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2.
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)

3.
JAMA Netw Open ; 4(11): e2136246, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1540039

ABSTRACT

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

4.
Eur J Clin Invest ; : e13703, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488194

ABSTRACT

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

5.
Echocardiography ; 38(10): 1778-1786, 2021 10.
Article in English | MEDLINE | ID: covidwho-1476163

ABSTRACT

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

6.
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.

7.
Andrology ; 2021 Aug 18.
Article in English | MEDLINE | ID: covidwho-1379554

ABSTRACT

BACKGROUND: Circulating testosterone levels have been found to be reduced in men with severe acute respiratory syndrome coronavirus 2 infection, COVID-19, with lower levels being associated with more severe clinical outcomes. OBJECTIVES: We aimed to assess total testosterone levels and the prevalence of total testosterone still suggesting for hypogonadism at 7-month follow-up in a cohort of 121 men who recovered from laboratory-confirmed COVID-19. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as total testosterone ≤9.2 nmol/L. The Charlson Comorbidity Index was used to score health-significant comorbidities. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and total testosterone levels at follow-up assessment. RESULTS: Circulating total testosterone levels increased at 7-month follow-up compared to hospital admittance (p < 0.0001), while luteinizing hormone and 17ß-estradiol levels significantly decreased (all p ≤ 0.02). Overall, total testosterone levels increased in 106 (87.6%) patients, but further decreased in 12 (9.9%) patients at follow-up, where a total testosterone level suggestive for hypogonadism was still observed in 66 (55%) patients. Baseline Charlson Comorbidity Index score (OR 0.36; p = 0.03 [0.14, 0.89]) was independently associated with total testosterone levels at 7-month follow-up, after adjusting for age, BMI, and IL-6 at hospital admittance. CONCLUSIONS: Although total testosterone levels increased over time after COVID-19, more than 50% of men who recovered from the disease still had circulating testosterone levels suggestive for a condition of hypogonadism at 7-month follow-up. In as many as 10% of cases, testosterone levels even further decreased. Of clinical relevance, the higher the burden of comorbid conditions at presentation, the lower the probability of testosterone levels recovery over time.

8.
Infect Dis Ther ; 10(4): 2791-2804, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1321899

ABSTRACT

Ribavirin is an inosine monophosphate dehydrogenase inhibitor with demonstrated activity against coronaviruses, including SARS-CoV-2. Five hospitalized patients with COVID-19 (confirmed by positive tests for SARS-CoV-2) received treatment with ribavirin for inhalation solution (ribavirin aerosol) as part of a compassionate use program. Patients included four men and one woman, with an age range of 29-72 years. Patients were managed according to international and Italian treatment guidelines for COVID-19. In addition, therapy with ribavirin aerosol 100 mg/mL was administered for 30 min twice daily for 6 days (i.e., 12 doses) in all patients. In order to address concerns about a possible increase in viral dispersal with the use of a nebulizer, healthcare providers remained outside the patient room during ribavirin aerosol administration. Pretreatment chest computed tomography (CT) scans showed pseudonodular areas of parenchymal thickening in the upper right lobe with associated ground glass opacities, multiple areas of parenchymal consolidation in both lower lobes with associated ground glass opacities, bilateral parenchymal thickening and multiple associated ground glass areas, or focal ground glass areas in the upper lobes bilaterally, which were almost completely resolved (three patients) or moderately cleared (one patient) on imaging at the end of ribavirin treatment. For a fifth patient, CT scans showed a stable pulmonary picture at the end of ribavirin treatment. No adverse reactions to ribavirin treatment were observed in any of the five patients. All patients recovered fully, and nasopharyngeal swabs obtained after hospital discharge tested negative for SARS-CoV-2. Ribavirin aerosol appears to be efficacious in the treatment of patients with COVID-19. A controlled trial of ribavirin aerosol is ongoing and will provide additional data across a broader patient population.

