Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
Viruses ; 14(6)2022 May 31.
Article in English | MEDLINE | ID: covidwho-1869828

ABSTRACT

Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated with remdesivir to assess the impact of major confounders on crude 15-day and 29-day mortality. Mortality was calculated using the Kaplan-Meier estimator and the Cox proportional-hazards model was applied to analyze the risks by patient's baseline features. In total, 16,462 patients treated with remdesivir from 29 October 2020 to 17 December 2020 were entered in the study. Crude 15-day and 29-day mortality were 7.1% (95% CI, 6.7-7.5%) and 11.7% (95% CI, 11.2-12.2%), respectively. Being treated within two days of admission reduced the risk of death by about 40% (HR 1.4, 95% CI, 1.2-1.6). Results from the largest cohort of remdesivir-treated patients suggests that mortality in SARS-CoV-2 hospitalized patients is substantially influenced by the days between SARS-CoV-2 diagnosis and drug prescription. Current recommendations and future clinical trials for remdesivir alone or in combination should carefully consider the target population and timing for best efficacy of treatment.

2.
Vaccine ; 40(31): 4090-4097, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1867869

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. METHODS: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. RESULTS: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. CONCLUSIONS: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands).


Subject(s)
COVID-19 , Clinical Trials as Topic , Patient Participation , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Europe/epidemiology , Humans , Registries , Volunteers
3.
Microorganisms ; 10(5)2022 May 12.
Article in English | MEDLINE | ID: covidwho-1855707

ABSTRACT

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients' characteristics.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336832

ABSTRACT

Background Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting SARS-CoV-2 varies according to the Variant of Concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with early COVID-19. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was COVID-19 progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results Overall, 319 patients were included. Among 141 patients infected with Delta, no disease progression was recorded and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.895). Among 170 patients infected with Omicron (80.6% BA.1, 19.4% BA.1.1), two disease progressions were recorded in the bamlanivimab/etesevimab group and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared to bamlanivimab/etesevimab and casirivimab/imdevimab (HR 0.526 and HR 0.451, 95% CI 0.359 - 0.77 and 95% CI 0.303 - 0.669, p 0.001 and 0.0001, respectively). Conclusions These results confirm the in-vitro data of superiority of sotrovimab versus casirivimab/imdevimab and bamlanivimab/etesivamab in reducing the time to recovery in patients infected with Omicron BA.1 and BA.1.1, while no difference was detected in Delta infections. Casirivimab/imdevimab seems to maintain a role in preventing severe COVID-19 in the Omicron population. Adaptive clinical trials comparing mAbs by VOC should be pursued to promptly inform clinical recommendations. Funding This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101016167. Clinical trial number NCT05205759

5.
Nutr Metab Cardiovasc Dis ; 31(9): 2612-2618, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1829287

ABSTRACT

BACKGROUND AND AIMS: Diabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19. METHODS AND RESULTS: Diabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19-1.45], 2.11 [1.83-2.44], 2.45 [1.96-3.07], 1.87 [1.68-2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20-39 years: 1.90 [1.04-3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40-59 years: 3.47 [2.00-5.70] and 5.54 [2.23-12.1], respectively. CONCLUSIONS: These data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.


Subject(s)
COVID-19/etiology , Diabetes Complications/etiology , SARS-CoV-2 , Adult , Age Factors , Aged , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Young Adult
6.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-333367

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the key role that vaccines play against infectious diseases. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE’s Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. Methods: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. Results: As of January 2022, the questionnaire is available in 9 countries and 11 languages. Up to date, more than 35,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched 13,719 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. Conclusion: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 9 countries. To date, more than 13,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 6 additional countries.

