Long-term recurrence interval of Vogt–Koyanagi–Harada disease post-COVID-19 vaccination: A case study (preprint)

Purpose This study aimed to report a case of Vogt–Koyanagi–Harada (VKH) disease that recurred 46 years after initial treatment; the recurrence occurred 2 months after the third dose of coronavirus disease 2019 vaccination.Case report: A 59-year-old female patient had bilateral blurring for 2 months; she received her third dose of coronavirus disease 2019 vaccine 4 months before the onset of blurring. The best-corrected visual acuity was 1.0 in the right eye and 0.15 he left eye at the initial visit. Iritis and synechia between lens and iris were observed bilaterally. Sunset glow fundus was found in both eyes with no serous retinal detachments or disk hyperemia. She had a history of VKH disease and was treated with whole-body corticosteroid administration at another hospital when she was 13 years old. She was diagnosed with VKH disease recurrence, and oral corticosteroid intake and corticosteroid eyedrop treatments were initiated. The treatment response was good, but left synechia remained between the lens and iris in the left eye. Recurrence was not observed for 10 months until this study, and her best-corrected visual acuity was 1.0 in both eyes.Conclusion To our knowledge, this case represents the longest recorded interval of VKH disease recurrence in the literature.

Cardiovascular and cerebral vascular health in females with postacute sequelae of COVID-19.

Many individuals who had coronavirus disease 2019 (COVID-19) develop detrimental persistent symptoms, a condition known as postacute sequelae of COVID-19 (PASC). Despite the elevated risk of cardiovascular disease following COVID-19, limited studies have examined vascular function in PASC with equivocal results reported. Moreover, the role of PASC symptom burden on vascular health has not been examined. We tested the hypothesis that peripheral and cerebral vascular function would be blunted and central arterial stiffness would be elevated in patients with PASC compared with age-matched controls. Furthermore, we hypothesized that impairments in vascular health would be greater in those with higher PASC symptom burden. Resting blood pressure (BP; brachial and central), brachial artery flow-mediated dilation (FMD), forearm reactive hyperemia, carotid-femoral pulse wave velocity (PWV), and cerebral vasodilator function were measured in 12 females with PASC and 11 age-matched female controls without PASC. The severity of persistent symptoms in those with PASC was reported on a scale of 1-10 (higher score: greater severity). Brachial BP (e.g., systolic BP, 126 ± 19 vs.109 ± 8 mmHg; P = 0.010), central BP (P < 0.050), and PWV (7.1 ± 1.2 vs. 6.0 ± 0.8 m/s; P = 0.015) were higher in PASC group compared with controls. However, FMD, reactive hyperemia, and cerebral vasodilator function were not different between groups (P > 0.050 for all). Total symptom burden was not correlated with any measure of cardiovascular health (P > 0.050 for all). Collectively, these findings indicate that BP and central arterial stiffness are elevated in females with PASC, whereas peripheral and cerebral vascular function appear to be unaffected, effects that appear independent of symptom burden.NEW & NOTEWORTHY We demonstrate for the first time that resting blood pressure (BP) and central arterial stiffness are higher in females with PASC compared with controls. In contrast, peripheral and cerebral vascular functions appear unaffected. Moreover, there was no relationship between total PASC symptom burden and measures of BP, arterial stiffness, or vascular function. Collectively, these findings suggest that females with PASC could be at greater risk of developing hypertension, which appears independent of symptom burden.

