Coxsackievirus A7 and Enterovirus A71 Significally Reduce SARS-CoV-2 Infection in Cell and Animal Models (preprint)

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Detection of Lung Cancer Cases in Chest CT Scans Utilizing Artificial Intelligence: A Retrospective Analysis of Data During the COVID-19 Pandemic (preprint)

PurposeTo evaluate the potential of using artificial intelligence (AI) focused pulmonary nodule search on chest CT data obtained during the COVID-19 pandemic to identify lung cancer (LC) patients. MethodsA multicenter, retrospective study in the Krasnoyarsk region, Russia analyzed CTs of COVID-19 patients using the automated algorithm, Chest-IRA by IRA Labs. Pulmonary nodules larger than 100 mm3 were identified by the AI and assessed by four radiologists, who categorized them into three groups: "high probability of LC", "insufficiently convincing evidence of LC", "without evidence of LC". Patients with findings were analyzed by radiologists, checked with the state cancer registry and electronic medical records. Patients with confirmed findings that were not available in the cancer registry were invited for chest CT and verification was performed according to the decision of the medical consilium. The study also estimated the economic impact of the AI by considering labor costs and savings on treatment for patients in the early stages compared to late stages, taking into account the saved life years and their potential contribution to the gross regional product. ResultsAn AI identified lung nodules in 484 out of 10,500 chest CTs. Of the 484, 355 could be evaluated, the remaining 129 had de-anonymization problems and were excluded. Of the 355, 252 cases having high and intermediate probabilities of LC, 103 were found to be false positives. From 252 was 100 histologically verified LC cases, 35 were in stages I-II and 65 were in stages III-IV. 2 lung cancers were diagnosed for the first time. Using AI instead of CT review by radiologists will save 2.43 million rubles (23,786 EUR/ 26690 USD/ 196,536 CNY) in direct salary, with expected savings to the regional budget of 8.22 million rubles (80,463 EUR/ 90,466 USD/ 666,162 CNY). The financial equivalent of the life years saved was 173.25 million rubles (1,695,892 EUR/ 1905750 USD/ 14,033,250 CNY). The total effect over five years is estimated at 183.9 million rubles (1,800,142 EUR/ 2,022,907 USD/ 14,895,949 CNY). ConclusionUsing AI to evaluate large volumes of chest CTs done for reasons unrelated to lung cancer screening may facilitate early and cost-effective detection of incidental pulmonary nodules that might otherwise be missed.

Safe plant Hsp90 adjuvants elicit an effective immune response against SARS-CoV2 derived RBD antigen (preprint)

To better understand the role of pHsp90 adjuvant in immune response modulation, we proposed the use of the Receptor Binding Domain (RBD) of the Spike protein of SARS-CoV2, the principal candidate in the design of subunit vaccines. We evaluated the humoral and cellular immune responses against RBD through the strategy "protein mixture" (Adjuvant + Antigen). The rRBD adjuvanted with rAtHsp81.2 group showed a higher increase of the anti-rRBD IgG1, while the rRBD adjuvanted with rNbHsp90.3 group showed a significant increase of anti-rRBD IgG2b/2a. These results were consistent with the cellular immune response analysis. Spleen cell cultures from rRBD+rNbHsp90.3-immunized mice showed significantly increased IFN-{gamma} production. In contrast, spleen cell cultures from rRBD+rAtHsp81.2-immunized mice showed significant increased IL-4 levels. Finally, vaccines adjuvanted with rNbHsp90.3 induced higher neutralizing antibody responses compared to those adjuvanted with rAtHsp81.2. To know whether both chaperones must form complexes to generate an effective immune response, we performed co-immunoprecipitation (co-IP) assays. The results indicated that the greater neutralizing capacity observed in the rRBD adjuvanted with rNbHsp90.3 group would be given by the rRBD-rNbHsp90.3 interaction rather than by the quality of the immune response triggered by the adjuvants. These results, together with our previous results, provide a comparative benchmark of these two novel and safe vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV2 subunit vaccines. Furthermore, these results revealed differences in the ability to modulate the immune response between these two pHsp90s, highlighting the importance of adjuvant selection for future rational vaccine and adjuvant design.

From External to Local: Opportunities and Lessons Learned from Transitioning COMSA-Mozambique.

