Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis. / Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Giving a Voice to Patients With Smell Disorders Associated With COVID-19: Cross-Sectional Longitudinal Analysis Using Natural Language Processing of Self-Reports.

BACKGROUND: Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. OBJECTIVE: This study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. METHODS: We included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non-long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants' self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non-long-haulers. RESULTS: We found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P<.001) as well as hyposmia (OR 1.74, 95% CI 1.34-2.26; P<.001) were more frequently reported in long-haulers than in non-long-haulers. Furthermore, a significant relationship was found between long-hauler status and sentiment of self-report (P<.001). Finally, we found specific keywords that were more typical for long-haulers than those for non-long-haulers, for example, fire, gas, wine, and vinegar. CONCLUSIONS: Our work shows consistent findings with those of previous studies, which indicate that self-reports, which can easily be extracted online, may offer valuable information to health care and understanding of smell disorders. At the same time, our study on self-reports provides new insights for future studies investigating smell disorders.

Effects of C-reactive protein rapid testing and communication skills training on antibiotic prescribing for acute cough. A cluster factorial randomised controlled trial.

This cluster randomised clinical trial carried out in 20 primary care centres in Barcelona was aimed at assessing the effect of a continuous intervention focused on C-reactive protein (CRP) rapid testing and training in enhanced communication skills (ECS) on antibiotic consumption for adults with acute cough due to lower respiratory tract infection (LRTI). The interventions consisted of general practitioners and nurses' use of CRP point-of-care and training in ECS separately and combined, and usual care. The primary outcomes were antibiotic consumption and variation of the quality-adjusted life years during a 6-week follow-up. The difference in the overall antibiotic prescribing between the winter seasons before and after the intervention was calculated. The sample size calculated could not be reached due to the COVID-19 outbreak. A total of 233 patients were recruited. Compared to the usual care group (56.7%) antibiotic consumption among patients assigned to professionals in the ECS group was significantly lower (33.9%, adjusted odds ratio [aOR] 0.38, 95% CI 0.15-0.94, p = 0.037), whereas patients assigned to CRP consumed 43.8% of antibiotics (aOR 0.70, 95% CI 0.29-1.68, p = 0.429) and 38.4% in the combined intervention group (aOR 0.45, 95% CI, 0.17-1.21; p = 0.112). The overall antibiotic prescribing rates in the centres receiving training were lower after the intervention compared to those assigned to usual care, with significant reductions in ß-lactam rates. Patient recovery was similar in all groups. Despite the limited power due to the low number of patients included, we observed that continuous training achieved reductions in antibiotic consumption.

Determinants of post-acute COVID-19 syndrome among hospitalized severe COVID-19 patients: A 2-year follow-up study.

BACKGROUND: Post-acute COVID-19 syndrome is a condition where individuals experience persistent symptoms after the acute phase of the COVID-19 infection has resolved, which lowers their quality of life and ability to return to work. This study assessed the prevalence and associated risk factors of post-acute COVID-19 syndrome (PACS) among severe COVID-19 patients who were discharged from Millennium COVID-19 Care Center, Addis Ababa, Ethiopia. METHODS: A cross-sectional study using data collected from patient charts and a follow-up telephone interview after two years of discharge. Systematic random sampling was used to select a total of 400 patients. A structured questionnaire developed from the case report form for PACS of the World Health Organization (WHO) was used. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression. RESULT: Out of the 400 patients, 20 patients were dead, 14 patients refused to give consent, and 26 patients couldn't be reached because their phones weren't working. Finally, 340 were included in the study. The majority (68.5%) were males and the mean age was 53.9 (±13.3 SD) years. More than a third (38.1%) of the patients reported the persistence of at least one symptom after hospital discharge. The most common symptoms were fatigue (27.5%) and Cough (15.3%). Older age (AOR 1.04, 95% CI 1.02-1.07), female sex (AOR 1.82, 95% CI 1.00-3.29), presence of comorbidity (AOR 2.38, 95% CI 1.35-4.19), alcohol use (AOR 3.05, 95% CI 1.49-6.26), fatigue at presentation (AOR 2.18, 95% CI 1.21-3.95), and longer hospital stay (AOR 1.06, 95% CI 1.02-1.10) were found to increase the odds of developing post-acute COVID-19 syndrome. Higher hemoglobin level was found to decrease the risk of subsequent post-acute COVID-19 syndrome (AOR 0.84, 95% CI 0.71-0.99). CONCLUSION: The prevalence of post-acute COVID-19 syndrome is high, with a wide range of persistent symptoms experienced by patients. COVID-19 survivors with the identified risk factors are more susceptible to post-acute COVID-19 and require targeted monitoring and care in a multidisciplinary approach.

