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The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Akhtar, Basher, Nizam, Kamruzzaman, Khaton, Banna, Kaisar, Karmakar, Hakim, Akter, Ahmed, Tauheed, Islam, Ahmmed, Mahamud, Hasnat, Sumon, Rashed, Ghosh, Calderwood, Harris, Charles, LaRocque, Ryan, Banu, Shirin, Chowdhury, Bhuiyan and Qadri.)

Background: The spread of COVID-19 pandemic in early 2020 compelled all the educational activities, including medical education to be shifted from face-to-face interaction to a virtual platform. This shift provided opportunities for exploring online assessment modalities. One such assessment method is an online open book exam which is a unique concept in medical education of Pakistan. Limited information is available in literature regarding open book exam for the basic science subjects. Hence, the objective of the study was to determine the quality of the open book exam administered as a pilot project to the first-year medical students., Methods: It was a cross-sectional analytical study that included 99 students of first year MBBS. The students were administered an online unrestricted type of open book exam as a formative assessment. The exam consisted of 30 open-ended, short answer type questions. The scores of the exam were analyzed for psychometric quality., Results: The mean score was 47.24 ± 15.30 SD %. The reliability of the exam was 0.79. The majority (66.6%) of items were found to be moderately difficult with their difficulty index ranging from 31 to 80%. The majority (86.6%) items were in the range of moderate to high discrimination. There were no questions with negative discrimination., Conclusions: The exam was found to be reliable and can be implemented with training of faculty and students. Online open book exam provides a good format for remote and formative assessment of students with minimum proctoring during times of constraints such as COVID-19 pandemic., (© 2022. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) has become a significant disease pandemic. Dhaka City alone has contributed about one-third to the total COVID-19 cases in Bangladesh. Globally, patients with infectious diseases, including COVID-19, experience stigma. There was no quantitative estimate of stigma experienced by patients with COVID-19 in the country. Therefore, this study aimed to assess the prevalence of stigma and its associated factors among patients with COVID-19 in Dhaka., Methods: A cross-sectional study was conducted among 384 respondents aged 18 years or older who had been hospitalized or had stayed at home and were tested negative 15 days to 6 months before the day of data collection. Data collection was done through in-person and telephone interviews using a semi-structured survey questionnaire. A 15-item COVID-19-related stigma scale questionnaire was used to assess stigma. Binary logistic regression analysis was performed to identify the predictors of stigma., Results: More than half (53.1%) of the respondents experienced stigma when they were COVID-19 positive. Females were at a 3.24 times higher risk of experiencing stigma than their male counterparts. Respondents from the 60+ age group and 40-59 age group were 63.0% and 48.0% less likely to experience stigma than those from the 18-39 age group. Non-hospitalised patients had 1.67 times higher odds of facing stigma than those hospitalised., Conclusions: This study reported a high prevalence of stigma among the patients with COVID-19 in Dhaka City. The current evidence base of stigma experience among patients with COVID-19 offers a solid foundation for creating effective strategies and policies and designing appropriate interventions to counter stigma, which will improve the psychological well-being of patients with COVID-19 in Bangladesh., Competing Interests: Md. Golam Kibria is the Executive Director of the Centre for Development Action, Bangladesh. Taslima Islam is a member of the Executive Committee of the Centre for Development Action, Bangladesh. Md. Tajul Islam is an Advisor of the Centre for Development Action, Bangladesh. Russell Kabir is an Advisor of the Centre for Development Action, Bangladesh and is an Academic Editor for PeerJ., (© 2022 Kibria et al.)