Acute exacerbation of ocular graft-versus-host disease and anterior uveitis after COVID-19 vaccination (preprint)

Background: To report a case of acute exacerbation of ocular graft-versus-host disease (GVHD) and anterior uveitis following coronavirus disease 2019 (COVID-19) vaccination. Case presentation: A 60-year-old man with primary myelofibrosis and GVHD after receiving allogeneic hematopoietic stem cell transplantation (HSCT), developed acute exacerbation of ocular GVHD and anterior uveitis after receiving first dose of COVID-19 vaccine. Erythema of the eyelids, conjunctival hyperemia, superficial punctate keratopathy, and prominent anterior chamber inflammation in both eyes were revealed. Ocular GVHD and anterior uveitis were managed with mainly topical corticosteroid, antibiotics, and systemic corticosteroid, but were difficult to control. Successful treatment was achieved with intravitreal injection of dexamethasone 6 months later. Conclusions: Clinicians should beware of the rare refractory anterior uveitis and acute exacerbation of ocular GVHD after COVID-19 vaccination in patients undergoing HSCT. Early diagnosis and aggressive treatment should be considered to reduce the likelihood of severe complications.

Meibomian gland secretion quality association with ocular parameters in university students during COVID- 19 restrictions.

PURPOSE: To determine if the Meibomian Gland (MG) secretion quality is associated with symptoms of ocular discomfort, hours of Video Display Terminals (VDT) use, eyelid margin abnormalities, conjunctival hyperemia, and Meibomian Gland Loss Area (MGLA) in a sample of university students. METHODS: An online survey that included an Ocular Surface Disease Index (OSDI) questionnaire and an extra question about hours of VDT use recruited an initial sample of 183 participants. Only 120 participants that fulfilled the inclusion criteria were scheduled for a battery of ocular surface and MG specific exam. The tests include: 1) meibometry, 2) slit lamp exploration of eyelid margin abnormalities (irregularity, hyperemia and MG orifices plugging), MG secretion quality and conjunctival hyperemia, and 3) Meibography. RESULTS: Significant positive correlations between the MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA, nasal conjunctival hyperemia, and temporal conjunctival hyperemia (Spearman Rho; all r>0.186, p<0.042) were found. Multivariate regression found association between OSDI with hours of VDT use (B=0.316, p=0.007), and eyelid hyperemia (B=0.434, p≤ 0.001). A statistical association between MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA and conjunctival hyperemia (Fisher's exact; all p<0.039) were found. Multivariate regression found association between MG secretion quality with MG orifices plugging (B=0.295, p=0.004) and meibometry (B=-0.001, p=0.029). CONCLUSION: Participants with higher values in MG secretion quality have higher values in eyelid margin hyperemia, MG plugging, MGLA, and conjunctival hyperemia. No direct relationship between MG secretion quality and hours of VDT use or OSDI were found.

Tracking peripheral vascular function for six months in young adults following SARS-CoV-2 infection.

SARS-CoV-2 infection is known to instigate a range of physiologic perturbations, including vascular dysfunction. However, little work has concluded how long these effects may last, especially among young adults with mild symptoms. To determine potential recovery from acute vascular dysfunction in young adults (8 M/8F, 21 ± 1 yr, 23.5 ± 3.1 kg⋅m-2 ), we longitudinally tracked brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH) in the arm and hyperemic response to passive limb movement (PLM) in the leg, with Doppler ultrasound, as well as circulating biomarkers of inflammation (interleukin-6, C-reactive protein), oxidative stress (thiobarbituric acid reactive substances, protein carbonyl), antioxidant capacity (superoxide dismutase), and nitric oxide bioavailability (nitrite) monthly for a 6-month period post-SARS-CoV-2 infection. FMD, as a marker of macrovascular function, improved from month 1 (3.06 ± 1.39%) to month 6 (6.60 ± 2.07%; p < 0.001). FMD/Shear improved from month one (0.10 ± 0.06 AU) to month six (0.18 ± 0.70 AU; p = 0.002). RH in the arm and PLM in the leg, as markers of microvascular function, did not change during the 6 months (p > 0.05). Circulating markers of inflammation, oxidative stress, antioxidant capacity, and nitric oxide bioavailability did not change during the 6 months (p > 0.05). Together, these results suggest some improvements in macrovascular, but not microvascular function, over 6 months following SARS-CoV-2 infection. The data also suggest persistent ramifications for cardiovascular health among those recovering from mild illness and among young, otherwise healthy adults with SARS-CoV-2.

