Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients.

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT05650905.

Trend differences in cervical spinal cord injuries before and after the coronavirus disease 2019 pandemic.

STUDY DESIGN: Cross-Sectional Study. OBJECTIVES: To investigate the changes in the characteristics of cervical spinal cord injuries (CSCI) before and after the coronavirus disease 2019 (COVID-19) pandemic among patients transported to our hospital in Japan. SETTING: Hospital with an emergency center in Chiba, Japan. METHODS: Patients eligible for the study were those transported within 24 h of injury and diagnosed with cervical spinal cord injury between January 2018 and December 2021 at our hospital. Medical records were retrospectively examined to investigate the number and characteristics of patients with CSCI. The clinical variables of patients with CSCI were compared according to the time of admission as related to the COVID-19 pandemic: 2018-19 (before) or 2020-21 (after). RESULTS: The total number of patients with CSCI from 2018 to 2021 was 108, with 57 before the COVID-19 pandemic and 51 after the COVID-19 pandemic. The number of severe cases with an injury severity score (ISS) of >16 decreased after COVID-19 (p < 0.05). Falls on level surfaces were the most common cause of injury both before and after COVID-19. Although the ranking of traffic accidents decreased after COVID-19, among those, the number of bicycle injuries tended to increase. CONCLUSIONS: The number of serious cases with an ISS > 16 decreased, presumably because of the decline in high-energy trauma due to the background decrease in the number of traffic accidents.

Acceptability of COVID-19 booster vaccine in malaysia: a cross-sectional study.

Despite the high efficacy and safety demonstrated in clinical trials, COVID-19 booster vaccination rates in Malaysia remain below 50% among the general public. This study explores the factors influencing public acceptance of the COVID-19 booster vaccine among the Malaysian population. The questionnaire included variables on sociodemographics, knowledge, and the Health Belief Model (HBM) constructs. Based on the Chi-squared test of contingencies, a t-test and multivariate logistic regression analysis on 411 collected responses, the findings revealed that older participants, individuals of Chinese ethnicity, and those with higher education levels and incomes were more willing to accept booster vaccinations. The analysis further identified perceived susceptibility, perceived severity and perceived barriers as significant predictors influencing booster vaccination acceptance rates. Healthcare policymakers may consider targeting interventions to diminish the obstacles associated with booster vaccinations. These intervention strategies include implementing health intervention programmes, such as public health awareness initiatives, to raise awareness of the risks and severity of COVID-19, ultimately encouraging higher uptake of booster vaccines.

Comprehensive analysis of immunogenic cell death-related gene and construction of prediction model based on WGCNA and multiple machine learning in severe COVID-19.

The death of coronavirus disease 2019 (COVID-19) is primarily due to from critically ill patients, especially from ARDS complications caused by SARS-CoV-2. Therefore, it is essential to contribute an in-depth understanding of the pathogenesis of the disease and to identify biomarkers for predicting critically ill patients at the molecular level. Immunogenic cell death (ICD), as a specific variant of regulatory cell death driven by stress, can induce adaptive immune responses against cell death antigens in the host. Studies have confirmed that both innate and adaptive immune pathways are involved in the pathogenesis of SARS-CoV-2 infection. However, the role of ICD in the pathogenesis of severe COVID-19 has rarely been explored. In this study, we systematically evaluated the role of ICD-related genes in COVID-19. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis based on ICD differentially expressed genes. The results showed that immune infiltration characteristics were altered in severe and non-severe COVID-19. In addition, we used multiple machine learning methods to screen for five risk genes (KLF5, NSUN7, APH1B, GRB10 and CD4), which are used to predict COVID-19 severity. Finally, we constructed a nomogram to predict the risk of severe COVID-19 based on the classification and recognition model, and validated the model with external data sets. This study provides a valuable direction for the exploration of the pathogenesis and progress of COVID-19, and helps in the early identification of severe cases of COVID-19 to reduce mortality.

The burden of anxiety, depression, and stress, along with the prevalence of symptoms of PTSD, and perceptions of the drivers of psychological harms, as perceived by doctors and nurses working in ICUs in Nepal during the COVID-19 pandemic; a mixed method evaluation.

