The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Neurologic manifestations associated with COVID-19: a multicentre registry.

OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

What Is in the Neuromuscular Junction Literature?

ABSTRACT: This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression.

Tonic Pupil Following COVID-19.

ABSTRACT: A 37-year-old patient presented to our emergency department with sudden onset decreased vision with a history of being treated for COVID 19 3 weeks earlier. On examination, she was found to have a tonic right pupil, which was confirmed with a dilute pilocarpine test. As tonic pupils are known to be caused by neurotropic viruses and our current understanding of the SARS-CoV-2 is that it does affect the nervous system, we feel that the tonic pupil in our patient may be secondary to COVID 19.

SARS-CoV-2 Impairs Vision.

OBJECTIVES: Affection of the central nervous system and the eyes is increasingly recognized as manifestations of a SARS-CoV-2 infection (COVID-19). This review aims at summarizing and discussing recent advances concerning causes and locations of impaired vision because of an infection with SARS-CoV-2. METHODS: On a literature search through PubMed and ScholarOne, all available publications about COVID-19 patients with impaired vision were retrieved. RESULTS: Visual impairment in SARS-CoV-2-infected patients may be due to infection of lacrimal glands (dacryoadenitis), conjunctivitis, tonic pupils, vitritis, central retinal artery/venous occlusion, retinitis, retinal bleeding, panuveitis, anterior ischemic optic neuropathy, optic nerve stroke, optic neuritis, optic perineuritis, or occipital ischemic stroke. Visual impairment may be the initial manifestation of SARS-CoV-2. CONCLUSIONS: This mini review shows that impaired vision may be the initial manifestation of COVID-19, that all sections of the visual tract may be affected and causative for visual impairment in COVID-19 patients, and that SARS-CoV-2 manifests along the visual tract with ischemia, focal infection, and immunological reactions.

Immune thrombocytopenia: options and new perspectives.

Immune thrombocytopenia is a haematological, autoimmune disorder characterized by elevated platelet demolition due to the presence of antiplatelet autoantibodies derived from B cells and to an irregular, deficient process of platelets production in bone marrow. In this review, after a brief presentation of 'old' strategies used nowadays yet, we focused on new drugs used in the treatment of immune thrombocytopenia and their mechanism of action and posology, basing on the last scientific literature. The observation that CoViD-19 can be associated with immune thrombocytopenia is also put in evidence. Particular attention will be dedicated on the concept that the ideal treatment should represent a solution not only for the failure of normal processes of production and survival of platelets, but also it should improve quality of life of patients, with minimum adverse events. Anyway, despite enormous advances of the last years, further investigations are necessary in order to define scrupulously long-term efficacy of new molecules proposed.

The Association between COVID-19 Infection and Kidney Damage in a Regional University Hospital.

Background and Objectives: Kidneys are one of the main targets for SARS-CoV-2. Early recognition and precautionary management are essential in COVID-19 patients due to the multiple origins of acute kidney injury and the complexity of chronic kidney disease management. The aims of this research were to investigate the association between COVID-19 infection and renal injury in a regional hospital. Materials and Methods: The data of 601 patients from the Vilnius regional university hospital between 1 January 2020 and 31 March 2021 were collected for this cross-sectional study. Demographic data (gender, age), clinical outcomes (discharge, transfer to another hospital, death), length of stay, diagnoses (chronic kidney disease, acute kidney injury), and laboratory test data (creatinine, urea, C-reactive protein, potassium concentrations) were collected and analyzed statistically. Results: Patients discharged from the hospital were younger (63.18 ± 16.02) than those from the emergency room (75.35 ± 12.41, p < 0.001), transferred to another hospital (72.89 ± 12.06, p = 0.002), or who died (70.87 ± 12.83, p < 0.001). Subsequently, patients who died had lower creatinine levels on the first day than those who survived (185.00 vs. 311.17 µmol/L, p < 0.001), and their hospital stay was longer (Spearman's correlation coefficient = -0.304, p < 0.001). Patients with chronic kidney disease had higher first-day creatinine concentration than patients with acute kidney injury (365.72 ± 311.93 vs. 137.58 ± 93.75, p < 0.001). Patients with acute kidney injury and chronic kidney disease complicated by acute kidney injury died 7.81 and 3.66 times (p < 0.001) more often than patients with chronic kidney disease alone. The mortality rate among patients with acute kidney injury was 7.79 (p < 0.001) times higher than among patients without these diseases. Conclusions: COVID-19 patients who developed acute kidney injury and whose chronic kidney disease was complicated by acute kidney injury had a longer hospital stay and were more likely to die.

