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1.
Clin Microbiol Infect ; 2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2086083

ABSTRACT

OBJECTIVE: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. RESULTS: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set. DISCUSSION: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.

2.
Drug design, development and therapy ; 16:3645-3654, 2022.
Article in English | EuropePMC | ID: covidwho-2073818

ABSTRACT

Background Evidence regarding the impact of remdesivir (RDV) on SARS-CoV-2 viral clearance (VC) is scarce. The aim of this study was to compare VC timing in hospitalized COVID-19 patients who did or did not receive RDV. Methods This was a matched-cohort study of patients hospitalized with pneumonia, a SARS-CoV-2-positive nasopharyngeal swab (NPS) at admission, and at least one NPS during follow-up. Patients who received RDV (cases) and those who did not (controls) were matched in a 1:2 ratio by age, sex, and PaO2/FiO2 (P/F) values at admission. NPSs were analyzed using real-time polymerase chain reaction. Time to VC (within 30 days after hospital discharge) was estimated using the Kaplan–Meier curve. A multivariable Cox proportional hazard model was fitted to determine factors associated with VC. Results There were 648 patients enrolled in the study (216 cases and 432 controls). VC was observed in 490 patients (75.6%), with a median time of 25 (IQR 16–34) days. Overall, time to VC was similar between cases and controls (p = 0.519). However, time to VC was different when considering both RDV treatment status and age (p = 0.007). A significant finding was also observed when considering both RDV treatment status and P/F values at admission (p = 0.007). A multivariate analysis showed that VC was associated with a younger age (aHR = 0.990, 95% CI 0.983–0.998 per every 10-year increase in age;p = 0.009) and a higher baseline P/F ratio (aHR=1.275, 95% CI 1.029–1.579;p=0.026), but not with RDV treatment status. Conclusion Time to VC was similar in cases and controls. However, there was a benefit associated with using RDV in regard to time to VC in younger patients and in those with a P/F ratio ≤200 mmHg at hospital admission.

3.
Open Forum Infect Dis ; 9(9): ofac454, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2051512

ABSTRACT

Background: This study's primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods: This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray's method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results: Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8-11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7-21.0) and 9.3 (95% CI, 7.9-11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018-3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions: In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321957

ABSTRACT

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients.Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs.The primary outcome was the time to nasopharyngeal swab negativization.A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization.Of 280 patients included, 59 (21.1%) patients were treated with steroids.Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO 2 /FiO 2 ≤200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively;p=0.023) or ≤100 mmHg (16.9% vs 12.7%;p=0.027), and length of hospitalization (20 vs 14 days;p<0.001).Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p=0.985).According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤70 years, a shorter duration of symptoms at admission, a baseline PaO 2 /FiO 2 >200 mmHg, and a lymphocyte count at admission >1.0*10 9 /L. SARS-CoV-2 clearance was not associated with corticosteroid use.Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with early use of corticosteroids