BACKGROUND: The COVID-19 pandemic resulted in significant physical and psychological impacts for survivors, and for the healthcare professionals caring for patients. Nurses and doctors in critical care faced longer working hours, increased burden of patients, and limited resources, all in the context of personal social isolation and uncertainties regarding cross-infection. We evaluated the burden of anxiety, depression, stress, post-traumatic stress disorder (PTSD), and alcohol dependence among doctors and nurses working in intensive care units (ICUs) in Nepal and explored the individual and social drivers for these impacts. METHODS: We conducted a mixed-methods study in Nepal, using an online survey to assess psychological well-being and semi-structured interviews to explore perceptions as to the drivers of anxiety, stress, and depression. Participants were recruited from existing national critical care professional organisations in Nepal and using a snowball technique. The online survey comprised of validated assessment tools for anxiety, depression, stress, PTSD, and alcohol dependence; all tools were analysed using published guidelines. Interviews were analysed using rapid appraisal techniques, and themes regarding the drivers for psychological distress were explored. RESULTS: 134 respondents (113 nurses, 21 doctors) completed the online survey. Twenty-eight (21%) participants experienced moderate to severe symptoms of depression; 67 (50%) experienced moderate or severe symptoms of anxiety; 114 (85%) had scores indicative of moderate to high levels of stress; 46 out of 100 reported symptoms of PTSD. Compared to doctors, nurses experienced more severe symptoms of depression, anxiety, and PTSD, whereas doctors experienced higher levels of stress than nurses. Most (95%) participants had scores indicative of low risk of alcohol dependence. Twenty participants were followed up in interviews. Social stigmatism, physical and emotional safety, enforced role change and the absence of organisational support were perceived drivers for poor psychological well-being. CONCLUSION: Nurses and doctors working in ICU during the COVID-19 pandemic sustained psychological impacts, manifesting as stress, anxiety, and for some, symptoms of PTSD. Nurses were more vulnerable. Individual characteristics and professional inequalities in healthcare may be potential modifiable factors for policy makers seeking to mitigate risks for healthcare providers.

Sociocultural adjustment and social support as predictors for international medical sciences students' anxiety during COVID-19.

BACKGROUND: The prevalence of anxiety is high among international medical sciences students and it increased even more during the COVID-19 pandemic due to different restrictions and social isolation. Successful sociocultural adjustment and social support could be important factors in overcoming those challenges, however, there is a lack of studies which would investigate the role of those factors among inter- national medical students. This study aimed to assess the role of sociocultural adjustment and social support as predictors for international medical students' anxiety during COVID-19. METHODS: Two measurements were conducted via self-reported questionnaires which consisted of three scales - SCAS, MSPSS and GAD-7. In total, 82 international medical students participated in both measurements in this longitudinal study. RESULTS: The findings indicated that 37% of international students had symptoms of moderate or severe anxiety during their first year of studies at university. In the second year, during the COVID-19 pandemic and an official lockdown, 35% of international students had symptoms of moderate or severe anxiety. In addition, this study showed that gender and sociocultural adjustment did not play a role as predictors of students' anxiety during the second year of studies. However, this study revealed that social support provided by family during the first year of studies, as well as having friends or family members who had been ill with COVID-19 predicted higher levels of anxiety at second measurement, while sociocultural adjustment was an even stronger predictor of anxiety in the second year of studies of international medical students. CONCLUSIONS: This knowledge can help to better understand how international medical students felt during the COVID-19 pandemic and what role the above- mentioned factors played in the students' anxiety. As the anxiety level is quite high among international medical students, universities and mental health service providers should take it into consideration and help them to overcome those challenges.

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection.

BACKGROUND: Escherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin. METHODS: A total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated. RESULTS: The E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin. CONCLUSIONS: The antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.

Implementation of COVID-19 vaccination services in prison in six European countries: translating emergency intervention into routine life-course vaccination.

BACKGROUND: Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP). METHODS: Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons' directors or medical directors between November 2021-May 2022. RESULTS: According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy. CONCLUSIONS: To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities.

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective pilot cohort study.

