Risk of Ischemic Stroke after COVID-19 Bivalent Booster Vaccination in an Integrated Health System (preprint)

Abstract: Purpose: What is the absolute occurrence of ischemic stroke and transient ischemic attack after a COVID-19 bivalent vaccination? Methods: We conducted a retrospective cohort study of Kaiser Permanente Northwest (KPNW) patients 18 years and older who were vaccinated with either the Pfizer or Moderna formulation of the COVID19 bivalent vaccine between September 1, 2022 and March 1st 2023. Patients were included in the study if they had KP membership at the time of vaccination and through the 21-day follow up period. We replicated the Vaccine Safety Datalink (VSD) rapid cycle analysis methodology and searched for possible cases of ischemic stroke or TIA in the 21 days following vaccination using ICD10CM diagnosis codes in both the primary position and any position. We waited 90 days from the end of the follow up (March 21, 2023) for complete non KP data accrual before analyzing the data to account for the lag in processing outside hospital insurance claims. Two physicians adjudicated possible cases by reviewing the clinical notes in the electronic health record. The analyses were stratified by age 65 years and older to allow for comparisons with VSDs reporting at the Advisory Committee on Immunization Practices (ACIP) meeting of incidence of ischemic stroke or TIA (VSD reported incidence; 24.6 cases of ischemic stroke or TIA per 100,000 patients vaccinated). Results: The incidence of ischemic stroke or TIA was 34.3 per 100,000 (95% CI, 17.7 to 59.9) in patients 65 years or older who received the bivalent Pfizer vaccine, based on a diagnosis code in the primary position of the emergency department or hospital discharge. The incidence increased to 45.7 per 100,000 (95% CI 26.1 to 74.2) when we expanded the search to a diagnosis in any position and did not adjudicate to confirm. However, most of those additional apparent stroke or TIA diagnoses were false-positive diagnoses based on physicians adjudications. Estimating the incidence based on the primary position agreed closely with estimating the incidence based on any position and physician adjudication: 37.1 per 100,000 (95% CI 19.8 to 63.5). Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system. Conclusion: We identified a 50% increase in the incidence of ischemic stroke per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the VSD. Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system and a delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making.

HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.

Characteristics associated with buying alcohol to-go and for delivery during the first year of the COVID-19 pandemic among a national sample of US adults.

INTRODUCTION: This study: (i) determined the population coverage of alcohol delivery and to-go/carryout policies (i.e., policies permitting bars/restaurants to sell individual drinks for off-site consumption) in 2019 and 2020; and (ii) identified characteristics associated with alcohol delivery and to-go purchases. METHODS: Data are from the National Alcohol Survey and Alcohol Policy Information System (n = 1677 adults, 52.1% female). Population coverage models summed state populations across state-level bar/restaurant delivery and to-go/carryout policies by beverage. Regression outcomes were past-year alcohol delivery and to-go purchases. Independent variables included demographics, excessive drinking, COVID-19 impacts and state COVID-19 bar/restaurant alcohol laws. Chi-squared tests and logistic regression models tested associations between delivery/to-go purchases and independent variables. RESULTS: Overall, 7.5% of adults had alcohol delivered and 14.5% bought alcohol to-go. From December 2019 to December 2020, the number of people living in states allowing beer/wine/spirits delivery (284%) and to-go sales (627%) rose steeply. People who were Black (vs. White; adjusted odds ratio [aOR] 2.92, p < 0.001), excessive drinkers (vs. non-excessive drinkers; aOR 2.06, p < 0.001) or lived in states allowing beer/wine/spirits to-go sales (aOR 2.20, p = 0.01) had higher odds of buying alcohol to-go. Conversely, older people had lower odds of buying alcohol to-go (aOR 0.97, p < 0.001). People with some college or more (vs. high school degree or less, aOR 2.21, p < 0.001) and a higher economic burden (vs. fewer COVID-19 impacts, aOR 2.32, p = 0.05) had higher odds of alcohol delivery. DISCUSSION AND CONCLUSIONS: A select sub-population defined by socioeconomic status, race, excessive drinking and state policies bought alcohol for delivery or to-go in the Unites States.

