utilizing TF-IDF, are used to analyze personality traits further. © 2022 IEEE.

A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8 (preprint)

Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and a versatile reagent and genetic toolbox. However, adult mice do not transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2) and omicron (B.1.1.529). We found that an index shedding threshold is a key determinant for viral transmissibility. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in delayed and reduced transmission. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein this context. We now have a tractable small animal model to help us decipher and counteract some of the most decisive aspects of SARS-CoV-2 continued spread in the human population.

Light In The Black: An Evaluation of Data Augmentation Techniques for COVID-19 CT's Semantic Segmentation (preprint)

With the COVID-19 global pandemic, computer-assisted diagnoses of medical images have gained much attention, and robust methods of Semantic Segmentation of Computed Tomography (CT) became highly desirable. Semantic Segmentation of CT is one of many research fields of automatic detection of COVID-19 and has been widely explored since the COVID-19 outbreak. In this work, we propose an extensive analysis of how different data augmentation techniques improve the training of encoder-decoder neural networks on this problem. Twenty different data augmentation techniques were evaluated on five different datasets. Each dataset was validated through a five-fold cross-validation strategy, thus resulting in over 3,000 experiments. Our findings show that spatial level transformations are the most promising to improve the learning of neural networks on this problem.

Safe urodynamic practices in times of COVID-19: What can be accomplished and what can be added?

AIM: To present feedback, after applying national and international urodynamic study (UDS) recommendations for safe practice during the COVID-19 pandemic. METHODS: We created a checklist to assess the feasibility of performing UDS recommendations for safe practice during the COVID-19 pandemic from the first week of May 2021 to the last week of July 2021. RESULTS: One hundred patients were analyzed during the study period. We observed that all preventive recommendations for the steps that precede UDS could be followed in full. However, some guidelines for performing the exam were not feasible in all patients. We have successfully adopted other safety measures for all patients. CONCLUSIONS: The COVID-19 pandemic will likely persist for several more years. We believe that continuous improvement, revision, and updating of existing protocols and guidelines for the safe practice of UDS in times of COVID-19, as we propose in this study, should be encouraged.

H-2A and H-2B temporary worker visas: Policy and related issues

Certain foreign workers, sometimes referred to as guest workers, may be admitted to the United States to perform temporary labor under two temporary worker visas: the H-2A visa for agricultural workers and the H-2B visa for nonagricultural workers. The H-2Avisa is not subject to any numerical limitations, while the H-2B visa is subject to a statutory annual cap of 66,000. H-2A and H-2B workers fill jobs that do not require much formal education. H-2A workers perform seasonal or temporary agricultural labor. They also engage in range herding and livestock production. H-2B workers perform temporary jobs in a variety of fields including landscaping, meat and seafood processing, and construction. The H-2A and H-2B programs are administered by the Department of Homeland Security (DHS) and the Department of Labor (DOL). These agencies and the Department of State (DOS) have made adjustments, and in the case of DHS issued H-2A and H-2B temporary final rules, related to guest worker visas in response to the coronavirus pandemic. Statutory and regulatory provisions establish processes for bringing in workers under the H-2A and H-2B programs that are intended to protect similarly employed U.S. workers. As an initial step in the process, a prospective H-2Aor H-2B employer must apply for DOL labor certification to ensure that U.S. workers are not available for the jobs in question and that the hiring of foreign workers will not adversely affect the wages and working conditions of U.S. workers. After receiving labor certification, the employer can submit an application, known as a petition, to DHS to bring in foreign workers. If the petition is approved, a foreign worker who is abroad can then go to a U.S. embassy or consulate to apply for an H-2A or H-2B nonimmigrant visa from DOS. If the visa application is approved, the worker is issued a visa that he or she can use to apply for admission to the United States at a port of entry. The final steps are different if the foreign worker is already in the United States;in such a case, there is no visa application. Over the years, a variety of legislative measures have been put forward concerning foreign temporary agricultural and nonagricultural workers. These have included bills to establish new temporary worker visas for agricultural and nonagricultural workers as well as proposals to change the existing H-2A and H-2B programs. In recent Congresses, the latter proposals have been more common. H-2A-related measures have sought to revise H-2Aprogram requirements on temporary need, wages, U.S. worker recruitment, and housing, among other items. Recent bills on the H-2B visa have focused largely on the annual cap. The H-2A and H-2B programs-and guest worker programs broadly-strive both to be responsive to legitimate employer needs for temporary labor and to provide adequate protections for U.S. and foreign temporary workers. There is much debate, however, about how to strike the appropriate balance between these goals. Key policy considerations for Congress include the labor market test to determine whether U.S. workers are available for the positions;required wages;and enforcement. The issue of unauthorized workers also arises in connection with guest worker programs. © 2021 by Nova Science Publishers, Inc.