A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients.

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.

Effect of COVID-19 on the characteristics and outcome of patients who have otitis media with effusion: a case-control study.

BACKGROUND: Few studies have examined the otologic symptoms of Coronavirus disease 2019 (COVID-19). The objective of this study was to identify the effect of COVID-19 on the characteristics and outcomes of patients who have otitis media with effusion (OME). METHODS: This case-control study compared the characteristics and outcomes of OME patients who did or did not have COVID-19. A total of 65 patients with previous COVID-19 and 40 patients who did not have COVID-19 (controls) were enrolled from October 1, 2022 to January 31, 2023 at a single institution in China. Demographics, medical histories, morbidities, hearing test results, treatments, and outcomes of the two groups were compared. RESULTS: The COVID-19 group had significantly better outcomes from OME than the control group, with higher rates of complete resolution (64.6% vs. 30%) and improvement (30.8% vs. 17.5%), and a lower rate of persistent OME (4.6% vs. 52.5%). Previous COVID-19 was independently associated with a more favorable OME outcome in three multivariate logistic regression models. The COVID-19 group also had a greater improvement in hearing threshold based on air-bone gap measurements. CONCLUSION: The outcomes of OME patients who had previous COVID-19 were generally good, in that most patients responded well to treatment and achieved complete resolution or improvement within one month.

[VASCULAR OPHTHALMIC MANIFESTATIONS IN COVID-19 PATIENTS].

INTRODUCTION: Although COVID-19 is mainly a respiratory disease, recent evidence has emerged of vascular and procoagulant pathologies even in young and otherwise healthy individuals. Ophthalmic manifestations include, among others, visual impairment due to arteritic and venous retinal obstructions, which at times precedes other aspects of the disease. We present two atypical cases of internal carotid dissection (ICAD) and review the different ocular symptoms of ICAD and its association with the COVID-19 pandemic. BACKGROUND: A 43-year-old otherwise healthy man was referred to the Emergency Department with a headache and monocular blurring of vision. A recent fever (2 weeks prior) was noted on anamnesis, in light of absence of available positive PCR test during the illness period, clinical suspicion of COVID-19 was assumed. An initial ophthalmic evaluation found a mild optic nerve function impairment with preserved visual acuity. Computed tomography (CT) showed sinusitis, and an initial diagnosis was made of mild optic neuropathy secondary to sphenoid sinusitis. A few hours after admission, the patient reported deterioration of symptoms and examination revealed no light perception in his right eye and pale edematous optic nerve. Urgent magnetic resonance angiography (MRA) demonstrated right ICAD with no additional findings. The second patient, a 43-year-old man developed an acute event of strabismus, left limb paralysis, and speech difficulties while on a hospital visit for his son. The patient underwent CT of the brain which demonstrated extensive infarction following the distribution of his right cerebral artery. Continued investigation using computed tomography angiography (CTA) demonstrated a dissection of the right internal carotid artery. The patient was positive for COVID-19. DISCUSSION: In this review, we discuss 2 cases of carotid artery dissection presenting with an acute ocular complaint in two otherwise healthy young individuals. Events were suspected to have been provoked by COVID-19 infection. The pathogenesis and mechanisms behind COVID-19 induced coagulopathy are not clear, and several mechanisms have been proposed including endothelial damage and dysfunction. The virus is thought to enter endothelial cells and lead to a pathological procoagulant state. Awareness should be drawn to uncommon signs especially in young adults. Clotting issues can arise and should be treated quickly as they might be life and vision threatening.

[Features of the Course of Arterial Hypertension in the Era of the COVID-19 Pandemic: Common Pathogenetic Links Between Hypertension and SARS-CoV-2].

The aim of this review was to present the mechanism of infection with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and its possible effect on the course of arterial hypertension. Another aim was to evaluate the relationship of the renin-angiotensin-aldosterone system with the pathogenetic stages of infection caused by SARS-CoV-2 virus.

Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients.

BACKGROUND: COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR's effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals. METHODS: We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network's electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR. RESULTS: The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR. CONCLUSION: Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients' functional status should be investigated in the future.

Clinical characteristics of liver transplant recipients with COVID-19 and analysis of risk factors for the severe disease.

INTRODUCTION: Liver transplant (LT) recipients were at a high risk of infection during the coronavirus disease 2019 (COVID-19) pandemic. Our purpose was to compare the clinical characteristics of severe and non-severe groups of LT recipients with COVID-19, and to analyze their risk factors for severe disease. METHODOLOGY: 79 LT recipients with COVID-19 were divided into a non-severe group (n = 60) and a severe group (n = 19), and differences in clinical characteristics, laboratory tests, and chest computed tomography (CT) performance were analyzed. Logistic regression was used to identify risk factors with severe COVID-19. Receiver operating characteristic (ROC) curves were plotted and the area under curve (AUC) values were calculated to assess the predictive value for severe COVID-19. RESULTS: Age was statistically different (p < 0.001) between the two groups. The difference in neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), D-dimer, urea, C-reactive protein (CRP), lactate dehydrogenase (LDH), and the number of lung segments involved in inflammation between the two groups were statistically significant (p < 0.05). The results revealed that age (OR = 1.255, 95% CI 1.079-1.460), NLR (OR = 1.172, 95% CI 1.019-1.348), and Scr (OR = 1.041, 95% CI 1.016-1.066) were independent risk factors for severe COVID-19. The ROC results showed that high values for age, NLR and Scr predicted severe COVID-19, with AUC values of 0.775, 0.841 and 0.820, respectively, and 0.925 for the three factors combined. CONCLUSIONS: Advanced age, and elevated NLR and Scr are independent risk factors for severe COVID-19 in LT recipients.

The role of thoracic surgery in the management of complicated acute and post-acute COVID-19 pneumonia (PASC).

INTRODUCTION: COVID-19 is considered a respiratory virosis in its classic form, although it may present with heterogeneous symptoms. Thoracic complications occur in a small percentage of patients. Our objective was to evaluate existing experience with this disease and its thoracic manifestations and to determine the real-world status of care of these patients. METHODS: This study is a retrospective, single-institution analysis of a group of patients hospitalized with acute and post-acute COVID-19 pneumonia at Thomayer Hospital in Prague in the period from December 2020 to March 2022 and indicated for a thoracic surgical procedure. RESULTS: During the peak of COVID-19 pandemic, a thoracic intervention was performed in 46 admitted patients. Thoracic drainage (due to pneumothorax in 18 cases, fluidothorax in 3 cases, CT-guided lung abscess drainage in 2 cases, and CT-guided pneumatocele drainage in 2 cases) were the most common thoracic surgical procedures. Pleurectomy/decortication surgery was done in 10 cases. Additionally, 12 lung parenchyma-sparing resections were performed, while lobectomy was required in 2 cases. Resection of postintubation tracheal stenosis due to a severe course of COVID-19 pneumonia was indicated in 2 patients. CONCLUSION: Even mild COVID-19 may cause a considerable morphological a functional alteration of the respiratory system. The most common complications of COVID-19 pneumonia that require a thoracic surgical intervention include pathologies associated with an air leak and accumulation of air (pneumothorax, pneumomediastinum and subcutaneous emphysema). The development of pulmonary necrosis, symptomatic bronchiectasis, pneumatocele, and bullous-fibrotic formations may result in pneumothorax, hemothorax or thoracic empyema in sporadic cases. An early thoracic surgical intervention to treat thoracic complications of COVID-19 pneumonia can improve the survival of COVID-19 patients.

Respiratory pathogen and clinical features of hospitalized patients in acute exacerbation of chronic obstructive pulmonary disease after COVID 19 pandemic.

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD might be given more consideration for treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

The prone position in COVID-19 impacts the thickness of peripapillary retinal nerve fiber layers and macular ganglion cell layers.

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19.

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer's-linked tauopathy and declined with progression of age in COVID19 + patients.

Implications of anti-ganglioside antibodies in isolated dysphagia following COVID-19 infection: Case series.

