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Background. The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods. This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: 'fit/resilient', 'fit/non-resilient', 'frail/resilient' and 'frail/non-resilient'. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results. 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Table 1 shows demographic, anthropometric and clinical characteristics, comorbidities and patient-reported outcomes according to four frailty-resilience phenotypes. With regards to study outcomes, Figure 1 depicts in radar graphs, mean scores of each domain of SF-36 (1A), EQ-5D5L (1B) and IC (1C). Figures shows polygon areas for each frailty/resilience phenotypes. Progressive increase of mean scores of each domain are plotted in the vertices of polygons, from the lowest (near the center) in frail and non-resilient, to highest (towards periphery) in fit and resilient. Multivariate logistic analyses were used to identify predictors of the total scores of SF-36 (Figure 2A), EQ-5D5L (Figure 2B) and IC (Figure 2C). Conclusion. Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS. Funding. This study is supported by a Gilead Sciences Inc. unrestricted grant.
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Background and Aims : Recently a proposal has been advanced to change the traditional definition of Non-Alcoholic Fatty Liver Disease to Metabolic Associated Fatty Liver Disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long COVID is a smoldering inflammatory condition, characterized by a number of symptom clusters. This study aims to determine the prevalence of MAFLD in patients with post-acute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Method(s): We included 235 patients followed at a single university outpatient clinic. The diagnosis of PACS was based on >=1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first post-discharge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Result(s): Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P<0.001). Insulin resistance (OR=1.5, 95%CI: 1.14-1.96), body mass index (OR=1.14, 95%CI: 1.04-1.24), and the metabolic syndrome (OR=2.54, 95%CI: 1.13-5.68), were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR=0.86, 95%CI: 0.76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusion(s): MAFLD was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications. Copyright © 2022
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Background: The vaccination campaign against COVID-19 has a substantial beneficial public health impact, but vaccine hesitancy or issues to the access to vaccine could undermine the efforts made. We aim to determine the proportion of people living with HIV (PLWH) not vaccinated for COVID-19 in a cohort of PLWH in Italy and identify predictors of missing vaccination. Methods: Cross sectional study conducted in the Icona network. All PLWH of the centers participating the study with at least 1 follow-up in 2020-2021 were included. Their vaccination status for COVID-19 has been evaluated till 08Oct2021, before entering in the 3rd booster dose campaign for fragile populations in Italy. Data on vaccination status have been collected by medical records and/or administrative databases. Descriptive statistics, crude and adjusted logistic regression models for identifying predictors of not being vaccinated (0 doses received) were used. Results: Vaccination status has been assessed for 3,242 subjects from 17 centers of the cohort. 319/3,242 resulted still not vaccinated (9.8%) and 2,923 received at least one dose (90.2%). The full cycle has been completed by 2,732 subjects (85.5%). 89.1% of PLWH received a mRNA vaccine, 6.6% a viral vector and 4.3% unknown. Characteristics of patients according to being vaccinated or not are shown in Table 1A. In the adjusted logistic regressions, PLWH who did not receive the vaccine were more frequently younger (per 10 years younger AOR=1.22, 95%CI 1.07-1.38), and current/ex injecting drug users (IDU) (AOR=1.61, 95%CI 1.01-2.57), while having a current HIV-RNA < 50 copies mL (AOR=0.62, 95%CI 0.44-0.89), no previous diagnosis of COVID-19 (AOR=0.52, 95%CI 0.30-0.92) and being MSM (AOR=0.63, 95%CI 0.46-0.86) had lower risk to miss vaccination. Conclusion: The acceptance and uptake of vaccine among PLWH has been high, with a proportion of patients who completed the full vaccination cycle higher than targeted general population in Italy (85.5% vs 78.3% at W40-2021). Access to vaccination has been favourable for PLWH but some challenges remain for IDU/ex-IDU PLWH. The vaccination hesitancy lasts in younger population. MSMs seem to have a stronger attitude to protection, whereas patients with unsuppressed HIV-RNA could have a lower compliance reflected also in a lower COVID-19 vaccine uptake. Some selection bias on the population in analysis cannot be ruled out. These findings could help to develop interventions for increasing vaccination uptake for PLWH in future.