Factors Associated with Physical Activity Increases and Decreases Among a Sample of Appalachian Residents During the COVID-19 Pandemic: A Cross-Sectional Study

Introduction: Physical activity (PA) can prevent and reduce the deleterious physical and mental health effects of COVID-19 and associated lockdowns. Research conducted early in the pandemic demonstrates that a greater proportion of adults in the U.S. have decreased than increased PA, and the effects vary by sociodemographic factors. Ongoing evidence is important to identify patterns in PA changes during the pandemic. Purpose: This study aims to identify factors associated with increases and decreases in PA during the COVID-19 pandemic in a convenience sample of adults residing in Appalachia. Methods: Surveys were collected from a convenience sample of adults from eight counties in West Virginia from January to March 2021. Logistic regression analysis was used to identify sociodemographic, health, and rurality factors associated with (1) increased PA and (2) decreased PA during the pandemic, assessed retrospectively via self-report. Results: Analysis of 1,401 survey responses revealed that better self-rated health, lower body mass index, and higher income and education were associated with a greater likelihood of more time spent doing PA during the pandemic (p ≤ .05). Respondents with lower self-rated health, higher body mass index, lower income, and lower levels of education—plus females and those living in a more urban county—were more likely to spend less time doing PA during the pandemic (p ≤ .05). Implications: Analyses suggest that pre-pandemic disparities in PA by health, wealth, and education were exacerbated during the pandemic. These must be addressed before physical inactivity and ill health become endemic to the Appalachian Region.

New Year's Eve in otorhinolaryngology: a 16-year retrospective evaluation.

PURPOSE: Pyrotechnics are a long-standing tradition at the turn of the year. There are little data available on New Year's Eve-associated ORL injuries. Due to restrictions during the Corona pandemic, the handling of fireworks and meetings on New Year's Eve 2020-2022 had been significantly changed. Our aim was to analyze first data about New Year's Eve-associated ORL injuries. METHODS: A retrospective analysis of 16 turns of the year (2006-2022) at a University ORL department was performed. The 2 recent years were influenced by the changes and restrictions of the COVID-19 pandemic. RESULTS: Of 343 emergency presentations, 69 presented with New Year's Eve-associated reasons (20%). 72% were male, 15.9% were underage. 74% presented for fireworks-related injuries, 19% due to violent altercations. Noise trauma was present in 71%. The average number of New Year's Eve-associated emergency patients per year and the average total number of patients were reduced by more than half under COVID-19 pandemic conditions. CONCLUSIONS: New Year's Eve-associated ORL injuries range from inner ear trauma to midface fractures. Long-term damage may include hearing loss and tinnitus. These results shall support the responsible use of fireworks even after the end of the special regulations of the COVID-19 pandemic.

Wild goose chase: Geese flee high and far, and with aftereffects from New Year's fireworks

In the present Anthropocene, wild animals are globally affected by human activity. Consumer fireworks during New Year (NY) are widely distributed in W-Europe and cause strong disturbances that are known to incur stress responses in animals. We analyzed GPS tracks of 347 wild migratory geese of four species during eight NYs quantifying the effects of fireworks on individuals. We show that, in parallel with particulate matter increases, during the night of NY geese flew on average 5–16 km further and 40–150 m higher, and more often shifted to new roost sites than on previous nights. This was also true during the 2020–2021 fireworks ban, despite fireworks activity being reduced. Likely to compensate for extra flight costs, most geese moved less and increased their feeding activity in the following days. Our findings indicate negative effects of NY fireworks on wild birds beyond the previously demonstrated immediate response.

An alphacoronavirus polymerase structure reveals conserved co-factor functions (preprint)

Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from the betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine the structure of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. Our structure shows an unexpected nsp8 stoichiometry in comparison to other published coronavirus polymerase structures. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha and betacoronaviruses as previously hypothesized. Our work shows the importance of studying diverse coronaviruses to reveal aspects of coronavirus replication while also identifying areas of conservation to be targeted by antiviral drugs.