BACKGROUND: Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers and illness severity in these conditions. METHODS: This single-site, prospective, cross-sectional, pilot cohort study aimed to distinguish between the two patient populations by using self-reported outcome measures and circulating biomarkers of endothelial function and systemic inflammation status. Thirty-one individuals with ME/CFS, 23 individuals with long COVID, and 31 matched sedentary healthy controls were included. All study participants underwent non-invasive cardiovascular hemodynamic challenge testing (10 min NASA lean test) for assessment of orthostatic intolerance. Regression analysis was used to examine associations between outcome measures and circulating biomarkers in the study participants. Classification across groups was based on principal component and discriminant analyses. RESULTS: Four ME/CFS patients (13%), 1 with long COVID (4%), and 1 healthy control (3%) presented postural orthostatic tachycardia syndrome (POTS) using the 10-min NASA lean test. Compared with matched healthy controls, ME/CFS and long COVID subjects showed higher levels of ET-1 (p < 0.05) and VCAM-1 (p < 0.001), and lower levels of nitrites (NOx assessed as NO2- + NO3-) (p < 0.01). ME/CFS patients also showed higher levels of serpin E1 (PAI-1) and E-selectin than did both long COVID and matched control subjects (p < 0.01 in all cases). Long COVID patients had lower TSP-1 levels than did ME/CFS patients and matched sedentary healthy controls (p < 0.001). As for inflammation biomarkers, both long COVID and ME/CFS subjects had higher levels of TNF-α than did matched healthy controls (p < 0.01 in both comparisons). Compared with controls, ME/CFS patients had higher levels of IL-1ß (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.01), IL-10 (p < 0.001), IP-10 (p < 0.05), and leptin (p < 0.001). Principal component analysis supported differentiation between groups based on self-reported outcome measures and biomarkers of endothelial function and inflammatory status in the study population. CONCLUSIONS: Our findings revealed that combining biomarkers of endothelial dysfunction and inflammation with outcome measures differentiate ME/CFS and Long COVID using robust discriminant analysis of principal components. Further research is needed to provide a more comprehensive characterization of these underlying pathomechanisms, which could be promising targets for therapeutic and preventive strategies in these conditions.

Adoption and Use of Telemedicine and Digital Health Services Among Older Adults in Light of the COVID-19 Pandemic: Repeated Cross-Sectional Analysis.

BACKGROUND: As the population ages and the prevalence of long-term diseases rises, the use of telecare is becoming increasingly frequent to aid older people. OBJECTIVE: This study aims to explore the use and adoption of 3 types of telehealth services among the older population in Israel before, during, and after the COVID-19 pandemic. METHODS: We explored the use characteristics of older adults (aged ≥65 years) belonging to Clalit Health Services in several aspects in the use of 3 types of telehealth services: the use of digital services for administrative tasks; the use of synchronous working-hours telehealth visits with the patient's personal physician during clinic business hours; and the use of after-hours consultations during evenings, nights, and weekends when the clinics are closed. The data were collected and analyzed throughout 3 distinct periods in Israel: before the COVID-19 pandemic, during the onset of the COVID-19 pandemic, and following the COVID-19 peak. RESULTS: Data of 618,850 patients who met the inclusion criteria were extracted. Telehealth services used for administrative purposes were the most popular. The most intriguing finding was that the older population significantly increased their use of all types of telehealth services during the COVID-19 pandemic, and in most types, this use decreased after the COVID-19 peak, but to a level that was higher than the baseline level before the COVID-19 pandemic. Before the COVID-19 pandemic, 23.1% (142,936/618,850) of the study population used working-hours telehealth visits, and 2.2% (13,837/618,850) used after-hours consultations at least once. The percentage of use for these services increased during the COVID-19 pandemic to 59.2% (366,566/618,850) and 5% (30,777/618,850) and then decreased during the third period to 39.5% (244,572/618,850) and 2.4% (14,584/618,850), respectively (P<.001). Multiple patient variables have been found to be associated with the use of the different telehealth services in each period. CONCLUSIONS: Despite the limitations and obstacles, the older population uses telehealth services and can increase their use when they are needed. These people can learn how to use digital health services effectively, and they should be given the opportunity to do so by creating suitable and straightforward telehealth solutions tailored to this population and enhancing their usability.

Now Is the Time to Strengthen Government-Academic Data Infrastructures to Jump-Start Future Public Health Crisis Response.

During public health crises, the significance of rapid data sharing cannot be overstated. In attempts to accelerate COVID-19 pandemic responses, discussions within society and scholarly research have focused on data sharing among health care providers, across government departments at different levels, and on an international scale. A lesser-addressed yet equally important approach to sharing data during the COVID-19 pandemic and other crises involves cross-sector collaboration between government entities and academic researchers. Specifically, this refers to dedicated projects in which a government entity shares public health data with an academic research team for data analysis to receive data insights to inform policy. In this viewpoint, we identify and outline documented data sharing challenges in the context of COVID-19 and other public health crises, as well as broader crisis scenarios encompassing natural disasters and humanitarian emergencies. We then argue that government-academic data collaborations have the potential to alleviate these challenges, which should place them at the forefront of future research attention. In particular, for researchers, data collaborations with government entities should be considered part of the social infrastructure that bolsters their research efforts toward public health crisis response. Looking ahead, we propose a shift from ad hoc, intermittent collaborations to cultivating robust and enduring partnerships. Thus, we need to move beyond viewing government-academic data interactions as 1-time sharing events. Additionally, given the scarcity of scholarly exploration in this domain, we advocate for further investigation into the real-world practices and experiences related to sharing data from government sources with researchers during public health crises.