[Morphological aspects of diaphragm dysfunction in COVID-19-associated pneumonia]. / Morfologicheskie aspekty disfunktsii diafragmy pri COVID-19-assotsiirovannoi pnevmonii.

OBJECTIVE: To assess morphological changes in the diaphragm and phrenic nerve in patients who died from COVID-19. MATERIAL AND METHODS: In a case-control study, an analysis was made of autopsy material of the diaphragm and phrenic nerve of those who died from COVID-19 infection complicated by SARS-CoV-2-associated pneumonia, confirmed in vivo by the presence of SARS-CoV-2 RNA (Group 1, n=12), and those who died with a diagnosis of acute cerebrovascular accident of the ischemic type without parenchymal respiratory failure (Group 2, n=3). RESULTS: The main histopathological features in the diaphragm of the 1st group were the edema of the pericellular spaces of muscle fibers, edema of perivascular spaces, diapedese hemorrhages, plethora in arteriolas, in most veins and capillaries, red blood clots were revealed; in the diaphragmatic nerve - swelling of the perineral space, severe edema around the nerve fibers inside the nerve trunk. In the diaphragm of group 2, edema of pericellular spaces of muscle fibers and edema of perivascular spaces were less pronounced (p<0.001), hemorrhages were not determined; in the diaphragmatic nerve, moderate edema of the perineral space, mild swelling inside the nerve trunk around the nerve fibers was revealed (p<0.001). The glycogen content in the muscle cells of group 1 is significantly lower compared to group 2 (p<0.001). CONCLUSION: The study confirms the characteristic pathological picture of organ damage in COVID-19. However, the leading pathological mechanism of organ damage requires further investigation.

No genetic causal association between systemic lupus erythematosus and COVID-19.

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

Clinical features, diagnosis, and management of COVID-19 vaccine-associated Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is a rare and serious ocular adverse reaction following COVID-19 vaccination. This study aimed to evaluate the clinical features, diagnosis and management of COVID-19 vaccine-associated VKH disease. Case reports of VKH disease after COVID-19 vaccination were collected up to February 11, 2023 for retrospective analysis. Twenty-one patients (9 males and 12 females) were included, with a median age of 45 years (range 19-78), from three main regions, Asia (12/21), the Mediterranean region (4/21), and South America (5/21). Fourteen patients developed symptoms after the first dose of the vaccine, and 8 after the second dose. Vaccines included mRNA vaccine (10 cases), virus vector vaccine (6 cases), and inactivated vaccine (5 cases). The average time interval from vaccination to onset of symptoms was 7.5 days (range 12 hours to 4 weeks). All 21 patients experienced visual impairment after vaccination, with 20 cases involving both eyes. Sixteen patients showed symptoms of meningitis. Serous retinal detachment was observed in 16 patients, choroidal thickening was observed in 14, aqueous cell in 9, and subretinal fluid in 6. CSF pleocytosis was detected in 7 patients and skin symptoms were found in 3 patients. All patients received corticosteroid therapy, and 8 also received immunosuppressive agents. All patients recovered well, with a mean recovery time of 2 months. Early diagnosis and early treatment are crucial to the prognosis of patients with VKH after vaccination with COVID-19 vaccine. The risk of vaccination against COVID-19 in patients with a history of VKH disease should be evaluated clinically.

Patients with prediabetes are at greater risk of developing diabetes 5 months postacute SARS-CoV-2 infection: a retrospective cohort study.