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Background: Treatment guidelines recommend the use of tocilizumab in patients with a current CRP >7.5 mg/dl. Recent data showed that survival benefit might be greater in those with higher CRP levels. We aimed to estimate the causal effect of intensification with tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio, CRP levels. Methods: Observational cohort study of patients with severe COVID-19 pneumonia. Primary endpoint was day-28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of tocilizumab intensification vs. glucocorticoids alone using Kaplan-Meier curves and Cox regression models with a time-varying variable for the intervention. Analysis was controlled for age, ethnicity, duration of symptoms, at hospital admission (baseline, BL) PaO2/FiO2 ratio, CRP (BL and current), Charlson comorbidity index and post-BL use of remdesivir and invasive mechanical ventilation. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. Results: 992 patients median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy and 395 (31.8%), adding tocilizumab upon respiratory deterioration were included. At BL, median CRP was 6.0 mg/dl (IQR 3.0-15.0) and median PaO2/FiO2 ratio was 261 mmHg (200-303). The two groups differed for median values of: CRP (6 vs 7 mg/dL;p<.001)), IL-6, (27.6 vs 175.0 mg/L;p<.001) LDH (525 vs 622 U/L;p<.001), lymphocytes (939 vs 835/mm3;p<.001) and PaO2/FiO2 ratio (276 vs 235 mmHg;p<.001) at BL. In the unadjusted analysis there was no statistically significant difference in mortality between the two groups, but there was strong evidence for an effect of the intensification after controlling for key BL and post-BL confounders, consistent with the estimate in trials (adjusted hazard ratio (aHR)=0.59, 95% CI:0.38-0.90). Although the study was not powered to detect interactions (p>0.57) there was a signal for intensification to have a larger effect in subsets, especially participants with high levels of CRP at intensification (Figure). Conclusion: Our data suggest that intensification with tocilizumab confers reduced survival benefit in those intensifying with a CRP of 0-7.5 mg/dl. It also provides substantial benefit even in patients who are intensified with a CRP>15 mg/dl. Large randomised studies are needed to establish an exact cut-off for clinical use.
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Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.
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Introduction: Some hemodialysis patients are reluctant to undergo COVID-19 vaccination for the fear of developing adverse events (AEs). The aim of this study was to verify the safety of the mRNA-1273 vaccine in hemodialysis patients. Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent mRNA-1273 vaccine from March 1st to April 30th, 2021. All AEs occurring after the first and the second doses were collected and classified as local or systemic. Results: Overall, 126 patients on chronic maintenance dialysis without a prior COVID-19 diagnosis were vaccinated with two doses of mRNA-1273 vaccine. Mean age was 68 (IQR, 54,7-76) years and 53.6% of patients were aged ≥65 years. During the observational period of 68 (IQR, 66-70) days, AEs occurred in 57.9% and 61.9% of patients after the first dose and second dose, respectively. The most common AEs were: injection-site pain (61.9%), erythema (4.8%), itching (4.8%), swelling (16.7%), axillary swelling/tenderness (2.4%), fever (17.5%) headache (7.9%), fatigue (23.8%), myalgia (17.5%), arthralgia (12.7%), dyspnoea (2.4%), nausea/vomiting (7.1%), diarrhoea (5.6%), shivers (4%) and vertigo (1.6%). The rates of local AEs were similar after the first and second doses (P=0.8), whereas systemic AEs occurred more frequently after the second dose (P=0.001). Fever (P=0.03), fatigue (P=0.02) and nausea/vomiting (P=0.03) were significantly more frequent after the second dose of the vaccine. There were no age-related differences in the rate of AEs. Overall, vaccine-related AEs in hemodialysis patients seem to be lower than in the general population. Conclusion: The RNA-1273 vaccine was associated with the development of transient AEs after the first and second doses in patients on chronic maintenance hemodialysis. They were mostly local, whereas systemic AEs were more prevalent after the second dose. Overall, all AEs lasted for a few days, without any apparent sequelae. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.
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AIM: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. MATERIALS AND METHODS: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO2/FiO2 ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. MEASUREMENTS AND MAIN RESULTS: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. DISCUSSION: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.
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We described a case of clinical reactivation of chronic P. malariae infection following CoVID-19 vaccination with BNT162b2 (Pifzer-Biontech CoVID-19 vaccine) in a 48-year old Italian man.The patient came to our attention for fever of unknown origin show a quartan pattern (every third day) associated to splenomegaly, the onset of the fever occurred one month after CoVID-19 vaccination with BNT162b2. P. malariae was diagnosed using Carestart™ malaria rapid test and Polymerase-Chain Reaction. Post-vaccine transient reduction of immune reactivity is described in literature, although the mechanism is unknown.
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Background: Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes due to the high burden of comorbidities and immunosuppression. The effects of immunosuppressive therapy (IST) reduction are unclear in patients with COVID-19.