Characterizing pandemic-related changes in smoking over time in a cohort of current and former smokers.

INTRODUCTION: We used a longitudinal cohort of U.S. adults who were current or former smokers to explore how three participant-reported factors - general stress, COVID-19 distress, and perceived risk of complications from COVID-19 related to smoking - were associated with changes in smoking status. METHODS: Smoking status was assessed at three time points. Timepoint 1 status was assessed at a prior study completion (2018-2020). Timepoint 2 (start of the pandemic) and Timepoint 3 (early phase of the pandemic) statuses were assessed using an additional survey in 2020. After classifying participants into eight groups per these time points, we compared the means of participant-reported factors and used a linear regression model to adjust for covariates. RESULTS: Participants (n=392) were mostly female (73.9%) and non-Hispanic White (70.1%). Between Timepoints 2 and 3, abstinence rates decreased by 11%, and 40% of participants reported a smoking status change. Among those reporting a change and the highest general stress levels, newly abstinent participants had higher perceived risk of complications from COVID-19 related to smoking than those who relapsed during pandemic (mean (standard deviation): 14.2 (3.3) vs. 12.6 (3.8)). Compared to participants who sustained smoking, those who sustained abstinence, on average, scored 1.94 less on the general stress scale (ßeta Coefficient (ß): -1.94, p-value <0.01) and 1.37 less on the perceived risk of complications from COVID-19 related to smoking scale (ß: -1.37, p-value 0.02). CONCLUSIONS: Decreased abstinence rates are concerning. Patterns of reported factors were as expected for individuals who sustained their smoking behavior but not for those who changed. IMPLICATIONS: We observed an increase in smoking rates during the COVID-19 pandemic. In exploring how combinations of general stress levels, COVID-19 distress levels, and perceived risk of complications from COVID-19 related to smoking were associated with changes in smoking, we observed expected patterns of these factors among individuals who sustained abstinence or smoking. Among individuals who changed smoking status and reported high stress levels, those who reported a higher perceived risk of complications from COVID-19 related to smoking abstained from smoking. In contrast, those who reported a lower perceived risk of complications from COVID-19 related to smoking, started smoking. An intersectional perspective may be needed to understand smokers' pandemic-related behavior changes.

Inequitable access to general and behavioral healthcare in the US during the COVID-19 pandemic: A role for telehealth?

Wide-ranging effects of the COVID-19 pandemic have led to increased psychological distress and alcohol consumption, and disproportionate hardship for disadvantaged groups. Early in the pandemic, telehealth services were expanded to maintain healthcare access amidst lockdowns, medical office closures, and fear of infection. This study examines general and behavioral healthcare access and disparities during the first year of the pandemic. Data are from the 2019-2020 US National Alcohol Survey (collected February 2019 to April 2020) and its COVID follow-up survey conducted January 30 to March 28, 2021 (N = 1819). General and behavioral healthcare-related outcomes were assessed at follow-up, and included perceived need for and receipt of care, delayed care, and use of telehealth since April 1, 2020. Results indicate that the majority of respondents with perceived need for healthcare received some behavioral healthcare (reported by 63%) and particularly general healthcare (88%), but nearly half (48%) delayed needed care. Delays were mostly due to COVID-related reasons, but cost barriers also were common and significantly impeded care-seeking by uninsured persons, young adults, rural residents, and persons whose employment was reduced by the pandemic. Disparities in the receipt of healthcare were pronounced for Hispanic/Latinx (vs. White) and lower-income (vs. higher-income) groups (AORs <0.37, p's < 0.05). Notably, telehealth was commonly used by Hispanic/Latinx and lower-income groups for general and particularly behavioral healthcare. Results suggest that telehealth has provided an important bridge to healthcare for certain medically underserved groups during the pandemic, and may be vital to future efforts to increase equity in healthcare access.

Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies.

Objective: The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey. Methods: Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, M age = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction. Results: Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004). Conclusions: Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.

ADVANCE CARE PLANNING MOTIVATED BY THE COVID-19 PANDEMIC

The COVID-19 pandemic has exposed older adults to complex healthcare situations, via personal experience or media stories about serious illness. Hearing about lengthy intubation, sedation, rapid decline, and distress at the end of life has the potential to prompt people to reevaluate their perspective on their own end-of-life care. This study explored advance care planning (ACP) among older adults and whether COVID-19 experiences altered their healthcare preferences and planning. One hundred and fifty-one respondents (M age = 71.2 yrs, range = 55–93) completed an online survey about ACP completion, ACP conversations, and life-prolonging interventions. Respondents were mainly female (78%), White (71%), and well educated (77% with at least a bachelor's degree). A substantial proportion had not completed an advance directive (31%) or chosen a medical power of attorney (33%), and 78% of them intended to complete them in the next year or had initiated ACP. Among those who had completed ACP, a quarter intended to make changes, with 13% less open to life-prolonging medical treatments and 13% more open to them. Despite these intentions, a small proportion of people had ACP conversations since the start of the pandemic with their spouse/partner (37%), children (25%), siblings, (19%), friends (27%), primary care physician (16%), or other healthcare provider (12%). Results of this study suggest that now may be a critical moment to encourage older adults to have ACP conversations, in light of how their experience during the pandemic has motivated a reconsideration of treatment preferences.

HOSPICE UTILIZATION AMONG LONG-STAY NURSING HOME RESIDENTS DURING THE COVID-19 PANDEMIC

Background: The COVID-19 pandemic has had significant impacts on nursing home residents. This study aims to examine how hospice utilization changed among long-stay nursing home residents between January and September in 2020, as compared with the same period in 2019, nationally. Design: A retrospective cohort study of residents present in US nursing homes as long-stay as of January 1st, 2019 and 2020, respectively. A subgroup of residents who died from January to September in each year was also examined. We utilized the Minimum Data and multiple administrative claims data. We compared hospice utilization rate between 2019 and 2020 nationally and by state.Outcomes: This study examined: 1) any hospice utilization among long-stay residents from January to September in 2019 and 2020 respectively, and 2) hospice utilization in the last 30 days of life among the decedent subgroup, which we also tracked as a factor of percent change in mortality rate at the state level. Results: The hospice utilization rate among long-stay residents was 19.4% in 2019 and 19.7% in 2020. The rate was 27.5% in 2019 and 24.2% in 2020 among the decedent subgroup (χ2=553.1, p< 0.001), although the absolute number of decedents using hospice in the last 30 days of life was higher in 2020 than 2019. Substantial state variation in hospice utilization was observed, mostly following patterns in community-level infections. Conclusions: Hospice managed to continue service delivery despite many challenges. The pandemic highlights the importance of integrating hospice and palliative care into emergency preparedness planning.

Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.

Some of the most efficacious antiviral therapeutics are ribonucleos(t)ide analogs. The presence of a 3'-to-5' proofreading exoribonuclease (ExoN) in coronaviruses diminishes the potency of many ribonucleotide analogs. The ability to interfere with ExoN activity will create new possibilities for control of SARS-CoV-2 infection. ExoN is formed by a 1:1 complex of nsp14 and nsp10 proteins. We have purified and characterized ExoN using a robust, quantitative system that reveals determinants of specificity and efficiency of hydrolysis. Double-stranded RNA is preferred over single-stranded RNA. Nucleotide excision is distributive, with only one or two nucleotides hydrolyzed in a single binding event. The composition of the terminal basepair modulates excision. A stalled SARS-CoV-2 replicase in complex with either correctly or incorrectly terminated products prevents excision, suggesting that a mispaired end is insufficient to displace the replicase. Finally, we have discovered several modifications to the 3'-RNA terminus that interfere with or block ExoN-catalyzed excision. While a 3'-OH facilitates hydrolysis of a nucleotide with a normal ribose configuration, this substituent is not required for a nucleotide with a planar ribose configuration such as that present in the antiviral nucleotide produced by viperin. Design of ExoN-resistant, antiviral ribonucleotides should be feasible.