A case of APMPPE-like panuveitis presenting with extensive outer retinal layer impairment following COVID-19 vaccination (preprint)

Background Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of newly onset uveitis after vaccination have been reported. We report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy-like (AMPPE-like) panuveitis after COVID-19 vaccination in which the patient’s pathological condition was evaluated using multimodal imaging. Case presentation A 31-year-old woman experienced bilateral hyperemia and blurred vision starting 6 days after her second inoculation of the COVID-19 vaccination. At her first visit, her visual acuity was decreased bilaterally, and severe bilateral anterior chamber inflammation and bilateral scattering of cream-white placoid lesions on the fundus were detected. Optical coherence tomography (OCT) showed serous retinal detachment (SRD) and choroidal thickening in both eyes (OU). Fluorescein angiography (FA) revealed hypofluorescence in the early phase and hyperfluorescence in the late phase corresponding to the placoid legions. Indocyanine green angiography (ICGA) showed sharply marginated hypofluorescent dots of various sizes throughout the mid-venous and late phases OU. The patient was diagnosed with APMPPE and was observed without any medications. Three days later, her SRD disappeared spontaneously. However, her anterior chamber inflammation continued, and oral prednisolone (PSL) was given to her. Seven days after the patient’s first visit, the hyperfluorescent lesions on FA and hypofluorescent dots on ICGA partially improved; however, the patient’s best corrected visual acuity (BCVA) dropped to 0.7 OD and 0.6 OS, and the impairment of the outer retinal layer was broadly detected as hyperautofluorescent lesions on fundus autofluorescence (FAF) examination and as irregularity in or disappearance of the ellipsoid and interdigitation zones on OCT, which were quite atypical for the findings of APMPPE. Steroid pulse therapy was performed. Five days later, the hyperfluorescence on FAF had disappeared, and the outer retinal layer improved on OCT. Moreover, the patient’s BCVA recovered to 1.0 OU. Twelve months after the end of treatment, the patient did not show any recurrences. Conclusions We observed a case of APMPPE-like panuveitis after COVID-19 vaccination featuring some atypical findings for APMPPE. COVID-19 vaccination may induce not only known uveitis but also atypical uveitis, and appropriate treatment is required for each case.

A Longitudinal Seroepidemiology Study to Evaluate Antibody Response to SARS-CoV-2 Virus and Vaccination in Children in Calgary, Canada from July 2020 to April 2022 (preprint)

Background: Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. Methods: Children with or without prior SARS-CoV-2 infections, was enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. Results: 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrollment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% after more than 200 days after diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated children after more than 200 days after diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. Conclusions: In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children had SARS-CoV-2 spike antibodies, in contrast to 53.4% of unvaccinated children. It is not yet known whether a high level of seropositivity at a point in time indicates sustained population-level protection against SARS-CoV-2 transmission or severe COVID-19 outcomes in children.

Atypical immunologic manifestations of COVID-19: A case report and a comprehensive review (preprint)