Donor transitions, where externally funded programs transfer to country ownership and management, are increasingly common. The Countrywide Mortality Surveillance for Action - Mozambique (COMSA) project established a nationwide surveillance system capturing vital events at the community level with funding from the Bill and Melinda Gates Foundation. COMSA was implemented in partnership between Johns Hopkins University (a U.S.-based academic institution) and the Instituto Nacional de Saúde (National Institute for Health) and Instituto Nacional de Estatística (National Institute for Statistics), two Mozambican public institutions. Midway through the project, the Gates Foundation directed COMSA's partners to develop and implement a transition plan that ensured COMSA's activities could be institutionalized after Gates Foundation funding ended. Here we describe the process and activities that COMSA underwent for transition planning, including stakeholder engagement and advocacy, securing financial commitments, documenting operational activities, capacity building, and supporting strategic planning. Facilitators included a project model that already embedded significant implementation and management responsibility with local agencies, high-level commitment to COMSA's activities from local stakeholders, establishing dedicated personnel and budget to manage transition, and fortuitous timing for financing. Challenges included needing to engage multiple government agencies to ensure buy-in, navigating tensions around future roles and responsibilities, reviewing and adjusting existing implementation structures, and the reality that this transition involved shifting financing from one development partner to another. Transition implementation was also constrained by the COVID-19 pandemic because key stakeholders were engaged in response efforts. COMSA's experience highlights lessons and threats for future programs facing donor transition in uncertain environments.

Cytokine Profiling in Different SARS-CoV-2 Genetic Variants.

This study is a successor of our previous work concerning changes in the chemokine profile in infection that are associated with different SARS-CoV-2 genetic variants. The goal of our study was to take into account both the virus and the host immune system by assessing concentrations of cytokines in patients infected with different SARS-CoV-2 variants (ancestral Wuhan strain, Alpha, Delta and Omicron). Our study was performed on 340 biological samples taken from COVID-19 patients and healthy donors in the timespan between May 2020 and April 2022. We performed genotyping of the virus in nasopharyngeal swabs, which was followed by assessment of cytokines' concentration in blood plasma. We noted that out of nearly 30 cytokines, only four showed stable elevation independently of the variant (IL-6, IL-10, IL-18 and IL-27), and we believe them to be 'constant' markers for COVID-19 infection. Cytokines that were studied as potential biomarkers lose their diagnostic value as the virus evolves, and the specter of potential targets for predictive models is narrowing. So far, only four cytokines (IL-6, IL-10, IL-18, and IL-27) showed a consistent rise in concentrations independently of the genetic variant of the virus. Although we believe our findings to be of scientific interest, we still consider them inconclusive; further investigation and comparison of immune responses to different variants of SARS-CoV-2 is required.

The results of thrombectomy from the arteries of the lower extremities in patients infected with SARS-CoV-2 Omicron variant with different severity of respiratory failure.

GOAL: Analysis of the results of thrombectomy from the arteries of the lower extremities in patients with COVID-19 against the background of different severity of respiratory failure. MATERIALS AND METHODS: This retrospective, cohort, comparative study for the period from 05/01/2022 to 20/07/2022 included 305 patients with acute thrombosis of the arteries of the lower extremities against the background of the course of COVID-19 (SARS-CoV-2 Omicron variant). Depending on the type of oxygen support, 3 groups of patients were formed: group 1 (n = 168) - oxygen insufflation through nasal cannulas; group 2 (n = 92) - non-invasive lung ventilation; and group 3 (n = 45) - artificial lung ventilation. RESULTS: Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1: 5.3%, n = 9; group 2: 72.8%, n = 67; group 3: 100%, n = 45; p < 0.0001), rethrombosis (group 1 : 18.4%, n = 31; group 2: 69.5%, n = 64; group 3: 91.1%, n = 41; p < 0.0001), and limb amputations (group 1: 9.5%, n = 16; group 2: 56.5%, n = 52; group 3: 91.1%, n = 41; p < 0.0001) was recorded in group 3 (ventilated) patients. CONCLUSION: In patients infected with COVID-19 and on artificial lung ventilation, a more aggressive course of the disease is noted, expressed in an increase in laboratory parameters (C-reactive protein, ferritin, interleukin-6, and D-dimer) of the degree of pneumonia (CT-4 in overwhelming number) and localization of thrombosis of the arteries of the lower extremities, mainly in the tibial arteries.

Antibody Responses to the SARS-CoV-2 Ancestral Strain and Omicron Variants in Moderna mRNA-1273 Vaccinated Active-Duty US Navy Sailors and Marines.

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.

Antivirals for adult patients hospitalised with SARS-CoV-2 infection: a randomised, phase II/III, multicentre, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn trial.

Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).

Performance Evaluation of Five Rapid At-Home COVID-19 Antigen Tests against the Omicron Variant.

