Single domain antibodies from camelids in the treatment of microbial infections.

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavy-chain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts.

COVID-19 Drug Treatments Are Prone to Sequestration in Extracorporeal Membrane Oxygenation Circuits: An Ex Vivo Extracorporeal Membrane Oxygenation Study.

Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.

[The use of immunoglobulins and monoclonal antibodies against COVID-19].

INTRODUCTION: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. RESULTS AND CONCLUSION: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.

Patients' and professionals' experiences with remote care during COVID-19: a qualitative study in general practices in low-income neighborhoods.

AIM: To explore how patients and general practice professionals in low-income neighborhoods experienced the increase of remote care during COVID-19. BACKGROUND: As the GP (general practitioner) is the first point of contact in Dutch health care, there are concerns about access to remote care for patients from low-income neighborhoods. Now that general practice professionals have returned to the pre-pandemic ways of healthcare delivery, this paper looks back at experiences with remote care during COVID-19. It investigates experiences of both patients and general practice professionals with the approachability and appropriateness of remote care and their satisfaction. METHODS: In this qualitative study, 78 patients and 18 GPs, 7 nurse practitioners and 6 mental health professionals were interviewed. Interviews were held on the phone and face-to-face in the native language of the participants. FINDINGS: Remote care, especially telephone consultation, was generally well-approachable for patients from low-income neighborhoods. Contrarily, video calling was rarely used. This was partly because patients did not know how to use it. The majority of patients thought remote care was possible for minor ailments but would also still like to see the doctor face-to-face regularly. Patients were generally satisfied with remote care at the time, but this did not necessarily reflect their willingness to continue using it in the future. Moreover, there was lack in consensus among general practice professionals on the appropriateness of remote care for certain physical and mental complaints. Nurse practitioners and mental health professionals had a negative attitude toward remote care. In conclusion, it is important to take the opinions and barriers of patients and care providers into account and to increase patient-centered care elements and care provider satisfaction in remote care. Integrating remote care is not only important in times of crisis but also for future care that is becoming increasingly digitalized.

Review of clinical characteristics and mortality outcomes in patients on maintenance hemodialysis during the Omicron surge: a single center experience.

BACKGROUND: This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge. METHODS: According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison. RESULTS: 366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group. CONCLUSIONS: Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities.

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. METHODS: We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. RESULTS: A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. CONCLUSION: This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic.

Background: Understanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic. Methods: A retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements. Results: Overall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26-130) mg/L, whereas the eosinophil count was 10 (0-60)/mm3. Eosinophil count normalization (≥100/mm3) by day 2 correlated significantly with decreased oxygen needs (<2 L) with hazard ratio (HR) = 3.7 [1.1-12.9] (p = 0.04). Likewise, CRP < 80 mg/L was associated with reduced oxygen requirements (p < 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06). Conclusion: The study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections.

[COVID-19 and autoimmune dysregulation: exploring common mechanisms and treatment strategies in interstitial lung disease].

COVID-19 is caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and manifests primarily as acute lung injury with diffuse interstitial lung disease evident in imaging. Patients often present with clinical features similar to those of autoimmune diseases and share imaging, treatment and serological similarities with autoimmune-related interstitial lung diseases. The association between autoimmune abnormalities and post-COVID-19 pulmonary fibrosis is also recognized. This article provided a comprehensive review of the pathogenic mechanisms, clinical manifestations, and therapeutic interventions associated with autoimmune abnormalities induced by SARS-CoV-2 infection.

