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1.
Vaccines ; 10(5):817, 2022.
Article in English | MDPI | ID: covidwho-1857399

ABSTRACT

The new Omicron variant of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. Omicron has become the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on the neutralizing activity of vaccinated sera against the Omicron variant are currently being carried out in many laboratories. In this study, we have shown the neutralizing activity of sera against the SARS-CoV-2 Omicron variant compared to the reference Wuhan D614G variant in individuals vaccinated with two doses of Sputnik V up to 6 months after vaccination and in individuals who experienced SARS-CoV-2 infection either before or after vaccination. As a control to our study we also measured neutralizing antibody titers in individuals vaccinated with two doses of BNT162b2. The decrease in NtAb titers to the Omicron variant was 8.1-fold for the group of Sputnik V-vaccinated individuals. When the samples were stratified for the time period after vaccination, a 7.6-fold or 8.8-fold decrease in NtAb titers was noticed after up to 3 and 3-to-6 months after vaccination. We observed a 6.7- and 5-fold decrease in Sputnik V-vaccinated individuals experiencing asymptomatic or symptomatic infection, respectively. These results highlight the observation that the decrease in NtAb to the SARS-CoV-2 Omicron variant compared to the Wuhan variant occurs for different COVID-19 vaccines in use, with some showing no neutralization at all, confirming the necessity of a third booster vaccination.

2.
Front Immunol ; 13: 868020, 2022.
Article in English | MEDLINE | ID: covidwho-1834408

ABSTRACT

Objectives: Comparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta. Methods: Allocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7.Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period. Results: COVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p<0.001) on D7. Conclusions: In a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , COVID-19/drug therapy , Humans , Observation , SARS-CoV-2
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335491

ABSTRACT

Purpose: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). With the increase of ARDS cases during COVID-19 pandemic, the use of non-invasive ventilation (NIV) has grown significantly in the hospital ward. However, there is a lack of evidence to support its efficacy in these patients. Methods We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy (Jan-Sep 2020). The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and its relative risk of death. The factors associated with the outcomes were identified through a logistic regression analysis. Results During the study period, a total of 942 COVID-19 patients were admitted, of which 307 (32.5%) with ARDS at hospitalization. Overall, 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. Moderate and severe ARDS had an increased risk of NIV failure within 28 days from starting NIV of 5- (aOR = 5.01, 95% CI 2.08–12.09) and 20-fold (aOR = 19.95, 5.31–74.94) respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, COVID-19 patients treated with NIV without intubation had 96% lower mortality (aOR 0.04, 0.01–0.32) in comparison with patients that underwent orotracheal intubation without prior NIV. Conclusions NIV failure was independently associated with COVID-19 ARDS severity. Starting NIV in COVID-19 patients with already mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV treatment seems to reduce the risk of ICU mortality within 28 days from ICU admission.

4.
J Clin Med ; 11(9)2022 May 05.
Article in English | MEDLINE | ID: covidwho-1820313

ABSTRACT

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86-51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH-but it was not statistically significant (OR 7.1, 95% CI 0.90-56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.

5.
Nat Commun ; 13(1): 2263, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815533

ABSTRACT

The emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is a potent Fc-engineered monoclonal antibody (mAb) able to neutralize in vitro all current SARS-CoV-2 variants of concern (VoCs) including the omicron variant even if with significantly reduced potency. Here we evaluated data obtained from the first 30 days of a phase 1 clinical study (EudraCT N.: 2020-005469-15 and ClinicalTrials.gov Identifier: NCT04932850). The primary endpoint evaluated the percentage of severe adverse events. Secondary endpoints evaluated pharmacokinetic and serum neutralization titers. A single dose administration of MAD0004J08 via intramuscular (i.m.) route is safe and well tolerated, resulting in rapid serum distribution and sera neutralizing titers higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralize major SARS-CoV-2 variants of concern (alpha, beta, gamma and delta). MAD0004J08 can be a major advancement in the prophylaxis and clinical management of COVID-19.


Subject(s)
Antibodies, Monoclonal , SARS-CoV-2 , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/blood , Antibodies, Viral , COVID-19 , Humans , Injections, Intramuscular , Neutralization Tests , SARS-CoV-2/immunology
6.
Clin Infect Dis ; 2022 Apr 02.
Article in English | MEDLINE | ID: covidwho-1774349

ABSTRACT

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm 3; intermediate CD4 recovery, ICDR: 200-500/mm 3 high CD4 recovery, HCDR: >500/mm 3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH after 1 month from the second dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2% and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm 3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters. CONCLUSION: Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm 3 versus those with >500 cell/mm 3 and HIV-negative controls. A decreased RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm 3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm 3 was comparable to HIV-negative population.