Rapid coronavirus disease 2019 (COVID-19) antigen tests can be used to aid in quickly identifying positive cases, which can help mitigate the spread of COVID-19 infection. Using previously characterized Omicron-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), non-Omicron-positive SARS-CoV-2, and negative samples, we evaluated five brands of at-home rapid COVID-19 antigen tests (On/Go at-home COVID-19 rapid antigen self-test, iHealth COVID-19 antigen rapid test, QuickVue SARS antigen test, Abbott BinaxNOW COVID-19 card home test, and InBios SCoV-2 Ag detect rapid self-test). Our results showed that these rapid tests had similar levels of sensitivity to Omicron and non-Omicron variants (On/Go, 76.4% and 71.0%; iHealth, 73.0% and 71.0%; QuickVue, 84.3% and 74.3%; BinaxNOW, 69.7% and 71.0%; and InBios, 66.3% and 64.5%, respectively). In conclusion, rapid COVID-19 antigen tests can continue to be used as part of public health measures to combat the spread of the Omicron variant, as their sensitivity was not significantly affected. IMPORTANCE The emergence of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to mutations as part of the virus evolution process. These mutations might affect the sensitivity of diagnostic tests that are currently being used to detect the virus. Because rapid coronavirus disease 2019 (COVID-19) antigen tests are commonly used in the general population, it is important to assess their performance in detecting the Omicron variant. Here, we compared the performance of five brands of rapid tests against Omicron and non-Omicron variants using nasopharyngeal swab samples in viral transport media. Our result found no difference in their performance, suggesting no reduction in sensitivity when used to detect the Omicron variant.

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aORs) for mortality were 1.58 (95% CI: 1.46, 1.70) and 1.04 (95% CI: 0.96, 1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and amongst those with current cancer (aOR = 0.69, 95% CI = 0.53 to 0.90). CONCLUSIONS: Current cancer, especially amongst younger patients, posed a substantially increased risk for death and ICU admission among COVID-19 patients; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic.

The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature.

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.

Transfer Learning using BERT & Comparative Analysis of ML Algorithms for Opinion Mining

Sentiment Analysis is an ongoing field of research in text mining that is concerned with the computational treatment of textual views, sentiments, and subjectivity. It's the task of distinguishing between positive and negative viewpoints, emotions, and assessments. Sentiment analysis has been the topic of intensive research since its inception. During COVID-19, there has been a subtle increase in the usage and the time spent on the social networking sites by people as most of the daily operations have moved online. Moreover, in addition to the illness itself, the pandemic has led to dread, anxiety, stress, concern, repugnance, and poignancy in individuals all around the world. Considering these indicators, experts are paying close attention to Twitter data analysis during this pandemic. BERT is used as a transfer learning model and this work analyses the efficacy of fine-tuning it for the task of opinion mining by comparing it to a baseline model that includes a TF-IDF vectorizer and a Naïve Bayes classifier. Its performance is also compared to that of Naïve Bayes, Logistic Regression, K Nearest Neighbor, Decision Tree and XGBoost classifier. To determine the most effective settings for the BERT model, hyper-parameter tweaking is used. After two epochs of training at a learning rate of le-5 and batch size of 16, the maximum accuracy of 87.6% is attained. These results outperform all of the machine learning models examined in this study. This work tackles a comprehensive overview of the last update in this field. It can be beneficial to scholars in this domain because it encapsulates the most well-known Sentiment analysis methodologies and their comparison in single research work. © 2022 IEEE.

SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures.

BACKGROUND: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort. METHODS: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens. RESULTS: Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks. CONCLUSIONS: Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.

Human Adenovirus and Influenza A Virus Exacerbate SARS-CoV-2 Infection in Animal Models.

In this study, we investigated the features of the infectious process by simulating co-infection with SARS-CoV-2 and human adenovirus type 5 (HAdV-5) or influenza A virus (IAV) in vitro and in vivo. The determination of infectious activity of viruses and digital PCR demonstrated that during simultaneous and sequential HAdV-5 followed by SARS-CoV-2 infection in vitro and in vivo, the HAdV-5 infection does not interfere with replication of SARS-CoV-2. The hamsters co-infected and mono-infected with SARS-CoV-2 exhibited nearly identical viral titers and viral loads of SARS-CoV-2 in the lungs. The hamsters and ferrets co-infected by SARS-CoV-2- and IAV demonstrated more pronounced clinical manifestations than mono-infected animals. Additionally, the lung histological data illustrate that HAdV-5 or IAV and SARS-CoV-2 co-infection induces more severe pathological changes in the lungs than mono-infection. The expression of several genes specific to interferon and cytokine signaling pathways in the lungs of co-infected hamsters was more upregulated compared to single infected with SARS-CoV-2 animals. Thus, co-infection with HAdV-5 or IAV and SARS-CoV-2 leads to more severe pulmonary disease in animals.