Introduction: COVID-19 usually presents with classic signs and symptoms, but it can involve multiple systems in atypical cases. SARS-CoV-2 has a complex interaction with the host immune system leading to atypical manifestations.  Case Presentation: In our case, a 32-year-old male patient presented with fatigue, sores on hands and feet, headache, productive cough with blood-tinged mucus, conjunctival hyperemia, purpuric rash on hands and feet, and splinter hemorrhages of fingernails for two weeks. The patient’s SARS-CoV-2 antigen and PCR test were positive. Chest x-ray showed mixed density perihilar opacities in both lungs. Computed tomography of the chest showed extensive airspace opacities in both lungs, suggesting COVID-19 multifocal, multilobar pneumonitis. A renal biopsy indicated limited thrombotic microangiopathy and tubulointerstitial nephritis, for which he was started on steroids, and his renal functions gradually improved. He tested positive for C-ANCA during an immune workup. He was discharged with a steroid taper for nephritis. Once the taper reached less than 10 mg/day, he developed acute scleritis and a new pulmonary cavitary lesion of 6 centimeters. The biopsy via bronchoscopy revealed acute inflammatory cells with hemosiderin-laden macrophages. He was restarted on systemic steroids for scleritis after failing topical steroids, which incidentally also reduced the size of the cavitary lesion, indicating an immune component.  Conclusions: Our case demonstrates the involvement of kidneys and vasculitis of the skin, sclera, and lungs by COVID-19. The patient’s symptoms were not explained by any diseases other than COVID-19. Atypical cases of COVID-19 disease with multifocal systemic symptoms involving the skin, sclera, lungs, and kidneys should be high on differentials. Early recognition and intervention may decrease hospital stays and morbidity.

Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects?

Purpose: The pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process. Patients and Methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high-intensity exercise as well as for a control group of 32 healthy age-matched individuals. Results: Based on the observed changes in the NOI (Normoxia Oscillatory Index) and RHR (Reactive Hyperemia Response) parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects, which are associated with vascular stress in the macrocirculation and microcirculation. Acute and chronic fatigue symptomatology shared similarly altered changes in the NOI and RHR parameters and both can be linked to calcium homeostasis modification. Conclusion: The NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome as well as for monitoring the rehabilitation process.

Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve.

AIMS: The aim of this study is to evaluate whether post-acute sequelae of COVID-19 cardiovascular syndrome (PASC-CVS) is associated with alterations in coronary circulatory function. MATERIALS AND METHODS: In individuals with PASC-CVS but without known cardiovascular risk factors (n = 23) and in healthy controls (CON, n = 23), myocardial blood flow (MBF) was assessed with 13 N-ammonia and PET/CT in mL/g/min during regadenoson-stimulated hyperemia, at rest, and the global myocardial flow reserve (MFR) was calculated. MBF was also measured in the mid and mid-distal myocardium of the left ventricle (LV). The Δ longitudinal MBF gradient (hyperemia minus rest) as a reflection of an impairment of flow-mediated epicardial vasodilation, was calculated. RESULTS: Resting MBF was significantly higher in PASC-CVS than in CON (1.29 ± 0.27 vs. 1.08 ± 0.20 ml/g/min, p ≤ .024), while hyperemic MBFs did not differ significantly among groups (2.46 ± 0.53 and 2.40 ± 0.34 ml/g/min, p = .621). The MFR was significantly less in PASC-CVS than in CON (1.97 ± 0.54 vs. 2.27 ± 0.43, p ≤ .031). In addition, there was a Δ longitudinal MBF gradient in PASC-CVS, not observed in CON (-0.17 ± 0.18 vs. 0.04 ± 0.11 ml/g/min, p < .0001). CONCLUSIONS: Post-acute sequelae of COVID-19 cardiovascular syndrome may be associated with an impairment of flow-mediated epicardial vasodilation, while reductions in coronary vasodilator capacity appear predominantly related to increases in resting flow in women deserving further investigations.

Comparing Objective Conjunctival Hyperemia Grading and the Ocular Surface Disease Index Score in Dry Eye Syndrome During COVID-19.

