Coronavirus pandemic in the South Asia region: Health policy and economy trade-off.

Background: The South Asian Association for Regional Cooperation (SAARC) covers Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. We conducted a comparative analysis of the trade-off between the health policies for the prevention of COVID-19 spread and the impact of these policies on the economies and livelihoods of the South Asia populations. Methods: We analyzed COVID-19 data on epidemiology, public health and health policy, health system capacity, and macroeconomic indicators from January 2020 to March 2021 to determine temporal trends by conducting joinpoint regression analysis using average weekly percent change (AWPC). Results: Bangladesh had the highest statistically significant AWPC for new COVID-19 cases (17.0; 95% CI = 7.7-27.1, P < 0.001), followed by the Maldives (12.9; 95% CI = 5.3-21.0, P < 0.001) and India (10.0; 95% CI = 8.4-11.5, P < 0.001). The AWPC for COVID-19 deaths was significant for India (6.5; 95% CI = 4.3-8.9, P < 0.001) and Bangladesh (6.1; 95% CI = 3.7-8.5, P < 0.001). Nepal (55.79%), and India (34.91%) had the second- and third-highest increase in unemployment, while Afghanistan (6.83%) and Pakistan (16.83%) had the lowest. The rate of change of real GDP had the highest decrease for Maldives (557.51%), and India (297.03%); Pakistan (46.46%) and Bangladesh (70.80%), however, had the lowest decrease. The government response stringency index for Pakistan had a see-saw pattern with a sharp decline followed by an increase in the government health policy restrictions that approximated the test-positivity trend. Conclusions: Unlike developed economies, the South Asian developing countries experienced a trade-off between health policy and their economies during the COVID-19 pandemic. South Asian countries (Nepal and India), with extended periods of lockdowns and a mismatch between temporal trends of government response stringency index and the test-positivity or disease incidence, had higher adverse economic effects, unemployment, and burden of COVID-19. Pakistan demonstrated targeted lockdowns with a rapid see-saw pattern of government health policy response that approximated the test-positivity trend and resulted in lesser adverse economic effects, unemployment, and burden of COVID-19.

Multiple Keratoacanthomas Following Moderna Messenger RNA-1273 COVID-19 Vaccination Resolved With 5-Fluorouracil Treatment: Case Report.

Cutaneous reactions have been commonly associated with the Moderna messenger RNA (mRNA) COVID-19 vaccine. Among the reported cutaneous side effects, there have not been any associations reported yet regarding keratoacanthoma development after COVID-19 mRNA vaccination. We report a novel case of an 86-year-old man who experienced an eruption of multiple keratoacanthomas 2 weeks after inoculation with the Moderna mRNA-1273 vaccine that resolved following treatment with intralesional 5-fluorouracil.

Multiple Keratoacanthomas Following Moderna Messenger RNA-1273 COVID-19 Vaccination Resolved With 5-Fluorouracil Treatment: Case Report

Cutaneous reactions have been commonly associated with the Moderna messenger RNA (mRNA) COVID-19 vaccine. Among the reported cutaneous side effects, there have not been any associations reported yet regarding keratoacanthoma development after COVID-19 mRNA vaccination. We report a novel case of an 86-year-old man who experienced an eruption of multiple keratoacanthomas 2 weeks after inoculation with the Moderna mRNA-1273 vaccine that resolved following treatment with intralesional 5-fluorouracil.

'Fight the parasite': raising awareness of cystic echinococcosis in primary school children in endemic countries.