7.
Epidemiol Infect ; 150: e48, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1758088

ABSTRACT

SARS-CoV-2 serological tests are used to assess the infection seroprevalence within a population. This study aims at assessing potential biases in estimating infection prevalence amongst healthcare workers (HCWs) when different diagnostic criteria are considered. A multi-site cross-sectional study was carried out in April-September 2020 amongst 1.367 Italian HCWs. SARS-CoV-2 prevalence was assessed using three diagnostic criteria: RT-PCR on nasopharyngeal swab, point-of-care fingerprick serological test (POCT) result and COVID-19 clinical pathognomonic presentation. A logistic regression model was used to estimate the probability of POCT-positive result in relation to the time since infection (RT-PCR positivity). Among 1.367 HCWs, 69.2% were working in COVID-19 units. Statistically significant differences in age, role and gender were observed between COVID-19/non-COVID-19 units. Prevalence of SARS-CoV-2 infection varied according to the criterion considered: 6.7% for POCT, 8.1% for RT-PCR, 10.0% for either POCT or RT-PCR, 9.6% for infection pathognomonic clinical presentation and 17.6% when at least one of the previous criteria was present. The probability of POCT-positive result decreased by 1.1% every 10 days from the infection. This study highlights potential biases in estimating SARS-CoV-2 point-prevalence data according to the criteria used. Although informative on infection susceptibility and herd immunity level, POCT serological tests are not the best predictors of previous COVID-19 infections for public health monitoring programmes.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , COVID-19/epidemiology , Health Personnel , Point-of-Care Testing , SARS-CoV-2 , Adult , Bias , Cross-Sectional Studies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Occupational Exposure , Prevalence , Probability , Seroepidemiologic Studies
8.
Clin Microbiol Infect ; 2022 Mar 12.
Article in English | MEDLINE | ID: covidwho-1734284

ABSTRACT

BACKGROUND: A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies. OBJECTIVES: We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population. DATA SOURCES: PubMed-MEDLINE and Scopus were independently searched until 13 October 2021. STUDY ELIGIBILITY CRITERIA: Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality. PARTICIPANTS: Participants were patients with confirmed COVID-19. INTERVENTIONS: Interventions reviewed were SOTs. METHODS: The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. RESULTS: A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94-1.35; I2 = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03-2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81-3.45) was found in SOT recipients. CONCLUSIONS: No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.

9.
Clin Microbiol Infect ; 28(5): 672-680, 2022 May.
Article in English | MEDLINE | ID: covidwho-1729650

ABSTRACT

SCOPE: This guideline addresses the indications for direct testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic individuals in health care facilities, with the aim to prevent SARS-CoV-2 transmissions in these settings. The benefit of testing asymptomatic individuals to create a safe environment for patients and health care workers must be weighed against potential unintended consequences, including delaying necessary treatments owing to false positive results and lower quality of care owing to strict isolation measures. METHODS: A total of nine PICOs (population, intervention, comparison, outcome) on the topic of testing asymptomatic individuals was selected by the panel members. Subsequently, a literature search for existing guidelines and systematic reviews was performed on PubMed, Epistemonikos, and RecMap using relevant filters available in each database. Data on article/recommendation type, setting, target population, intervention, and quality of the evidence were extracted. Credibility of the systematic reviews was evaluated using the AMSTAR tool, and level of agreement with available recommendation was evaluated with the AGREE II score. Because the evidence available from systematic reviews was deemed insufficiently updated to formulate relevant recommendations, an additional search targeting relevant guidance documents from major public health institutions and original studies was performed. Provisional recommendations were discussed via web conferences until agreement was reached, and final recommendations were formulated according to the GRADE approach. RECOMMENDATIONS: Recommendations were formulated regarding systematic testing in asymptomatic individuals upon admission to a health care setting, during hospital stay, before elective procedures, and before scheduled nonsurgical procedures. Moreover, recommendations regarding testing of asymptomatic visitors, personal caregivers, and health care workers in health care facilities were presented. Recommendations also were given on contact tracing in asymptomatic patients or health care workers and the possibility of a negative screening test to shorten the quarantine period. Furthermore, if applicable, recommendations were specified to transmission rate and vaccination coverage.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/prevention & control , Delivery of Health Care , Health Personnel , Humans , Quarantine
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311015

