Risk factors for acute kidney injury in patients hospitalized with COVID-19 / Fatores de risco para lesão renal aguda em pacientes hospitalizados com COVID-19

Abstract Introduction: Acute kidney injury (AKI) occurs frequently in COVID-19 patients and is associated with greater morbidity and mortality. Knowing the risks of AKI allows for identification, prevention, and timely treatment. This study aimed to identify the risk factors associated with AKI in hospitalized patients. Methods: A descriptive, retrospective, cross-sectional, and analytical component study of adult patients hospitalized with COVID-19 from March 1 to December 31, 2020 was carried out. AKI was defined by the creatinine criteria of the KDIGO-AKI guidelines. Information, regarding risk factors, was obtained from electronic medical records. Results: Out of the 934 patients, 42.93% developed AKI, 60.59% KDIGO-1, and 9.9% required renal replacement therapy. Patients with AKI had longer hospital stay, higher mortality, and required more intensive care unit (ICU) admission, mechanical ventilation, and vasopressor support. Multivariate analysis showed that age (OR 1.03; 95% CI 1.02-1.04), male sex (OR 2.13; 95% CI 1.49-3.04), diabetes mellitus (DM) (OR 1.55; 95% CI 1.04-2.32), chronic kidney disease (CKD) (OR 2.07; 95% CI 1.06-4.04), C-reactive protein (CRP) (OR 1.02; 95% CI 1.00-1.03), ICU admission (OR 1.81; 95% CI 1.04-3.16), and vasopressor support (OR 7.46; 95% CI 3.34-16.64) were risk factors for AKI, and that bicarbonate (OR 0.89; 95% CI 0.84-0.94) and partial pressure arterial oxygen/inspired oxygen fraction index (OR 0.99; 95% CI 0.98-0.99) could be protective factors. Conclusions: A high frequency of AKI was documented in COVID-19 patients, with several predictors: age, male sex, DM, CKD, CRP, ICU admission, and vasopressor support. AKI occurred more frequently in patients with higher disease severity and was associated with higher mortality and worse outcomes.

RESUMO Introdução: Lesão renal aguda (LRA) ocorre frequentemente em pacientes com COVID-19 e associa-se a maior morbidade e mortalidade. Conhecer riscos da LRA permite a identificação, prevenção e tratamento oportuno. Este estudo teve como objetivo identificar fatores de risco associados à LRA em pacientes hospitalizados. Métodos: Realizou-se estudo descritivo, retrospectivo, transversal e de componente analítico de pacientes adultos hospitalizados com COVID-19 de 1º de março a 31 de dezembro, 2020. Definiu-se a LRA pelos critérios de creatinina das diretrizes KDIGO-LRA. Informações sobre fatores de risco foram obtidas de prontuários eletrônicos. Resultados: Dos 934 pacientes, 42,93% desenvolveram LRA, 60,59% KDIGO-1 e 9,9% necessitaram de terapia renal substitutiva. Pacientes com LRA apresentaram maior tempo de internação, maior mortalidade e necessitaram de mais internações em UTIs, ventilação mecânica e suporte vasopressor. A análise multivariada mostrou que idade (OR 1,03; IC 95% 1,02-1,04), sexo masculino (OR 2,13; IC 95% 1,49-3,04), diabetes mellitus (DM) (OR 1,55; IC 95% 1,04-2,32), doença renal crônica (DRC) (OR 2,07; IC 95% 1,06-4,04), proteína C reativa (PCR) (OR 1,02; IC 95% 1,00-1,03), admissão em UTI (OR 1,81; IC 95% 1,04-3,16) e suporte vasopressor (OR 7,46; IC 95% 3,34-16,64) foram fatores de risco para LRA, e que bicarbonato (OR 0,89; IC 95% 0,84-0,94) e índice de pressão parcial de oxigênio arterial/fração inspirada de oxigênio (OR 0,99; IC 95% 0,98-0,99) poderiam ser fatores de proteção. Conclusões: Documentou-se alta frequência de LRA em pacientes com COVID-19, com diversos preditores: idade, sexo masculino, DM, DRC, PCR, admissão em UTI e suporte vasopressor. LRA ocorreu mais frequentemente em pacientes com maior gravidade da doença e associou-se a maior mortalidade e piores desfechos.

