Sex-related patient-reported brain fog symptoms in non-hospitalised COVID-19 patients.

INTRODUCTION: Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex. MATERIAL AND METHODS: We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0-4, 4-12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab. RESULTS: The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161-248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38-6.72; 4-12 weeks, OR 2.51, 95% CI: 1.02-6.14; > 12 weeks, OR 3.74, 95% CI: 1.12-12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41-4.54; 4-12 weeks, OR 3.74, 95% CI: 1.93-7.24; > 12 weeks, OR 2.00, 95% CI: 1.01-3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36-5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44-4.48 and OR 2.43, 95% CI: 1.37-4.31 for < 4 and 4-12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted. CONCLUSIONS: Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog.

Course of fatigue among patients previously hospitalised due to COVID-19.

INTRODUCTION: Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. MATERIAL AND METHODS: Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection. RESULTS: We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [ß 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, ß -0.12 (-0.28; -0.01), p = 0.029]. CONCLUSIONS: Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and - only for the acute phase - age.

Fatigue after COVID-19 in non-hospitalized patients according to sex.

BACKGROUND: Limited evidence exists on sex differences in post-COVID fatigue among non-hospitalized patients. Therefore, aim of the study was to evaluate the course of chronic fatigue symptoms in non-hospitalized subjects with the SARS-CoV-2 infection, according to sex. METHODS: Patients and staff from the University Hospital in Krakow anonymously and retrospectively completed neuropsychological questionnaire that included eight symptoms of chronic fatigue syndrome. The presence of these symptoms was assessed before COVID-19 and 0-4, 4-12, and >12 weeks postinfection. The inclusion criteria were as follows: age 18 or more years, >12 weeks since the onset of the SARS-CoV-2 infection, and diagnosis confirmed by the RT-PCR from anasopharyngeal swab. RESULTS: We included 303 patients (79.53% women, 47.52% medical personnel) assessed retrospectively after a median of 30 (interquartile range: 23-35) weeks since the onset of symptoms. A higher prevalence of at least one chronic fatigue symptom was found in females in all time intervals after the onset of COVID-19 compared to males (p < .036). Women, compared to men, more often experienced persistent fatigue, not caused by effort and persisting after rest (for <4 weeks, odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.13-4.73; for 4-12 weeks, OR = 1.95, 95% CI: 1.06-3.61), non-restorative sleep (for <4 weeks, OR = 2.17, 95% CI: 1.23-3.81; for >12 weeks, OR = 1.95, 95% CI: 1.03-3.71), and sore throat (for <4 weeks, OR = 1.97, 95% CI: 1.03-3.78; for 4-12 weeks, OR = 2.76, 95% CI: 1.05-7.27). Sex differences in headache, arthralgia, and prolonged postexercise fatigue were observed only during the first 4 weeks (OR = 2.59, 95% CI: 1.45-4.60, OR = 2.97, 95% CI: 1.02-8.64, and OR = 1.87, 95% CI: 1.01-3.51, respectively). There were no differences between women and men in myalgia and self-reported lymph node enlargement. CONCLUSIONS: The course of post-COVID fatigue differs significantly between sexes in non-hospitalized individuals with COVID-19, with women more often suffering from persistent fatigue, not caused by effort and persisting after rest, non-restorative sleep, and sore throat.

SARS-CoV-2 infection and SLE: endothelial dysfunction, atherosclerosis, and thrombosis.

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract). Key Points • The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps. • Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications. • This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction. Covid-19 and systemic lupus erythematosus-potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery).

Brain Fog and Quality of Life at Work in Non-Hospitalized Patients after COVID-19.

Background: There is still a need for studies on the quality of life (QoL) at work among COVID-19 survivors. Therefore, we aimed to evaluate the association between the brain fog symptoms and the QoL at work in non-hospitalized patients with previous SARS-CoV-2 infection. Methods: Three hundred non-hospitalized patients (79.33% women; median age, 36 years; interquartile range, 30-48 years) were included in the final analysis. An anonymous neuropsychological questionnaire containing eight different questions on the presence of brain fog symptoms in four time intervals, i.e., pre-COVID-19 and 0-4, 4-12, and >12 weeks after infection, was retrospectively introduced to patients and staff of the University Hospital in Krakow. Additionally, a four-point Likert scale was used to evaluate QoL at work in four time periods. Included were participants aged ≥ 18 years in whom the diagnosis of COVID-19 was confirmed by the RT-PCR from nasopharyngeal swab and the first symptoms occurred no earlier than 3 months before the completion of the questionnaire. Results: Before SARS-CoV-2 infection, 28.00% (n = 84) of patients reported poor QoL at work. Within 4, 4-12, and >12 weeks after infection, a decrease in QoL was observed in 75.67% (n = 227), 65.00% (n = 195), and 53.66% (n = 161) of patients, respectively (p < 0.001). With increasing deterioration of the QoL at work, the number of brain fog symptoms increased, and patients with severe QoL impairment exhibited a median of five symptoms for <4, 4-12, and >12 weeks post-COVID-19. In the multivariable logistic regression model, predictors of the deterioration of the QoL at work depended on the time from COVID-19 onset; in the acute phase of the disease (<4 weeks), it was predicted by impairment in remembering information from the past (OR 1.88, 95%CI: 1.18-3.00, p = 0.008) and multitasking (OR 1.96, 95%CI: 1.48-2.58, p < 0.001). Furthermore, an impairment in the QoL at work 4-12 weeks and >12 weeks after COVID-19 was independently associated with age (OR 0.46, 95%CI: 0.25-0.85, p = 0.014 and OR 1.03, 95%CI: 1.01-1.05, p = 0.025, respectively), problems with multitasking (OR 2.05, 95%CI: 1.40-3.01, p < 0.001 and OR 1.75, 95%CI: 1.15-2.66, p = 0.009, respectively), answering questions in an understandable/unambiguous manner (OR 1.99, 95%CI: 1.27-3.14, p = 0.003 and OR 2.00, 95%CI: 1.47-2.36, p = 0.001, respectively), and, only for the >12 week interval, problems with remembering information from the past (OR 2.21, 95%CI: 1.24-3.92, p = 0.007). Conclusions: Certain brain fog symptoms, such as impaired memory or multitasking, are predictors of a poorer QoL at work not only during the acute phase of COVID-19 but also within more than 12 weeks after the onset of infection.