Mechanical Rotatory Method of Anticoagulation-Free Hemodialysis Using a Hemodialysis Filter Rotator With the NxStage Hemodialysis Machine: A UVMMC-UVM Burlington VT Research Collaboration Effort

Background: The maintenance of blood fluidity in the extracorporeal circuit during hemodialysis (HD) often requires systemic anticoagulation. While effective, these anticoagulants cause bleeding, have other side effects, cannot be used in critically ill patients and in the peri-operative period, and add to costs. We recently described a novel mecahnical rotational approach to anticoagulation-free HD using the "Locke-Onuigbo" maneuver (Figure 1).1 Methods: Prototype Completion: In collaboration with the University of Vermont Center for Biomedical Innovation (UVM CBI), five Senior Engineering students from the UVM, under the supervision of Yves Dubief PhD, Associate Professor of Mechanical Engineering, UVM, the first author and his Home Dialysis Program at the UVM Medical Center, have successfully prototyped an AI-modulated hemodialysis filter rotator that enables anticoagulation-free HD using the NxStage HD machine (Figure 2). Result(s): The Hemodialysis Filter Rotator Prototype running test on the HD machine (Figure 2) Conclusion(s): This Hemodialysis Filter Rotator enhances the capabilities of enabling sustainable Home HD for ESRD patients and represents a most welcome option in a "post-COVID" world and expands the offering of a convenient, safe and effective Home HD option to thousands of patients who prefer this choice of treatment. Moreover, we would argue that our novel prototype will deliver the unmet need for anticoagulation-free HD in critically ill patients, in the peri-operative period, and in hospitalized patients, in general. Investors and sponsors are welcome. (Figure Presented).

What predicts wellbeing amidst crisis? A study of promotive and protective psychological factors among Malaysians during the COVID-19 pandemic

Resilience promotes psychological growth and buffers against the effects of negative events, but the factors that promote optimal wellbeing beyond resilience remain poorly understood. The current study addresses this gap through a positive psychology perspective by examining how (i) promotive factors – optimism and hope, and (ii) protective factors – nostalgia and spirituality promote wellbeing. We hypothesized that both factors will be positively related to wellbeing above and beyond that predicted by resilience. A representative sample of six hundred and twenty-six (n = 626;M age = 32.66, SD = 10.11, 43.45% female) Malaysians responded to an online survey at the end of the country’s second wave of the COVID-19 pandemic (June-September 2020). We conducted a series of regression analyses, controlling for resilience, socioeconomic status, age, and perceptions towards government crisis management efforts. Results indicate that optimism and hope positively predicted wellbeing above and beyond that predicted by resilience. Results also showed that the only significant protective factor contributing to wellbeing is spirituality. Nostalgia did not significantly predict wellbeing beyond resilience. The findings are of theoretical relevance for wellbeing and resilience research, and practically beneficial in informing mental health interventions. © belongs to the author(s).

Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after COVID-19 infection are partially improved at twelve months

Introduction: COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk. Purpose: We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection Methods: We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker. Results: At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p<0.001) which increased at twelve months (p<0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p>0.05 for all the comparisons) and higher than those in controls (p<0.001, p=0.057, p=0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p=0.002, p=0.069 respectively), though remained impaired compared to controls (p=0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p=0.001,) and showed no statistically significant difference compared to controls (p>0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p=0.01, p=0.006 respectively). There was a modest improvement in GWW and GWE at twelve months,(p=0.043, p=0.001, respectively);however, these markers remained impaired compared to controls (p>0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p<0.001);however, these values remain higher than in controls (p=0.002) (Table 1). Conclusions: SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection. Funding Acknowledgement: Type of funding sources: None.Table 1