Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Persistent respiratory failure after SARS-CoV-2 infection: The role of dual energy computed tomography. A case report.

Background: COVID-19 disease is often complicated by respiratory failure, developing through multiple pathophysiological mechanisms, with pulmonary embolism (PE) and microvascular thrombosis as key and frequent components. Newer imaging modalities such as dual-energy computed tomography (DECT) can represent a turning point in the diagnosis and follow-up of suspected PE during COVID-19. Case presentation: A 78-year-old female presented to our internal medicine 3 weeks after initial hospitalization for COVID-19 disease, for recrudescent respiratory failure needing oxygen therapy. A computed tomography (CT) lungs scan showed a typical SARSCoV-2 pneumonia. Over the following 15 days, respiratory function gradually improved. Unexpectedly, after 21 days from symptom onset, the patient started complaining of breath shortening with remarkable desaturation requiring high-flow oxygen ventilation. CT pulmonary angiography and transthoracic echocardiography were negative for signs of PE. Thereby, Dual-energy CT angiography of the lungs (DECT) was performed and detected diffuse peripheral microembolism. After 2 weeks, a second DECT was performed, showing a good response to the anticoagulation regimen, with reduced extent of microembolism and some of the remaining emboli partially recanalized. Discussion: DECT is an emerging diagnostic technique providing both functional and anatomical information. DECT has been reported to produce a much sharper delineation of perfusion defects than pulmonary scintigraphy, using a significantly lower equivalent dose of mSv. We highlight that DECT is particularly useful in SARS-Cov-2 infection, in order to determine the predominant underlying pathophysiology, particularly when respiratory failure prolongs despite improved lung parenchymal radiological findings.

Cerebral lesions in hematological malignancies: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy is a rare central nervous system disease, resulting from reactivation of latent John Cunningham virus. Monoclonal antibodies have recently become a relevant risk factor for developing progressive multifocal leukoencephalopathy. We report the case of a 62-year-old Caucasian man who was admitted to our department in June 2020 because of right homonymous hemianopia. Magnetic resonance imaging findings were first interpreted as an intracranial relapsed lymphoma, so brain biopsy was performed, but no neoplastic cell was found. Histological sample only showed a large number of macrophages. The patient came back to our attention because of the worsening of neurological symptoms. A second magnetic resonance imaging showed widespread lesions suggestive of a demyelinating process. John Cunningham virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid (over 9 million units/µL). The patient was treated supportively, but the outcome was poor. DISCUSSION: A multidisciplinary assessment should be performed for differential diagnosis of cerebral lesions in hematologic malignancies. Progressive multifocal leukoencephalopathy should be suspected in cases of subacute neurological symptoms and imaging findings consistent with it, especially if the patient received immunosuppressive or immunomodulatory drugs.

Cardiopulmonary exercise testing in patients with COVID-19 at 3 months from hospital discharge

Aims The long-term COVID-19 effects are currently unknown. Whether and for how long symptoms extend beyond the acute phase of the disease is unresolved. Aim of this study was to determine the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET) and describe its association with dyspnoea, the most frequent symptom after discharge from a tertiary care hospital. Methods and results All COVID-19 patients discharged from our tertiary care institution were enrolled in a prospective follow-up study which would assess clinical, instrumental and laboratory characteristics of COVID-19 survivors at 3 months from hospital discharge (i.e. long-covid). To limit bias in dyspnoea quantification, patients hospitalized in residential care facilities with severe cognitive impairment/disability, ischaemic cardiopathy, and/or heart failure and severe respiratory disease (i.e. chronic obstructive pulmonary disease) were excluded. Clinical evaluation included: peripheral blood samples including inflammatory cytokines, pulmonary function testing (functional respiratory and 6 min-walking test), lung ultrasound, ECG recording, and a comprehensive echocardiographic exam. All patients with peripheral oxygen desaturation at 6 min-walking test (SpO2 < 92%), dyspnoea and with a history of hospitalization in critical care settings were referred for CPET. Dyspnoea was classified with the Medical Research Council (MRC) scale. From June 2020 to May 2021, 198 patients were enrolled;overall, 42% of patients presented with dyspnoea at 3 months from hospital discharge with no difference according to disease severity on hospital admission (P = 0.233). Clinical, laboratory, and echocardiographic parameters were similar between patients with and without dyspnoea. At CPET, 61% of patients complaining dyspnoea showed a %peak VO2 lower than 85% of the predicted value, associated with a lower exercising tolerance and duration and with a globally reduced equivalent metabolic load (METS: 5.3 ± 1.2 vs. 6.6 ± 1.6, P = 0.003). Mean anaerobic threshold was lower for symptomatic patients (46 + 13 vs. 50 + 10, P = 0.03). At multivariable logistic regression analysis, after adjustment for age, number of comorbidities, and body mass index, only %peak VO2 (HR: 0.973;95% CI: 0.948–0.998) and male gender (HR: 0.548;95% CI: 0.328–0.999) were associated with dyspnoea. Conclusions At 3-months, almost 1-in-2 patients discharged for COVID-19 pneumonia presented with dyspnoea, irrespective of disease severity. Among patients undergoing CPET, only %peak VO2 and gender were associated with symptoms suggesting a potential systemic inflammatory-mediated response and important gender related differences for the long-covid.