INTRODUCTION: Patients with prediabetes who contract SARS-CoV-2 infection (COVID-19) could be at higher risk of developing frank diabetes compared those who do not. This study aims to investigate the incidence of new-onset diabetes in patients with prediabetes after COVID-19 and if it differs from those not infected. RESEARCH DESIGN AND METHODS: Using electronic medical record data, 42 877 patients with COVID-19, 3102 were identified as having a history of prediabetes in the Montefiore Health System, Bronx, New York. During the same time period, 34 786 individuals without COVID-19 with history of prediabetes were identified and 9306 were propensity matched as controls. SARS-CoV-2 infection status was determined by a real-time PCR test between March 11, 2020 and August 17, 2022. The primary outcomes were new-onset in-hospital diabetes mellitus (I-DM) and new-onset persistent diabetes mellitus (P-DM) at 5 months after SARS-CoV-2 infection. RESULTS: Compared with hospitalized patients without COVID-19 with history of prediabetes, hospitalized patients with COVID-19 with history of prediabetes had a higher incidence of I-DM (21.9% vs 6.02%, p<0.001) and of P-DM 5 months postinfection (14.75% vs 7.51%, p<0.001). Non-hospitalized patients with and without COVID-19 with history of prediabetes had similar incidence of P-DM (4.15% and 4.1%, p>0.05). Critical illness (HR 4.6 (95% CI 3.5 to 6.1), p<0.005), in-hospital steroid treatment (HR 2.88 (95% CI 2.2 to 3.8), p<0.005), SARS-CoV-2 infection status (HR 1.8 (95% CI 1.4 to 2.3), p<0.005), and hemoglobin A1c (HbA1c) (HR 1.7 (95% CI 1.6 to 1.8), p<0.005) were significant predictors of I-DM. I-DM (HR 23.2 (95% CI 16.1 to 33.4), p<0.005), critical illness (HR 2.4 (95% CI 1.6 to 3.8), p<0.005), and HbA1c (HR 1.3 (95% CI 1.1 to 1.4), p<0.005) were significant predictors of P-DM at follow-up. CONCLUSIONS: SARS-CoV-2 infection confers a higher risk for developing persistent diabetes 5 months post-COVID-19 in patients with prediabetes who were hospitalized for COVID-19 compared with COVID-19-negative counterparts with prediabetes. In-hospital diabetes, critical illness, and elevated HbA1c are risk factors for developing persistent diabetes. Patients with prediabetes with severe COVID-19 disease may need more diligent monitoring for developing P-DM postacute SARS-CoV-2 infection.

Emerging research on postacute COVID-19 complications.

ABSTRACT: An estimated 21.5% of patients in the United States who have had COVID-19 report development of a prolonged postviral syndrome that has been called postacute sequelae of COVID-19 (PASC). Symptoms can range from very mild to debilitating damage to organ systems caused directly by the virus and indirectly by the body's inflammatory response. Research into defining PASC and discovering effective treatments is ongoing. This article discusses the common presentations of PASC in patients who have had COVID-19; describes specific effects on the pulmonary, cardiovascular, and central nervous systems; and identifies potential treatments based on current literature.

Impact of fatigue as the primary determinant of functional limitations among patients with post-COVID-19 syndrome: a cross-sectional observational study.

OBJECTIVES: To describe self-reported characteristics and symptoms of treatment-seeking patients with post-COVID-19 syndrome (PCS). To assess the impact of symptoms on health-related quality of life (HRQoL) and patients' ability to work and undertake activities of daily living. DESIGN: Cross-sectional single-arm service evaluation of real-time user data. SETTING: 31 post-COVID-19 clinics in the UK. PARTICIPANTS: 3754 adults diagnosed with PCS in primary or secondary care deemed suitable for rehabilitation. INTERVENTION: Patients using the Living With Covid Recovery digital health intervention registered between 30 November 2020 and 23 March 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the baseline Work and Social Adjustment Scale (WSAS). WSAS measures the functional limitations of the patient; scores of ≥20 indicate moderately severe limitations. Other symptoms explored included fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), depression (Patient Health Questionnaire-Eight Item Depression Scale), anxiety (Generalised Anxiety Disorder Scale, Seven-Item), breathlessness (Medical Research Council Dyspnoea Scale and Dyspnoea-12), cognitive impairment (Perceived Deficits Questionnaire, Five-Item Version) and HRQoL (EQ-5D). Symptoms and demographic characteristics associated with more severe functional limitations were identified using logistic regression analysis. RESULTS: 3541 (94%) patients were of working age (18-65); mean age (SD) 48 (12) years; 1282 (71%) were female and 89% were white. 51% reported losing ≥1 days from work in the previous 4 weeks; 20% reported being unable to work at all. Mean WSAS score at baseline was 21 (SD 10) with 53% scoring ≥20. Factors associated with WSAS scores of ≥20 were high levels of fatigue, depression and cognitive impairment. Fatigue was found to be the main symptom contributing to a high WSAS score. CONCLUSION: A high proportion of this PCS treatment-seeking population was of working age with over half reporting moderately severe or worse functional limitation. There were substantial impacts on ability to work and activities of daily living in people with PCS. Clinical care and rehabilitation should address the management of fatigue as the dominant symptom explaining variation in functionality.

