Post-acute sequelae of COVID-19 in older persons: multi-organ complications and mortality.

INTRODUCTION: Evidence on long-term associations between COVID-19 and risks of multi-organ complications and mortality in older population is limited. This study evaluates these associations. RESEARCH DESIGN AND METHODS: The cohorts included patients aged ≥60 year diagnosed with COVID-19 infection (cases), between 16 March 2020 and 31 May 2021 from the UK Biobank (UKB cohort, n = 11 330); and between 01 April 2020 and 31 May 2022 from the electronic health records in Hong Kong (HK cohort, n = 213 618). Each patient was randomly matched with up to 10 individuals without COVID-19 infection based on age and sex (UKB, n = 325 812; HK, n = 1 411 206) and were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK cohort. Caracteristics between cohorts were further adjusted with propensity score-based marginal mean weighting through stratification. For evaluating long-term association of COVID-19 with multi-organ disease complications and mortality after 21-days of diagnosis, Cox regression was employed. RESULT: Older adults with COVID-19 were associated with a significantly higher risk of cardiovascular outcomes [major cardiovascular disease (stroke, heart failure and coronary heart disease): hazard ratio (UKB): 1.4 (95% Confidence interval: 1.2,1.7), HK:1.2 (95% CI: 1.1,1.3)]; myocardial infarction: HR (UKB): 1.8 (95% CI: 1.4,2.5), HK:1.2 (95% CI: 1.1,1.5)]; respiratory outcomes [interstitial lung disease: HR (UKB: 3.5 (95% CI: 2.6,4.7), HK:6.6 (95% CI: 2.1,21.2); chronic pulmonary disease: HR (UKB): 1.6 (95% CI: 1.2,2.1), HK:1.7 (95% CI: 1.4,2.1)]; neuropsychiatric outcomes [seizure: HR (UKB): 2.7 (95% CI: 1.7,4.2), HK:1.8 (95% CI: 1.4,2.3)]; and renal outcomes [acute kidney disease: HR (UKB): 1.4 (95% CI: 1.1,1.6), HK:1.7 (95% CI: 1.4,2.1)]; and all-cause mortality [HR (UKB): 4.8 (95% CI: 4.4,5.4), HK:2.7 (95% CI: 2.6,2.8)]. CONCLUSION: COVID-19 is associated with long-term risks of multi-organ complications in older adults (aged ≥60). Infected patients in this age-group may benefit from appropriate monitoring of signs/symptoms for developing these complications.

Training certified detectives to track down the intrinsic shortcuts in COVID-19 chest x-ray data sets.

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can then identify these intrinsic shortcuts in a curated data set.

Long-term post-acute sequelae of COVID-19 infection: a retrospective, multi-database cohort study in Hong Kong and the UK.

Background: Evidence on post-acute sequelae of SARS-CoV-2 (PASC) has shown inconsistent findings. This study aimed to generate coherent evidence on the post-acute sequelae of COVID-19 infection using electronic healthcare records across two regions. Methods: In this retrospective, multi-database cohort study, patients with COVID-19 aged 18 or above between April 1st 2020 and May 31st 2022 from the Hong Kong Hospital Authority (HKHA) and March 16th 2020 and May 31st 2021 from the UK Biobank (UKB) databases and their matched controls were followed for up to 28 and 17 months, respectively. Covariates between patients with COVID-19 and non-COVID-19 controls were adjusted using propensity score-based inverse probability treatment weighting. Cox proportional regression was used to estimate the hazard ratio (HR) of clinical sequelae, cardiovascular, and all-cause mortality 21 days after COVID-19 infection. Findings: A total of 535,186 and 16,400 patients were diagnosed with COVID-19 from HKHA and UKB, of whom 253,872 (47.4%) and 7613 (46.4%) were male, with a mean age (±SD) of 53.6 (17.8) years and 65.0 (8.5) years, respectively. Patients with COVID-19 incurred greater risk of heart failure (HR 1.82; 95% CI 1.65, 2.01), atrial fibrillation (1.31; 1.16, 1.48), coronary artery disease (1.32; 1.07, 1.63), deep vein thrombosis (1.74; 1.27, 2.37), chronic pulmonary disease (1.61; 1.40, 1.85), acute respiratory distress syndrome (1.89; 1.04, 3.43), interstitial lung disease (3.91; 2.36, 6.50), seizure (2.32; 1.12, 4.79), anxiety disorder (1.65; 1.29, 2.09), post-traumatic stress disorder (1.52; 1.23, 1.87), end-stage renal disease (1.76; 1.31, 2.38), acute kidney injury (2.14; 1.69, 2.71), pancreatitis (1.42; 1.10, 1.83), cardiovascular (2.86; 1.25, 6.51) and all-cause mortality (4.16; 2.11, 8.21) mortality during their post-acute phase of infection. Interpretation: The consistent greater risk of PASC highlighted the need for sustained multi-disciplinary care for COVID-19 survivors. Funding: Health Bureau, The Government of the Hong Kong Special Administrative Region, Collaborative Research Fund, The Government of the Hong Kong Special Administrative Region and AIR@InnoHK, administered by the Innovation and Technology Commission, The Government of the Hong Kong Special Administrative Region.

