Predictors of moderate-to-severe side-effects following COVID-19 mRNA booster vaccination: A prospective cohort study among primary health care providers in Belgium. (preprint)

Background COVID-19 vaccine effectiveness declines months after vaccination. Therefore, it is likely that during the next few years, people may be repeatedly offered a booster vaccine to enhance humoral immunity levels. A growing number of people are questioning whether the benefits of a booster vaccine outweigh the side-effects.Objective This study aims (1) to identify the most frequently reported side-effects after different doses of COVID-19 mRNA vaccines, (2) and the longest lasting symptoms; and (3) to predict the likelihood of having moderate-to-severe side-effects after a booster COVID-19 mRNA vaccine given individual- and vaccine-specific characteristics.Design, setting, and participants : Secondary analysis of a prospective cohort study in primary health care providers (PHCPs) in Belgium conducted between December 2020 and December 2021, and in February-March 2023.Methods In nine subsequent surveys over a period of 2 years vaccine dose-number and side-effects after COVID-19 vaccines were collected. A Generalized Estimation Equations approach on the data of the first and second booster dose was used to investigate the probability of having moderate-to-severe side-effects after mRNA booster vaccination. Predictive performance of a binary classifier was assessed by looking at discrimination (i.e., quantified in terms of the area under the receiver operating characteristic curve). The final prediction model was validated using data with regard to the third booster by assessing misclassification rate, sensitivity and specificity.Results In total, 11% of the PHCPs had moderate-to-severe side-effects after their booster COVID-19 mRNA vaccine. The most common side-effects of COVID-19 mRNA doses included fatigue, local pain at the injection site, general pains, and headache. These side-effects typically lasted for a median of 1 to 2 days. The final model included five predictors: sex, alcohol consumption, history of moderate-to-severe side-effects after any previous dose, recent COVID-19 infection, and the booster dose-number (first, second). Having experienced moderate-to-severe side-effects after any previous dose was the strongest predictor of moderate-to-severe side-effects following an mRNA vaccine booster, with an odds ratio (OR) of 3.64 (95% CI: 2.80–4.75). The OR for female sex was 1.49 (95% CI: 1.21–1.84) implying that females have a higher odds of moderate-to-severe side-effects following booster vaccination. The differences in effect for booster dose-number, alcohol consumption and recent COVID-19 infection was not significant.Conclusion and Relevance: COVID-19 mRNA booster vaccination implies a low prevalence of moderate-to-severe side-effects among PHCPs, with a short median duration of symptoms if any. The strongest predictors are a history of moderate-to-severe side-effects after any previous dose and being female. These reassuring findings can help addressing concerns about booster vaccination and encourage their uptake.Trial Registration: NCT04779424

Pre-event psychiatric states predict trajectories of post-traumatic stress symptoms during the COVID-19 pandemic (preprint)

Recent time-dependent analyses of stress-related disorders have identified heterogeneity of trajectories and their modifying factors. While psychiatric patients are vulnerable to stress events, it is unclear how psychiatric conditions in the general population modulate subsequent stress responses. Using our longitudinal online survey from before the COVID-19 pandemic to post-pandemic follow-ups (n = 3815 Japanese adults), here we identified four trajectories of post-traumatic stress symptoms (PTSS) a latent growth mixture model; resilient, chronic, mild chronic, and early response. The depression/anxiety were identified as specific risk factors for the early-response trajectory. In contrast, general psychiatric burden and social withdrawal were identified as common risk/protective factors. Further, we estimated "baseline" PTSS to determine the predictability of the PTSS prognosis from pre-pandemic states. The chronic group showed significantly higher baseline PTSS scores than the mild-chronic and early-response groups, both of which were significantly higher than the resilient group. We concluded that prior psychiatric conditions significantly affect the PTSS trajectory. These results suggest that prior psychiatric conditions may be considered for the prevention and treatment of maladaptive stress responses.