Myocarditis, Coagulopathy, and Small Fibre, Sensory, and Multiple Cranial Nerve Neuropathy Complicating BNT162b2 Vaccination: A Case Report.

SARS-CoV-2 vaccinations can lead to complications, including post-acute COVID-19 vaccination syndrome (PACVS). There has been no report of a patient with PACVS presenting with Guillain-Barre syndrome (GBS), myocarditis/pericarditis, immunodeficiency, or coagulopathy after the second BNT162b2 dose. The patient is a 51-year-old woman with chronic myopericarditis, coagulopathy due to factor-VIII increase and protein-S deficiency, GBS, and a number of other ocular, dermatological, immunological, and central nervous system abnormalities related to the second dose of the BNT172b2 vaccine. GBS manifested with mild, multiple cranial nerve lesions, small fibre neuropathy (SFN) affecting the autonomic system with postural tachycardia syndrome (POTS) and orthostatic hypotension, and sensory disturbances in the upper and lower limbs. PACVS was diagnosed months after onset, but despite the delayed diagnosis, the patient benefited from glucocorticoids, repeated HELP apheresis, and multiple symptomatic treatments. The case shows that SARS-CoV-2 vaccination can be complicated by PACVS manifesting as chronic myopericarditis, coagulopathy, GBS with predominant dysautonomia, and impaired immune competence, and that diagnosis of PACVS can be delayed for months. Delayed diagnosis of PACVS may result in a delay in appropriate treatment and the prolongation of disabling symptoms. Patients and physicians should be made aware of PACVS to improve diagnostic and therapeutic management in terms of patient and healthcare system costs.

Evaluating the spike in the symptomatic proportion of SARS-CoV-2 in China in 2022 with variolation effects: a modeling analysis.

Despite most COVID-19 infections being asymptomatic, mainland China had a high increase in symptomatic cases at the end of 2022. In this study, we examine China's sudden COVID-19 symptomatic surge using a conceptual SIR-based model. Our model considers the epidemiological characteristics of SARS-CoV-2, particularly variolation, from non-pharmaceutical intervention (facial masking and social distance), demography, and disease mortality in mainland China. The increase in symptomatic proportions in China may be attributable to (1) higher sensitivity and vulnerability during winter and (2) enhanced viral inhalation due to spikes in SARS-CoV-2 infections (high transmissibility). These two reasons could explain China's high symptomatic proportion of COVID-19 in December 2022. Our study, therefore, can serve as a decision-support tool to enhance SARS-CoV-2 prevention and control efforts. Thus, we highlight that facemask-induced variolation could potentially reduces transmissibility rather than severity in infected individuals. However, further investigation is required to understand the variolation effect on disease severity.

COVID-19 and vaccination in hereditary angioedema: Single center experience.

Like many microbial agents, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccination may increase the frequency and/or severity of attacks. We aimed to observe/evaluate patients with hereditary angioedema (HAE) followed by Sakarya University Research/Training Hospital pediatric allergy unit, Sakarya, Türkiye, for the effects of SARS-CoV-2 infection and COVID-19 vaccination. Ten HAE patients-3 males and 7 females-were evaluated retrospectively. Their mean age was 31.80 ± 19.15 (min. 12 - max. 66) years. Four of 10 patients were diagnosed with type 1 HAE and 6 with type 2 HAE. Two out of 6 patients (mother and daughter) diagnosed with type 2 HAE had angioedema attacks during COVID-19 disease. Six out of 10 HAE patients received different COVID-19 vaccines available in Türkiye up to third and fourth doses. There was no increase in COVID-19 vaccine-related attacks during, after 72 hours, and up to the year after vaccination. As a result, we consider it safe to administer inactivated and/or mRNA vaccines in our patients with HAE. In addition, catching SARS-CoV-2 infection was not always associated with disease exacerbation or activation.

Endovascular management of KILT syndrome and COVID-19-related extensive deep vein thrombosis in a pregnant patient: A case report.