9.
Open Forum Infect Dis ; 8(7): ofab278, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1317924

ABSTRACT

Background: Remdesivir is approved by the US Food and Drug Administration for the treatment of patients hospitalized with coronavirus disease 2019 (COVID-19) and has been shown to shorten time to recovery and improve clinical outcomes in randomized trials. Methods: This was the final day 28 comparative analysis of data from a phase 3, randomized, open-label study comparing 2 remdesivir regimens (5 vs 10 days, combined for this analysis [remdesivir cohort]) and a real-world retrospective longitudinal cohort study of patients receiving standard-of-care treatment (nonremdesivir cohort). Eligible patients, aged ≥18 years, had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), oxygen saturation ≤94% on room air or required supplemental oxygen, with pulmonary infiltrates. Propensity score matching (up to 1:10 ratio) was used to ensure comparable populations. We assessed day 14 clinical recovery (determined using a 7-point ordinal scale) and day 28 all-cause mortality (coprimary endpoints). Results: A total of 368 (remdesivir) and 1399 (nonremdesivir) patients were included in the matched analysis. The day 14 clinical recovery rate was significantly higher among the remdesivir versus the nonremdesivir cohort (65.2% vs 57.1%; odds ratio [OR], 1.49; 95% confidence interval [CI], 1.16-1.90; P = 0.002). The day 28 mortality rate was significantly lower in the remdesivir cohort versus the nonremdesivir cohort (12.0% vs 16.2%; OR, 0.67; 95% CI, 0.47-.95; P = .03). Conclusions: Remdesivir was associated with significantly higher rates of day 14 clinical recovery, and lower day 28 mortality, compared with standard-of-care treatment in hospitalized patients with COVID-19. These data, taken together, support the use of remdesivir to improve clinical recovery and decrease mortality from SARS-CoV-2 infection.

10.
Nutr Metab Cardiovasc Dis ; 31(7): 2156-2164, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1249046

ABSTRACT

BACKGROUND AND AIMS: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. METHODS AND RESULTS: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). CONCLUSION: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. TRIAL REGISTRATION: NCT04318366.


Subject(s)
Adiposity , COVID-19/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , Obesity/diagnostic imaging , Radiography, Thoracic , Tomography, X-Ray Computed , Aged , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Female , Hospital Mortality , Humans , Intra-Abdominal Fat/physiopathology , Italy , Male , Middle Aged , Obesity/mortality , Obesity/physiopathology , Pericardium , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors
11.
Front Immunol ; 12: 675678, 2021.
Article in English | MEDLINE | ID: covidwho-1231339

ABSTRACT

Background: Restraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established. Objectives: To identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19. Methods: Survival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation. Results: 107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO2 ≥ 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO2 < 100 mmHg (p = 0.04). Conclusions: IL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , SARS-CoV-2/immunology , Aged , COVID-19/drug therapy , COVID-19/immunology , COVID-19/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Interleukin-1/immunology , Interleukin-6/immunology , Male , Middle Aged , Severity of Illness Index , Survival Rate
12.
Lancet Rheumatol ; 3(4): e253-e261, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1228198