Pre-event psychiatric states predict trajectories of post-traumatic stress symptoms during the COVID-19 pandemic (preprint)

Recent time-dependent analyses of stress-related disorders have identified heterogeneity of trajectories and their modifying factors. While psychiatric patients are vulnerable to stress events, it is unclear how psychiatric conditions in the general population modulate subsequent stress responses. Using our longitudinal online survey from before the COVID-19 pandemic to post-pandemic follow-ups (n = 3815 Japanese adults), here we identified four trajectories of post-traumatic stress symptoms (PTSS) a latent growth mixture model; resilient, chronic, mild chronic, and early response. The depression/anxiety were identified as specific risk factors for the early-response trajectory. In contrast, general psychiatric burden and social withdrawal were identified as common risk/protective factors. Further, we estimated “baseline” PTSS to determine the predictability of the PTSS prognosis from pre-pandemic states. The chronic group showed significantly higher baseline PTSS scores than the mild-chronic and early-response groups, both of which were significantly higher than the resilient group. We concluded that prior psychiatric conditions significantly affect the PTSS trajectory. These results suggest that prior psychiatric conditions may be considered for the prevention and treatment of maladaptive stress responses.

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia (preprint)

Age is a major risk factor for coronavirus disease (COVID-19)-associated severe pneumonia and mortality; however, the underlying mechanism remains unclear. Herein, we investigated whether age-related deregulation of RNAi components and RNA splicing factors affects COVID-19 severity. Decreased expression of RNAi components (Dicer and XPO5) and splicing factors (SRSF3 and hnRNPA3) correlated with increased severity of COVID-19 and SARS-CoV-2 nucleocapsid (N) protein-induced pneumonia. N protein induced autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, repressing miRNA biogenesis and RNA splicing and inducing DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 were downregulated with age in mouse lung tissues. Older mice experienced more severe N protein-induced pneumonia than younger mice. However, treatment with a poly(ADP-ribose) polymerase inhibitor (PJ34) or aromatase inhibitor (anastrozole) relieved N protein-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Human coronaviruses activate and hijack the proteostasis guardian HSF1 to enhance viral replication (preprint)

Organisms respond to proteotoxic stress by activating a cellular defense mechanism, known as the heat shock response (HSR), that triggers the expression of cytoprotective heat shock proteins (HSP) to counteract the damaging effects of proteostasis disruption. The HSR is regulated by a family of transcription factors (heat shock factors, HSFs); among six human HSFs, HSF1 acts as a proteostasis guardian regulating acute and severe stress-driven transcriptional responses. Seasonal coronaviruses HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 (sHCoV) are globally circulating in the human population. Although sHCoV generally cause only mild upper respiratory diseases in immunocompetent hosts, severe complications may occur in specific populations. There is no effective treatment for sHCoV infections, also due to the limited knowledge on sHCoV biology. We now show that both Alpha- and Beta- sHCoV are potent inducers of HSF1, selectively promoting HSF1 phosphorylation at serine-326 residue and nuclear translocation, and triggering a powerful HSF1-driven transcriptional response in infected cells at late stages of infection. Despite the coronavirus-mediated shut-down of the host cell translational machinery, high levels of selected canonical and non-canonical HSF1-target genes products, including HSP70, HSPA6 and the zinc-finger AN1-type domain-2a gene/AIRAP, were found in HCoV-infected cells. Interestingly, silencing experiments demonstrate that HSR activation does not merely reflect a cellular defense response to viral infection, but that sHCoV activate and hijack the HSF1-pathway for their own gain. Notably, nuclear HSF1 pools depletion via Direct-Targeted HSF1 inhibitor (DTHIB) treatment was highly effective in hindering sHCoV replication in lung cells. Altogether the results open new scenarios for the search of innovative antiviral strategies in the treatment of coronavirus infections.

Correlates of COVID-19 Vaccination Intentions and opinions about mandates among four groups of adults in South Africa with distinct vaccine intentions: Evidence from a large national survey (preprint)