Use of Defibrotide in Patients with COVID-19 Pneumonia;Results of the Defi-VID19 Phase 2 Trial

Background: The clinical spectrum of COVID-19 ranges from pauci-symptomatic forms to severe disease characterized by respiratory failure requiring mechanical ventilation and intensive care unit (ICU) management, as well as multisystem involvement characterized by sepsis, organ dysfunction and death. Treatment of COVID-19 is not standardized, and respiratory failure from ARDS is the leading cause of mortality;in-hospital mortality at 28-days in our tertiary care center in Lombardia, northern Italy was 23% during the first wave in 2020(Ciceri et al. 2020). Endothelial damage and thrombo-inflammation have been identified as common to both COVID-19 pathophysiology and veno-occlusive disease (VOD/SOS). Defibrotide (DF) has endothelial-protective properties, with pro-fibrinolytic, anti-thrombotic, anti-ischemic, anti-inflammatory, and anti-adhesive activity, but no significant systemic anticoagulant effects and is approved for the treatment of severe VOD/SOS. Aim: A prospective, multicenter, phase II, single-arm, open label trial (DEFI-VID19, NCT04335201) was conducted in patients (pts) with COVID-19 ARDS to evaluate the efficacy of DF in addition to best available therapy per institutional guidelines. The primary endpoint was respiratory-failure rate (RFR) defined as progression of respiratory failure, i.e. severe gas transfer deficit (PaO2/FiO2<200 mmHg), need of ICU or death at day+14 from treatment start. Secondary endpoints included overall survival (OS) at 28 days, duration of hospitalization and safety. A sample size of 50 pts was calculated to detect an absolute reduction of 20% in RFR at day+14, assuming a failure rate in non-treated pts of 70% (alpha=5%, power=90%, two-sided test). Pts received DF intravenously at 6.25 mg/kg/dose by 2-hour infusion repeated every 6 hours. Expected treatment duration was 14 days, with earlier discontinuation if clinical improvement occurred. LMWH at prophylactic dose was allowed. Approval was provided by the National IRB for COVID-19 trials at Institute Spallanzani (Rome) and by the Italian Agency for Drug (AIFA). All patients provided written informed consent. Results: Overall, 52 pts were enrolled from September 2020 to April 2021;48 were evaluated for efficacy and safety;4 pts were excluded due to screen failure (n=2) or withdrawal of informed consent at day 2 after defibrotide was initiated (n=2). Median age was 60.5 years (range 53-71);35 pts (73%) were male and 65% had comorbidities, with high blood pressure, obesity and COPD most common. Two pts had pre-existing diagnoses of non-Hodgkin lymphoma. Median time from onset of COVID-19 symptoms and from Sars-COV2 PCR by nasal swab to enrollment were 8 (range 7-10) and 3 days (range 1-6), respectively. All pts were hospitalized and scale 5 of 8-category ordinal scale by WHO criteria, requiring noninvasive ventilation with CPAP or high-flow oxygen, with a median P/F ratio of 211 (range 134-275) mmHg. At treatment start, the median and (range) lymphocyte counts, LDH, CRP, ferritin, D-dimer and IL-6 were 0.7 (0.5-0.9) x 10e9/L;404 (291-491) U/L;49 (22-97) mg/L;823 (363-1088) ng/ml;0.44 (0.28-1.29) µg/mL and 20 (11-32), respectively. Median treatment duration was 8.5 days (range 6-11). Overall, 13/48 pts (27%) discontinued the treatment due to clinical worsening and/or need of further therapies: 9 pts experienced progressive respiratory failure and 6 of those were transferred to ICU for IOT (one pt required ECMO), and 4 required full anticoagulation due to pulmonary embolism (n=1), ischemic stroke (n=1), and femoral deep venous thrombosis (n=2). All pts who completed the treatment 35/48 (73%) were discharged with no need of oxygen support. Overall, 14 SAEs have been reported in a median time of 6 days (range 2-10): all unrelated to DF. No pts experienced hemorrhagic events. The incidence of RFR at day 14 was 25 (+/- 6)%, and at day 28, 27 (+/- 6) %. Probability of OS at day 28 was 89 (+/-4) %, at day 60 83 (+/- 5)%. Overall, 8 pts died from COVID-19 -related complications. No pts required re-admission after hospital discha ge (median 14 days) or died after discharge. Conclusion: Treatment with DF in pts with grade 5 WHO COVID 19 ARDS does not induce bleeding, and is associated with rapid restoration of respiratory function (73% of pts). Notably, no oxygen support was needed at discharge and a 1-month OS rate of 89% was observed, which is higher than historical controls (77%) treated in the same setting. Disclosures: Richardson: Takeda: Consultancy, Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy, Research Funding;AstraZeneca: Consultancy;Oncopeptides: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding;Protocol Intelligence: Consultancy;Secura Bio: Consultancy;Regeneron: Consultancy;Celgene/BMS: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Janssen: Consultancy;Sanofi: Consultancy. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Carlo-Stella: Incyte: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi: Consultancy, Research Funding;AstraZeneca: Honoraria;Celgene: Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Oncology: Honoraria;Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Outpatient prescription patterns of COVID-19 drugs in the metropolitan area of Mexico City.