ABSTRACT

Background: Patients with severe COVID-19 develop a life-threatening hyperinflammatory response to the virus. Interleukin (IL)-1 or IL-6 inhibitors have been used to treat this patient population, but the comparative effectiveness of these different strategies remains undetermined. We aimed to compare IL-1 and IL-6 inhibition in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. Methods: This cohort study included patients admitted to San Raffaele Hospital (Milan, Italy) with COVID-19, respiratory insufficiency, defined as a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of 300 mm Hg or less, and hyperinflammation, defined as serum C-reactive protein concentration of 100 mg/L or more or ferritin concentration of 900 ng/mL or more. The primary endpoint was survival, and the secondary endpoint was a composite of death or mechanical ventilation (adverse clinical outcome). Multivariable Cox regression analysis was used to compare clinical outcomes of patients receiving IL-1 inhibition (anakinra) or IL-6 inhibition (tocilizumab or sarilumab) with those of patients who did not receive interleukin inhibitors, after accounting for baseline differences. All patients received standard care. Interaction tests were used to assess the probability of survival according to C-reactive protein or lactate dehydrogenase concentrations. Findings: Of 392 patients included between Feb 25 and May 20, 2020, 275 did not receive interleukin inhibitors, 62 received the IL-1 inhibitor anakinra, and 55 received an IL-6 inhibitor (29 received tocilizumab and 26 received sarilumab). In the multivariable analysis, compared with patients who did not receive interleukin inhibitors, patients treated with IL-1 inhibition had a significantly reduced mortality risk (hazard ratio [HR] 0·450, 95% CI 0·204-0·990, p=0·047), but those treated with IL-6 inhibition did not (0·900, 0·412-1·966; p=0·79). In the multivariable analysis, there was no difference in adverse clinical outcome risk in patients treated with IL-1 inhibition (HR 0·866, 95% CI 0·482-1·553; p=0·63) or IL-6 inhibition (0·882, 0·452-1·722; p=0·71) relative to patients who did not receive interleukin inhibitors. For increasing C-reactive protein concentrations, patients treated with IL-6 inhibition had a significantly reduced risk of mortality (HR 0·990, 95% CI 0·981-0·999; p=0·031) and adverse clinical outcome (0·987, 0·979-0·995; p=0·0021) compared with patients who did not receive interleukin inhibitors. For decreasing concentrations of serum lactate dehydrogenase, patients treated with an IL-1 inhibitor and patients treated with IL-6 inhibitors had a reduced risk of mortality; increasing concentrations of lactate dehydrogenase in patients receiving either interleukin inhibitor were associated with an increased risk of mortality (HR 1·009, 95% CI 1·003-1·014, p=0·0011 for IL-1 inhibitors and 1·006, 1·001-1·011, p=0·028 for IL-6 inhibitors) and adverse clinical outcome (1·006, 1·002-1·010, p=0·0031 for IL-1 inhibitors and 1·005, 1·001-1·010, p=0·016 for IL-6 inhibitors) compared with patients who did not receive interleukin inhibitors. Interpretation: IL-1 inhibition, but not IL-6 inhibition, was associated with a significant reduction of mortality in patients admitted to hospital with COVID-19, respiratory insufficiency, and hyperinflammation. IL-6 inhibition was effective in a subgroup of patients with markedly high C-reactive protein concentrations, whereas both IL-1 and IL-6 inhibition were effective in patients with low lactate dehydrogenase concentrations. Funding: None.

13.
The New Microbiologica ; 43(4):161, 2020.
Article in English | ProQuest Central | ID: covidwho-1136736

ABSTRACT

We describe the outcome of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG/IgM rapid test, and discuss the potential suitability of antibody testing. Retrospective single cohort study on patients with suspected Coronavirus Disease 2019 (COVID-19) and asymptomatic Healthcare Workers, enrolled from March to April 2020. Subjects had quantitative PCR (qPCR) test for detection of SARS-CoV-2 via nasal swab and serological testing using the COVID-19 IgG/ IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay. Some subjects underwent chemiluminescence immunoassay (CLIA) after rapid test. The aim of the study was to analyse the proportion of those who developed a positive IgM/IgG response for SARS-CoV-2. The correspondence between the results from rapid testing and CLIA, when available, was evaluated. 97 subjects underwent qPCR for SARS-CoV-2 through nasal swab, which resulted positive in 40/43 (93.0%) of symptomatic patients, 2/40 (5%) of asymptomatic HCW, in no subjects with suspected COVID-19 (clinical and radiological findings) then excluded by repeated nasal swabs and alternative diagnosis (COVID-19-negative patients, CNPs), and in 6/6 (100%) of patients with confirmed diagnosis and negative follow-up nasal swabs (COVID-19-recovered patients, CRPs). IgM resulted positive in 8/43 (18.6%) of symptomatic patients and in 1/6 (16.7%) of CRPs. IgG resulted positive in 36/43 (83.7%) of symptomatic patients, 2/40 (5%) of HCW, and in 1/8 (12.5%) and 6/6 (100%) of CNPs and CRPs, respectively. A comparison between an IgG/IgM Rapid Test and a following CLIA test showed consistency in negative results in 25/28 of HCW and 8/8 of CNPs tested. Our preliminary data support the role of IgG/IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay as a point-of-care test that may complement molecular tests in the screening of SARS-CoV-2 carriers. The test may gain particular relevance in shortening the time needed to refer patients to a COVID or non-COVID Hospital area and to achieve diagnosis in patients with persistently negative nasal swabs.