A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases.

SARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analogue, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for SARS-CoV-2 to methylate the N7 position of viral 5'-RNA guanine cap. The assay is universal and suitable for any SAM-dependent viral MTases such as the SARS-CoV-2 NSP16/NSP10 MTase complex and the NS5 MTase of Zika virus (ZIKV). Pilot screening demonstrated that the HTS assay was very robust and identified two candidate inhibitors, NSC 111552 and 288387. The two compounds inhibited the FL-NAH binding to the NSP14 MTase with low micromolar IC50. We used three functional MTase assays to unambiguously verified the inhibitory potency of these molecules for the NSP14 N7-MTase function. Binding studies indicated that these molecules are bound directly to the NSP14 MTase with similar low micromolar affinity. Moreover, we further demonstrated that these molecules significantly inhibited the SARS-CoV-2 replication in cell-based assays at concentrations not causing cytotoxicity. Furthermore, NSC111552 significantly synergized with known SARS-CoV-2 drugs including nirmatrelvir and remdesivir. Finally, docking suggested that these molecules bind specifically to the SAM-binding site on the NSP14 MTase. Overall, these molecules represent novel and promising candidates to further develop broad-spectrum inhibitors for the management of viral infections.

Association of COVID-19 with short- and long-term risk of cardiovascular disease and mortality: a prospective cohort in UK Biobank.

AIMS: This study aims to evaluate the short- and long-term associations between COVID-19 and development of cardiovascular disease (CVD) outcomes and mortality in the general population. METHODS AND RESULTS: A prospective cohort of patients with COVID-19 infection between 16 March 2020 and 30 November 2020 was identified from UK Biobank, and followed for up to 18 months, until 31 August 2021. Based on age (within 5 years) and sex, each case was randomly matched with up to 10 participants without COVID-19 infection from two cohorts-a contemporary cohort between 16 March 2020 and 30 November 2020 and a historical cohort between 16 March 2018 and 30 November 2018. The characteristics between groups were further adjusted with propensity score-based marginal mean weighting through stratification. To determine the association of COVID-19 with CVD and mortality within 21 days of diagnosis (acute phase) and after this period (post-acute phase), Cox regression was employed. In the acute phase, patients with COVID-19 (n = 7584) were associated with a significantly higher short-term risk of CVD {hazard ratio (HR): 4.3 [95% confidence interval (CI): 2.6- 6.9]; HR: 5.0 (95% CI: 3.0-8.1)} and all-cause mortality [HR: 81.1 (95% CI: 58.5-112.4); HR: 67.5 (95% CI: 49.9-91.1)] than the contemporary (n = 75 790) and historical controls (n = 75 774), respectively. Regarding the post-acute phase, patients with COVID-19 (n = 7139) persisted with a significantly higher risk of CVD in the long-term [HR: 1.4 (95% CI: 1.2-1.8); HR: 1.3 (95% CI: 1.1- 1.6)] and all-cause mortality [HR: 5.0 (95% CI: 4.3-5.8); HR: 4.5 (95% CI: 3.9-5.2) compared to the contemporary (n = 71 296) and historical controls (n = 71 314), respectively. CONCLUSIONS: COVID-19 infection, including long-COVID, is associated with increased short- and long-term risks of CVD and mortality. Ongoing monitoring of signs and symptoms of developing these cardiovascular complications post diagnosis and up till at least a year post recovery may benefit infected patients, especially those with severe disease.

Resilience resources and coping strategies of COVID-19 female long haulers: A qualitative study.