Determinants of mortality in hypertensive patients admitted with COVID-19: a single-centre retrospective study at a tertiary hospital in South Africa.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has significantly impacted global health, with successive outbreaks leading to substantial morbidity and mortality. Hypertension, a leading cause of cardiovascular disease globally, has been identified as a critical comorbidity in patients with severe COVID-19, exacerbating the risk of adverse outcomes. This study aimed to elucidate the impact of hypertension on COVID-19 outcomes within the South African context. METHODS: A retrospective analysis was conducted at King Edward VIII Hospital, KwaZulu-Natal, South Africa, encompassing patients aged 13 years and above admitted with laboratory-confirmed SARS-CoV-2 infection between June 2020 and December 2021. The study investigated the association between hypertension and COVID-19 outcomes, analysing demographic, clinical, and laboratory data. Statistical analysis involved univariate and multivariate logistic regression to identify predictors of mortality among the hypertensive cohort. RESULTS: The study included 420 participants-encompassing 205 with hypertension. Hypertensive patients demonstrated significantly greater requirements for oxygen and steroid therapy (p < 0.001), as well as higher mortality rates (44.88%, p < 0.001)) compared to their non-hypertensive counterparts. Key findings demonstrated that a lower oxygen saturation (adjusted odds ratio (aOR) 0.934, p = 0.006), higher pulse pressure (aOR 1.046, p = 0.021), elevated CRP (aOR 1.007, p = 0.004) and the necessity for mechanical ventilation (aOR 5.165, p = 0.004) were independent risk factors for mortality in hypertensive COVID-19 patients. Notably, the study highlighted the pronounced impact of hypertension-mediated organ damage (HMOD) on patient outcomes, with ischemic heart disease being significantly associated with increased mortality (aOR 8.712, p = 0.033). CONCLUSION: Hypertension significantly exacerbates the severity and mortality risk of COVID-19 in the South African setting, underscoring the need for early identification and targeted management of hypertensive patients. This study contributes to the understanding of the interplay between hypertension and COVID-19 outcomes, emphasising the importance of considering comorbidities in the management and treatment strategies for COVID-19. Enhanced pandemic preparedness and healthcare resource allocation are crucial to mitigate the compounded risk presented by these concurrent health crises.

Lessons from community engagement to improve COVID-19 diagnosis and treatment in Cochabamba, Bolivia.

BACKGROUND: Community engagement is recognized as a vital component of health-related research and programs, particularly during infectious disease outbreaks and epidemics. Despite the importance of engaging communities in the response to COVID-19, relatively little research has examined how this was (or was not) achieved, and even less in low- and middle-income countries. This article describes the community engagement that accompanied efforts to strengthen COVID-19 diagnosis and treatment as part of the ECO Project in Cochabamba, Bolivia and highlights lessons for future pandemic response. METHODS: Community engagement involved formative assessment, co-creation to develop a health information campaign, ongoing community listening and evaluation. Qualitative data were collected during workshops, project meetings and focus groups. Questionnaire-based surveys were conducted to assess COVID-19-related attitudes, knowledge and practices. RESULTS: The collected data highlighted the value of working closely with well-established community health committees and involving community members with social media skills in the design of COVID-19-related messages to address on- and offline misinformation. Co-creation sessions enabled the adjustment of the information campaign in terms of content and approach based on the needs and preferences of community members and health staff. The continuous listening with community and health personnel facilitated the ongoing adaptation of project activities. CONCLUSION: Through a stepped and multi-pronged approach, incorporating co-creation and community listening, the engagement could respond to emerging local challenges during the pandemic. The project created spaces for dialogue and opportunities for collaboration that strengthened links between the community and the health services.

Main findings Key elements of community engagement to improve COVID-19 diagnosis and treatment in Cochabamba, Bolivia, included working closely with well-established community health committees, involving community members with social media skills in the co-design of COVID-19-related messages, and continuous listening with community and health personnel facilitated the ongoing adaptation of project activities.Added knowledge With little research on community engagement for COVID-19 diagnosis and treatment in Latin America, this study reports the results of mixed methods research on the impact of a comprehensive approach to engagement that highlights lessons for future health emergencies.Global health impact for policy and action Lessons for engagement in health emergencies include the need for a multi-pronged approach, incorporating co-creation and community listening, to respond to emerging local challenges.

Clinical presentation, diagnosis and management of multisystem inflammatory syndrome in children (MIS-C): a systematic review.

BACKGROUND: Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our review aims to summarise the clinical and diagnostic features, management strategies and outcomes of MIS-C and evaluate the variances in disease parameters and outcomes between high-income countries (HIC) and middle-income countries (MIC). METHODS: We searched four databases from December 2019 to March 2023. Observational studies with a sample size of 10 or more patients were included. Mean and prevalence ratios for various variables were pooled by random effects model using R. A mixed generalised linear model was employed to account for the heterogeneity, and publication bias was assessed via funnel and Doi plots. The primary outcome was pooled mean mortality among patients with MIS-C. Subgroup analysis was conducted based on the income status of the country of study. RESULTS: A total of 120 studies (20 881 cases) were included in the review. The most common clinical presentations were fever (99%; 95% CI 99.6% to 100%), gastrointestinal symptoms (76.7%; 95% CI 73.1% to 79.9%) and dermatological symptoms (63.3%; 95% CI 58.7% to 67.7%). Laboratory investigations suggested raised inflammatory, coagulation and cardiac markers. The most common management strategies were intravenous immunoglobulins (87.5%; 95% CI 82.9% to 91%) and steroids (74.7%; 95% CI 68.7% to 79.9%). Around 53.1% (95% CI 47.3% to 58.9%) required paediatric intensive care unit admissions, and overall mortality was 3.9% (95% CI 2.7% to 5.6%). Patients in MIC were younger, had a higher frequency of respiratory distress and evidence of cardiac dysfunction, with a longer hospital and intensive care unit stay and had a higher mortality rate than patients in HIC. CONCLUSION: MIS-C is a severe multisystem disease with better mortality outcomes in HIC as compared with MIC. The findings emphasise the need for standardised protocols and further research to optimise patient care and address disparities between HIC and MIC. PROSPERO REGISTRATION NUMBER: CRD42020195823.