Perceptions of Racial-Ethnic Inequities in COVID-19 Healthcare and Willingness to Receive the COVID-19 Vaccine.

BACKGROUND: Perceptions of the US healthcare system can impact individuals' healthcare utilization, including vaccination intentions. This study examined the association between perceived racial-ethnic inequities in COVID-19 healthcare and willingness to receive the COVID-19 vaccine. METHODS: This study used data from REACH-US, a nationally representative online survey of a large, diverse sample of U.S. adults (N=5145 January 26, 2021-March 3, 2021). Confirmatory factor and regression analyses examined a latent factor of perceived racial-ethnic inequities in COVID-19 healthcare, whether the factor was associated with willingness to receive the COVID-19 vaccine, and whether associations varied across racial-ethnic groups reported as probit estimates (B) and 95% confidence intervals (CIs). RESULTS: Perceived racial-ethnic inequities in COVID-19 healthcare were highest among Black/African American adults (mean latent factor score: 0.65 ± 0.43) and lowest among White adults (mean latent factor score: 0.04 ± 0.67). Black/African American (B = -0.08; 95% CI = -0.19, 0.03) and Native Hawaiian/Pacific Islander (B = -0.08; 95% CI = -0.23, 0.07) adults who perceived greater racial-ethnic inequities in COVID-19 healthcare were less willing than participants who perceived lower inequities. In contrast, American Indian/Alaska Native (B = 0.15; 95% CI = -0.01, 0.30), Asian (B = 0.20; 95% CI = 0.08, 0.31), Hispanic/Latino (English language preference) (B = 0.22; 95% CI = 0.01, 0.43), Multiracial (B = 0.23; 95% CI = 0.09, 0.36), and White (B = 0.31; 95% CI = 0.19, 0.43) adults who perceived greater racial-ethnic inequities in COVID-19 healthcare were more willing to receive the COVID-19 vaccine than participants perceiving higher inequities. CONCLUSIONS: Greater perceived racial-ethnic inequities in COVID-19 healthcare were associated with less willingness to receive the COVID-19 vaccine among Black/African American and Native Hawaiian/Pacific Islander adults.

Adverse events related to drug-drug interactions in COVID-19 patients. A persistent concern in the post-pandemic era: a systematic review.

INTRODUCTION: Since COVID-19 patients are often polytreated, monitoring drug-drug interaction (DDIs) is necessary. We evaluated whether drugs used after the second COVID-19 pandemic wave were associated with DDI-related adverse events and the role of drug interaction checkers in identifying them. METHODS: The study (PROSPERO-ID: CRD42024507634) included: 1) consulting the drug interaction checkers Drugs.com, Liverpool COVID-19 Interactions, LexiComp, Medscape, and Micromedex; 2) systematic review; 3) reviewed studies analysis; 4) evaluating drug interaction checkers potential to anticipate DDI-related adverse events.The systematic review was performed searching PubMed, Scopus, ScienceDirect, and Cochrane databases from 1 March 2022 to 11 November 2023. Observational studies, and clinical trials were included. Article without reporting direct association between DDIs and adverse events were excluded. The risk of bias was assessed by Newcastle-Ottawa scale. RESULTS: The most frequent DDIs involved nirmatrelvir/ritonavir (N/R) and fluvoxamine. Fifteen studies, including 150 patients and 35 DDI-related outcomes, were analyzed. The most frequent DDIs involved tacrolimus with N/R, resulting in creatinine increase.Eighty percent of reported DDI-related adverse events would have been identified by all drug-interaction checkers, while the remaining 20% by at least 2 of them. CONCLUSIONS: Drug interaction checkers are useful but show inconsistencies. Multiple sources are needed to tailor treatment in the context of COVID-19.

Public Discourse, User Reactions, and Conspiracy Theories on the X Platform About HIV Vaccines: Data Mining and Content Analysis.