BACKGROUND: Cystic echinococcosis (CE) is a widespread zoonosis and a significant economic concern and cause of morbidity in humans. A scarcity of education on the sources of CE infection and containment measures is considered to be a key factor responsible for persistent transmission within communities. Recently, edutainment approaches have captured the attention of health education (HE) professionals due to the benefits of integrating cognitive and emotional learning processes. METHODS: A study was carried out in Sardinia, Italy, between 2020 and 2022, amid the SARS-Covid-19 pandemic. The project, designed to involve primary school children (via remote or face-to-face learning depending on the evolving Covid-19 containment measures) consisted of four distinct phases: (i) creation of material for school children and teachers focused on cystic echinococcosis; (ii) pre-intervention evaluation of CE knowledge (i.e. True False Don't Know [TFD] pre-intervention questionnaire based on CE-related knowledge and practices); (iii) edutainment activity (e.g. interactive lessons enhanced by the comic booklet and the "Fight the parasite" cartoon video, hands-on educational activities and drawing activities on CE); and (iv) post-intervention evaluation of CE knowledge (via TFD post-intervention questionnaire [same questionnaire as used for the pre-intervention assessment] on CE-related knowledge and practices) and on-site edutainment tour in primary schools taking part to the project. RESULTS: The percentage of correct answers increased from 65% for the questionnaire administered pre-intervention to 87.9% for the same questionnaire administered post-intervention (χ2 = 648.12, df = 1, P < 0.0001), while the percentage of uncertain answers (i.e. 'I don't know') decreased from 23% pre-intervention to 5% post-intervention (χ2 = 603.44, df = 1, P < 0.0001). These differences indicate a significantly enhanced understanding of CE among participating school children after the intervention. CONCLUSIONS: The results of the present survey indicate that the use of digital educational tools, the use of video animations as a model for science communication, as well as other participatory teaching methods, enabled children to retain key knowledge of the routes of CE transmission and ways to prevent it.

Coronavirus pandemic in the Nordic countries: Health policy and economy trade-off.

Background: Countries making up the Nordic region - Denmark, Finland, Iceland, Norway, and Sweden - have minimal socioeconomic, cultural, and geographical differences between them, allowing for a fair comparative analysis of the health policy and economy trade-off in their national approaches towards mitigating the impact of the COVID-19 pandemic. Methods: This study utilized publicly available COVID-19 data of the Nordic countries from January 2020 to January 3, 2021. COVID-19 epidemiology, public health and health policy, health system capacity, and macroeconomic data were analysed for each Nordic country. Joinpoint regression analysis was performed to identify changes in temporal trends using average monthly percent change (AMPC) and average weekly percent change (AWPC). Results: Sweden's health policy, being by far the most relaxed response to COVID-19, was found to have the largest COVID-19 incidence and mortality, and the highest AWPC increases for both indicators (13.5, 95% CI = 5.6, 22.0, P < 0.001; 6.3, 95% CI = 3.5, 9.1, P < 0.001). Denmark had the highest number of COVID-19 tests per capita, consistent with their approach of increased testing as a preventive strategy for disease transmission. Iceland had the second-highest number of tests per capita due to their mass-testing, contact tracing, quarantine and isolation response. Only Norway had a significant increase in unemployment (AMPC = 2.8%, 95% CI = 0.7-4.9, P < 0.009) while the percentage change in real Gross Domestic Product (GDP) was insignificant for all countries. Conclusions: There was no trade-off between public health policy and economy during the COVID-19 pandemic in the Nordic region. Sweden's relaxed and delayed COVID-19 health policy response did not benefit the economy in the short term, while leading to disproportionate COVID-19 hospitalizations and mortality.

The fourth dose: My "me-first" experience.

Vaccine inequality is the biggest obstacle to curbing the Covid-19 pandemic and accelerating socio-economic recovery in the developing countries. Many people, including myself, living in developing countries, were initially inoculated with the WHO-approved vaccines unwelcome to developed countries, such as Sinovac. Presently, governments in developing countries are offering the third and fourth doses of mRNA vaccines to facilitate cross-border travel. This creates a devastating burden on ongoing Covid-19 vaccination in developing countries, increasing the injustice and inequality between the developed and developing countries. Here, I share my thoughts as a public health specialist while I was receiving the fourth dose of the Covid-19 vaccine to fulfil travel requirements.

Chest radiological finding of COVID-19 in patients with and without diabetes mellitus: Differences in imaging finding.