We report on a 20-year-old pregnant woman who tested positive for SARS-CoV-2 and was diagnosed with KILT syndrome, a rare condition that increases the risk of thrombotic events. The patient showed signs of deep vein thrombosis that extended from the bilateral iliac vein to the inferior vena cava (IVC), which was treated with placement of an IVC filter and endovascular thromboaspiration/thrombolysis. The IVC was successfully recanalized; however, during follow-up, thrombotic restenosis occurred at the filter level, requiring filter removal. This case highlights the potential benefits of endovascular thromboaspiration/thrombolysis and IVC filter placement in patients with KILT syndrome presenting with acute thrombotic events.

Exploring the viability of Zeatin as a prospective therapeutic candidate for investigating the complex interplay between severe acute respiratory syndrome coronavirus (SARS-CoV) and Alzheimer's disease.

The present research aims to explore the intricate link between SARS-CoV infection and susceptibility to Alzheimer's disease, focusing on the role of APOE4, a genetic factor associated with both conditions. Our research aims to uncover shared molecular pathways, considering APOE4's impact on lipid metabolism, immune responses, and neuroinflammation relevant to COVID-19 and AD. The Chyawanprash phytocompounds were subjected to in-silico ADMET profiling and Zeatin a neuroprotective cytokinin emerged as a promising regulator of the ACE2-SPIKE complex as it exhibits favourable pharmacological attributes, presenting as a non-substrate for Permeability glycoprotein, low Protein Binding Percentage, and distinctive toxicity endpoints. Therapeutic candidate. Zeatin's robust binding disrupts the intricate APOE4-ACE2-SPIKE interplay (AAS), offering a potential therapeutic avenue that is further corroborated by Molecular dynamic simulation as the system remained stable without any major fluctuation throughout the 100ns simulation. The AAS binding free energy, determined as -124.849 +/- 15.513 KJ/mol using MMPBSA assay, reveals significant contributions to complex stability from amino acids including, GLN41: 1.211 kcal/mol, GLU340: 1.188 kcal/mol, ALA344: 1.198 kcal/mol, while ARG38: 2.011 kcal/mol establishes pivotal strong bonds integral to the interaction between AAS and Zeatin. Rigorous cytotoxicity assessments reveal Zeatin's safety profile, highlighting its inhibitory effect on LN18 cell viability that sharply decreases to 32.47% at 200 µg/ml, underscoring its modulatory impact on cellular metabolism. These findings enhance our understanding of the convergent mechanisms linking SARS-CoV and AD, providing valuable insights for potential therapeutic interventions. Further research is warranted to elucidate the specific pathways and molecular mechanisms through which zeatin exerts its protective effects.

Identification of receptors and factors associated with human coronaviruses in the oral cavity using single-cell RNA sequencing.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) ravaged the world, and Coronavirus Disease 2019 (COVID-19) exhibited highly prevalent oral symptoms that had significantly impacted the lives of affected patients. However, the involvement of four human coronavirus (HCoVs), namely SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-229E, in oral cavity infections remained poorly understood. We integrated single-cell RNA sequencing (scRNA-seq) data of seven human oral tissues through consistent normalization procedure, including minor salivary gland (MSG), parotid gland (PG), tongue, gingiva, buccal, periodontium and pulp. The Seurat, scDblFinder, Harmony, SingleR, Ucell and scCancer packages were comprehensively used for analysis. We identified specific cell clusters and generated expression profiles of SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) in seven oral regions, providing direction for predicting the tropism of four HCoVs for oral tissues, as well as for dental clinical treatment. Based on our analysis, it appears that various SCARFs, including ACE2, ASGR1, KREMEN1, DPP4, ANPEP, CD209, CLEC4G/M, TMPRSS family proteins (including TMPRSS2, TMPRSS4, and TMPRSS11A), and FURIN, are expressed at low levels in the oral cavity. Conversely, BSG, CTSB, and CTSL exhibit enrichment in oral tissues. Our study also demonstrates widespread expression of restriction factors, particularly IFITM1-3 and LY6E, in oral cells. Additionally, some replication, assembly, and trafficking factors appear to exhibit broad oral tissues expression patterns. Overall, the oral cavity could potentially serve as a high-risk site for SARS-CoV-2 infection, while displaying a comparatively lower degree of susceptibility towards other HCoVs (including SARS-CoV, MERS-CoV and HCoV-229E). Specifically, MSG, tongue, and gingiva represent potential sites of vulnerability for four HCoVs infection, with the MSG exhibiting a particularly high susceptibility. However, the expression patterns of SCARFs in other oral sites demonstrate relatively intricate and may only be specifically associated with SARS-CoV-2 infection. Our study sheds light on the mechanisms of HCoVs infection in the oral cavity as well as gains insight into the characteristics and distribution of possible HCoVs target cells in oral tissues, providing potential therapeutic targets for HCoVs infection in the oral cavity.