7.
J Clin Med ; 11(6)2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1742502

ABSTRACT

BACKGROUND: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. METHODS: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. RESULTS: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75-322) cells/µL; CD4 at COVID-19 diagnosis was 272 cells/µL (127-468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2-17.3) in PLWH versus 18.9% (16.9-21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5-36.4) in PLWH versus 37.6% (35.1-40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12-1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53-2.00, p = 0.926). CONCLUSION: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323308

ABSTRACT

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia.Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50-77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95%CI 3.2-26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7-15.9) in those exposed to pLMWH;p-value=0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95%CI 0.51-3.79) for patients with an admission PaO2/FiO2 < 300 mmHg and 0.27 (0.03-2.18) for those with PaO2/FiO2 >300 mmHg;p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322655

ABSTRACT

(1) Background: Benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high risk procedure for transmission of SARS CoV-2 to health care workers (HCWs). The present study analyzed optimal timing of PDT, clinical outcomes of patients undergoing PDT and safety of HCWs performing PDT. (2) Methods: 133 COVID-19 patients underwent PDT in our ICU from April 1, 2020 to March 31, 2021, 23 patients were excluded and 110 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history and outcome data were collected. Patients who underwent PDT were stratified into two groups: early group, PDT ≤12 days from orotracheal-intubation (OTI) and late group, &gt;12 days from OTI;HCW surveillance program was performed. (3) Results: Early group included 57 patients and late group included 53 patients. Early group patients showed shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p&lt;0.001). At day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of ventilation parameters, PaO2/FiO2-Ratio, PEEP and FiO2 (p&lt;0.001). No difference in case fatality ratio between the two groups was reported. No SARS-CoV-2 infection was reported in HCWs performing PDT. (4) Conclusions: PDT was safe and effective for COVID-19 patients, since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented and PDT procedure could be considered as first line approach in ICU COVID-19 requiring prolonged mechanical ventilation.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314865

ABSTRACT

Background: More detailed temporal analyses of complete (Full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease could help identify prognostic clinical biomarkers. Methods: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. Nine CBC parameters as a continuous variable were studied [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates and difference between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values were obtained by marginal prediction and ANOVA-style joint tests. All analyses were carried out by STATA 15 statistical package. Main Findings: 379 COVID-19 patients [273 (72% were male;mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophil counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Reverse temporal trends were observed for lymphocyte and neutrophil counts in survivors and non-survivors. Average platelets counts (P<0.001) and median platelets volume (P<0.001) were significantly different in survivors and in non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis were observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (p=0.005), obesity (p=0.010), chronic renal failure (p=0.001), COPD (p=0.033) cardiovascular diseases (p=0.001) and those >60 years(p=0.001). Age (p=0.042), obesity (p=0.002), chronic renal failure (p=0.002) and cardiovascular diseases (p=0.009) were independently associated with poor patient clinical outcome at 30 day after symptom onset. Interpretation: Increased neutrophil counts, reduced lymphocyte counts, higher median platelet volume, anemia with anisocytosis, in association with obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years predict poor prognosis in COVID19 patients.Funding Statement: Ricerca Corrente e Finalizzata Italy Ministry of Health, AIRC (IG2018-21880);Regione Lazio (Gruppi di ricerca, E56C18000460002).Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the IRB of Italian National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), in Rome (Italy).

11.
Ann Med ; 53(1): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575822

ABSTRACT

INTRODUCTION: Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. MATERIALS AND METHODS: We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. RESULTS: Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. CONCLUSIONS: Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients. KEY MESSAGE Critically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended. Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases. An incidence of 7.6 cases per 1000 admission of IPHs was reported. Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.


Subject(s)
Anticoagulants/adverse effects , COVID-19/complications , Hematoma/epidemiology , Psoas Muscles/diagnostic imaging , Thrombophilia/drug therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Female , Glucocorticoids/therapeutic use , Hematoma/chemically induced , Hematoma/diagnosis , Hematoma/drug therapy , Heparin, Low-Molecular-Weight , Hospital Mortality , Humans , Incidence , Intensive Care Units , Italy/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Muscular Diseases , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Thrombophilia/etiology , Tomography, X-Ray Computed , Treatment Outcome
12.
J Clin Med ; 10(23)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1566682

ABSTRACT

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate-severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate-severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate-severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate-severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate-severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294112