Introduction Despite a high number of recorded COVID-19 infections and deaths in South Africa, COVID-19 vaccine coverage remained low in March 2022, ten months into the national vaccine roll-out. This study provides evidence on the correlates of vaccine intentions, attitudes towards vaccination and opinions about mandates. Methods We used data from the second COVID-19 Vaccine Survey (CVACS), a telephone survey conducted February-March 2022 among 3,608 South African adults who self-reported not being vaccinated against COVID-19. The survey instrument was designed in consultation with government, policymakers, and civil society; and segmented the sample into four distinct groups with different vaccine intentions (synonymous with vaccine hesitancy levels). Kruskal-Wallis and Mann-Whitney tests were used to examine the sociodemographic characteristics, attitudes and behaviours associated with the different vaccination intentions groups. Thematic coding of responses to open-ended questions elicited insights on reasons for not being vaccinated and attitudes towards mandates. Results Intentions to get vaccinated were greater among individuals with lower socio-economic status (Mann-Whitney Z=-11.3, p<0.001); those believing the vaccine protects against death (Kruskal-Wallis 𝛸2=494, p<0.001); and those who perceived themselves at risk of COVID-19-related illness (𝛸2=126, p<0.01). Vaccine intentions were lower among individuals who believed that the vaccine causes death (𝛸2=163, p<0.001); believed that the vaccine is unsafe for the babies of pregnant/breastfeeding mothers, or the chronically ill (𝛸2=123, p<0.01); those not trusting government health information about COVID-19 and the COVID-19 vaccine (Kendall’s 𝜏=-0.41, p<0.01); and those in opposition to mandates (𝜏=0.35, p<0.001). Only 25% supported mandates, despite 48% thinking mandates would work well, with 54% citing individual rights as their main reason for mandate opposition.  Conclusion The profile of individuals not vaccinated against COVID-19 as of March 2022 differed markedly by self-reported vaccination intentions, underscoring the importance of tailored demand-creation efforts. To achieve comprehensive vaccination coverage, interventions to instill trust in government health information, and in the safety and efficacy of vaccines are required early in a vaccination program given the rapid emergence of pervasive vaccine hesitancy. Mandates remain an option to increase coverage but need to be carefully considered given widespread opposition.

Impacts of the COVID-19 pandemic impact on healthcare professional delivery of opportunistic behaviour change interventions: a retrospective cohort study (preprint)

BACKGROUND The public health policy “Making Every Contact Count” (MECC) compels healthcare professionals to deliver behaviour change interventions during routine consultations. The COVID-19 pandemic and its mitigations have stretched services, yet supporting people to modify health behaviours is more important now than when the policy was introduced. The present study aims to: (a) examine changes in healthcare professionals’ awareness of, and engagement with the policy over a five-year period, (b) examine the psychosocial drivers associated with delivering behaviour change interventions, and (c) identify targets to increase healthcare professionals’ delivery of interventions.METHODS Comparison of data from two independent representative surveys of NHS healthcare professionals working in the UK. In both surveys (July-September 2017; N = 1387, and February-March 2022; N = 1008), participants were asked to report: (1) awareness of the MECC policy, (2) the prevalence of MECC-related practice (perceived patient benefit, how often interventions were delivered, and time spent delivering interventions), and (3) perceptions of capabilities, opportunities and motivations to deliver behaviour change interventions. T- tests (independent-samples), MANOVA, multiple linear regression, and chi-square analyses were used to generate comparisons between the surveys.RESULTS Awareness of the policy increased from 2017 (31.4%) to 2022 (52.0%). However, in 2022 compared with 2017, healthcare professionals reported (a) fewer patients would benefit from behaviour change interventions (49.1% versus 55.9%), (b) they delivered behaviour change interventions to a lower proportion of patients (38.0% versus 50.0%), and (c) they spent a lower proportion of the consultation time delivering interventions (26.5% versus 35.3%). Further, in 2022, compared with 2017, healthcare professionals reported fewer physical opportunities, fewer social opportunities, and fewer psychological capabilities to deliver behaviour change interventions. In the 2022 survey, perceptions of patient benefit and delivery of interventions was associated with greater perceptions of opportunities and motivations.CONCLUSIONS Health behaviour change interventions are crucial to avert an impending public health crisis following COVID-19, however reported engagement with MECC-related practices appears to have reduced over time. Future research should consider how healthcare professionals identify patients who might benefit from opportunistic behaviour change interventions, and to increase capabilities, opportunities, and motivations to deliver interventions during routine consultations.

Factors Related to Stress in Children with Online Media Learning Methods during a Pandemic at Jaya Mulya 1 Elementary School, Karawang-Indonesia (preprint)

Stress on students is a condition that occurs when there is pressure at school that makes students feel burdened. This study aims to determine the factors related to stress in students who attend school with online media during the covid-19 pandemic at SDN Jayamulya 1 Kab. Karawang. This study uses a descriptive analytic design with a cross sectional approach with a population of 57 respondents and the sample used is 57 respondents. The results of this study there is a relationship between high achievement pressure factors and stress with a p-value of 0.022 < 0.05, a busy schedule factor with stress with a p-value of 0.012 < 0.05, academic achievement factors with stress with a p-value of 0.000 <0.05, physical demands factor with stress with p-value 0.036 < 0.05. Keywords: high achievement pressure, busy schedule, academic achievement, physical demands, task demands, role demands, interpersonal demands.