ABSTRACT

Background: A major limitation of predictive prognostic models in COVID-19 patients is the heterogeneity of disease stage and population. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression within 11 days in hospitalized COVID-19 patients.Methods: Single-centre, prospective cohort study on hospitalized adult COVID-19 patients. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day-5, -10, and -15 from symptoms onset and in case of intensive care unit (ICU) admission, discharge, or death. COVID-19 progression was defined as in-hospital death and/or ICU and/or respiratory failure (PaO2/FiO2 ratio<200) within 11 days after symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values.Results: Among 235 patients with COVID-19 prospectively admitted in a 3-month period, 88 (37%) experienced COVID-19 progression. A model including male sex, age >65 years, cardiovascular disease, and at least three abnormal laboratory parameters among CRP > 80 U/L, AST > 45 U/L, ALT > 40 U/L, NLR > 4·5, LDH > 250 U/L, and CK > 80 U/L showed an AUC of 0·73 (95%CI: 0·66 - 0·81) for predicting disease progression. Conclusion: An easy-to-use panel of laboratory/clinical parameters computed at day-5 from symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 from symptoms onset could facilitate clinicians’ decision making and be used to increase patient population in clinical trials in hospitalized patients.Trial Registration: COVID 19-VR registry (ClinicalTrials.gov NCT04497194).Funding Statement: This study is part of React-COVID-19 project funded by Fondazione CARIVERONA.Declaration of Interests: The authors have no conflict of interests to be declared.Ethics Approval Statement: The study was approved by the hospital Institutional Review Board (IRB 2577CESC).

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311014

ABSTRACT

Background: A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. Methods: : Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or ICU and/or respiratory failure (PaO 2 /FiO 2 ratio<200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. Results: : A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age >65 years, dyspnea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) showed an AUC of 0.73 (95%CI: 0.66 - 0.81) for predicting disease progression by day-11. Conclusion: An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate assessment of clinicians’ decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305489

ABSTRACT

Objective: to compare COVID-19 patients’ vessel caliber with that of normal lungs and lungs interested by other inflammatory and thromboembolic processes. Methods: between March and April 2020, 42 patients affected by COVID-19 pneumonia [COV-P] underwent a CT scan of the lung at Verona University Hospital for clinical indications. Lung images were compared to 4 different groups of patients (normal lung [NL], distal thromboembolism [DTE], bacterial and fungal pneumonia [Bact-P, Fung-P]) by a 4-year-experienced radiologist. Results: COV-P patients’ segmental and subsegmental vessels, as evaluated as the ratio with the corresponding bronchial branch (V/B ratio) were larger with respect to NL, DTE in the apparently healthy parenchyma, a result confirmed in the zones of opacification with respect to Bact-P and Fung-P. Conclusions: This is the first study to comparatively showing that segmental and subsegmental COVID-19 patients’ vessel caliber is significantly enlarged. This is a distinctive feature of COVID-19 pneumonia suggesting distinct pathophysiology as compared to other inflammatory and thromboembolic diseases and alerting radiologists to consider it when evaluating CT scan of suspected patients.

13.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-326281

ABSTRACT

Background: The omicron variant has spread globally at unprecedented speed due to a combination of epidemiological and virological factors that still need to be fully unraveled. Although boosting of immunity in vaccinated populations has proven to increase the antibody recognition for this variant, we still ignore the impact that this intervention has on protection from infection and disease. Methods: Relying on a live virus neutralization assay and a commercial chemiluminescence immunoassay targeting antibodies against the receptor binding domain (RBD) of the parental Spike protein, we tested the efficacy of homologous and heterologous booster vaccinations in inducing antibodies against SARS-CoV-2 parental, delta, beta and omicron variants by history of SARS-CoV-2 infection and age of population. Booster vaccination was performed with the BNT126b2 vaccine, while individuals who underwent heterologous booster vaccination were primed with the ChAdOx1 nCov-19 vaccine. Moreover, we studied the impact that prior immunity has on vaccination, in mildly infected individuals who received 2-3 doses of the BNT1262b vaccine at different times after infection. Children previously infected with delta were evaluated 3·5 months after infection. To translate neutralization data into estimates of protection, we relied on published predictive models and inferred variant-specific thresholds of protection for both assays and assessed the accuracy of the commercial assay at identifying highly protected individuals. Findings: We confirm that boosting significantly restores the ability of antibodies to recognize omicron and other variants, and that the homologous protocol with the BNT126b2 vaccine achieves higher and more broadly reactive neutralizing antibody titers, than those observed among individuals who crossed-over vaccines. On the other hand, mild prior infection with the parental virus and subsequent homologous vaccination with BNT126b2 induces high antibody levels, but with moderate breadth of response, while children aged 5-11 show negligible neutralizing antibodies against the omicron variant few months from infection. Neutralizing and binding antibodies correlate across all variants and allow the identification of variant-specific anti-RBD thresholds for 90% protection efficacy. Interpretation: Boosting with the BNT126b2 vaccine is an immediate and effective measure to increase the protection against omicron, in naïve, as well as in previously infected individuals. Identification through serological commercial assays of thresholds of protection against the omicron and delta variants is a crucial step towards large-scale serosurveys to finely assess infection risk both at population and individual level.