ABSTRACT

Background: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count and predictive role on immune response to vaccination in PLWH.<br><br>Methods: PLWH attending a single-center SARS-CoV-2 vaccination program in Italy, were included in a prospective evaluation for immunogenicity after receiving BNT162b2 or mRNA-1273. PLWH were stratified according to current CD4 T-cell count (severe immunodeficiency, SID: <200/mm 3 ;minor immunodeficiency, MID: 200-500/mm 3 ;no immunodeficiency, NID: >500/mm 3 ). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and cell-mediated (IFN-γ/IL-2) immune response were measured. As control group, not-matched HIV-negative healthcare workers (HCWs) were used.<br><br>Findings: Participants were 166 PLWH (SID=32;MID=56;NID=78) on ART. After 1 month from the booster dose, detectable RBD-binding IgG in 86.7% of SID, in 100% of MID, in 98.7% of NID (SID vs NID, p=0.021) and nAbs (titre ≥1:10) in 70.0%, 88.2% and 93.1%, respectively (SID vs NID, p=0.002), were elicited. Compared to NID, magnitude of anti-RBD, nAbs and IFN-γ production was significantly lower in SID and comparable in MID. After adjusting for confounders, current CD4 T-cell <200/mm 3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ production. As compared with HCWs, SID elicited a consistently reduced immunogenicity for all parameters, MID only a reduced RBD-binding antibody response, NID a comparable response to HIV-negative controls for all parameters.<br><br>Interpretation: Neutralizing and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH receiving ART, albeit significantly poorer in those with current CD4 T-cell <200/mm 3 versus those with CD4 T-cell >500/mm 3 and HIV-negative controls. A marginal decreased immunogenicity than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm 3 , whereas immune response elicited in PLWH with a CD4 T-cell >500/mm 3 was comparable to HIV-negative population.<br><br>Funding: Italian Ministry of Health;European Commission, European Virus Archive – GLOBAL.<br><br>Declaration of Interest: None to declare. <br><br>Ethical Approval: The study was approved by the Scientific Committee of the Italian Drug Agency (AIFA) and by the Ethical Committee of the Lazzaro Spallanzani Institute, as National Review Board for COVID-19 pandemic in Italy (approval number 323/2021).

14.
J Clin Med ; 10(23)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542621

ABSTRACT

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate-severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate-severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate-severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate-severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate-severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

15.
Biol Sex Differ ; 12(1): 63, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528694

ABSTRACT

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.


Subject(s)
Biomarkers/blood , COVID-19/complications , Hospitalization , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Sex Characteristics , Adult , Angiotensin-Converting Enzyme 2/blood , Angiotensins/blood , COVID-19/blood , Estradiol/blood , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Insufficiency/blood , SARS-CoV-2 , Testosterone/blood
16.
Sci Transl Med ; 14(627): eabj1996, 2022 Jan 12.
Article in English | MEDLINE | ID: covidwho-1483986

ABSTRACT

Safe and effective vaccines against coronavirus disease 2019 (COVID-19) are essential for ending the ongoing pandemic. Although impressive progress has been made with several COVID-19 vaccines already approved, it is clear that those developed so far cannot meet the global vaccine demand alone. We describe a COVID-19 vaccine based on a replication-defective gorilla adenovirus expressing the stabilized prefusion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein named GRAd-COV2. We assessed the safety and immunogenicity of a single-dose regimen of this vaccine in healthy younger and older adults to select the appropriate dose for each age group. For this purpose, a phase 1, dose-escalation, open-labeled trial was conducted including 90 healthy participants (45 aged 18 to 55 years old and 45 aged 65 to 85 years old) who received a single intramuscular administration of GRAd-COV2 at three escalating doses. Local and systemic adverse reactions were mostly mild or moderate and of short duration, and no serious adverse events were reported. Four weeks after vaccination, seroconversion to spike protein and receptor binding domain was achieved in 43 of 44 young volunteers and in 45 of 45 older participants. Consistently, neutralizing antibodies were detected in 42 of 44 younger-age and 45 of 45 older-age volunteers. In addition, GRAd-COV2 induced a robust and T helper 1 cell (TH1)­skewed T cell response against the spike protein in 89 of 90 participants from both age groups. Overall, the safety and immunogenicity data from the phase 1 trial support the further development of this vaccine.