6.
Open forum infectious diseases ; 8(Suppl 1):S354-S355, 2021.
Article in English | EuropePMC | ID: covidwho-1564848

ABSTRACT

Background Evidence regarding the impact of remdesivir (RDV) on SARS-CoV-2 viral clearance (VC) is scarce. Aim of this study was to compare VC timing in COVID-19 patients who received RDV with those who did not. Methods Matched-cohort study conducted (25 February 2020-15 April 2021) at the IRCSS San Raffaele, Milan, Italy. The study enrolled hospitalized patients with pneumonia and a SARS-CoV-2 positive nasopharyngeal swab (NPS) at admission and at least one NPS during follow-up. Follow-up started at hospital admission and ended at the date of the first negative NPS (within 30 days after discharge). Patients who received RDV (cases) and patients who did not (controls) were matched based on age (±5 years), sex and PaO2/FiO2 (P/F;±10 mmHg) values at admission. NPS were analyzed with RT-PCR. Results described as median (IQR) or frequency (%). Time to VC was estimated with Kaplan-Meier curve and compared with log-rank test. Results 648 patients were enrolled: 216 cases and 432 controls. Patients’ characteristics at admission are reported in Table 1. VC was observed in 490 patients (75.6%) in a median time of 25 (16-34) days. Overall, time to VC was similar in patients receiving or not receiving remdesivir (p=0.519). However, time to VC was different when considering both the use of RDV (yes vs no) and age (≤ or > 63 years), as shown in Figure 1A. A significant finding was also observed considering the use of RDV and P/F values at admission (≤ or > 200 mmHg), as reported in Figure 1B. Among the 490 patients who reached VC during follow-up, overall time to VC was similar in patients receiving or not receiving RDV (p=0.075;Figure 2A);however, RDV use was associated with a higher probability of VC in the subgroup of patients with P/F admission values ≤ 200mmHg (p=0.035;Figure 2B), in the age group 55-65 years (p=0.025;Figure 2C) and in patients with comorbidities (p=0.028). Time to viral clearance among the 490 patients who reached VC during follow-up. Panel A: time to VC according to RDV use. Panel B: time to VC according to RDV and P/F ratio value at admission. Panel C: time to VC according to RDV in the age group 55-65 years. Conclusion Time to viral clearance was similar in patients receiving or not receiving remdesivir;however the use of RDV was associated with a benefit on time to viral clearance in younger patients and in those with a P/F ratio at admission ≤200 mmHg. Disclosures Vincenzo Spagnuolo, MD, ViiV Healthcare (Other Financial or Material Support, Preparation of educational material) Antonella Castagna, MD, Gilead Sciences (Other Financial or Material Support, Speaking fee)Jansenn-Cilag (Other Financial or Material Support, Speaking fee)MSD (Other Financial or Material Support, Speaking fee)Theratechnologies (Other Financial or Material Support, Speaking fee)ViiV Healthcare (Other Financial or Material Support, Speaking fee)

7.
J Ophthalmic Inflamm Infect ; 11(1): 35, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1435221

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce conjunctivitis signs and symptoms. However, limited information is available on their impact on COVID-19 disease phenotype. Quantification of ocular signs/symptoms can provide a rapid, non-invasive proxy for predicting clinical phenotype. Moreover, the existence and entity of conjunctival viral shedding is still debated. This has relevant implications to manage disease spread. The purpose of this study was to investigate conjunctivitis signs and symptoms and their correlation with clinical parameters, conjunctival viral shedding in patients with COVID-19. METHODS: Fifty-three patients hospitalized between February 25th and September 16th, 2020 at the San Raffaele Hospital, in Milan, Lombardy, Italy with a confirmed diagnosis of SARS-CoV-2 were evaluated. Presence of interstitial pneumonia was confirmed with computed tomography scan imaging. Ocular signs and symptoms, anosmia/ageusia, clinical/laboratory parameters, and reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for COVID-19 virus were analyzed. RESULTS: Forty-six out of 53 patients showed a positive nasopharyngeal swab for SARS-CoV-2 infection at the time of conjunctival evaluation. All the conjunctival swabs were negative. Conjunctivitis symptoms were present in 37% of patients. Physician-assessed ocular signs were detected in 28% of patients. Patients with ocular symptoms or signs tended to be older: 76.8 years (62.4-83.3) vs 57.2 years (48.1-74.0), p = 0.062 and had a longer hospitalization: 38 days (18-49) vs. 14 days (11-21), p = 0.005. Plasma levels of Interleukin-6 were higher in patients with signs or symptoms in comparison with those without them: 43.5 pg/ml (19.7-49.4) vs. 8 pg/ml (3.6-20.7), p = 0.02. Red cell distribution width was also significantly higher: 15 (14.3-16.7) vs 13.2 (12.4-14.4), p = 0.001. CONCLUSIONS: We found that over a third of the patients had ocular signs or symptoms. These had higher prevalence in patients with a more severe infection. No viral shedding was detected in the conjunctiva. Our results suggest that prompt detection of conjunctivitis signs/symptoms can serve as a helpful proxy to predict COVID-19 clinical phenotype.

8.
J Cardiothorac Vasc Anesth ; 35(12): 3631-3641, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1026847

ABSTRACT

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.


Subject(s)
COVID-19 , Pulmonary Embolism , Thrombosis , Venous Thrombosis , Humans , Prospective Studies , Pulmonary Embolism/diagnostic imaging , SARS-CoV-2
9.
Phlebology ; 36(5): 375-383, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-947896