Inequalities in mental and social wellbeing during the COVID-19 pandemic: prospective longitudinal observational study of five UK cohorts (preprint)

Background. Research suggests that there have been inequalities in the impact of the COVID-19 pandemic and related non-pharmaceutical interventions on population mental health. We explored these inequalities during the first year of the pandemic using nationally representative cohorts from the UK. Methods. We analysed data from 26,772 participants from five longitudinal cohorts representing generations born between 1946 and 2000, collected in May 2020, September-October 2020, and February-March 2021 across all five cohorts. We used a multilevel growth curve modelling approach to explore sociodemographic and socioeconomic differences in levels of anxiety and depressive symptomatology, loneliness, and life satisfaction over time. Results. Younger generations had worse levels of mental and social wellbeing throughout the first year of the pandemic. Whereas these generational inequalities narrowed between the first and last observation periods for life satisfaction (-0.33 [95% CI: -0.51, -0.15]), they became larger for anxiety (0.22 [0.10, 0.33]). Pre-existing generational inequalities in depression and loneliness did not change, but initial depression levels of the youngest cohort were worse than expected if the generational inequalities had not accelerated. Women and those experiencing financial difficulties had worse initial mental and social wellbeing levels than men and those financially living comfortably, respectively, and these gaps did not substantially differ between the first and last observation periods. Inequalities by additional factors are reported. Conclusions. By March 2021, mental and social wellbeing inequalities persisted in the UK adult population. Pre-existing generational inequalities may have been exacerbated with the pandemic onset. Policies aimed at protecting vulnerable groups are needed.

ARTIFICIAL INTELLIGENCE TOOLS FOR EFFECTIVE MONITORING OF POPULATION AT DISTANCE DURING COVID-19 PANDEMIC. RESULTS FROM AN ITALIAN PILOT FEASIBILITY STUDY (RICOVAI-19 STUDY). (preprint)

In order to reduce the burden on healthcare systems and in particular to support an appropriate way to the Emergency Department (ED) access, home tele-monitoring patients was strongly recommended during the COVID-19 pandemic. Furthermore, paper from numerous groups has shown the potential of using data from wearable devices to characterize each individual's unique baseline, identify deviations from that baseline suggestive of a viral infection, and to aggregate that data to better inform population surveillance trends. However, no evidence about usage of Artificial Intelligence (AI) applicatives on digitally data collected from patients and doctors exists. With a growing global population of connected wearable users, this could potentially help to improve the earlier diagnosis and management of infectious individuals and improving timeliness and precision of tracking infectious disease outbreaks. During the study RICOVAI-19 (RICOVero ospedaliero con strumenti di Artificial Intelligence nei pazienti con COVid-19) performed in a Marche Region, Italy, we evaluated N129 subjects monitored at home in a six-months period between March 22, 2021 and October 22, 2021. During the monitoring, personal on demand health technologies were used to collect clinical and vital data in order to feed the database and the machine learning engine. The AI output resulted in a clinical stability index (CSI) which enables the system to deliver suggestions to the population and doctors about how intervene . Results showed the beneficial influence of CSI for predicting clinical classes of subjects and identifying who of them need to be admitted at ED. The same pattern of results was confirming the alert included in the decision support system in order to request further testing or clinical information in some cases. In conclusion, our study does support an high impact of AI tools on COVID outcomes to fight this pandemic by driving new approaches to public awareness.

‘Not finding causal effect’ is not ‘finding no causal effect’ of school closure on COVID-19 (preprint)

In a paper recently published in Nature Medicine , Fukumoto et al. tried to assess the government-led school closure policy during the early phase of the COVID-19 pandemic in Japan. They compared the reported incidence rates between municipalities that had and had not implemented school closure in selected periods from March–May 2020, where they rigorously matched for potential confounders, and claimed that they found no causal effect on the incidence rates of COVID-19. However, the effective sample size (ESS) of their dataset had been substantially reduced in the process of matching due to imbalanced covariates between the treatment (i.e. with closure) and control (without) municipalities, which led to the wide uncertainty in the estimates. That said, the study title "No causal effect…" is a rather strong statement because the results are also consistent with a strong mitigating effect of school closure on incidence of COVID-19.