Preparing correctional settings for the next pandemic: a modeling study of COVID-19 outbreaks in two high-income countries.

Introduction: Correctional facilities are high-priority settings for coordinated public health responses to the COVID-19 pandemic. These facilities are at high risk of disease transmission due to close contacts between people in prison and with the wider community. People in prison are also vulnerable to severe disease given their high burden of co-morbidities. Methods: We developed a mathematical model to evaluate the effect of various public health interventions, including vaccination, on the mitigation of COVID-19 outbreaks, applying it to prisons in Australia and Canada. Results: We found that, in the absence of any intervention, an outbreak would occur and infect almost 100% of people in prison within 20 days of the index case. However, the rapid rollout of vaccines with other non-pharmaceutical interventions would almost eliminate the risk of an outbreak. Discussion: Our study highlights that high vaccination coverage is required for variants with high transmission probability to completely mitigate the outbreak risk in prisons.

Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells.

Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of in vitro experiments can be beneficial in a number of aspects, such as model simplification (e.g., the absence of adaptive immune response and innate immunity cells), better measurement accuracy, and the possibility to measure additional data types in comparison with in vivo case. In this study, we consider a refinement of our previously developed and validated model based on a system of integro-differential equations. We fit the model to the experimental data of Omicron and Delta infections in Caco-2 (human intestinal epithelium model) and Calu-3 (lung epithelium model) cell lines. The data include known information on initial conditions, infectious virus titers, and intracellular viral RNA measurements at several time points post-infection. The model accurately explains the experimental data for both variants in both cell lines using only three variant- and cell-line-specific parameters. Namely, the cell entry rate is significantly lower for Omicron, and Omicron triggers a stronger cytokine production rate (i.e., innate immune response) in infected cells, ultimately making uninfected cells resistant to the virus. Notably, differences in only a single parameter (e.g., cell entry rate) are insufficient to obtain a reliable model fit for the experimental data.

COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Cu-based thin rolled foils: relationship among alloy composition, micromechanical and antiviral properties against SARS-CoV-2.

The healthcare-associated infections (HAIs) and pandemics caused by multidrug-resistant (MDR) and new-generation pathogens threaten the whole world community. Cu and its alloys have been attracting widespread interest as anti-contamination materials due to the rapid inactivation of MDR-superbugs and viruses. Applying thin Cu-based foils on pre-existing surfaces in hygiene-sensitive areas represents a quick, simple, cost-effective self-sanitising practice. However, the influence of chemical composition and microstructure should be deeply investigated when evaluating the antimicrobial capability and durability of Cu-based materials. The effect of composition on micromechanical and antiviral properties was investigated by comparing Cu15Zn and Cu18Ni20Zn (foil thickness from 13 to 27 µm) with Phosphorous High-Conductivity (PHC) Cu. The influence of recrystallisation annealing of PHC Cu was also investigated. Microstructural characterisation was carried out by optical (OM) and scanning electron (FEG-SEM) microscopy, Energy-dispersive Spectroscopy (EDS) and Electron-Backscattered Diffraction (EBSD). The micromechanical behaviour was assessed by microhardness, microscale abrasion and scratch tests. Cu-based foils were exposed to SARS-CoV-2 for different time points in quasi-dry conditions (artificial sweat solution), evaluating their antiviral capability by quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Surface morphology, contact angle measurements and Cu release were measured. All Cu-based surfaces completely inactivated SARS-CoV-2 in 10 min: pure Cu was the best option regarding antiviral efficiency, while Cu15Zn showed the best trade-off between micromechanical and antiviral properties.

Antibody-labelled gold nanoparticles synthesized by laser ablation to detect SARS-CoV-2 antigen spike.