Transforming global health education during the COVID-19 era: perspectives from a transnational collective of global health students and recent graduates.

Inspired by the 2021 BMJ Global Health Editorial by Atkins et al on global health (GH) teaching during the COVID-19 pandemic, a group of GH students and recent graduates from around the world convened to discuss our experiences in GH education during multiple global crises. Through weekly meetings over the course of several months, we reflected on the impact the COVID-19 pandemic and broader systemic inequities and injustices in GH education and practice have had on us over the past 2 years. Despite our geographical and disciplinary diversity, our collective experience suggests that while the pandemic provided an opportunity for changing GH education, that opportunity was not seized by most of our institutions. In light of the mounting health crises that loom over our generation, emerging GH professionals have a unique role in critiquing, deconstructing and reconstructing GH education to better address the needs of our time. By using our experiences learning GH during the pandemic as an entry point, and by using this collective as an incubator for dialogue and re-imagination, we offer our insights outlining successes and barriers we have faced with GH and its education and training. Furthermore, we identify autonomous collectives as a potential viable alternative to encourage pluriversality of knowledge and action systems and to move beyond Western universalism that frames most of traditional academia.

COVID-19 and drivers of excess death rate in Peru: A longitudinal ecological study.

Background: Peru has experienced unprecedented mortality and economic toll due to the COVID-19 (Coronavirus disease 2019) pandemic in 2020. We aimed to assess the association between socioeconomic factors and excess death rate, and to explore the relative contribution of these factors to the differences in excess death rate during January-December 2020. Methods: Different national secondary data sources were used to describe excess death rates and different determinants, from distal to proximal. A confounding-adjusted multilevel mixed-effects linear regression was used to assess the association between these variables and excess death rates. Their relative contributions to the differences in excess death rate between the periods with the highest and lowest excess death rates were analyzed through regression-based Oaxaca-Blinder decomposition methods. Findings: The excess death rate showed an increasing trend in all regions, with different slopes. The confounding-adjusted multilevel analysis showed that higher healthcare access was associated with lower excess death rates (difference (95%CI) -0.004 (-0.005, -0.002)), whereas COVID-19 incidence was associated with higher excess death rates (difference (95%CI) 0.052 (0.042, 0.063)). The decomposition analysis showed COVID-19 incidence (41.9%), per capita income (19.4%) and unemployment rate (14.6%) as the main risk factors, while the main protective factors included per capita health expenditure (44.7%), healthcare access (33.2%) and health insurance (12.1%). Interpretation: Our study suggests that the excess death rate during the COVID-19 pandemic in Peru may have been influenced by other factors besides COVID-19 incidence, from distal to proximal drivers, including socioeconomic determinants, factors outside and within the health sector, and susceptibility factors. Further studies at individual level are needed to corroborate our findings.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose.

OBJECTIVE: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. METHODS: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). RESULTS: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. CONCLUSION: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Countries Response for People With Disabilities During the COVID-19 Pandemic.

Background and Objectives: During the Coronavirus disease 19 (COVID-19) pandemic, isolation and prevention measures to reduce COVID-19 contagions are essential for the care of all people; these measures should comply with the principles of inclusion and accessibility for people with disabilities (PWD), with all kinds of deficiencies and levels of dependency. Thereby, the aim of this article is to present the measures adopted for PWD or people with rehabilitation needs, for containment, mitigation, or suppression of the SARS-CoV-2 virus in different countries of all continents and of all income levels. Methods: A narrative approach was used in this article. First, a broad search was carried out in the 193 member states of the UN, and then 98 countries that issued any document, report, or information related to disability and COVID-19 were selected. Finally, 32 countries were included in this article because they presented official information. We considered official sources, the information available in the government, or on the health ministry page of the country. In this way, the countries that presented information which did not correspond to an official source were excluded. The search was conducted in August 2020 and updated in March 2021. Results: First, the non-pharmacological general interventions for PWD included informative measures and general recommendations during the stay at home, isolation, and biosecurity measures, contagion prevention, detection of positive cases, mobilization measures, and measures implemented in institutions or residences of PWD. Second, we identified the economic and social benefits provided to PWD during the pandemic. Finally, we identified the measures taken by countries according to the type of impairment (visual, hearing, physical, mental, and cardiopulmonary impairment) during the COVID-19 pandemic. Conclusion: In response to the COVID-19 pandemic, only 50% of countries from the five world regions created and implemented specific measures for PWD to containment, mitigation, or suppression of the SARS-CoV-2 virus. There is very little specific information available about the measures to continue with the care of people with rehabilitation needs and the long-term follow-up of PWD, and for the prevention and response to violence, especially for women with disabilities.