Prognostic significance of age in patients with acute ischaemic stroke treated with intravenous thrombolysis.

AIM OF THE STUDY: To assess the influence of age on long-term functional outcome in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). MATERIAL AND METHODS: We performed retrospective analysis of 362 AIS patients treated with IVT or IVT and subsequent mechanical thrombectomy in the University Hospital in Krakow, Poland. Patients were categorised into four subgroups by age: (I) below the age of 60, (II) 60 to 69, (III) 70 to 79, and (IV) 80 or more. The outcomes were assessed with modified Rankin scale (mRS) 90 days after stroke onset, and defined as favourable (mRS 0-2), poor (mRS 3-5), or death (mRS = 6). RESULTS: Patients aged 80 or more compared to those below 60 were more often women (72.64% vs. 26.76%, < 0.001), more often suffered from hypertension (94.34% vs. 60.56%, p < 0.001), ischaemic heart disease (27.36% vs. 8.45%, p = 0.002), atrial fibrillation (49.06% vs. 5.63%, p < 0.001), and premorbid disability (pre-stroke mRS ≥ 1: 17.92% vs. 1.41%, p < 0.001), less often were active smokers (0% vs. 27.14%, p < 0.001), more often had cardioembolic aetiology (50.00% vs. 16.90%, p < 0.001), and less often other stroke aetiology (1.89% vs. 15.49%, < 0.008), had shorter time from stroke onset to IVT (125 [93-180] vs. 140 [110-186] min, p < 0.008), less often underwent mechanical thrombectomy (18.87% vs. 46.48%, p < 0.001), had higher CRP levels (10.3 [3.2-39.8] vs. 4.3 [2.1-9.6] mg/L, p = 0.003), higher maximal systolic blood pressure within 24 hours after IVT (153 [140-170] vs. 138 [120-145] mmHg, p < 0.001), and higher creatinine concentration (88 [68-108] vs. 77 [67-87] µmol/l, p = 0.004), less often had a favourable outcome (48.04% vs. 85.51%, odds ratio [OR] 0.16, 95%CI: 0.07-0.34, p < 0.001), and had a greater risk of death (26.47% vs. 5.80%, OR 5.85, 95%CI: 1.95-17.59, p < 0.001) within three months of stroke onset. Multivariable logistic regression analysis showed that the independent predictors of worse outcome in patients aged 80 or more were NIHSS score after IVT (OR 0.64, 95%CI: 0.53-0.78, p < 0.001), pre-stroke mRS score ≥ 1 (OR 0.10, 95%CI: 0.02-0.61, p = 0.012), and CRP levels (OR 0.96, 95%CI: 0.93-0.99, p = 0.007). CONCLUSIONS: AIS patients treated with reperfusion therapy and aged 80 or more have around a six times higher risk of an unfavourable outcome or death within three months of stroke onset compared to those aged below 60. Higher NIHSS score after IVT, any signs of disability before stroke as measured with mRS, and higher CRP levels are independent risk factors for worse prognosis in the elderly.

Neurological Prognostic Factors in Hospitalized Patients with COVID-19.

We aimed to search whether neurological symptoms or signs (NSS) and the MEWS (Modified Early Warning Score) score were associated with in-hospital mortality or oxygen requirement during the first 14 days of hospitalization in COVID-19 patients recruited at the University Hospital in Krakow, Poland. The detailed clinical questionnaires on twenty NSS were either filled out by patients prospectively or retrospectively assessed by neurologists based on daily medical records. NSS were considered high or low-risk if they were associated with increased or decreased mortality in the univariable analysis. This cohort study included 349 patients with COVID-19 (median age 64, interquartile range (51-77), women 54.72%). The presence of high-risk NSS (decreased level of consciousness, delirium, seizures, and symptoms of stroke or transient ischemic attack) or its combination with the absence of low-risk NSS (headache, dizziness, decreased mood, and fatigue) increased the risk of in-hospital mortality in SARS-CoV-2 infection 3.13 and 7.67-fold, respectively. The presence of low-risk NSS decreased the risk of in-hospital mortality in COVID-19 patients more than 6-fold. Death in patients with SARS-CoV-2 infection, apart from NSS, was predicted by older age, neoplasm, and higher MEWS scores on admission. High-risk NSS or their combination with the absence of low-risk NSS increased the risk of oxygen requirement during hospitalization in COVID-19 patients 4.48 and 1.86-fold, respectively. Independent predictors of oxygen therapy during hospitalization in patients with SARS-CoV-2 infection were also older age, male sex, neoplasm, and higher MEWS score on admission.

Neurological symptoms in hospitalised patients with COVID-19 and their association with in-hospital mortality.

OBJECTIVES: To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality. MATERIAL AND METHODS: We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology. RESULTS: During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003). CONCLUSIONS: Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.