Background and purpose: Rapid detection test via lateral flow immunoassay (LFIA) is employed as an alternate method to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Gold nanoparticles (AuNPs), a vital component of LFIA, can be synthesized by laser ablation technique. This intense laser radiation may result in monodisperse gold nanoclusters, which are impurity-free and demonstrate innovative biocompatible surface chemistry. In this current research, laser-ablated AuNPs are produced and coupled with an anti-spike SARS-CoV-2 monoclonal antibody (mAb) generated in our prior study. Experimental approach: The AuNPs from 30,000 shots of laser ablation exhibited a robust red color with a maximum absorbance peak at 520 nm. The performance of AuNPs-mAb conjugates as a signal reporter was then evaluated in half-stick LFIA. Key results: The size distribution of AuNPs shows a relatively monodisperse and unimodal distribution with average particle diameters of 44.77 nm and a surface potential of -38.5 mV. The purified anti-spike mAb SARS-CoV-2 yielded two protein bands, representing the mAb heavy chain at 55 kDa and its light chain at 25 kDa. The immobilization of anti-spike mAb onto the surface of AuNPs revealed that 25 g/ml of mAb at phosphate buffer pH 9 was required to stabilize the AuNPs. The functional test of this conjugate was performed using dipstick LFIA, and the result shows that the AuNPs-mAb conjugates could successfully detect commercial spike antigen of SARS-CoV-2 at 10 ng level. Conclusion: In this study, laser-ablated AuNPs were functionalized with anti-spike mAb SARS-CoV-2 and successfully used as a signal reporter in half-stick LFIA for detecting antigen spike SARS-CoV-2.

Effects of long-term exposure to outdoor air pollution on COVID-19 incidence: A population-based cohort study accounting for SARS-CoV-2 exposure levels in the Netherlands.

Several studies have linked air pollution to COVID-19 morbidity and severity. However, these studies do not account for exposure levels to SARS-CoV-2, nor for different sources of air pollution. We analyzed individual-level data for 8.3 million adults in the Netherlands to assess associations between long-term exposure to ambient air pollution and SARS-CoV-2 infection (i.e., positive test) and COVID-19 hospitalisation risks, accounting for spatiotemporal variation in SARS-CoV-2 exposure levels during the first two major epidemic waves (February 2020-February 2021). We estimated average annual concentrations of PM10, PM2.5 and NO2 at residential addresses, overall and by PM source (road traffic, industry, livestock, other agricultural sources, foreign sources, other Dutch sources), at 1 × 1 km resolution, and weekly SARS-CoV-2 exposure at municipal level. Using generalized additive models, we performed interval-censored survival analyses to assess associations between individuals' average exposure to PM10, PM2.5 and NO2 in the three years before the pandemic (2017-2019) and COVID-19-outcomes, adjusting for SARS-CoV-2 exposure, individual and area-specific confounders. In single-pollutant models, per interquartile (IQR) increase in exposure, PM10 was associated with 7% increased infection risk and 16% increased hospitalisation risk, PM2.5 with 8% increased infection risk and 18% increased hospitalisation risk, and NO2 with 3% increased infection risk and 11% increased hospitalisation risk. Bi-pollutant models suggested that effects were mainly driven by PM. Associations for PM were confirmed when stratifying by urbanization degree, epidemic wave and testing policy. All emission sources of PM, except industry, showed adverse effects on both outcomes. Livestock showed the most detrimental effects per unit exposure, whereas road traffic affected severity (hospitalisation) more than infection risk. This study shows that long-term exposure to air pollution increases both SARS-CoV-2 infection and COVID-19 hospitalisation risks, even after controlling for SARS-CoV-2 exposure levels, and that PM may have differential effects on these COVID-19 outcomes depending on the emission source.

Health Literacy Among University Students in the COVID-19 Pandemic: A Systematic Review.