Telehealth Management and Risk Stratification of Older Patients With Chronic Heart Failure During COVID-19 Pandemic: Prognostic Evaluation of the TeleHFCovid19-Score.

OBJECTIVES: To evaluate 6-month risk stratification capacity of the newly developed TeleHFCovid19-Score for remote management of older patients with heart failure (HF) during the coronavirus disease 2019 pandemic. DESIGN: Monocentric observational prospective study. SETTING AND PARTICIPANTS: Older HF outpatients remotely managed during the first pandemic wave. METHODS: The TeleHFCovid19-Score (0-29) was obtained by an ad hoc developed multiparametric standardized questionnaire administered during telephone visits to older HF patients (and/or caregivers) followed at our HF clinic. Questions were weighed on the basis of clinical judgment and review of current HF literature. According to the score, patients were divided in progressively increasing risk groups: green (0-3), yellow (4-8), and red (≥9). RESULTS: A total of 146 patients composed our study population: at baseline, 112, 21, and 13 were classified as green, yellow, and red, respectively. Mean age was 81±9 years, and women were 40%. Compared to patients of red and yellow groups, those in the green group had a lower use of high-dose loop diuretics (P < .001) or thiazide-like diuretics (P = .027) and had reported less frequently dyspnea at rest or for basic activities, new or worsening extremity edema, or weight increase (all P < .001). At 6 months, compared with red (62.2%) and yellow patients (33.3%), green patients (8.9%) presented a significantly lower rate of the composite outcome of cardiovascular death and/or HF hospitalization (P < .001). Moreover, receiver operating characteristic curve analysis showed a high sensibility and specificity of our score at 6 months (area under the curve = 0.789, 95% CI 0.682-0.896, P < .001) with a score <4.5 (very close to green group cutoff) that identified lower-risk subjects. CONCLUSIONS AND IMPLICATIONS: The TeleHFCovid19-Score was able to correctly identify patients with midterm favorable outcome. Therefore, our questionnaire might be used to identify low-risk chronic HF patients who could be temporarily managed remotely, allowing to devote more efforts to the care of higher-risk patients who need closer and on-site clinical evaluations.

Factors associated with persistence of symptoms 1 year after COVID-19: A longitudinal, prospective phone-based interview follow-up cohort study.

OBJECTIVE: To investigate the persistence of symptoms compatible with COVID-19 in a real-file prospective cohort of patients at 12 months from hospital discharge. METHODS: Longitudinal, prospective, single-center, cohort telephone follow-up (FU) study in a Tertiary Care Hospital. All consecutive patients >18 years admitted for COVID-19 were prospectively enrolled in a telephone FU program aimed at monitoring symptoms after 1,3,6,9 and 12 months from hospital discharge. The survey screened for somatic (fatigue, dyspnea, dyspnea, palpitations, cough, chest pain, abdominal pain, ageusia, anosmia, bowel symptoms) and emotional symptoms (insomnia, confusion, altered sense of reality, loss of appetite, fear, and depression) and frailty. Only patients with 12 months FU data were analyzed (N=254). Prevalence and factors associated with symptoms were the main outcomes. Frailty was defined by the presence of ≥3 indicators: weakness, slowness/impaired mobility, weight-loss, low physical activity, and exhaustion. RESULTS: At 12 months, 40.5% of patients reported at least one symptom. The most common somatic ones were fatigue, exertional dyspnea, cough, bowel complaints while the most common psycho-emotional were insomnia, confusion, fear, and depression. Age, gender, gender, frailty, multiple symptoms at baseline and chronic obstructive pulmonary disease (COPD) were associated with symptoms persistence. Furthermore, frailty, COPD and multiple symptoms at baseline were associated with increased risk of somatic symptoms at 12 months, while age and gender were associated with emotional ones. CONCLUSIONS: Burden of the long COVID-19 symptoms decreased over time but remained as high as 40% at 12 months with important gender and functional differences, highlighting potential patient categories who may benefit from specific follow up strategies.