The rampant spread of highly pathogenic avian influenza A (H5N6) virus has drawn additional concerns along with ongoing Covid-19 pandemic. Due to its migration-related diffusion, the situation is deteriorating. Without an existing effective therapy and vaccines, it will be baffling to take control measures. In this regard, we propose a revers vaccinology approach for prediction and design of a multi-epitope peptide based vaccine. The induction of humoral and cell-mediated immunity seems to be the paramount concern for a peptide vaccine candidate; thus, antigenic B and T cell epitopes were screened from the surface, membrane and envelope proteins of the avian influenza A (H5N6) virus, and passed through several immunological filters to determine the best possible one. Following that, the selected antigenic with immunogenic epitopes and adjuvant were linked to finalize the multi-epitope-based peptide vaccine by appropriate linkers. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLR8). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, molecular dynamics simulation was performed within the highest binding affinity complex to observe the stability, and minimize the designed vaccine's high mobility region to order to increase its stability. Then, Codon optimization and other physicochemical properties were performed to reveal that the vaccine would be suitable for a higher expression at cloning level and satisfactory thermostability condition. In conclusion, predicting the overall in silico assessment, we anticipated that our designed vaccine would be a plausible prevention against avian influenza A (H5N6) virus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Authors declare that they have no conflict of interests., (Copyright © 2022. Published by Elsevier B.V.)

It was previously reported that coronavirus caused myocardial injury in hospitalized patients. However, delayed cardiac involvement in symptomatic patient recovery from COVID-19 is not yet well known. The objective of this study was to evaluate cardiac involvement by using cardiac magnetic resonance (CMR) in symptomatic post-COVID-19 recovered patients. Thirty (30) patients who recovered from COVID-19 and had recently reported cardiac symptoms were studied in a prospective observational study performed at Popular Medical College Hospital, Dhaka, Bangladesh from March 2021 to September 2021. They underwent CMR examinations. CMR scanning protocol included the following: black blood, cine sequence, both short-axis and long-axis, T2-weight short tau inversion recovery (STIR) sequence, T2- weighted imaging (T2WI) and late gadolinium enhancement (LGE) and quantitative mapping sequences-native T1/T2 mapping and post-contrast T1 mapping. Myocardial edema and late gadolinium enhancement were assessed in all patients. Quantitative evaluation of native T1/T2 and ECV value and cardiac function were evaluated. There were 30 people in all in this study. The average age of the participants in the study was 36.6 years. Fourteen (46.6%) of the patients had abnormal cardiac MRI results, while the remaining 15(53.3%) had negative CMR findings. Among positive findings patients, 8(57.1%) of 14 had increased T2 signal. Increased myocardial edema was found in the same no of patients, involving 53.2% (128 of 224) of LV segments. Only 2 cases (2 of 14) showed mid myocardial and subepicardial LGE, involving 18 of 224, 8.03% of myocardial segments. Global native T1, T2 and ECV values are significantly elevated in all CMR positive findings patients. Native T1 1231ms (IQR: 1281.25-1257.5 versus 1155.5 (IQR: 1137.25-1172.75), T2 40 (IQR: 34.5-43.25) versus 35.5 (IQR: 34-37), ECV 31 (29.75-33.25) versus 23.5 (21.25-24.0), p<0.001; p<0.011 and p<0.001 respectively. Reduced RV functional were found in positive as compared with negative CMR findings patients, EF, 32.05 (IQR: 25.25-39.0) versus 54.5 (IQR: 52.0-57.75) and EDV, 117.5 (IQR: 102.0-134.25) versus 95.0 (IQR: 71.75-99.75), p<0.001 and p<0.001 respectively. In this study cardiac involvement was found in the post-COVID-19 recovered patient with cardiac symptoms. Cardiac MRI findings included myocardial edema, fibrosis and reduced right ventricular function. So attention should be paid to symptomatic post-COVID-19 recovered patients.