The pandemic of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diabetes mellitus is a risk factor for developing severe illness and a leading cause of death in patients with COVID-19. Diabetes can precipitate hyperglycaemic emergencies and cause prolonged hospital admissions. Insulin resistance is thought to cause endothelial dysfunction, alveolar capillary micro-angiopathy and interstitial lung fibrosis through pro-inflammatory pathways. Autopsy studies have also demonstrated the presence of microvascular thrombi in affected sections of lung, which may be associated with diabetes. Chest imaging using x-ray (CXR) and computed tomography (CT) of chest is used to diagnose, assess disease progression and severity in COVID-19. This article reviews current literature regarding chest imaging findings in patients with diabetes affected by COVID-19. A literature search was performed on PubMed. Patients with diabetes infected with SARS-CoV-2 are likely to have more severe infective changes on CXR and CT chest imaging. Severity of airspace consolidation on CXR is associated with higher mortality, particularly in the presence of co-morbidities such as ischaemic heart disease. Poorly controlled diabetes is associated with more severe acute lung injury on CT. However, no association has been identified between poorly-controlled diabetes and the incidence of pulmonary thromboembolism in patients with COVID-19.

Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a novel deep neural network.

BACKGROUND: The nextwave of COVID-19 pandemic is anticipated to be worse than the initial one and will strain the healthcare systems even more during the winter months. Our aim was to develop a novel machine learning-based model to predict mortality using the deep learning Neo-V framework. We hypothesized this novel machine learning approach could be applied to COVID-19 patients to predict mortality successfully with high accuracy. METHODS: We collected clinical and laboratory data prospectively on all adult patients (≥18 years of age) that were admitted in the inpatient setting at Aga Khan University Hospital between February 2020 and September 2020 with a clinical diagnosis of COVID-19 infection. Only patients with a RT-PCR (reverse polymerase chain reaction) proven COVID-19 infection and complete medical records were included in this study. A Novel 3-phase machine learning framework was developed to predict mortality in the inpatients setting. Phase 1 included variable selection that was done using univariate and multivariate Cox-regression analysis; all variables that failed the regression analysis were excluded from the machine learning phase of the study. Phase 2 involved new-variables creation and selection. Phase 3 and final phase applied deep neural networks and other traditional machine learning models like Decision Tree Model, k-nearest neighbor models, etc. The accuracy of these models were evaluated using test-set accuracy, sensitivity, specificity, positive predictive values, negative predictive values and area under the receiver-operating curves. RESULTS: After application of inclusion and exclusion criteria (n=)1214 patients were selected from a total of 1228 admitted patients. We observed that several clinical and laboratory-based variables were statistically significant for both univariate and multivariate analyses while others were not. With most significant being septic shock (hazard ratio [HR], 4.30; 95% confidence interval [CI], 2.91-6.37), supportive treatment (HR, 3.51; 95% CI, 2.01-6.14), abnormal international normalized ratio (INR) (HR, 3.24; 95% CI, 2.28-4.63), admission to the intensive care unit (ICU) (HR, 3.24; 95% CI, 2.22-4.74), treatment with invasive ventilation (HR, 3.21; 95% CI, 2.15-4.79) and laboratory lymphocytic derangement (HR, 2.79; 95% CI, 1.6-4.86). Machine learning results showed our deep neural network (DNN) (Neo-V) model outperformed all conventional machine learning models with test set accuracy of 99.53%, sensitivity of 89.87%, and specificity of 95.63%; positive predictive value, 50.00%; negative predictive value, 91.05%; and area under the receiver-operator curve of 88.5. CONCLUSION: Our novel Deep-Neo-V model outperformed all other machine learning models. The model is easy to implement, user friendly and with high accuracy.

A Retrospective Study Assessing the Effect of Diabetes on Mortality in Patients With COVID-19 at a Teaching Hospital in the United Kingdom.