14.
J Nephrol ; 34(2): 305-314, 2021 04.
Article in English | MEDLINE | ID: covidwho-1114333

ABSTRACT

BACKGROUND: In February 2020 the corona virus disease 2019 (COVID-19) infection started spreading throughout Italy, hitting the Lombardy region very hard. Despite the high diffusion, only a subset of patients developed severe COVID-19: around 25% of them developed acute kidney injury (AKI) and one-third of them died. Elderly patients and patients with high comorbidities were identified as being at higher risk of severe COVID-19. METHODS: Our prospective observational cohort study includes 392 consecutive patients hospitalized for COVID-19 in Milan (median age 67 years, 75% male). We evaluated the relationship between blood pressure at presentation, presence of AKI at Emergency Department admission and during hospitalization, and total in-hospital mortality (24%). RESULTS: Although 58% of our study patients reported a history of hypertension (HYP) (86% on treatment), 30% presented with low blood pressure levels. Only 5.5% were diagnosed with AKI on admission; 75% of hypertensive patients discontinued therapy during hospitalization (only 20% were on treatment at discharge). Gender and hypertension were strongly associated with AKI at admission (odds ratio 11). Blood pressure was inversely correlated with increased risk of AKI upon admission, regardless of the severity of respiratory distress. Age over 65, history of hypertension, and severity of respiratory distress were the main predictors of AKI, which developed in 34.7% of cases during hospitalization. AKI was associated with increased in-hospital mortality. Hypertension and low blood pressure at presentation were the main predictors of in-hospital mortality, together with age over 65, baseline pulmonary involvement, and severity of illness. CONCLUSIONS: In patients hospitalized for COVID-19, hypertension and low blood pressure at presentation are important risk factors for AKI and mortality. Early reduction of antihypertensive therapy may improve outcomes in patients with SARS-CoV-2 infection.


Subject(s)
Acute Kidney Injury/physiopathology , Blood Pressure/physiology , COVID-19/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Aged , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Intensive Care Units , Italy/epidemiology , Male , Prospective Studies , Retrospective Studies , Risk Factors , Survival Rate/trends
15.
J Clin Invest ; 130(12): 6366-6378, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-1112390

ABSTRACT

BACKGROUNDSerological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals.METHODSWe studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010-2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients.RESULTSAntibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival.CONCLUSIONThe measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.TRIAL REGISTRATIONCOVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDINGIRCCS Ospedale San Raffaele and Università Vita Salute San Raffaele.


Subject(s)
Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/immunology , COVID-19/mortality , Epitopes/immunology , SARS-CoV-2/immunology , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Protein Domains , Spike Glycoprotein, Coronavirus
17.
Andrology ; 9(4): 1043-1052, 2021 07.
Article in English | MEDLINE | ID: covidwho-1105200

ABSTRACT

BACKGROUND: Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19). OBJECTIVES: We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory-confirmed COVID-19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID-19, and clinical outcomes. MATERIALS AND METHODS: Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health-significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes. RESULTS: Overall, a significantly lower levels of LH and tT were found in patients with COVID-19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E2 (p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS-CoV-2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL-6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters. CONCLUSIONS: We unveil an independent association between SARS-CoV-2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.


Subject(s)
COVID-19/blood , Testosterone/blood , Adult , Aged , Biomarkers/blood , COVID-19/complications , Case-Control Studies , Cohort Studies , Gonadal Steroid Hormones/blood , Humans , Hypogonadism/blood , Hypogonadism/etiology , Male , Middle Aged , Treatment Outcome
18.
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
19.
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
20.
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
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