The incidence of dry eye syndrome (DES) has increased due to wearing masks, utilizing digital devices, and working remotely during the pandemic. A survey was conducted during the COVID-19 pandemic to determine the prevalence of dry eye syndrome. A cross-sectional study investigated how prevalent DES is during COVID-19 in healthy patients aged 20-45 in the United States. An Ocular Surface Disease Index (OSDI) questionnaire was given to 40 individuals remotely from October 31, 2021, to December 1, 2021. The AOS and the OSDI survey were used to evaluate DES. The subjects were 29 years old on average (SD 14.14), with 23 males (57.5%) and 17 females (42.5%). According to the OSDI survey, low DES, moderate DES, and severe DES had prevalence rates of 15%, 77.5%, and 7.5%, respectively. White (W) people represent 50% of the population, while African Americans (AA) represent 35%, Asians represent 7.5%, and Hispanics represent 7.5%. Mild DES affected 77.5% of subjects, with 64.50% males and 35.50% females. According to the AOS objective grading system, mild (M) DES, moderate (MO) DES, and severe (S) DES had prevalence rates of 40%, 12.5%, and 15%, respectively. Linear regression was used to compare the two grading systems, and it demonstrated a strong relationship between the two grading systems.

Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults.

We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%; P = 0.544). Similarly, reactive hyperemia (P = 0.884) and arterial stiffness were not different between groups (e.g., cfPWV; control, 5.9 ± 0.6 m/s and Omicron, 5.7 ± 0.8 m/s; P = 0.367). Finally, measures of HR variability and cardiac BRS were not different between groups (all, P > 0.05). Collectively, these data suggest preserved vascular health and cardiac autonomic function in young, otherwise healthy adults who had breakthrough cases of COVID-19 during the Omicron wave.NEW & NOTEWORTHY We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.

Chronic fatigue associated with post-COVID syndrome versus transient fatigue caused by high intensity exercise: are they comparable in terms of vascular effects? (preprint)

Purpose: The pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process. Patients and Methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high intensity exercise, as well as for a control group of 32 healthy age-matched individuals. Results: Based on the NOI and RHR parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects. Both chronic fatigue associated with post-COVID syndrome and transient fatigue caused by high-intensity exercise are associated with vascular stress in the macrocirculation and microcirculation. Conclusion: The NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome, as well as for monitoring the rehabilitation process.

In-vivo evidence of systemic endothelial vascular dysfunction in COVID-19.

BACKGROUND: Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID-19. We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID-19 patients from a non-invasive approach with reactive hyperemia peripheral arterial tonometry (PAT). METHODS: This is a prospective, observational, case-control and blinded study. The population was comprised by 3 groups: patients investigated during acute COVID-19 (group 1), patients investigated during past COVID-19 (group 2), and controls 1:1 matched to COVID-19 patients by demographics and cardiovascular risk factors (group 3). The natural logarithmic scaled reactive hyperemia index (LnRHI), a measure of endothelium-mediated dilation of peripheral arteries, was obtained in all the participants and compared between study groups. RESULTS: 144 participants were enrolled (72 COVID-19 patients and 72 matched controls). Median time from COVID-19 symptoms to PAT assessment was 9.5 and 101.5 days in groups 1 and 2, respectively. LnRHI was significantly lower in group 2 compared to both group 1 and controls (0.53 ± 0.23 group 2 vs. 0.72 ± 0.26 group 1, p = 0.0043; and 0.79 ± 0.23 in group 3, p < 0.0001). In addition, within group 1, it was observed a markedly decrease in LnRHI from acute COVID-19 to post infection stage (0.73 ± 0.23 vs. 0.42 ± 0.26, p = 0.0042). CONCLUSIONS: This study suggests a deleterious effect of SARS-CoV-2 infection on systemic vascular endothelial function. These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID-19 patients and post-COVID syndrome using non-invasive techniques.

Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention.

Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40-70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 µg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (p = 0.91), the percentage of positive FFR (p = 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (p = 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.

Vascular alterations among young adults with SARS-CoV-2.