Diffuse prothrombotic syndrome after ChAdOx1 nCoV-19 vaccine administration: a case report.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia is emerging as one of the most relevant side effects of adenoviral-based vaccines against coronavirus disease 2019. Given the novelty of this disease, the medical community is seeking new evidence and clinical experiences on the management of these patients. CASE PRESENTATION: In this article, we describe the case of a 73-year-old Caucasian woman who presented with diffuse prothrombotic syndrome, both in the arterial and venous districts, following the first dose administration of ChAdOx1 CoV-19 vaccine. The main thrombotic sites included the brain, with both a cortical ischemic lesion and thromboses of the left transverse and sigmoid sinuses and the lower limbs, with deep venous thrombosis accompanied by subsegmental pulmonary thromboembolism. The deep venous thrombosis progressively evolved into acute limb ischemia, requiring surgical intervention with thromboendoarterectomy. Anticoagulation was maintained throughout the whole hospitalization period and continued in the outpatient setting using vitamin K antagonists for a recommended period of 6 months. CONCLUSIONS: This case describes the management of vaccine-induced immune thrombotic thrombocytopenia in a complicated clinical scenario, including multisite arterial and venous thromboses. Given the complexity of the patient presentation, this case may implement the comprehension of the mechanisms and clinical features of this disease; it also provides a picture of the challenges related to the management, often requiring a multidisciplinary approach.

Predicting Mortality Risk in Older Hospitalized Persons With COVID-19: A Comparison of the COVID-19 Mortality Risk Score with Frailty and Disability.

OBJECTIVES: To assess the association of pre-morbid functional status [Barthel Index (BI)] and frailty [modified Frailty Index (mFI)] with in-hospital mortality and a risk scoring system developed for COVID-19 in patients ≥75 years diagnosed with COVID-19. DESIGN: Retrospective bicentric observational study. SETTING AND PARTICIPANTS: Data on consecutive patients aged ≥75 years admitted with COVID-19 at 2 Italian tertiary care centers were collected from February 22 to May 30, 2020. METHODS: Overall, 221 consecutive patients with COVID-19 aged ≥75 years were admitted to 2 hospitals in the study period and were included in the analysis. Clinical, functional (BI), frailty (mFI), laboratory, and imaging data were collected. Mortality risk on admission was assessed with the COVID-19 Mortality Risk Score (COVID-19 MRS), a dedicated score developed for hospital triage. RESULTS: Ninety-seven (43.9%) patients died. BI, frailty, age, dementia, respiratory rate, Pao2/Fio2 ratio, creatinine, and platelet count were associated with mortality. Analysis of the area under the receiver operating characteristic (AUC) indicated that the predictivity of age was modest and the combination of BI, mFI, and COVID-19 MRS yielded the highest prediction accuracy (AUCCOVID-19MRS+BI+mFI vs AUCAge: 0.87 vs 0.59; difference: +0.28, lower bound-upper bound: 0.17-0.34, P < .001). CONCLUSIONS AND IMPLICATIONS: Premorbid BI and mFI are associated with mortality and improved the accuracy of the COVID-19 MRS. Functional status may prove useful to guide clinical management of older individuals.

Clinical and Laboratory Follow-up After Hospitalization for COVID-19 at an Italian Tertiary Care Center.

We evaluated 100 postacute coronavirus disease 2019 (COVID-19) patients a median (interquartile range) of 60 (48-67) days after discharge from the Careggi University Hospital, Italy. Eighty-four (84%) had at least 1 persistent symptom, irrespective of COVID-19 severity. A considerable number of hospital readmissions (10%) and/or infectious diseases (14%) during the postdischarge period were reported.

COVID-19 in patients recovering from cardiac surgery: A surprising mild disease course.