COVID-19 pneumonia in lung transplant recipients: understanding risk factors and treatment outcomes in Japan.

Lung transplant (LTx) recipients face a significant risk from coronavirus disease 2019 (COVID-19), with elevated hospitalization mortality rates even post-vaccination. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically induces pneumonia in even healthy individuals, it can also infect the transplanted lungs of LTx recipients, potentially leading to graft dysfunction. Despite the prevalence of COVID-19 pneumonia in LTx recipients, data on its characteristics and associated risk factors remain limited. This retrospective study analyzed data from LTx recipients at Tohoku University Hospital between January 2001 and November 2023. COVID-19 cases were identified, and patient records, including thoracic computed tomography (CT) evaluations, were reviewed. Patient characteristics, vaccination history, immunosuppressant use, and comorbidities were assessed. Descriptive analysis was utilized for data presentation. Among 172 LTx recipients, 39 (22.7%) contracted COVID-19, with 9 (23%) developing COVID-19 pneumonia. COVID-19 incidence in LTx recipients aligned with national rates, but pneumonia risk was elevated. Delayed antiviral therapy initiation was noted in pneumonia cases. Remdesivir was uniformly administered and remained the primary treatment choice. LTx recipients are susceptible to COVID-19 pneumonia, warranting vigilance and tailored management strategies. Pre-transplant vaccination and prompt COVID-19 diagnosis and treatment are imperative for optimizing outcomes in this population.

Factors associated with unfavorable treatment outcomes among multidrug-resistant tuberculosis patients, Sierra Leone: a cross-sectional secondary data analysis.

BACKGROUND: Globally, multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The tuberculosis rate in Sierra Leone is 298 per 100,000 people, and Sierra Leone is considered a country with a high burden of tuberculosis. In Sierra Leone, there are few studies on the outcomes of MDR-TB treatment, especially those exacerbated by COVID-19. We identified factors associated with unfavorable treatment outcomes among people with MDR-TB in Sierra Leone. METHODS: We conducted a cross-sectional study to analyze hospital-based MDR-TB data from 2017 to 2021. Demographic, clinical, and treatment outcome data were extracted from the main MDR-TB referral hospital database. We defined unfavorable outcomes as patients who died, were lost to follow-up, or defaulted. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to identify predictors of the outcomes of MDR-TB treatment. RESULTS: Between 2017 and 2021, 628 people with MDR-TB were reported at Lakka Hospital; 441 (71%) were male, with a median age of 25 years (interquartile ranges: 17-34). Clinically, 21% of the 628 MDR-TB patients were HIV positive, and 413 were underweight (66%). 70% (440) of MDR-TB patients received tuberculosis treatment. The majority of patients, 457 (73%), were treated with a short treatment regimen, and 126 (20%) experienced unfavorable outcomes. Age 45 years or younger (aOR = 5.08; CI:1.87-13.82), 21-45 years (aOR = 2.22; CI:140-3.54), tuberculosis retreatment (aOR = 3.23; CI:1.82-5.73), age group, HIV status (aOR = 2.16; CI:1.33-3.53), and malnourishment status (aOR = 1.79; CI:1.12-2.86) were significantly associated with unfavorable treatment outcomes for DR-TB patients. CONCLUSION: This analysis revealed a high proportion of unfavorable treatment outcomes among MDR-TB patients in Sierra Leone. Malnourishment, TB retreatment, HIV coinfection, and age 45 years or younger were associated with unfavorable outcomes of MDR-TB treatment. Increasing patients' awareness, mainly among young people, heightens treatment adherence and HIV monitoring by measuring the amount of HIV in patient blood, which can reduce adverse treatment outcomes in Sierra Leone and other sub-Saharan African countries.

COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Introduction: Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. Methods: This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. Results: No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Conclusion: Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Association of chest computed tomography severity score at ICU admission and respiratory outcomes in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit. METHODS: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated. RESULTS: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission. CONCLUSION: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia.