While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin-converting enzyme 2 receptor and initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. To establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (control: 5 M/15 F, 23.0 ± 1.3 y, 167 ± 9 cm, 63.0 ± 7.4 kg) and young adults who, 3-4 wk prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4 M/7 F, 20.2 ± 1.1 y, 172 ± 12 cm, 69.5 ± 12.4 kg) (means ± SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Carotid-femoral pulse wave velocity (PWVcf) was asvsessed as a marker of arterial stiffness. FMD was lower in the SARS-CoV-2 group (2.71 ± 1.21%) compared with the control group (8.81 ± 2.96%) (P < 0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04 ± 0.02 AU, control: 0.13 ± 0.06 AU, P < 0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3 ± 91 mL) compared with the control group (118 ± 114 mL) (P < 0.01). PWVcf was higher in the SARS-CoV-2 group (5.83 ± 0.62 m/s) compared with the control group (5.17 ± 0.66 m/s) (P < 0.01). Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared with controls.NEW & NOTEWORTHY This study was the first to investigate the vascular implications of contracting SARS-CoV-2 among young, otherwise healthy adults. Using a cross-sectional design, this study assessed vascular function 3-4 wk after young adults tested positive for SARS-CoV-2. The main findings from this study were a strikingly lower vascular function and a higher arterial stiffness compared with healthy controls. Together, these results suggest rampant vascular effects seen weeks after contracting SARS-CoV-2 in young adults.

Normal Pressure Hydrocephalus Associated with COVID-19 Infection: A Case Report (preprint)

COVID-19 is a pandemic disease responsible for a large number of deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) two months after acute COVID19 infection, in a patient without other risk factors. A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms. Other infections such Syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.

Distinct patterns of blood cytokines beyond a cytokine storm predict mortality in COVID-19 (preprint)

Background COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. Patients and methods Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Findings The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. Interpretation Several newly identified blood markers were increased in patients with severe COVID-19 (AAT, EN-RAGE, ICAM-1, myoglobin, SAP, TIMP-1, vWF, decorin, HGF, MMP7, PECAM-1) or in patients that died (FRTN, SCF, TIMP-1, CA-9, CEA, decorin, HGF). The use of established assay technologies allows for rapid translation into clinical practice.

A Single Drop of Fingerstick Blood for Quantitative Antibody Response Evaluation After SARS-CoV-2 Vaccination (preprint)

Among several COVID vaccines that have been approved, the Moderna and Pfizer-BioNTech vaccines are mRNA vaccines that are safe and highly effective at preventing COVID-19 illness. Studies have demonstrated that neutralizing antibody responses elicited by these vaccines correlate strongly with antibodies measured by immunoassays such as ELISA. To monitor the antibody level duration of vaccine-induced immune responses in vaccinated population, cost-effective and easily implementable antibody testing methodologies are urgently needed. In this study, we evaluated the feasibility of using a single drop of fingerstick blood collected with flocked swabs for a high-throughput and quantitative anti-SARS-CoV-2 spike (S1) IgG antibody immunoassay. A total of 50 voluntary subjects participated and donated fingerstick blood samples before and after receiving the Moderna mRNA vaccine. Among all individuals tested, no anti-SARS-CoV-2 S1 IgG antibody was detected before vaccination and on day 7 after receiving the first vaccine dose. On day 14 after the first dose, a significant amount of anti-SARS-CoV-2 S1 IgG antibody was detected in all participants samples. By the end the third week from the first dose, the median anti-SARS-CoV-2 S1 IgG concentration increased to 44.9 ug/mL. No anti-SARS-CoV-2 nucleocapsid (N) protein IgG antibody was detected in any of the participants during the study period, indicating that the anti-SARS-CoV-2 S1 IgG assay is specific for the mRNA vaccine induced antibodies. Comaprison of venous blood plasma and fingerstick blood for anti-SARS-CoV-2 S1 IgG shown a higher correlation. Furthermore, the fingerstick blood dried swab samples are stable for at least 4 days. In summary, we demonstrated that a single drop of fingerstick blood collected with flocked swab can be used for quantitative detection and monitoring of anti-SARS-CoV-2 spike IgG responses after receiving COVID-19 vaccination. This testing platform does not require venous blood draw and can be easily implemented for large scale antibody testing in vaccinated populations.