BACKGROUND: We aimed to describe the use of drugs with apparent efficacy in ambulatory patients with confirmed COVID-19 and the relationship of Google Trends searches with prescriptions and the total number of COVID-19 cases in Mexico City. METHODS: Between March 2020 and February 2021, we surveyed 350 patients confirmed to have COVID-19 across 3 hospitals in Mexico City for their ambulatory prescriptions. We analysed the correlation between prescription patterns of 4 drugs with apparent efficacy against COVID-19, Google Trends searches for these drugs, and the overall number of confirmed COVID-19 cases in Mexico City. RESULTS: We included 350 patients, of whom 59% were women with a median age of 38 years (interquartile range, 29-51), and 72% had a bachelor's degree or higher. There were ambulatory medical prescriptions in 172 (49%) patients, and self-prescriptions were reported in 99 (28%) patients. The prescription rate was high for hydroxychloroquine/azithromycin (19%) and dexamethasone (25%). There was a decrease in the prescription of hydroxychloroquine (P < 0.001) and a strong positive correlation between hydroxychloroquine (r = 0.66; 95% confidence interval, 0.11-0.90; P = 0.02) prescription and online searches for hydroxychloroquine. There was a strong positive correlation between online searches for azithromycin, dexamethasone, ivermectin, and vitamin D and the number of confirmed COVID-19 cases. CONCLUSIONS: During the COVID-19 pandemic, there was a high proportion of prescriptions for hydroxychloroquine/azithromycin and dexamethasone despite their unproven efficacy. Analysis of Google Trends showed a strong correlation between the overall number of confirmed COVID-19 cases and searches for such drugs, suggesting a higher rate of prescriptions. Analysis of online searches could thus help to actively survey public health behaviours in the future.

Atovaquone and Berberine Chloride Reduce SARS-CoV-2 Replication In Vitro.

Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.