Aim The aim of the study was to compare the clinical characteristics and outcomes (mortality, intensive care admission, mechanical ventilation, and length of stay, LoS) of patients with and without diabetes with confirmed COVID-19.  Methods This retrospective study evaluated clinical and laboratory variables in adult inpatients from Brighton and Sussex University Hospitals NHS Trust with laboratory-confirmed COVID-19 between March 10, 2020, and June 30, 2020. Univariate and multivariate analyses were performed to compare the outcomes of patients with and without diabetes.  Results Over 457 patients were included in this study (140 with diabetes and 317 without diabetes), of which 143 (31.9%) died. The median age was 80 years and were predominantly males (59.1%). Baseline characteristics at the time of COVID-19 diagnosis demonstrated that the patients with diabetes were younger than those without diabetes (p=0.008). Mortality increased with age. There was no difference in adverse outcomes in those with and without diabetes. However, subgroup analysis of patients aged ≤60 years demonstrated a significantly increased mortality in those with diabetes (p=0.016). Patients with diabetes had an increased length-of-stay compared to those without diabetes, which was more evident in those aged ≤60 years. Conclusion Age is the most important predictor of mortality. Patients with diabetes did not have increased mortality from COVID-19, which is likely due to their younger age in our cohort. More patients with diabetes stayed in the hospital longer than seven days than those without diabetes.

The effect of the COVID-19 pandemic on paediatric cancer care: lessons learnt from a major paediatric oncology department in Turkey.

The COVID-19 pandemic has disrupted cancer care. An audit at a major Paediatric Oncology Department in Turkey was performed to determine its impact on paediatric cancer care. A comparison was made among the number of daily paediatric cancer patients, diagnostic and treatment procedures. The data for the 'COVID-19 period' (10 March to 31 October 2020) were compared with the corresponding 'prior year control period' (10 March to 31 October 2019). Moreover, presentation delay (duration between first symptoms to healthcare visit) was calculated for new cases. The findings indicate that the mean 34.7 outpatients per day during 'COVID-19 period' was significantly lower than the 'prior year control period' (52.2). There were 17.7 inpatients per day during the 'COVID-19 period' which was significantly lower than 23.8 inpatients per day during the 'prior year control period'. Significant reduction in the daily mean number of patients undergoing chemotherapy, radiotherapy, surgery and imaging studies during the 'COVID-19 period' was also evident. A negative trend in the diagnosis of new paediatric cancers was evident with 128 new cancer cases during the 'COVID-19 period', whereas the corresponding number was 212 for the 'prior year control period'. The presentation delay (median 31 days) remain unchanged during the 'COVID-19 period'. The findings suggest significant damage to paediatric cancer care during the COVID-19 pandemic. Appropriate obligatory actions by oncology societies and policymakers can minimise longer term negative impacts.

Handwashing with soap: A concern for overuse of water amidst the COVID-19 pandemic in Bangladesh.

Handwashing is one of the vital public health measures. It helps to prevent the spread of the COVID-19 pandemic. However, water overuse during hand scrubbing with soap keeping the tap on may put enormous pressure on the already overstretched groundwater resources and households' economic well-being. Therefore, this study aimed to determine the overuse of water while scrubbing hands with soap for handwashing when the tap is on amid the COVID-19 pandemic in Bangladesh. Sociodemographic data were collected using a web-based survey tool among 1980 participants and an experiment was conducted among 126 participants to estimate the overuse of water during hand scrubbing while the tap is on. A total of 80% of the participants washed their hands regularly after returning home from outside. About 57.3% of participants did not turn off their tap throughout the handwashing process. A single participant, who kept his tap on throughout the handwashing process, overused approximately 1.7 L of water per handwash and 14.9 L of water per day. Hand scrubbing with soap keeping the tap on, raised the overuse of water 13-fold during this pandemic compared to the non-pandemic situation which cost an extra 225.0 BDT (2.7$) per day for 1980 participants. Minimize the speed of tap, using automatic taps, and using taps operated by legs might be an effective solution to reduce the water overuse. Furthermore, behavioral change interventions are needed to aware people turn off the tap during hand scrubbing with soap.

Is the "Common Cold" Our Greatest Ally in the Battle Against SARS-CoV-2?