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BACKGROUND AND AIMS: Acid-base disorders are common in severely ill patients and reflect the severity of the underlying pathologic process. The incidence and effects of acid-base derangement in COVID-19 patients have been poorly evaluated until now. Tropism of the virus for the lungs and kidneys may theoretically lead to frequent acidbase alterations due to pneumonia and kidney injury, respectively. To verify the derangement of acid-base disorders in COVID-19, we investigated the distribution and the impact of acid-base disorders on the survival of symptomatic patients with a diagnosis of COVID-19. METHOD: We retrospectively collected data from electronic charts of all COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Arterial blood gas (ABG) analysis was required to monitor pulmonary gas exchange and acid-base status. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.42 was categorized as alkalemia. 211 patients were included in the study population. In patients with multiple ABG analyses, we selected only the first measurement. RESULTS: The estimated mean age of the population was 64.7 ±15,3 years with a high predominance of males (71.6%). Half of the population referred dyspnea and 61.4% at physical examination. Most patients (82.6%) were on oxygen therapy when ABG analysis was performed. Overall, ABG analyses revealed acute respiratory compromise manifesting with a low arterial partial pressure of oxygen (P02, 70.2±25.1 mmHg), oxygen saturation (SO2, 92%) and a mild reduction of PO2/FiO2 ratio (231±129). Acid-base disturbance was found in the 79.7% of the patients, and contrary to our expectation, metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%) respiratory acidosis (3.3%) metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%). ANOVA with post hoc Tukey, revealed statistically significant differences in age, sex, serum level of K, Na, bicarbonate, creatinine of PCO2, PO2/FiO2 ratio, CKD, symptoms (caught, diarrhea) and fatality rate among groups. Metabolic acidosis was associated with death (HR=8.2;CI 95%, 1,93-32,39;P<0.004), after adjustment for lung injury (PaO2/FiO2 ratio) tissue hypoperfusion (lactate) and renal involvement (estimated as GFR< 60 ml/min or development of acute kidney injury), Pathological pH (alkalosis or acidosis), variations of PCO2 or hypobicarbonatemia were not associated with mortality in our study population. Metabolic acidosis occurred in patients with a mean creatinine of 4.5±4.5 mg/dl. Notably, 33.3% of patients were on hemodialysis, 33.3% developed COVID-19- associated acute kidney injury and 33.3% had a GFR <60 ml/min. Patients with metabolic acidosis had the highest death-fatality rate (100%) after 7±5.6 days from admission, 50% died of acute respiratory distress syndrome and 50% of septic shock. CONCLUSION: In conclusion, all kinds of acid-base alterations were found in patients with COVID-19. Metabolic and respiratory alkalosis were the most common acid-base disorders, whereas metabolic acidosis was the only acid-base disturbance associate with poor outcome in our cohort of patients. (Table Presented).
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Background: A large global effort is ongoing to develop vaccines against SARS-CoV-2, the causative agent of COVID-19. While there is accumulating information on the antibody response against SARS-CoV-2, less is known about the SARS-CoV-2 antigens that are targeted by CD8 T cells. Such knowledge will be of high value to gain fundamental insights into the antigenic landscape of SARS-CoV-2 recognized by CD8 T cells, to develop tool allowing focused analysis of the SARS-CoV-2 specific T cell responses directly ex vivo, and to understand whether current vaccine designs are covering the CD8 T cell recognized antigens. Methods: To address this issue, we have analyzed samples from 18 COVID-19 patients for CD8 T cell recognition of 500 predicted SARS-CoV-2-derived epitopes restricted to 10 common HLA-A and HLA-B alleles. For each HLA allele, the top 50 epitopes were selected based on predicted binding affinity and likelihood of successful proteasomal processing. To probe for CD8 T cell recognition of the selected epitope-HLA complexes, we made use of our in-house technology based on multiplexing of peptide HLA (pHLA) multimers conjugated to fluorescent dyes. Results: In addition to previous studies showing CD8 T cell reactivity towards epitopes derived from the spike protein of SARS-CoV-2, we have identified several CD8 T cell recognized epitopes derived from the ORF1ab, including one epitope displaying clear immunodominant properties across patients positive for HLA-A*01:01. Investigation of the functional status of part of the identified responses (including 4 responses specific for the immunodominant epitope) revealed that the T cell responses were highly dysfunctional. In addition the SARS-CoV-2 specific CD8 T cell responses displayed an increased expression of NKG2A in comparison with bulk CD8 T cells, which may explain their dysfunctional state. Conclusions: Our data suggest that part of the ORF1ab encodes multiple CD8 T cell antigens including one immunodominant epitope. Noteworthy these epitopes were derived from a part of the viral genome that is not included in the majority of vaccine candidates in development, and this may potentially influence their clinical activity and safety profile. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation.
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The Covid-19 crisis caught health care services around the world by surprise, putting unprecedented pressure on Intensive Care Units (ICU). To help clinical staff to manage the limited ICU capacity, we have developed a Machine Learning model to estimate the probability that a patient admitted to hospital with COVID-19 symptoms would develop severe respiratory failure and require Intensive Care within 48 hours of admission. The model was trained on an initial cohort of 198 patients admitted to the Infectious Disease ward of Modena University Hospital, in Italy, at the peak of the epidemic, and subsequently refined as more patients were admitted. Using the Light- GBM Decision Tree ensemble approach, we were able to achieve good accuracy (AUC = 0.84) despite a high rate of missing values. Furthermore, we have been able to provide clinicians with explanations in the form of personalised ranked lists of features for each prediction, using only 20 out of more than 90 variables, using Shapley values to describe the importance of each feature. Copyright © 2020 for this paper by its authors.