Background: Female long haulers deal with persistent post-acute COVID-19 symptoms that have serious health implications. This study aimed to identify resilience resources at multiple socio-ecological levels for female long haulers and describe how resilience resources affect their responses to long COVID. Methods: Purposive sampling was adopted to recruit participants through social media from April to June 2021 followed by 15 semi-structured interviews. An inductive analytical approach was adopted to categorize themes by open and axial coding that were verified by peer review. Results: Female long haulers relied on resources at various socio-ecological levels to foster their resilience in response to long COVID. At the individual level, they utilized cognitive and emotional resources to increase knowledge, learn new skills, set goals, and manage emotions; behavioral resources (e.g., internal motivation and executive functioning) to perform physical, creative, and recreational activities, and adopt healthier eating habits; and spiritual resources to perform spiritual rituals and connect with God. At the social level, the support from existing relationships and/or online social support groups enhanced their social identity and provided material and informational resources. At the health systems level, the guidance from counselors and physicians and availability of clinics, medicines, and health equipment assisted them in symptom management and medication adherence. Conclusion: The resilience of female long haulers can be enhanced through (1) offering financial and health-related resources, (2) developing online social-support groups, (3) counseling and care service training for healthcare professionals, and (4) implementing more psychosocial interventions by labor organizations.

Pulmonary tuberculosis screening in emigrants and travellers: A retrospective analysis of Guangzhou Port in China.

BACKGROUND: China is beginning to transform from a migrant exporting country to a migrant importing country. Our study aimed to assess risks of imported tuberculosis among travellers and to determine risk factors, to tailor institutional guidelines. METHODS: We conducted an observational, retrospective, population-based cohort study. Molecular epidemiology surveillance methods were used to screen travellers for cases of pulmonary tuberculosis (PTB) at Guangzhou Port in China from January 2010 to December 2016. RESULTS: A total of 165,369 travellers from 190 countries and regions were screened for PTB. The rate of suspected PTB, laboratory confirmed rate, and the total detection rate in emigrants were significantly higher than those in travellers (p<0.01). There were four differences in the PTB screening process between emigrants and travellers. According to the transmission risk degree of the tuberculosis, forty high-risk PTB importing countries were divided into five levels. The travellers diagnosed with PTB were significantly younger than the emigrants (p<0.01). The distribution of genotypes differed significantly between the travellers and emigrants (p<0.001). CONCLUSIONS: PTB screening process in travellers at ports should include a risk assessment of high-risk groups. It should reduce diagnosis time by rapid molecular detection methods and strengthen drug resistant (DR) transmission and monitoring of imported PTB strains through molecular genotyping at ports.

Social Life of Females with Persistent COVID-19 Symptoms: A Qualitative Study.

Persistent COVID-19 symptoms (long COVID) may bring challenges to long haulers' social lives. Females may endure more profound impacts given their special social roles and existing structural inequality. This study explores the effects of long COVID on the social life of female long haulers. We conducted semi-structured interviews via Zoom between April and June 2021 with 15 female long haulers in the United States, purposely recruited from Facebook and Slack groups and organization websites related to long COVID. Interviews were audio-recorded and transcribed verbatim with consent. The interview data were managed using MAXQDA and examined by thematic analysis. Long COVID negatively affected female long haulers' social lives by causing physical limitations, economic issues, altered social relationships, social roles' conflicts, and social stigma. Long COVID prevented female long haulers' recovery process. Physical limitations altered their perceptions on body, and family-work conflicts caused tremendous stress. They also experienced internalized stigma and job insecurities. This study provides insights into challenges that COVID-19 female long haulers could face in their return to normal social life, underscoring the vulnerability of females affected by long COVID due to significant alterations in their social lives. Shifting to new methods of communication, especially social media, diminished the adverse effects of long COVID (e.g., social isolation).

Listening to Voices from African American Communities in the Southern States about COVID-19 Vaccine Information and Communication: A Qualitative Study.

The high uptake of COVID-19 vaccines is one of the most promising measures to control the pandemic. However, some African American (AA) communities exhibit vaccination hesitancy due to mis- or disinformation. It is important to understand the challenges in accessing reliable COVID-19 vaccine information and to develop feasible health communication interventions based on voices from AA communities. We conducted 2 focus group discussions (FGDs) among 18 community stakeholders recruited from 3 counties in South Carolina on 8 October and 29 October 2021. The FGDs were conducted online via Zoom meetings. The FGD data were managed and thematically analyzed using NVivo 12. Participants worked primarily in colleges, churches, and health agencies. We found that the challenges of accessing reliable vaccine information in AA communities primarily included structural barriers, information barriers, and a lack of trust. Community stakeholders recommended recruiting trusted messengers, using social events to reach target populations, and conducting health communication campaigns through open dialogue among stakeholders. Health communication interventions directed at COVID-19 vaccine uptake should be grounded in ongoing community engagement, trust-building activities, and transparent communication about vaccine development. Tailoring health communication interventions to different groups may help reduce misinformation spread and thus promote vaccination in AA communities in the southern states.