Impact of COVID-19 on asthma management in general practice: A qualitative study.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic catalysed unprecedented changes to healthcare delivery in Australia, leading to a rapid transformation of asthma management, to which healthcare providers and patients have had to adapt. Understanding the impact of these changes is critical as we emerge from pandemic-affected workflows. METHOD: A qualitative study using semistructured interviews was conducted with 19 general practitioners across Sydney and regional New South Wales. Reflexive thematic analysis of interview data was undertaken. RESULTS: Four key themes were identified: disorganised asthma care before COVID­19; chaotic asthma care during the pandemic; adapting to non-guideline-driven telehealth asthma care; and widening health agenda misalignment. DISCUSSION: This study highlights the triumphs and gaps in asthma management during the pandemic and the vulnerability of existing asthma care systems to disruption. These lessons can be used to re-evaluate how we deliver asthma care and inform future models of care as we transition towards a 'post-COVID' landscape.

Functional availability of medical oxygen for the management of hypoxaemia in Cameroon: A nationwide facility-based cross-sectional survey.

Background: Medical oxygen is essential for managing hypoxaemia, which has a multifactorial origin, including acute and chronic lung diseases such as pneumonia, asthma, and severe malaria. The coronavirus disease 2019 (COVID-19) revealed substantial gaps in the availability and accessibility of safe medical oxygen, especially in low- and middle-income countries (LMICs). This study aimed to assess the availability and sources, as well as the barriers to the availability of functional medical oxygen in hospitals in Cameroon. Methods: This was a nationwide cross-sectional descriptive study conducted from 26 March to 1 June 2021. Using a convenient sampling technique, we sampled accredited public and private COVID-19 treatment centres in all ten regions in Cameroon. Representatives from the selected hospitals were provided with a pre-designed questionnaire assessing the availability, type, and state of medical oxygen in their facilities. All analyses were performed using R. Results: In total, 114 hospitals were included in this study, with functional medical oxygen available in 65% (74/114) of the hospitals. About 85% (23/27) of the reference hospitals and only 59% (51/87) of the district hospitals had available functional medical oxygen. Compared to district hospitals, reference hospitals were more likely to have central oxygen units (reference vs. district: 10 vs. 0%), oxygen cylinders (74 vs. 42%), and oxygen concentrators (79 vs. 51%). The most common barriers to the availability of medical oxygen were inadequate oxygen supply to meet needs (district vs. reference hospitals: 55 vs. 30%), long delays in oxygen bottle refills (51 vs. 49%), and long distances from oxygen suppliers (57 vs. 49%). Conclusions: The availability of medical oxygen in hospitals in Cameroon is suboptimal and more limited in districts compared to reference hospitals. The cost of medical oxygen, delays related to refills and supplies, and long distances from medical sources were the most common barriers to availability in Cameroon.

Lack of racial and ethnic disparities in mortality in minority patients hospitalised with COVID-19 in a mid-Atlantic healthcare system.

INTRODUCTION: In the USA, minoritised communities (racial and ethnic) have suffered disproportionately from COVID-19 compared with non-Hispanic white communities. In a large cohort of patients hospitalised for COVID-19 in a healthcare system spanning five adult hospitals, we analysed outcomes of patients based on race and ethnicity. METHODS: This was a retrospective cohort analysis of patients 18 years or older admitted to five hospitals in the mid-Atlantic area between 4 March 2020 and 27 May 2022 with confirmed COVID-19. Participants were divided into four groups based on their race/ethnicity: non-Hispanic black, non-Hispanic white, Latinx and other. Propensity score weighted generalised linear models were used to assess the association between race/ethnicity and the primary outcome of in-hospital mortality. RESULTS: Of the 9651 participants in the cohort, more than half were aged 18-64 years old (56%) and 51% of the cohort were females. Non-Hispanic white patients had higher mortality (p<0.001) and longer hospital length-of-stay (p<0.001) than Latinx and non-Hispanic black patients. DISCUSSION: In this large multihospital cohort of patients admitted with COVID-19, non-Hispanic black and Hispanic patients did not have worse outcomes than white patients. Such findings likely reflect how the complex range of factors that resulted in a life-threatening and disproportionate impact of incidence on certain vulnerable populations by COVID-19 in the community was offset through admission at well-resourced hospitals and healthcare systems. However, there continues to remain a need for efforts to address the significant pre-existing race and ethnicity inequities highlighted by the COVID-19 pandemic to be better prepared for future public health emergencies.