Background: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19., Methods: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes., Findings: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS; hazard ratio [HR] 3·31 [95% CI 1·49-7·33], p=0·0033; and 2·58 [1·10-6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16-31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69-7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways., Interpretation: Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy., Funding: Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation., Competing Interests: Declaration of Interests CA, KC, CS, and SN are founders, shareholders, and directors of Caristo Diagnostics, a CT image analysis company. CS is a full-time employee and MS is a part-time employee of Caristo diagnostics. JD is shareholder and chair of the advisory board of Caristo Diagnostics. EKO is a consultant and minor shareholder of Caristo Diagnostics. The technology described in this work is subject to patent US10,695,023B2 and patent applications PCT/GB2017/053262, GB2018/1818049.7, GR20180100490, and GR20180100510, licensed through exclusive license to Caristo Diagnostics. Caristo Diagnostics and the authors linked to it have no further conflicts of interest, beyond the above. JD is CMO of Our Future Health; Senior Advisor for Cardiovascular Disease Prevention, NHS Healthcheck Expert Scientific and Clinical Advisory Panel; and Chair of the Review of the National Health Check Programme for Public Health England. JCLR received a Research for Patient Benefit Grant from NIHR, and consulting fees from HeartFlow for physician services. DAd received support from Leicester NIHR Biomedical Research Unit and Innovate UK; grants and contracts from the Medical Research Council; and has two patents issued (Cardiac assist device: EP3277337A1; and angioplasty of calcified arteries: PCT/GB2017/050877) outside the scope of the current study. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

With healthcare professionals being the frontline warriors in battling the Covid pandemic, their risk of exposure to the virus is extremely high. We present our experience in building a system, aimed at monitoring the physiology of these professionals 24/7, with the hope of providing timely detection of infection and thereby better care. We discuss a machine learning approach and model using signals from a wrist wearable device to predict infection at a very early stage. In a double-blind test on a small group of patients, our model could successfully identify the infected versus non-infected cases with near 100% accuracy. We also discuss some of the challenges we faced, both technical and non-technical, to get this system off the ground as well as offer some suggestions that could help tackle these hurdles.

Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19-mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.

Background: E-learning is a relatively trending system of education that has been placed over conventional campus-based learning worldwide, especially since the emergence of the COVID-19 pandemic. This study aimed to assess e-learning readiness among university students of a developing country like Bangladesh and identify the independent predictors of e-learning readiness., Methods: From 26 December 2020 to 11 January 2021, a total of 1162 university students who had enrolled for e-learning completed a semi-structured questionnaire. Data were collected online via "Google Form" following the principles of snowball sampling through available social media platforms in Bangladesh. A multivariable linear regression model was fitted to investigate the association of e-learning readiness with perceived e-learning stress and other independent predictor variables., Results: A total of 1162 university students participated in this study. The results indicated that with the increase of students' perceived e-learning stress score, the average e-learning readiness score was significantly decreased (β = -0.43, 95% CI: -0.66, -0.20). The students did not seem ready, and none of the e-learning readiness scale items reached the highest mean score (5.0). The age, gender, divisional residence, preference of students and their parents, devices used, and having any eye problems were significantly associated with the students' e-learning readiness., Conclusion: During the prolonged period of the COVID-19 pandemic, e-learning implication strategies are needed to be assessed systematically with the level of readiness and its' impacts among students for the continuation of sound e-learning systems. The study findings recommend evaluating the e-learning readiness of university students and the mental health outcomes during the COVID-19 catastrophe in Bangladesh., Competing Interests: The authors have declared that no competing interests exist.