Impact of Different Waves of COVID-19 on Emergency Medical Services and Out-of-hospital Cardiopulmonary Arrest in Madrid, Spain (preprint)

Background: COVID-19 has led to decreased survival of out-of-hospital cardiorespiratory arrest (OHCA). We analysed the impact of the first COVID-19 pandemic year on emergency medical services and OHCA care compared with the previous year. Methods: Data for this observational study were collected for OHCAs attended by the SUMMA 112 emergency service during March 2019 to March 2021. We compared data covering 15 March 2020–14 March 2021 (pandemic year) to retrospective data covering 15 March 2019–14 March 2020 (non-pandemic year). Results: During the pandemic period, 1743 OHCA patients were attended, compared to 1781 during the non-pandemic year. Median patient age during the pandemic period was lower than in the non-pandemic period (71 vs 72, p=0·037). Emergency services response activation time increased during the pandemic year, to 3 minutes, 16 seconds from 2 minutes, 48 seconds in the non-pandemic period (p=0·001). Time to arrival at the scene also increased during the pandemic (12 minutes vs 11 minutes, 25 seconds before the pandemic; p=0·001). The percentage of OHCAs in which resuscitation was attempted was lower during the pandemic (59·4% vs 62·9%, p=0·034), as were survival on hospital arrival (30·3% vs 34·6%, p=0·04). Differences in response activation time (p=0·003) and scene arrival times (p=0·003) were greater during the first pandemic wave compared with the later phases. Conclusions: The different phases of the pandemic variably affected OHCA care. The first wave led to longer resource activation, increased home events and scene arrival times, as well as lower patient survival.

Psychological responses to the COVID-19 pandemic are heterogeneous but have stabilised over time: One year longitudinal follow-up of the COVID-19 Psychological Research Consortium (C19PRC) Study (preprint)

Shevlin et al. (2021) recently demonstrated heterogeneity in mental health and psychological responses to the COVID-19 pandemic over time from a nationally representative sample of UK adults (March–July 2020). Five subpopulations representing either stability, deterioration or improvement in both anxiety-depression and COVID-19 PTSD were identified. The majority of the sample were characterised by low levels of anxiety-depression (56.6%) and COVID-19 traumatic stress (68.3%) during this early phase of the pandemic but some showed deterioration and some showed mental health benefits. Here we extend these findings using two additional survey waves from the C19PRC Study, thereby modelling mental health trajectories for the UK population within the entire first year of the pandemic.

After COVID-19 Future Planning Regarding Higher Education System in India: A Phenomenological Study in Higher Education Institutes of West Bengal (preprint)

India is facing a big challenge to continue uninterrupted higher education process after COVID-19 situation. Students come from heterogeneous socio-economic strata. Many are susceptible to the contagious disease because of their mal-nutritious condition, co-morbid situation like juvenile diabetes etc. We have elderly (60–65 years age) teachers also who are in vulnerable situation. So, we need specific and extremely cautious future planning to protect the lives of our future generations from this pandemic morbidity along with their progress in education so that they can keep pace with the tide of education process as in some other countries of the world. This study aims to explore the lived experience of the teachers of the higher education institutes of the state of West-Bengal, India to gain a deeper understanding of their individual experiences and future planning regarding higher education system in mind. Phenomenological approach of Moustake with pragmatic world view along with interpretive lens is used here. Through Purposive sampling method 12 study participants are identified. Participants are theteachers of different urban, suburban and rural colleges in West Bengal who had experienced a sudden turmoil in teaching-learning interaction due to prolonged emergency lockdown from March’2020 to combat COVID-19.In-depth interviews with consented call-recorded over telephone were conducted to collect primary dataduring April 2020. Participant observation also used for data collection. Fear of infection, even death and uncertainty haunted both teachers and students lead to the half-hearted motivation to study. Majority of the faculties felt awkward to teach through online method as they are new to it. During teaching there were many problems faced like insufficient data consumption power by many students, lack of required smart phone, frequent network failure. Majority of students are generally spoon fed by their private tutors. Participants supported the physical classes could not give the feasible suggestion to maintain social distance and personal protection in campus and public transport system. Some told about the herd immunity also. Some firmly supported online mode of teaching as the only safe way to teach now. Teaching-learning from home is cost efficient (direct and indirect cost), time efficient, space efficient, surveillance efficient. It has time flexibility. It also has productivity efficiency as less physical movement perhaps increases intellectual productivity. More quality time spending with the family increases happiness index. Even after the pandemic situation this online mode of education will be best suited for the holistic development of society. Single online platform should be used countrywide and teachers and students should adopt slowly to the new system for the sake of safety of majority of people. Government should subsidize data for academic websites, provide cheap smart phones to the students, focus on infrastructure of internet network. Students can be motivated through one to one telephonic conversation also. Only laboratory-based classes can be taken physically fragmenting the entire class into suitable sections. If the online teaching, learning, examination infrastructure cannot be developed in time extension of semester duration can be considered. But no physical classes should be allowed till we feel fully protected from the virus.