BACKGROUND: We describe the baseline, operative, and postoperative features of a group of 18 patients who contracted the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection in a rehabilitation facility after cardiac surgery, and present some potential explanations for the surprisingly benign course of the COVID-19 in this cohort. METHODS: All patients were operated on an urgent or emergency basis (acute aortic syndrome, 3; refractory heart failure, 12; and endocarditis, 3) during the first lockdown period of the COVID-19 pandemic. The mean age was 70 years, and 12 patients were male. After the diagnosis of COVID-19, patients were treated according to the most recent recommendations. Eleven asymptomatic patients were discharged home or to a COVID-19 hotel and underwent close monitoring. Patients with fever, dyspnea, or a significant rise of the polymerase chain reaction levels were hospitalized, three received antivirals, three azithromicyne, and five hydroxychloroquine. Nasal swabs were repeated on a weekly basis, and all patients were quarantined until the collection of two consecutive negative samples. RESULTS: Diversely from other observations on perioperative COVID-19 reporting mortality rates of 30%-40%, the COVID-19 had a benign course in our cohort: only seven patients required hospitalization, and one required short intensive care unit admission. There were no deaths, and at the latest follow-up, all patients had been discharged home. COMMENT: Our data show that the SARS-CoV2 infection after cardiac surgery may have a benign course. Further studies are needed to investigate the relationship between the timing of the infection, some potentially protective therapies (e.g., anticoagulants), and the course of the COVID-19.

Protocol for Telehealth Evaluation and Follow-up of Patients With Chronic Heart Failure During the COVID-19 Pandemic.

Because of the Coronavirus Disease 2019 (COVID-19) pandemic, we were forced to cancel scheduled visits for nearly 150 patients followed in our heart failure (HF) outpatient clinic. Therefore, we structured a telephone follow-up, developing a standardized 23-item questionnaire from which we obtained the Covid-19-HF score. The questionnaire was built to reproduce our usual clinical evaluation investigating a patient's social and functional condition, mood, adherence to pharmacological and nonpharmacological recommendations, clinical and hemodynamic status, pharmacological treatment, and need to contact emergency services. The score was used as a clinical tool to define patients' clinical stability and timing of the following telephone contact on the basis of the assignment to progressively increasing risk score groups: green (0-3), yellow (4-8), and red (≥9). Here we present our experience applying the score in the first 30 patients who completed the 4-week follow-up, describing baseline clinical characteristics and events that occurred in the period of observation.

Clinical risk score to predict in-hospital mortality in COVID-19 patients: a retrospective cohort study.

OBJECTIVES: Several physiological abnormalities that develop during COVID-19 are associated with increased mortality. In the present study, we aimed to develop a clinical risk score to predict the in-hospital mortality in COVID-19 patients, based on a set of variables available soon after the hospitalisation triage. SETTING: Retrospective cohort study of 516 patients consecutively admitted for COVID-19 to two Italian tertiary hospitals located in Northern and Central Italy were collected from 22 February 2020 (date of first admission) to 10 April 2020. PARTICIPANTS: Consecutive patients≥18 years admitted for COVID-19. MAIN OUTCOME MEASURES: Simple clinical and laboratory findings readily available after triage were compared by patients' survival status ('dead' vs 'alive'), with the objective of identifying baseline variables associated with mortality. These were used to build a COVID-19 in-hospital mortality risk score (COVID-19MRS). RESULTS: Mean age was 67±13 years (mean±SD), and 66.9% were male. Using Cox regression analysis, tertiles of increasing age (≥75, upper vs <62 years, lower: HR 7.92; p<0.001) and number of chronic diseases (≥4 vs 0-1: HR 2.09; p=0.007), respiratory rate (HR 1.04 per unit increase; p=0.001), PaO2/FiO2 (HR 0.995 per unit increase; p<0.001), serum creatinine (HR 1.34 per unit increase; p<0.001) and platelet count (HR 0.995 per unit increase; p=0.001) were predictors of mortality. All six predictors were used to build the COVID-19MRS (Area Under the Curve 0.90, 95% CI 0.87 to 0.93), which proved to be highly accurate in stratifying patients at low, intermediate and high risk of in-hospital death (p<0.001). CONCLUSIONS: The COVID-19MRS is a rapid, operator-independent and inexpensive clinical tool that objectively predicts mortality in patients with COVID-19. The score could be helpful from triage to guide earlier assignment of COVID-19 patients to the most appropriate level of care.