A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice.

Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) resulting in significant economic losses worldwide. Vaccination is the most effective approach to disease prevention. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against these pathogens is required for the global swine industry. Compared with traditional vaccines, multi-epitope vaccines have several advantages, they are comparatively easy to produce and construct, are chemically stable, and do not have an infectious potential. In this study, to develop a safe and effective vaccine, B cell and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46, and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM that has good hydrophilicity, strong antigenicity, and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies, and it had good immunoreactivity with anti-rEP-PM, anti-PRRSV, and anti-Mhp antibodies. The anti-rEP-PM antibody specifically recognizes proteins from PRRSV and Mhp. Moreover, rEP-PM induced a Th1-dominant cellular immune response in mice. Our results showed that the rEP-PM protein could be a potential candidate for the development of a safe and effective multi-epitope peptide combined vaccine to control PRRSV and Mhp infections.

Association between perceived stress and depression among medical students during the outbreak of COVID-19: The mediating role of insomnia.

BACKGROUND: The purpose of this study was to explore the association between perceived stress and depression among medical students and the mediating role of insomnia in this relationship during the COVID-19 pandemic in China. METHODS: A cross-sectional survey was conducted from March to April 2020 in medical university. Levels of perceived stress, insomnia and depression were measured using Perceived Stress Scale (PSS), Insomnia Severity Index (ISI) and Patient Health Questionnaire 9 (PHQ-9). The descriptive analyses of the demographic characteristics and correlation analyses of the three variables were calculated. The significance of the mediation effect was obtained using a bootstrap approach with SPSS PROCESS macro. RESULTS: The mean age of medical students was 21.46 years (SD=2.50). Of these medical students, 10,185 (34.3%) were male and 19,478 (65.7%) were female. Perceived stress was significantly associated with depression (ß=0.513, P < 0.001). Insomnia mediated the association between perceived stress and depression (ß=0.513, P < 0.001). The results of the non-parametric bootstrapping method confirmed the significance of the indirect effect of perceived stress through insomnia (95% bootstrap CI =0.137, 0.149). The indirect effect of insomnia accounted for 44.13% of the total variance in depression. CONCLUSIONS: These findings contribute to a better understanding of the interactive mechanisms underlying perceived stress and depression, and elucidating the mediating effects of insomnia on the association. This research provides a useful theoretical and methodological approach for prevention of depression in medical students. Findings from this study indicated that it may be effective to reduce depression among medical students by improving sleep quality and easing perceived stress.

Attitudes to Being Vaccinated Against COVID-19: A Survey of People With Epilepsy in China.

Objective: We conducted a survey to assess vaccination coverage, vaccination willingness, and variables associated with vaccination hesitancy to provide evidence on coronavirus disease (COVID-19) vaccination strategies. Methods: This anonymous questionnaire study conducted a multicenter, cross-sectional survey of outpatients and inpatients with epilepsy (PWE) registered in epilepsy clinics, in 2021, in 10 hospitals in seven cities of Shandong Province. Results: A total of 600 questionnaires were distributed, and 557 valid questionnaires were returned. A total of 130 people were vaccinated against COVID-19. Among 427 unvaccinated participants, 69.32% (296/427) were willing to receive the COVID-19 vaccine in the future, and the remaining 30.68% (131/427) were unwilling to receive vaccination. Most (89.9%) of the participants believed that the role of vaccination was crucial in response to the spread of COVID-19. A significant association was found between willingness to receive the COVID-19 vaccine and the following variables: age, marital status, level of education, occupation, residence, seizure type, and seizure control after antiepileptic drug therapy. It is noteworthy that education level, living in urban areas, and seizure freedom were significantly related to willingness to receive COVID-19 vaccination. Conclusions: Vaccination is a key measure for the prevention and control of COVID-19, and most PWE are willing to be vaccinated. Vaccine safety, effectiveness, and accessibility are essential in combatting vaccine hesitation and increasing vaccination rates.

Latent class analysis of depression and anxiety among medical students during COVID-19 epidemic.