India's Second Covid-19 Wave: A Hit to the Country's Economic Recovery (preprint)

Amidst fears of a third wave, India is beginning to reopen after the second wave of COVID-19 infections that wreaked havoc in the country in April and May 2021. The number of average daily cases has fallen to just over 50,000 in recent days, down from the peak of around 400,000 on May 9. Several factors are behind the second wave of the pandemic in India. Among many factors, election rallies and religious festivals were blamed for the second wave. The situation only got worse as India's health system collapsed during the second wave. India was on a good track for economic recovery after a devastating loss in 2020. In January‒March 2021, right before the second wave, India’s annual economic growth rate was estimated at 1.6 percent, recording a slight pick-up compared with the previous three months. Also, GDP growth in the year 2021 was estimated to be in double digits initially. However, India’s economic recovery will now be slowed down due to the economic damage from an enormous second COVID-19 wave, and further localized mobility restrictions since March 2021. As of June 2021, the second wave appears to be over with most of India’s major cities easing restrictions and reopening the economy. We can expect India will be back on track for economic recovery as manufacturing and export restart. But this does not mean that India's economy can recover to the pre-pandemic level anytime soon. There is already talk about the next wave with medical experts making predictions of a possible third wave in September. The solution to the impending crisis and minimizing an additional economic hit from the third wave would be speeding up the vaccination programs.

HIF1alpha cardioprotection in COVID-19 patients (preprint)

ImportanceSARS-CoV-2 infection directly causes severe acute respiratory illness, leading to systemic tissue hypoxia and ischemia including the heart. Myocardial cytopathy associated with hypoxic response has been largely overlooked in COVID-19 patients. Additionally, histology analysis and cardiac function of COVID-19 cases are often reported separately, rendering an incomplete understanding of COVID-19 cardiac symptoms. ObjectiveTo examine the relationship between myocardial cellular responses to hypoxic stress versus cardiac functional alterations within the same COVID-19 patients. Design, Setting, and ParticipantsCellular hypoxia Inducible Factor 1 alpha (HIF1) expression was analyzed by immunohistochemistry using post-mortem COVID-19 heart and lung tissues with known cardiac echocardiography records from a total of 8 patients. Clinical echocardiography data were obtained from Mount Sinai Heart between March to December, 2020. All gender and age groups were considered as long as cardiac involvement meets the preserved (EF > 50%) or moderate to severe (EF < 45%) criteria with confirmed SARS-CoV-2 infection. Cell-type specific subcellular localization of HIF1 expression and nuclear stability was examined by immunohistochemistry and transmission electronic microscopy (TEM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to quantify apoptosis. Main Outcomes and MeasuresNo planned outcomes of this study as this is a retrospective analysis based on post-mortem specimens exclusively. ResultsCardiac HIF1 expression was found to be significantly higher in patients with preserved EF levels than it was in the low EF group. In the preserved EF group, HIF1 is protective against apoptosis predominantly in endothelial cells and cardiac fibroblasts. In the low EF group, HIF1 protects cardiomyocyte nuclear integrity as evident by its nuclear accumulation with nuclear envelope preservation. Conclusions and RelevanceThis study establishes a direct link of cardiac cellular responses to hypoxic stress with matching functional and histological data, serving as one of the first studies to bridge previous stand-alone clinical data and cellular data. The protective role of HIF1 in hearts may help predict cardiac involvement in not only COVID-19 patients, but also decipher the underlying mechanisms in other forms of viral cardiomyopathy. KEY POINTSO_ST_ABSQuestionC_ST_ABSAre hypoxic signaling pathways associated with cardiac functional alterations in COVID-19 patients? FindingsCardiac HIF1 expression of COVID-19 patients with EF>50% or EF<45% was analyzed and quantified. Increased cardiac HIF1+ cells were found in patients with higher EF. HIF1+ endothelial cells are resistant to apoptosis, and HIF1+ cardiomyocytes are able to retain nuclear envelope under hypoxic stress. MeaningHIF1 is cardioprotective in hearts of COVID-19 patients.

