Diplopia, COVID-19 and Vaccination: Results from a Cross-Sectional Study in Croatia.

The aim of this study was to explore diplopia as a symptom of undetected COVID-19 infection or as a possible side effect of COVID-19 vaccination. We examined 380 patients with diplopia admitted to the Department of Ophthalmology of the University Hospital Centre Sestre milosrdnice in Zagreb, Croatia, from July 2020 to June 2022. After excluding patients with confirmed organic underlying diplopia causes or monocular diplopia, we linked the patient information with the national COVID-19 and vaccination registries. Among the 91 patients included in this study, previously undetected COVID-19 infection as the possible cause of diplopia was confirmed in five of them (5.5%). An additional nine patients (9.9%) were vaccinated within one month from the onset of their symptoms, while the remaining 77 had neither and were therefore considered as controls. The breakdown according to the mechanism of diplopia showed no substantial difference between the vaccinated patients and the controls. We detected marginally insignificant excess abducens nerve affection in the COVID-positive group compared with that in the controls (p = 0.051). Post-vaccination diplopia was equally common in patients who received vector-based or RNA-based vaccines (21.4 vs. 16.7%; p = 0.694). COVID-19 testing should be performed for all cases of otherwise unexplained diplopia. The risk of post-vaccination diplopia was similar in both types of vaccines administered, suggesting a lack of evidence linking specific vaccine types to diplopia.

Modeling the COVID-19 epidemic in Croatia: a comparison of three analytic approaches.

AIM: To facilitate the development of a COVID-19 predictive model in Croatia by analyzing three different methodological approaches. METHOD: We used the historical data to explore the fit of the extended SEIRD compartmental model, the Heidler function, an exponential approximation in analyzing electromagnetic phenomena related to lightning strikes, and the Holt-Winters smoothing (HWS) for short-term epidemic predictions. We also compared various methods for the estimation of R0. RESULTS: The R0 estimates for Croatia varied from 2.09 (95% CI 1.77-2.40) obtained by using an empirical post-hoc method to 2.28 (95% CI 2.27-2.28) when we assumed an exponential outbreak at the very beginning of the COVID-19 epidemic in Croatia. Although the SEIRD model provided a good fit for the early epidemic stages, it was outperformed by the Heidler function fit. HWS achieved accurate short-term predictions and depended the least on model entry parameters. Neither model performed well across the entire observed period, which was characterized by multiple wave-form events, influenced by the re-opening for the tourist season during the summer, mandatory masks use in closed spaces, and numerous measures introduced in retail stores and public places. However, an extension of the Heidler function achieved the best overall fit. CONCLUSIONS: Predicting future epidemic events remains difficult because modeling relies on the accuracy of the information on population structure and micro-environmental exposures, constant changes of the input parameters, varying societal adherence to anti-epidemic measures, and changes in the biological interactions of the virus and hosts.

Research priorities to reduce the impact of COVID-19 in low- and middle-income countries

Background The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs. Methods The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability;2) potential for burden reduction;3) potential for a paradigm shift;4) potential for translation and implementation;and 5) impact on equity. Results Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients’ needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts. Interpretation Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.

Genetic Landscape of the ACE2 Coronavirus Receptor.

BACKGROUND: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. METHODS: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. RESULTS: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells. CONCLUSIONS: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.

Rapid COVID-19 Antigen Testing in Croatia: Risk Perception Plays an Important Role in the Epidemic Control.

Aim: To explore the clinical presentation and epidemiological history of the subjects who underwent SARS-CoV-2 antigen testing. Methods: We included 1,000 consecutive subjects who presented themselves at the diagnostic clinic in Croatia and analyzed their symptoms and epidemiological history. All subjects were classified into three groups, according to their reason of arrival; symptomatic, contacts of confirmed patients, and those who were tested due to administrative reasons. Results: On average, there were 24% of positive antigen results; the positivity rate was 51% among symptomatic, 16% in contacts, and 5% of administrative patients. The commonest symptoms of the disease included febrility and anosmia. We developed a clinical score to predict SARS-CoV-2 positivity, which had an area under the curve of 79.3 [95% confidence intervals (CI) 75.8-82.8]. Contact with the isolated person [odds ratio 0.54 (95% CI 0.31-0.94)] and international travel had a protective effect [0.20 (0.09-0.43)], suggesting that risk perception and mandatory pretravel measures had a key role in the determination of the infection risk. Conclusions: A combination of clinical symptoms can have reasonable predictive power for an antigen-positive test result. Risk perception seems to have a role in the epidemic spread, probably via stricter adherence to personal preventative measures.