Development of giant cell arteritis after vaccination against SARS-CoV2: A case report and literature review.

RATIONALE: Giant cell arteritis (GCA) is an autoimmune vasculitis that affects large and medium-sized blood vessels. The mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has been associated with the development of immune-mediated diseases. In this article, we present a case of GCA that developed after vaccination against SARS-CoV2. PATIENT CONCERNS: A 77-year-old man developed fever, general fatigue, and headache 1 day after the third dose of vaccination against SARS-CoV2. Nodular swelling and tenderness of the bilateral temporal arteries were observed. DIAGNOSES: Although right temporal artery biopsies were negative, the patient was diagnosed with GCA based on criteria established by the American College of Rheumatology for the classification of GCA. INTERVENTIONS: The patient received methylprednisolone 1000 mg for 3 days. This was followed by prednisolone 1 mg/kg/d, which was decreased by 10 mg every week to 30 mg. From day 16 of hospitalization, the patient received tocilizumab 162 mg/wk every other week. OUTCOMES: There was no occurrence of acute side effects. After 38 days of treatment, the condition improved and the patient was discharged from the hospital; as stated above, the dose of prednisolone was tapered to 30 mg/d. LESSONS: We experienced a case of GCA that occurred immediately after vaccination against SARS-CoV2 with an mRNA vaccine. Early signs of GCA include fever, fatigue, and headache, and often resemble those noted after vaccination against SARS-CoV2. The potential presence of GCA should be determined in individuals with persistent fever and headache after vaccination against SARS-CoV2.

Mild Hyperglycaemia in Hospitalised Children with Moderate COVID-19 Infection.

Background and Objectives: COVID-19 infection may influence many physiological processes, including glucose metabolism. Acute hyperglycaemia has been related to a worse prognosis in patients with severe COVID-19 infection. The aim of our study was to find out if moderate COVID-19 infection is associated with hyperglycaemia. Materials and Methods: A total of 235 children were enrolled in the study between October 2021 and October 2022, 112 with confirmed COVID-19 infection and 123 with other RNA viral infection. In all patients, types of symptoms, glycaemia at the time of admission, and basic anthropometric and biochemical parameters were recorded. Results: Average glycaemia was significantly higher in COVID-19 patients compared to other viral infections (5.7 ± 1.12 vs. 5.31 ± 1.4 mmol/L, p = 0.011). This difference was more obvious in subgroups with gastrointestinal manifestations (5.6 ± 1.11 vs. 4.81 ± 1.38 mmol/L, p = 0.0006) and with fever (5.76±1.22 vs. 5.11±1.37 mmol/L, p = 0.002), while no significant difference was found in subgroups with mainly respiratory symptoms. The risk of hyperglycaemia (>5.6 mmol/L) was higher in COVID-19 patients compared to other viral infections (OR = 1.86, 95%CI = 1.10-3.14, p = 0.02). The risk of hyperglycaemia was significantly higher in COVID-19 compared to other viral infections in the subgroups of patients with fever (OR = 3.59, 95% CI 1.755-7.345, p = 0.0005) and with gastrointestinal manifestations (OR = 2.48, 95% CI 1.058-5.791, p = 0.036). Conclusion: According to our results, mild hyperglycaemia was significantly more common in children with moderate COVID-19 infection compared to other RNA virus respiratory and gastrointestinal infections, especially when accompanied by fever or gastrointestinal symptoms.

[Cryptogenic new-onset super-refractory status epilepticus following SARS-CoV-2 vaccination. A case report]. / Estado epiléptico superrefractario de nueva aparición criptógeno tras vacunación contra el SARS-CoV-2. A propósito de un caso.