ABSTRACT

OBJECTIVES: A high rate of thrombotic events has been reported in COVID-19 population. The study aims to assess the incidence of deep vein thrombosis (DVT) in COVID-19 patients admitted to a single tertiary hospital. METHODS: From April 2nd to April 18th, 2020, hospitalized patients with SARS-CoV-2 infection were screened by lower limb duplex ultrasound (DUS). Patients were on (low molecular weight heparin) LMWH prophylaxis in medical wards, and on therapeutic anticoagulation in intensive care unit (ICU). DVT risk factors, reported by the Padua prediction score and blood tests, were retrieved from institutional electronic charts. The study primary endpoint was the incidence of DVT in the in-hospital COVID-19 population and its association with clinical and laboratory risk factors. The secondary endpoint was the association of DVT with mortality. RESULTS: Two hundred patients (median age 62 years, 72% male, 40 in ICU) received DUS screening. DVT was observed in 29 patients (14.5%), with proximal extension in 16 patients, and in association with symptoms in four patients. The DVT rate was similar in ICU (12.5%) and non-ICU patients (15%). Eighty-seven patients underwent a computed tomography angiography (CTA) that showed pulmonary embolism in 35 patients (40.2%) not associated with DVT in 25/35 cases (71.4%). DVT in the ten patients with pulmonary embolism were symptomatic in four and with a proximal localization in eight cases. A D-dimer level ≥5 mg/l at admission was predictive of DVT (OR 1.02; IC95% 1.03-1.16; p = .003). At the multivariate analysis in-hospital mortality was predicted by age (OR 1.06; 95% CI 0.02-1.15; p = .004) and by being an ICU patient (OR 1.23; 95% CI 0.30-2.25; p = .01). CONCLUSIONS: Despite LMWH prophylaxis or full anticoagulant therapy, the incidence of DVT, mainly asymptomatic, in hospitalized COVID-19 patients was 14.5%. Further research should focus on the appropriate antithrombotic therapy for COVID-19 patients.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Hospitalization , SARS-CoV-2 , Venous Thrombosis/epidemiology , Aged , COVID-19/complications , COVID-19/therapy , Female , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Venous Thrombosis/etiology , Venous Thrombosis/therapy
10.
Clin Microbiol Infect ; 27(3): 451-457, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-938846

ABSTRACT

OBJECTIVES: The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine-Gray models to assess factors associated with risk of secondary infections. RESULTS: Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4-21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 109/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11-3.35), baseline PaO2/FiO2 (per 100 points lower: sdHRs 1.56, 95%CI 1.21-2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04-6.05). CONCLUSIONS: Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Hospitalization/statistics & numerical data , Aged , Cohort Studies , Coinfection/microbiology , Female , Humans , Incidence , Italy/epidemiology , Male , Middle Aged , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/microbiology , Risk Factors , SARS-CoV-2 , Sepsis/epidemiology , Sepsis/etiology , Sepsis/microbiology
11.
Panminerva Med ; 64(2): 244-252, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-875064

ABSTRACT

BACKGROUND: Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic, and therapeutic strategies. METHODS: We established a COVID-19 biobank with the aim of collecting high-quality and well-annotated human biospecimens, in the effort to understand the pathogenic mechanisms underlying COVID-19 and identify therapeutic targets (COVID-BioB, NCT04318366). Here we describe our experience and briefly review the characteristics of the biobanks for COVID-19 that have been so far established. RESULTS: A total of 46,677 samples have been collected from 913 participants (63.3% males, median [IQR] age 62.2 [51.2-74.0] years) since the beginning of the program. Most patients (66.9%) had been admitted to hospital for COVID-19, with a median length of stay of 15.0 (9.0-27.0) days. A minority of patients (13.3% of the total) had been admitted for other reasons and subsequently tested positive for SARS-CoV-2. The remainder were managed at home after being seen at the Emergency Department. CONCLUSIONS: Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.


Subject(s)
Biomedical Research , COVID-19 , Biological Specimen Banks , Female , Hospitalization , Humans , Male , Middle Aged , SARS-CoV-2
12.
Clin Immunol ; 217: 108509, 2020 08.
Article in English | MEDLINE | ID: covidwho-597932

ABSTRACT

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.


Subject(s)
Coronary Disease/diagnosis , Coronavirus Infections/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Kidney Failure, Chronic/diagnosis , Pneumonia, Viral/diagnosis , Pulmonary Edema/diagnosis , Severe Acute Respiratory Syndrome/diagnosis , Age Factors , Aged , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/immunology , Coronary Disease/mortality , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/epidemiology , Hypertension/immunology , Hypertension/mortality , Infectious Disease Incubation Period , Italy/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/mortality , Lymphocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pulmonary Edema/epidemiology , Pulmonary Edema/immunology , Pulmonary Edema/mortality , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severity of Illness Index , Survival Analysis
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