Familial Mechanisms Linking COVID-19 Lockdown with Mental Health Problems in Singaporean Children and Adolescents (preprint)

The COVID-19 pandemic and related confinement measures have profound impacts on the mental health of children and adolescents. This study investigated familial mechanisms underlying such impacts by studying the unique case of Singapore, which has undergone a period of local transmission without many restrictions (February–March 2020), followed by a nationwide lockdown (April–May 2020). In June 2020, we collected retrospective reports on everyday activities, social relationships, and mental health of 164 children and adolescents (Mage = 14.3, Range = 7-18, 49% female) across three timepoints: Pre-pandemic, Pre-lockdown, and Lockdown. Parental mental health, parenting values and practices were also collected. Multilevel modelling showed increased mental health problems in children from Pre-pandemic to Pre-lockdown, and from Pre-lockdown to Lockdown. Mediation analyses indicated that the increase in children’s mental health problems from Pre-pandemic to Pre-lockdown was partially explained by a decrease in time spent outdoors, an increase in their conflict with fathers, and an increase in their mothers’ mental health problems, with the last factor being the only significant mediator when all three factors were considered simultaneously. The increase in children’s mental health problems from Pre-lockdown to Lockdown was partially explained by a further increase in their mother’s mental health problems. These findings suggest that lockdown measures issued by authority may lead to further deterioration of children’s mental health beyond the pandemic itself. Multiple personal and familial factors may underlie these deteriorations, among which maternal mental health could be especially influential and should be targeted in family support service and intervention.

COVID-19 and Auto Loan Origination Trends (preprint)

We study the impact of the COVID-19 crisis on auto loan origination activity during 2020. We focus on the dynamic impact of the crisis across lending channels, Equifax Risk Score (Risk Score) segments, and relevant geographic characteristics such as urbanization rate. We measure a significant drop in auto loan originations in March‒April followed by a near rebound in May‒June. Originations remain slightly depressed until October and fall again in November‒December. We document the largest drop and the smallest rebound in the subprime segment. We do not find any suggestive evidence that used car loan originations exhibited patterns significantly different from the rest of the market. We also document a more pronounced impact in the Northeast and the Pacific, seemingly influenced by the higher urbanization rate in these regions. Bank-financed originations experienced the largest drop and the smallest rebound, thus resulting in a loss of market share and continuing a 10-year trend of bank share loss in auto lending. We find that the drop in auto loans originated by banks was particularly significant among subprime borrowers. The impact of the COVID-19 crisis across origination channels contrasts with the experience during the Great Recession when banks contributed the largest support to the auto loan origination segment during periods of stress and finance company-originated auto loans were depressed.

Sacral Stress Fracture due to Excess Weight Gain during Pregnancy while Self-Quarantining during the COVID-19 Pandemic.

Most pregnancy-related sacral stress fractures occur after delivery. This case aims to emphasise that stress fractures can occur before delivery, and since excessive weight gain is a risk factor, pregnant women should avoid gaining excess weight, especially during quarantine. This patient, who gained 20 kgs during first pregnancy, started complaining of severe pain in the left sacral region in the 40th week of pregnancy, without any trauma. Despite conservative follow-up, her pain increased, and a caesarean section was performed. The patient continued to complain of pain in the left sacral region. Magnetic resonance imaging (MRI) identified a sacral stress fracture which was treated conservatively and resolved after 4 months. Complaints of severe back pain during the last stage of pregnancy require a detailed physical examination. When localised sensitivity is detected in the sacral region during pregnancy, a diagnosis can be made using MRI, thereby avoiding radiation exposure. Key Words: Stress fractures, COVID-19, Sacrum, Pregnancy.

SARS-CoV-2 seroprevalence in Chattogram, Bangladesh before the Delta surge, March-June 2021 (preprint)

In a representative serosurvey conducted March–June 2021, 64.1% (95%CrI 60.0– 68.1%) of Sitakunda subdistrict (Bangladesh) had anti-SARS-CoV-2 IgG antibodies after adjusting for age, sex, household clustering and test performance. Before the surge of Delta, most of the population had been infected despite low incidence of virologically-confirmed COVID-19.