BACKGROUND: There have been multiple reports about the occurrence of dysphagia after the contraction of coronavirus disease 2019 (COVID-19). However, a detailed pathology and epidemiologic relation between COVID-19 infection and dysphagia have yet to be established. Here, we report three cases of unexplained dysphagia after COVID-19 diagnosis, with atypical clinical presentations. CASE REPORT: All patients showed severe isolated lower cranial nerve involvement with dysphagia and aspiration, which required full tube feeding but showed no evidence of limb weakness or sensory symptoms. All tested positive for anti-ganglioside antibody tests, which all commonly (GD1b, GM1, and GQ1b) are known to have terminal NeuNAc(α2-3)Gal epitope. DISCUSSION: We report a series of cases featuring severe, isolated dysphagia post-COVID-19 infection, concomitant with positive anti-ganglioside antibodies. One potential etiology is a variant of Guillain-Barré syndrome. Because only isolated dysphagia with sparing of the facial and extraocular muscles was evident in these cases, we explore the association between anti-ganglioside antibodies specific to NeuNAc(α2-3)Gal, which has been frequently associated with the development of bulbar dysfunction. Given that NeuNAc(α2-3)Gal exhibits an affinity for the spike glycoprotein of SARS-CoV-2, a cross-reaction against NeuNAc(α2-3)Gal may possibly contribute to isolated dysphagia following COVID-19 infection.

SARS-CoV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice.

The coronavirus disease of 2019 (COVID-19) pandemic has led to more than 700 million confirmed cases and nearly 7 million deaths. Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains an important question, which is also centered on the mystery of whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to neurological complications both acutely and in long COVID.

Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms 2 years after hospitalization: The VIPER study.

The SARS-CoV-2 VIrus PERsistence (VIPER) study investigated the presence of long-lasting SARS-CoV-2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID-19 survivors. The presence of SARS-CoV-2 RNA reverse transcription polymerase chain reactions (RT-PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID-19 survivors with post-COVID symptoms and a comparison group of COVID-19 survivors without post-COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self-reported the presence of any post-COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty-seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID-19 survivors with post-COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS-CoV-2 infection without post-COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS-CoV-2 RNA was identified in three nasopharyngeal samples of patients with post-COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS-CoV-2 RNA was not identified in any sample of survivors without post-COVID symptoms. The most prevalent post-COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS-CoV-2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS-CoV-2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post-COVID symptoms. These results do not support the association between SARS-CoV-2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post-COVID symptomatology in the recruited population.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Chronotropic incompetence is associated with reduced aerobic conditioning and sedentary behavior in patients with post-acute COVID-19 syndrome.

Post-acute COVID-19 syndrome, or long COVID, presents with persistent symptoms, including cough, dyspnea, and fatigue, extending beyond one month after SARS-CoV-2 infection. Cardiac complications such as chest pain and arrhythmias have raised concerns, with chronotropic incompetence (CI), an inadequate heart rate increase during exercise, emerging as a significant condition contributing to diminished exercise tolerance and quality of life. This study estimated the prevalence of CI and explored its association with aerobic capacity and physical activity levels in long COVID patients. A cross-sectional study was conducted at a private hospital in Sergipe, Brazil, involving 93 patients over 18 years old with persistent post-COVID-19 symptoms after confirmed SARS-CoV-2 infections. Exclusion criteria included beta-blocker use, inadequate respiratory exchange ratio, and inability to complete cardiopulmonary exercise testing (CPET). Clinical histories, CPET results, and chronotropic index calculation were used to identify CI, with logistic regression analyzing associated factors. Of the participants (mean age 45 years; average duration since COVID-19 diagnosis 120 days), 20.4% were diagnosed with CI. Logistic regression identified a strong association between CI and sedentary behavior (OR 11.80; 95% CI 2.54 to 54.78; p=0.001). Patients with CI showed lower predicted peak heart rates and maximal oxygen uptake. The prevalence of CI among long COVID patients in this study was approximately 20%, associated with decreased aerobic capacity and increased sedentary behavior. These findings highlight the need for timely diagnosis and therapeutic interventions, including cardiopulmonary rehabilitation, to enhance the quality of life in post-COVID patients with CI. The study's cross-sectional design and its specific context have limited causality inference and generalizability, underscoring the importance of further research in diverse settings.