Subject(s)
Adenovirus Vaccines , COVID-19 , Adenoviridae , Aged , Animals , COVID-19 Vaccines , Gorilla gorilla , Humans , SARS-CoV-2
17.
Nutrients ; 13(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1463781

ABSTRACT

To date, vitamin D seems to have a significant role in affecting the prevention and immunomodulation in COVID-19 disease. Nevertheless, it is important to highlight that this pro-hormone has other several activities, such as affecting drug concentrations, since it regulates the expression of cytochrome P450 (CYP) genes. Efavirenz (EFV) pharmacokinetics is influenced by CYPs, but no data are available in the literature concerning the association among vitamin D levels, seasonality (which affects vitamin D concentrations) and EFV plasma levels. For this reason, the aim of this study was to evaluate the effect of 25-hydroxy vitamin D (25(OH)D3) levels on EFV plasma concentrations in different seasons. We quantified 25(OH)D3 by using chemiluminescence immunoassay, whereas EFV plasma concentrations were quantified with the HPLC-PDA method. A total of 316 patients were enrolled in Turin and Rome. Overall, 25(OH)D3levels resulted in being inversely correlated with EFV concentrations. Some patients with EFV levels higher than 4000 ng/mL showed a deficient 25(OH)D3 concentration in Turin and Rome cohorts and together. EFV concentrations were different in patients without vitamin D supplementation, whereas, for vitamin D-administered individuals, no difference in EFV exposure was present. Concerning seasonality, EFV concentrations were associated with 25(OH)D3 deficiency only in winter and in spring, whereas a significant influence was highlighted for 25(OH)D3 stratification for deficient, insufficient and sufficient values in winter, spring and summer. A strong and inverse association between 25(OH)D3and EFV plasma concentrations was suggested. These data suggest that vitamin D is able to affect drug exposure in different seasons; thus, the achievement of the clinical outcome could be improved by also considering this pro-hormone.


Subject(s)
Alkynes/blood , Alkynes/therapeutic use , Benzoxazines/blood , Benzoxazines/therapeutic use , Cyclopropanes/blood , Cyclopropanes/therapeutic use , HIV Infections/blood , HIV Infections/drug therapy , Vitamin D/pharmacology , Vitamins/pharmacology , Adult , Cohort Studies , Female , Humans , Italy , Male , Middle Aged , Retrospective Studies , Reverse Transcriptase Inhibitors/blood , Reverse Transcriptase Inhibitors/therapeutic use , Seasons , Treatment Outcome , Vitamin D/blood , Vitamins/blood
18.
J Clin Med ; 10(18)2021 Sep 12.
Article in English | MEDLINE | ID: covidwho-1409878

ABSTRACT

BACKGROUND: critically ill patients with SARS-CoV-2 infection present a hypercoagulable condition. Anticoagulant therapy is currently recommended to reduce thrombotic risk, leading to potentially severe complications like spontaneous bleeding (SB). Percutaneous transcatheter arterial embolization (PTAE) can be life-saving in critical patients, in addition to medical therapy. We report a major COVID-19 Italian Research Hospital experience during the pandemic, with particular focus on indications and technique of embolization. METHODS: We retrospectively included all subjects with SB and with a microbiologically confirmed SARS-CoV-2 infection, over one year of pandemic, selecting two different groups: (a) patients treated with PTAE and medical therapy; (b) patients treated only with medical therapy. Computed tomography (CT) scan findings, clinical conditions, and biological findings were collected. RESULTS: 21/1075 patients presented soft tissue SB with an incidence of 1.95%. 10/21 patients were treated with PTAE and medical therapy with a 30-days survival of 70%. Arterial blush, contrast late enhancement, and dimensions at CT scan were found discriminating for the embolization (p < 0.05). CONCLUSIONS: PTAE is an important tool in severely ill, bleeding COVID-19 patients. The decision for PTAE of COVID-19 patients must be carefully weighted with particular attention paid to the clinical and biological condition, hematoma location and volume.

19.
Int J Infect Dis ; 108: 244-251, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1351698

ABSTRACT

OBJECTIVES: To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. DESIGN AND METHODS: This case-control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO2/FiO2 <250 mmHg and who needed ventilatory support during hospitalization (severe COVID-19). The 24 controls were selected in a 1:1 ratio, matched by age, from patients who maintained PaO2/FiO2 >300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. RESULTS: Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate. CONCLUSIONS: A low level of testosterone was found to be a marker of clinical severity of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Biomarkers , Case-Control Studies , Humans , Male , Testosterone , Virulence Factors
20.
Viruses ; 13(7)2021 07 19.
Article in English | MEDLINE | ID: covidwho-1344395

ABSTRACT

OBJECTIVES: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. METHODS: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. RESULTS: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). CONCLUSIONS: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.


Subject(s)
Disease Eradication/statistics & numerical data , HIV Infections/virology , Hepacivirus/genetics , Hepatitis C/prevention & control , Lipid Metabolism , Antiviral Agents/therapeutic use , Cholesterol/blood , Cholesterol, LDL/blood , Cohort Studies , Female , Genotype , Hepacivirus/classification , Hepacivirus/drug effects , Hepatitis C/drug therapy , Humans , Italy , Male , Middle Aged , Sustained Virologic Response
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