OBJECTIVE: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. The mental health of medical students under the COVID-19 epidemic has attracted much attention. This study aims to identify subgroups of medical students based on depression and anxiety and explore the influencing factors during the COVID-19 epidemic in China. METHODS: A total of 29,663 medical students were recruited during the epidemic of COVID-19 in China. Depression and anxiety symptoms were assessed using Patient Health Questionnaire 9 (PHQ9) and Generalized Anxiety Disorder 7 (GAD7) respectively. Latent class analysis was performed based on depression and anxiety symptoms in medical students. The latent class subtypes were compared using the chi-square test. Multinomial logistic regression was used to examine associations between identified classes and related factors. RESULTS: In this study, three distinct subgroups were identified, namely, the poor mental health group, the mild mental health group and the low symptoms group. The number of medical students in each class is 4325, 9321 and 16,017 respectively. The multinomial logistic regression results showed that compared with the low symptoms group, the factors influencing depression and anxiety in the poor mental health group and mild mental health group were sex, educational level, drinking, individual psychiatric disorders, family psychiatric disorders, knowledge of COVID-19, fear of being infected, and participate in mental health education on COVID-19. CONCLUSIONS: Our findings suggested that latent class analysis can be used to categorize different medical students according to their depression and anxiety symptoms during the outbreak of COVID-19. The main factors influencing the poor mental health group and the mild mental health group are basic demographic characteristics, disease history, COVID-19 related factors and behavioural lifestyle. School administrative departments can carry out targeted psychological counseling according to different subgroups to promote the physical and mental health of medical students.

Coupling of N7-methyltransferase and 3'-5' exoribonuclease with SARS-CoV-2 polymerase reveals mechanisms for capping and proofreading.

The capping of mRNA and the proofreading play essential roles in SARS-CoV-2 replication and transcription. Here, we present the cryo-EM structure of the SARS-CoV-2 replication-transcription complex (RTC) in a form identified as Cap(0)-RTC, which couples a co-transcriptional capping complex (CCC) composed of nsp12 NiRAN, nsp9, the bifunctional nsp14 possessing an N-terminal exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase), and nsp10 as a cofactor of nsp14. Nsp9 and nsp12 NiRAN recruit nsp10/nsp14 into the Cap(0)-RTC, forming the N7-CCC to yield cap(0) (7MeGpppA) at 5' end of pre-mRNA. A dimeric form of Cap(0)-RTC observed by cryo-EM suggests an in trans backtracking mechanism for nsp14 ExoN to facilitate proofreading of the RNA in concert with polymerase nsp12. These results not only provide a structural basis for understanding co-transcriptional modification of SARS-CoV-2 mRNA but also shed light on how replication fidelity in SARS-CoV-2 is maintained.

Diagnosis of Coronavirus Disease 2019 Pneumonia by Using Chest Radiography: Value of Artificial Intelligence.

Background Radiologists are proficient in differentiating between chest radiographs with and without symptoms of pneumonia but have found it more challenging to differentiate coronavirus disease 2019 (COVID-19) pneumonia from non-COVID-19 pneumonia on chest radiographs. Purpose To develop an artificial intelligence algorithm to differentiate COVID-19 pneumonia from other causes of abnormalities at chest radiography. Materials and Methods In this retrospective study, a deep neural network, CV19-Net, was trained, validated, and tested on chest radiographs in patients with and without COVID-19 pneumonia. For the chest radiographs positive for COVID-19, patients with reverse transcription polymerase chain reaction results positive for severe acute respiratory syndrome coronavirus 2 with findings positive for pneumonia between February 1, 2020, and May 30, 2020, were included. For the non-COVID-19 chest radiographs, patients with pneumonia who underwent chest radiography between October 1, 2019, and December 31, 2019, were included. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to characterize diagnostic performance. To benchmark the performance of CV19-Net, a randomly sampled test data set composed of 500 chest radiographs in 500 patients was evaluated by the CV19-Net and three experienced thoracic radiologists. Results A total of 2060 patients (5806 chest radiographs; mean age, 62 years ± 16 [standard deviation]; 1059 men) with COVID-19 pneumonia and 3148 patients (5300 chest radiographs; mean age, 64 years ± 18; 1578 men) with non-COVID-19 pneumonia were included and split into training and validation and test data sets. For the test set, CV19-Net achieved an AUC of 0.92 (95% CI: 0.91, 0.93). This corresponded to a sensitivity of 88% (95% CI: 87, 89) and a specificity of 79% (95% CI: 77, 80) by using a high-sensitivity operating threshold, or a sensitivity of 78% (95% CI: 77, 79) and a specificity of 89% (95% CI: 88, 90) by using a high-specificity operating threshold. For the 500 sampled chest radiographs, CV19-Net achieved an AUC of 0.94 (95% CI: 0.93, 0.96) compared with an AUC of 0.85 (95% CI: 0.81, 0.88) achieved by radiologists. Conclusion CV19-Net was able to differentiate coronavirus disease 2019-related pneumonia from other types of pneumonia, with performance exceeding that of experienced thoracic radiologists. © RSNA, 2021 Online supplemental material is available for this article.