A 26-year-old woman was sent to the emergency room by her primary care physician for a new petechial rash and thrombocytopenia 2 weeks after receiving the Moderna mRNA-1273 SARS-CoV-2 vaccine. Her hospital course was complicated by transaminitis. Her platelet count improved to normal on hospital day 5 after receiving intravenous steroids and intravenous immunoglobulin to treat her suspected diagnosis of immune thrombocytopenic purpura. Extensive workup for her thrombocytopenia and transaminitis was unremarkable including ruling out infectious, autoimmune and toxic causes. A liver biopsy was unrevealing and her transaminitis was improved on discharge. Although not proven, the temporal relationship of her vaccination with thrombocytopenia and abnormal liver enzymes points towards the Moderna mRNA-1273 SARS-CoV-2 vaccine as the most likely inciting factor., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Novel Coronavirus Disease 2019 (COVID-19) has caused serious repercussions both physically and mentally. The crisis has laid an enormous workload on the global healthcare fraternity. This article has attempted to study the emotional and psychological status of the medical and dental fraternity across seven Asian countries (India, Malaysia, the Gulf Cooperation countries (GCC) and, others) and also deduce the degree of mental preparedness as they spearhead the war against COVID-19. A cross-sectional, descriptive online survey was carried out among potential participants from online forums and other health-related social communities. Bivariate analysis with descriptive statistics was applied to decipher the results. A total of 788 complete responses were analyzed. The response rate was 77.1%. Results revealed the perception of the Healthcare Professionals about COVID-19 and its implications in their personal and professional lives. Many categories from psychological and emotional standpoints were analyzed. Older HCPs (above 35 years) reported high levels of stress at the workplace (p = 0.002). About 43.5% of the HCPs from India reported that they have not received any specialized training on containing COVID-19 or any contagious disease. Intense emotional stress was reported by the HCPs when colleagues get infected. The medical professionals (61.7%) exhibited more work stress compared to their dental counterparts. Analyzing the psychological and emotional status of HCPs is imperative especially in this COVID-19 situation. Similar analyses are crucial to gauge the quality of our healthcare system and take necessary actions like training the workforce, revamping the infrastructure, and regulating the workflow.

Importance: In-hospital mortality rates from COVID-19 are high but appear to be decreasing for selected locations in the United States. It is not known whether this is because of changes in the characteristics of patients being admitted., Objective: To describe changing in-hospital mortality rates over time after accounting for individual patient characteristics., Design, Setting, and Participants: This was a retrospective cohort study of 20 736 adults with a diagnosis of COVID-19 who were included in the US American Heart Association COVID-19 Cardiovascular Disease Registry and admitted to 107 acute care hospitals in 31 states from March through November 2020. A multiple mixed-effects logistic regression was then used to estimate the odds of in-hospital death adjusted for patient age, sex, body mass index, and medical history as well as vital signs, use of supplemental oxygen, presence of pulmonary infiltrates at admission, and hospital site., Main Outcomes and Measures: In-hospital death adjusted for exposures for 4 periods in 2020., Results: The registry included 20 736 patients hospitalized with COVID-19 from March through November 2020 (9524 women [45.9%]; mean [SD] age, 61.2 [17.9] years); 3271 patients (15.8%) died in the hospital. Mortality rates were 19.1% in March and April, 11.9% in May and June, 11.0% in July and August, and 10.8% in September through November. Compared with March and April, the adjusted odds ratios for in-hospital death were significantly lower in May and June (odds ratio, 0.66; 95% CI, 0.58-0.76; P < .001), July and August (odds ratio, 0.58; 95% CI, 0.49-0.69; P < .001), and September through November (odds ratio, 0.59; 95% CI, 0.47-0.73)., Conclusions and Relevance: In this cohort study, high rates of in-hospital COVID-19 mortality among registry patients in March and April 2020 decreased by more than one-third by June and remained near that rate through November. This difference in mortality rates between the months of March and April and later months persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity and did not appear to be associated with changes in the characteristics of patients being admitted.

The current pandemic of coronavirus disease 19 (COVID-19) has been a global concern since early 2020, where the number of COVID-19 cases is also on a rapid surge in Bangladesh with the report of a total of 276,549 cases after the detection of the first three cases in this country on 8 March 2020. The COVID-19 pandemic has made a seismic shift in the healthcare delivery system, where physician offices have accelerated digital health solutions at record speed, putting telemedicine (i.e., telehealth) at centre stage. Amid the severely contagious COVID-19, telemedicine has moved from being an optional service to an essential one. As the developing country, there are some barriers to get evenly distributed advantages of this approach due to the digital divides and disparities. In this commentary, we have described the importance of telemedicine service amid the outbreak of COVID-19 in Bangladesh, the barriers and challenges that the country is facing to implement this approach and the strategies to overcome these barriers in this developing country., (© 2020 John Wiley & Sons Ltd.)