BACKGROUND: The initiation of clinical trials for messenger RNA (mRNA) HIV vaccines in early 2022 revived public discussion on HIV vaccines after 3 decades of unsuccessful research. These trials followed the success of mRNA technology in COVID-19 vaccines but unfolded amid intense vaccine debates during the COVID-19 pandemic. It is crucial to gain insights into public discourse and reactions about potential new vaccines, and social media platforms such as X (formerly known as Twitter) provide important channels. OBJECTIVE: Drawing from infodemiology and infoveillance research, this study investigated the patterns of public discourse and message-level drivers of user reactions on X regarding HIV vaccines by analyzing posts using machine learning algorithms. We examined how users used different post types to contribute to topics and valence and how these topics and valence influenced like and repost counts. In addition, the study identified salient aspects of HIV vaccines related to COVID-19 and prominent anti-HIV vaccine conspiracy theories through manual coding. METHODS: We collected 36,424 English-language original posts about HIV vaccines on the X platform from January 1, 2022, to December 31, 2022. We used topic modeling and sentiment analysis to uncover latent topics and valence, which were subsequently analyzed across post types in cross-tabulation analyses and integrated into linear regression models to predict user reactions, specifically likes and reposts. Furthermore, we manually coded the 1000 most engaged posts about HIV and COVID-19 to uncover salient aspects of HIV vaccines related to COVID-19 and the 1000 most engaged negative posts to identify prominent anti-HIV vaccine conspiracy theories. RESULTS: Topic modeling revealed 3 topics: HIV and COVID-19, mRNA HIV vaccine trials, and HIV vaccine and immunity. HIV and COVID-19 underscored the connections between HIV vaccines and COVID-19 vaccines, as evidenced by subtopics about their reciprocal impact on development and various comparisons. The overall valence of the posts was marginally positive. Compared to self-composed posts initiating new conversations, there was a higher proportion of HIV and COVID-19-related and negative posts among quote posts and replies, which contribute to existing conversations. The topic of mRNA HIV vaccine trials, most evident in self-composed posts, increased repost counts. Positive valence increased like and repost counts. Prominent anti-HIV vaccine conspiracy theories often falsely linked HIV vaccines to concurrent COVID-19 and other HIV-related events. CONCLUSIONS: The results highlight COVID-19 as a significant context for public discourse and reactions regarding HIV vaccines from both positive and negative perspectives. The success of mRNA COVID-19 vaccines shed a positive light on HIV vaccines. However, COVID-19 also situated HIV vaccines in a negative context, as observed in some anti-HIV vaccine conspiracy theories misleadingly connecting HIV vaccines with COVID-19. These findings have implications for public health communication strategies concerning HIV vaccines.

SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV. To determine how nsp15 functions during SARS-CoV-2 infection, we constructed a recombinant SARS-CoV-2 (nsp15mut) expressing catalytically inactivated nsp15, which we show promoted increased dsRNA accumulation. Infection with SARS-CoV-2 nsp15mut led to increased activation of the IFN signaling and PKR pathways in lung-derived epithelial cell lines and primary nasal epithelial air-liquid interface (ALI) cultures as well as significant attenuation of replication in ALI cultures compared to wild-type virus. This replication defect was rescued when IFN signaling was inhibited with the Janus activated kinase (JAK) inhibitor ruxolitinib. Finally, to assess nsp15 function in the context of minimal (MERS-CoV) or moderate (SARS-CoV-2) innate immune induction, we compared infections with SARS-CoV-2 nsp15mut and previously described MERS-CoV nsp15 mutants. Inactivation of nsp15 had a more dramatic impact on MERS-CoV replication than SARS-CoV-2 in both Calu3 cells and nasal ALI cultures suggesting that SARS-CoV-2 can better tolerate innate immune responses. Taken together, SARS-CoV-2 nsp15 is a potent inhibitor of dsRNA-induced innate immune response and its antagonism of IFN signaling is necessary for optimal viral replication in primary nasal ALI cultures.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Atypical presentation of Lemierre's syndrome caused by penicillin-susceptible Staphylococcus aureus in a patient with chronic stomatitis and COVID-19.

A healthy man in his late 20s was admitted to the emergency department due to a flare-up in his severe chronic stomatitis, along with flu-like symptoms. CXR showed multiple bilateral consolidations and subsequent CT revealed thrombosis of the left facial and internal jugular vein, together with septic embolism in both lungs. Blood cultures showed penicillin-susceptible Staphylococcus aureus The patient was diagnosed with Lemierre's syndrome, despite atypical bacteria and clinical presentation. During hospitalisation, he developed pulmonary empyema as a complication and was admitted for 4 weeks. During hospitalisation and after discharge, the patient was examined for multiple rheumatic, immunological and dermatological diseases, but no underlying cause for Lemierre's syndrome has been found. We present this case due to the rarity of its nature, with atypical clinical presentation and pathogen for Lemierre's syndrome, but with classic radiological findings.