BACKGROUND: The purpose of this systematic review was to assess different studies that worked on university students' health literacy during covid19 pandemic and to make an overview of this issue to recognize possible determinants associated with health literacy. METHODS: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Four databases (Google Scholar, Web of Science, Pubmed, and Scopus) were used for searching cross-sectional works that assessed the health literacy of university students. We searched papers from December 1st, 2019 up to June 10th, 2022. English language articles were used. Studies were done in countries including; Iran, Pakistan, the USA, Vietnam, China, Colombia, Germany, and Indonesia. RESULTS: The systematic review contains 12 research studies involving 17773 students. There was a relationship between health literacy and some determinants. Positive determinants included age, female gender, Urban background, cognitive maturity, Higher educational qualification, information source (Health workers), number of semesters, and parental education. Some negative determinants were male gender, Rural background, smoking, drinking, being able to pay for medication, lower conspiracy beliefs, and higher fear of COVID-19. CONCLUSION: University students around the world should have courses about health literacy according to university disciplines. These courses should be available for students of different fields to enhance their effectiveness, and training should be associated with students' needs and their subgroup traits.

The association of three vaccination doses with reduced gastrointestinal symptoms after severe acute respiratory syndrome coronavirus 2 infections in patients with inflammatory bowel disease.

Background: The protective efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination against the new-onset gastrointestinal (GI) symptoms following COVID-19 infection is critical among patients with inflammatory bowel disease (IBD); however, the optimal protective vaccine dose remains unknown. Therefore, this study aimed to clarify whether there is a correlation between SARS-CoV-2 vaccinations and GI symptoms following Omicron infection in patients with IBD. Methods: We conducted a multicenter cross-sectional study of IBD patients among three tertiary hospitals in eastern China. Professional physicians collected all data using online questionnaires. The patients were stratified into four groups: patients who were unvaccinated and patients who received one, two, or three vaccination doses. The primary outcome was the presence of any new-onset GI symptoms after SARS-CoV-2 infection before a negative SARS-CoV-2 nucleic acid test or a negative self-testing for antigens. Results: In total, 536 patients with IBD (175 unvaccinated, 31 vaccinated, 166 vaccinated with two doses, and 164 vaccinated with three doses) reported having COVID-19 infection. Compared with the unvaccinated, the three vaccination doses group was associated with reduced GI symptoms after infection (adjusted odds ratio = 0.56, 95% confidence interval 0.34-0.90, P < 0.05). Reduced diarrhea (adjusted odds ratio = 0.54, 95% confidence interval 0.31-0.92, P < 0.05) and nausea or vomiting (adjusted odds ratio = 0.45, 95% confidence interval 0.21-0.92, P < 0.05) were observed in the three vaccination doses group compared with the unvaccinated group. Conclusions: In conclusion, in the 536 patients with IBD who reported COVID-19 infection, we found that the three vaccination doses, but not the one or two doses group, were associated with reduced GI symptoms after infection compared with the unvaccinated group.

Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection.

Purpose: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lingering threat to public health has fueled the search for effective therapeutics to treat SARS-CoV-2. This study aimed to develop lipid nanoparticle (LNP) inhibitors of SARS-CoV-2 entry to reduce viral infection in the nose and upper airway. Methods: Two types of LNP formulations were prepared following a microfluidic mixing method. The LNP-Trap consisted of DOPC, DSPC, cholesterol, and DSPE-PEG-COOH modified with various spike protein binding ligands, including ACE2 peptide, recombinant human ACE2 (rhACE2) or monoclonal antibody to spike protein (mAb). The LNP-Trim consisted of ionizing cationic DLin-MC3-DMA, DSPC, cholesterol, and DMG-PEG lipids encapsulating siACE2 or siTMPRSS2. Both formulations were assayed for biocompatibility and cell uptake in airway epithelial cells (Calu-3). Functional assessment of activity was performed using SARS-CoV-2 spike protein binding assays (LNP-Trap), host receptor knockdown (LNP-Trim), and SARS-CoV-2 pseudovirus neutralization assay (LNP-Trap and LNP-Trim). Localization and tissue distribution of fluorescently labeled LNP formulations were assessed in mice following intranasal administration. Results: Both LNP formulations were biocompatible based on cell impedance and MTT cytotoxicity studies in Calu-3 cells at concentrations as high as 1 mg/mL. LNP-Trap formulations were able to bind spike protein and inhibit pseudovirus infection by 90% in Calu-3 cells. LNP-Trim formulations reduced ACE2 and TMPRSS2 at the mRNA (70% reduction) and protein level (50% reduction). The suppression of host targets in Calu-3 cells treated with LNP-Trim resulted in over 90% inhibition of pseudovirus infection. In vivo studies demonstrated substantial retention of LNP-Trap and LNP-Trim in the nasal cavity following nasal administration with minimal systemic exposure. Conclusion: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway.