Role of Lung Ultrasound in Predicting Clinical Severity and Fatality in COVID-19 Pneumonia.

BACKGROUND: Lung ultrasound (LUS) is a useful imaging method for identifying COVID-19 pneumonia. The aim of this study was to explore the role of LUS in predicting the severity of the disease and fatality in patients with COVID-19. METHODS: This was a single-center, follow-up study, conducted from 1 November 2020, to 22 March 2021. The LUS protocol was based on the assessment of 14 lung zones with a total score up to 42, which was compared to the disease severity and fatality. RESULTS: A total of 133 patients with COVID-19 pneumonia confirmed by RT-PCR were enrolled, with a median time from hospital admission to lung ultrasound of one day. The LUS score was correlated with clinical severity at hospital admission (Spearman's rho 0.40, 95% CI 0.24 to 0.53, p < 0.001). Patients with higher LUS scores were experiencing greater disease severity; a high flow nasal cannula had an odds ratio of 1.43 (5% CI 1.17-1.74) in patients with LUS score > 29; the same score also predicted the need for mechanical ventilation (1.25, [1.07-1.48]). An LUS score > 30 (1.41 [1.18-1.68]) and age over 68 (1.26 [1.11-1.43]) were significant predictors of fatality. CONCLUSIONS: LUS at hospital admission is shown to have a high predictive power of the severity and fatality of COVID-19 pneumonia.

Optimizing the diagnostic capacity for COVID-19 PCR testing for low resource and high demand settings: The development of information-dependent pooling protocol.

AIM: To compare different pooling methods in an attempt to improve the COVID-19 PCR diagnostic capacities. METHOD: We developed a novel information-dependent pooling protocol (indept), based on transmission of less informative sequential pools on to the next pooling cycle to maximize savings. We then compared it to the halving, generalized halving, splitting and hypercube protocols in a simulation study, across variety of scenarios. RESULTS: All five methods yielded various amount of test savings, which mostly depended on the virus prevalence in the population. In situations of low prevalence (up to 5%), indept had the best performance, requiring on average 20% of tests needed for singular testing across scenarios that were analyzed. Nevertheless, this comes at the expense of speed, with the worst-case scenario of indept protocol requiring up to twice the time needed to test the same number of samples in comparison to the hypercube protocol. In order to offset this, we developed a faster version of the protocol (indeptSp), which minimizes the number of terminal pools and manages to retain savings compared to other protocols, despite marginally longer processing times. CONCLUSION: The increasing demand for more testing globally can benefit from application of pooling, especially in resource-restrained situations of the low- and middle-income countries or situations of high testing demand. Singular testing in situations of low prevalence should be systematically discouraged.

Have Lifestyle Habits and Psychological Well-Being Changed among Adolescents and Medical Students Due to COVID-19 Lockdown in Croatia?

OBJECTIVE: To investigate dietary habits, sleep and psychological well-being of adolescents and medical students during COVID-19 lockdown in Split, Croatia. METHODS: We surveyed 1326 students during 2018 and 2019, and compared their responses with 531 students enrolled in May 2020. Perceived stress, quality of life (QoL), happiness, anxiety, and optimism were assessed as proxies of psychological well-being, using general linear modelling. RESULTS: We found no substantial differences in dietary pattern between pre-lockdown and lockdown periods, including the overall Mediterranean diet (MD) adherence. However, the MD pattern changed, showing increased adherence to the MD pyramid for fruit, legumes, fish, and sweets, while cereals, nuts, and dairy intake decreased during COVID-19 lockdown. A third of students reported weight loss during lockdown, 19% reported weight gain, while physical activity remained rather stable. The most prominent change was feeling refreshed after a night's sleep, reported by 31.5% of students during lockdown vs. 8.5% before; median length of sleep duration increased by 1.5 h. Lockdown significantly affected QoL, happiness, optimism (all p < 0.001), and perceived stress in students (p = 0.005). MD adherence was positively correlated with QoL and study time, and negatively with TV and mobile phone use in pre-lockdown period (all p < 0.001). Interestingly, higher MD adherence was correlated with less perceived hardship and greater happiness and QoL during lockdown. CONCLUSION: These insights provide valuable information for tailored interventions aimed at maintaining healthy lifestyle in young population. Given the numerous beneficial effects associated with MD adherence, modification of lifestyle through application of lifestyle medicine deserves a priority approach.