INTRODUCTION: New-onset super-refractory status epilepticus (NOSRSE) is a neurological emergency characterised by the development of status epilepticus in a patient without epilepsy or any known prior neurological disease and with no clear structural, toxic or metabolic cause, which recurs after 24 hours of induced coma. The most common identifiable cause is inflammatory-autoimmune. Consequently, we present a case of NOSRSE related to SARS-CoV-2 vaccination as an opportunity to investigate the dysimmune origin of this pathology. CASE REPORT: We report the case of a 40-year-old male who presented at the emergency department with fever and headache with no clear source of infection. His personal history included bacterial meningitis in childhood without any sequelae and protein S deficiency without treatment at the time, as well as vaccination with ChAdOx1 nCoV-19 21 days earlier. He was initially diagnosed with a urinary tract infection and treated with cefuroxime. Two days later, he was taken back to the emergency department with confusional symptoms and tonic-clonic seizures. He did not respond to midazolam and finally required sedation and orotracheal intubation for refractory status epilepticus. While in hospital, he required a number of lines of antiepileptic drugs, ketamine, a ketogenic diet, immunotherapy and plasmapheresis in order to successfully limit NOSRSE. The aetiological study offered normal results for serology, antineuronal antibodies in serum and cerebrospinal fluid, transthoracic echocardiography, testicular ultrasound and computed tomographic angiography. Only the control MRI scan showed a diffuse and bilateral alteration of the right hemispheric cortex and thalamic pulvinar as the only finding. CONCLUSION: It is crucial to report suspected adverse reactions associated with SARS-CoV-2 vaccination, thereby allowing continued monitoring of the risk/benefit ratio of vaccination.

TITLE: Estado epiléptico superrefractario de nueva aparición criptógeno tras vacunación contra el SARS-CoV-2. A propósito de un caso.Introducción. El estado epiléptico superrefractario de nueva aparición (NOSRSE) es una emergencia neurológica caracterizada por el desarrollo de estado epiléptico en un paciente sin epilepsia ni enfermedad neurológica previa conocida y sin clara causa estructural, tóxica o metabólica, que recurre tras 24 horas del coma inducido. La causa identificable más frecuente es la inflamatoria-autoinmune. En consecuencia, planteamos un caso de NOSRSE relacionado con la vacunación para el SARS-CoV-2 como una oportunidad de indagar el origen disinmune de esta patología. Caso clínico. Varón de 40 años que acude al servicio de urgencias refiriendo fiebre y cefalea sin claro foco infeccioso. Entre sus antecedentes personales destacamos una meningitis bacteriana en la infancia sin secuelas y un déficit de proteína S sin tratamiento en ese momento, así como vacunación con ChAdOx1 nCoV-19 21 días antes. Fue inicialmente diagnosticado de infección del tracto urinario y tratado con cefuroxima. Dos días después, se le llevó de nuevo a urgencias con cuadro confusional y crisis tonicoclónicas, sin respuesta al midazolam, y requirió finalmente sedación e intubación orotraqueal por estado epiléptico refractario. Durante su ingreso requirió múltiples líneas de antiepilépticos, quetamina, dieta cetógena, inmunoterapia y plasmaféresis para conseguir limitar el NOSRSE. El estudio etiológico ofrecía normalidad de los resultados de serología, anticuerpos antineuronales en el suero y líquido cefalorraquídeo, ecocardiografía transtorácica, ecografía testicular y angiotomografía computarizada. Únicamente la resonancia magnética de control mostró una alteración difusa y bilateral de la corteza hemisférica y pulvinar talámica derecha como único hallazgo. Conclusión. Es crucial notificar las sospechas de reacciones adversas asociadas a la vacunación frente al SARS-CoV-2, permitiendo así una supervisión continuada de la relación riesgo/beneficio de ésta.

Anemia as a risk factor for disease progression in patients admitted for COVID-19: data from a large, multicenter cohort study.

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital "P. Giaccone" Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox's regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student's t test for continuous variables and the Mantel-Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox's regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43-48%). Patients with anemia were significantly older (p < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59-4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65-3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.