Influence of simultaneous comorbidities on COVID-associated acute respiratory distress syndrome mortality in people with diabetes.

Objectives: This study analyzed the influence of 23 comorbidities on COVID-associated acute distress respiratory syndrome (CARDS) mortality in people with a history of diabetes mellitus. Methods: An observational, analytical, cross sectional study was utilized to investigate data from 6723 health services in Brazil, comprising 5433 people with diabetes. Adjusted logistic regression models for demographic factors such as age, sex, and race were used to analyze the association between CARDS mortality and comorbidities. Results: Persons with two (p < 0.001), three (p < 0.001), four (p < 0.001), and five (p < 0.001) simultaneous comorbidities had a higher chance of dying. We identified that diabetes patients who had concomitant metabolic diseases (p = 0.019), neurological disorders (p < 0.001), or were smokers (p < 0.001) had a higher predicted mortality risk based on CADRS. Conclusion: The number of comorbidities plays a determining role in CARDS mortality in people with diabetes, especially those who suffer from smoking and neurological diseases simultaneously.

Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters.

Background: Characterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines. Methods: This study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants. Results: Multiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster. Conclusion: Overall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination.

Evolutionary trajectory of diverse SARS-CoV-2 variants at the beginning of COVID-19 outbreak.

Despite extensive scientific efforts directed toward the evolutionary trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans at the beginning of the COVID-19 epidemic, it remains unclear how the virus jumped into and evolved in humans so far. Herein, we recruited almost all adult coronavirus disease 2019 (COVID-19) cases appeared locally or imported from abroad during the first 8 months of the outbreak in Shanghai. From these patients, SARS-CoV-2 genomes occupying the important phylogenetic positions in the virus phylogeny were recovered. Phylogenetic and mutational landscape analyses of viral genomes recovered here and those collected in and outside of China revealed that all known SARS-CoV-2 variants exhibited the evolutionary continuity despite the co-circulation of multiple lineages during the early period of the epidemic. Various mutations have driven the rapid SARS-CoV-2 diversification, and some of them favor its better adaptation and circulation in humans, which may have determined the waxing and waning of various lineages.

The impact of the COVID-19 pandemic on non-COVID-associated mortality: A descriptive longitudinal study of UK data.

Background: It has been previously reported in the literature that the COVID-19 pandemic resulted in overall excess deaths and an increase in non-COVID deaths during the pandemic period.Specifically, our research elucidates the impact of the COVID-19 pandemic on non-COVID associated mortality. Study aim: To compare mortality rates in non-COVID conditions before and after the onset of the COVID-19 pandemic in England and Wales. Study design: Annual mortality data for the years 2011-2019 (pre-pandemic) and 2020 (pandemic) in England and Wales were retrieved from the Office for National Statistics (ONS). These data were filtered by ICD-10 codes for nine conditions with high associated mortality. We calculated mortality numbers - overall and age stratified (20-64 and 65+ years) and rates per 100 000, using annual mid-year population estimates. Methods: Interrupted time series analyses were conducted using segmented quasi-Poisson regression to identify whether there was a statistically significant change (p < 0.05) in condition-specific death rates following the pandemic onset. Results: Eight of the nine conditions investigated in this study had significant changes in mortality rate during the pandemic period (2020). All-age mortality rate was significantly increased in: 'Symptoms Signs and Ill-defined conditions', 'Cirrhosis and Other Diseases of the Liver', and 'Malignant Neoplasm of the Breast', whereas 'Chronic Lower Respiratory Disorders' saw a significant decrease. Age-stratified analyses also revealed significant increases in the 20-64 age-group in: 'Cerebrovascular Disorders', 'Dementia and Alzheimer's Disease', and 'Ischaemic Heart Diseases'. Conclusion: Trends in non-COVID condition-specific mortality rates from 2011 to 2020 revealed that some non-COVID conditions were disproportionately affected during the pandemic. This may be due to the direct impact COVID-19 had on these conditions or the effect the public health response had on non-COVID risk factor development and condition-related management. Further work is required to understand the reasons behind these disproportionate changes.