The discovery of T-cell responses to SARS-CoV-2 in non-infected individuals indicates cross-reactive immune memory from prior exposure to human coronaviruses (HCoV) that cause the common cold. This raises the possibility that "immunity" could exist within populations at rates that may be higher than serology studies estimate. Besides specialized research labs, however, there is limited ability to measure HCoV CD4+ and CD8+ T-cell responses to SARS-CoV-2 infection, which currently impedes interpretation of any potential correlation between COVID-19 disease pathogenesis and the calibration of pandemic control measures. Given this limited testing ability, an alternative approach would be to exploit the large cohort of currently available data from which statistically significant associations may be generated. This would necessitate the merging of several public databases including patient and contact tracing, which could be created by relevant public health organizations. Including data from both symptomatic and asymptomatic patients in SARS-CoV-2 databases and surveillance systems could provide the necessary information to allow for more informed decisions.

Paired Heavy and Light Chain Signatures Contribute to Potent SARS-CoV-2 Neutralization in Public Antibody Responses (preprint)

Understanding protective mechanisms of antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We discovered a new antibody, 910-30, that targets the SARS-CoV-2 ACE2 receptor binding site as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. We performed sequence and structural analyses to explore how IGHV3-53/IGHV3-66 antibody features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer revealed its binding interactions and ability to disassemble spike. Despite heavy chain sequence similarity, biophysical analyses of IGHV3-53/3-66 antibodies highlighted the importance of native heavy:light pairings for ACE2 binding competition and for SARS-CoV-2 neutralization. We defined paired heavy:light sequence signatures and determined antibody precursor prevalence to be ~1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These data reveal key structural and functional neutralization features of the IGHV3-53/3-66 public antibody class to accelerate antibody-based efforts against SARS-CoV-2.

A Case of Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State in a Patient With COVID-19.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). Diabetes mellitus (DM) is one of the risk factors associated with severe illness in COVID-19 leading to increased hospital admissions and mortality. COVID-19 can precipitate hyperglycemic emergencies like diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in patients with DM. We present a case of a patient with COVID-19 admitted to the hospital with combined DKA and HHS. The case highlights the challenge of managing patients with DM suffering from COVID-19.

Structure-Based Design with Tag-Based Purification and In-Process Biotinylation Enable Streamlined Development of SARS-CoV-2 Spike Molecular Probes (preprint)

Biotin-labeled molecular probes, comprising specific regions of the SARS-CoV-2 spike, would be helpful in the isolation and characterization of antibodies targeting this recently emerged pathogen. To develop such probes, we designed constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, the probe region of interest, and a C-terminal sequence targeted by biotin ligase. Probe regions included full-length spike ectodomain as well as various subregions, and we also designed mutants to eliminate recognition of the ACE2 receptor. Yields of biotin-labeled probes from transient transfection ranged from ~0.5 mg/L for the complete ectodomain to >5 mg/L for several subregions. Probes were characterized for antigenicity and ACE2 recognition, and the structure of the spike ectodomain probe was determined by cryo-electron microscopy. We also characterized antibody-binding specificities and cell-sorting capabilities of the biotinylated probes. Altogether, structure-based design coupled to efficient purification and biotinylation processes can thus enable streamlined development of SARS-CoV-2 spike-ectodomain probes.Funding: Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID). Support for this work was also provided by COVID-19 Fast Grants, the Jack Ma Foundation, the Self Graduate Fellowship Program, and NIH grants DP5OD023118, R21AI143407, and R21AI144408. Some of this work was performed at the Columbia University Cryo-EM Center at the Zuckerman Institute, and some at the Simons Electron Microscopy Center (SEMC) and National Center for Cryo-EM Access and Training (NCCAT) located at the New York Structural Biology Center, supported by grants from the Simons Foundation (SF349247), NYSTAR, and the NIH National Institute of General Medical Sciences (GM103310). Conflict of Interest: The authors declare that they have no conflict of interest.Ethical Approval: Peripheral blood mononuclear cells (PBMCs) for B cell sorting were obtained from a convalescent SARS-CoV-2 patient (collected 75 days post symptom onset under an IRB approved clinical trial protocol, VRC 200 – ClinicalTrials.gov Identifier: NCT00067054) and a healthy control donor from the NIH blood bank pre-SARS-CoV-2 pandemic.