14.
J Infect ; 84(4): 566-572, 2022 04.
Article in English | MEDLINE | ID: covidwho-1670759

ABSTRACT

BACKGROUND: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients. METHODS: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed. RESULTS: 465 patients (54% males, 51% hospitalized) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalization and ICU stay vs. non-hospitalized status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress. CONCLUSIONS: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.


Subject(s)
COVID-19 , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Fatigue/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2
16.
Am J Cardiol ; 165: 109-115, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1568471

ABSTRACT

Evidence of the involvement of the cardiovascular system in patients with COVID-19 is increasing. The evaluation of the subclinical cardiac involvement is crucial for risk stratification at admission, and left ventricular global longitudinal strain (LVGLS) may be useful for this purpose. A total of 87 consecutive patients admitted to the COVID Center were enrolled from December 2020 to April 2021. A complete echocardiography examination was performed within 72 hours from admission. The main outcome was the need for mechanical ventilation by way of orotracheal intubation (OTI) and mortality, and the secondary outcome was the worsening of the respiratory function during hospitalization, interpreted as a decrease of the ratio between the partial pressure of oxygen and the fraction of inspired oxygen (P/F) <100. Of 87 patients, 14 had severe disease leading to OTI or death, whereas 24 had a P/F <100. LVGLS was significantly impaired in patients with severe disease. After adjustment for risk factors, by considering LVGLS as continuous variable, the latter remained significantly associated with severe acute respiratory distress syndrome (P/F <100) (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.18 to 1.88, p = 0.001) and OTI/death (HR 1.63, 95% CI 1.13 to 2.38, p = 0.012). When using an LVGLS cutoff of -16.1%, LVGLS ≥ -16.1% was independently associated with a higher risk of severe acute respiratory distress syndrome (HR 4.0, 95% CI 1.4 to 11.1, p= 0.008) and OTI/death (HR 7.3, 95% CI 1.6 to 34.1, p = 0.024). LVGLS can detect high-risk patients at the admission, which can help to guide in starting early treatment of the admitted patients.


Subject(s)
COVID-19/complications , COVID-19/mortality , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/virology , Ventricular Dysfunction, Left/diagnostic imaging , Aged , Aged, 80 and over , COVID-19/therapy , Echocardiography , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Survival Rate , Ventricular Dysfunction, Left/virology
18.
Clin Microbiol Infect ; 28(1): 13-22, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1445304

ABSTRACT

BACKGROUND: Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community. OBJECTIVES: To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections. DATA SOURCES: Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions. STUDY ELIGIBILITY CRITERIA: Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori. ASSESSMENT OF RISK OF BIAS: Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2. METHODS OF DATA SYNTHESIS: The measures of diagnostic test accuracy were calculated with 95% CI. RESULTS: A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%). DISCUSSION: Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate.


Subject(s)
Pneumonia, Bacterial/diagnosis , Pneumonia, Viral , Point-of-Care Testing , Bias , Biomarkers , Diagnosis, Differential , Humans , Pneumonia, Viral/diagnosis , Sensitivity and Specificity , Ultrasonography
19.
Cell Death Differ ; 29(2): 420-438, 2022 02.
Article in English | MEDLINE | ID: covidwho-1406388

ABSTRACT

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.


Subject(s)
COVID-19/physiopathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/metabolism , Inflammation/metabolism , STAT3 Transcription Factor/metabolism , Aged , Aged, 80 and over , Animals , COVID-19/metabolism , Caspase 8/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , SARS-CoV-2/immunology , STAT3 Transcription Factor/genetics , Signal Transduction
20.
Cancer Med ; 10(18): 6310-6316, 2021 09.
Article in English | MEDLINE | ID: covidwho-1378924

ABSTRACT

BACKGROUND: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. METHODS: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. RESULTS: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. CONCLUSIONS: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population.


Subject(s)
COVID-19/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/virology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19 Serological Testing/methods , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Italy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Male , Middle Aged , Prevalence , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL