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1.
Cell Rep Med ; 4(6): 101084, 2023 06 20.
Article in English | MEDLINE | ID: covidwho-2327715

ABSTRACT

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.


Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , COVID-19 Vaccines , COVID-19/prevention & control , Immunity, Cellular
2.
Antibiotics (Basel) ; 11(11)2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2089985

ABSTRACT

Secondary bloodstream infections (BSIs) caused by KPC- and NDM-producing Klebsiella pneumoniae (K.p.) during the course of COVID-19 infections lead to significant mortality. Herein, a comparative retrospective case series of KPC- or NDM-K.p. BSIs occurring in COVID-19 subjects treated with Ceftazidime/Avibactam (CAZ/AVI) for KPC-K.p., or CAZ/AVI+ Aztreonam (ATM) for NDM-K.p is reported. All patients hospitalized for COVID-19 in two Italian hospitals with a BSI between March and September 2021 were included. The main outcome was 14-day mortality. Overall, 44 patients were included: 23 with KPC-K.p. and 21 with NDM-K.p. BSIs. The median (q1-q3) age was 67 (57-75) years, and 32 (72%) were males. The two groups were similar in terms of baseline comorbidity, or severity of COVID-19. Notably, 14-day mortality of KPC-K.p. BSIs and NDM-K.p. BSIs (26% vs. 38%, p = 0.521) and 28-day mortality (35% vs. 48%, p = 0.541) were similar. A Cox regression model of delayed initiation of an appropriate antibiotic therapy after the onset of symptoms independently predicted mortality: initiation between 24 and 72 h (aHR = 12.03; 95% CI = 1.10-130, p = 0.041); and initiation after 72h (aHR = 36.9, 95% CI = 3.22-424, p = 0.004). Moreover, a trend towards an increased risk of mortality was observed for polymicrobial infections (aHR = 3.73, 95% CI = 0.87-15.8, p = 0.074), while a protective effect was observed for a beta-lactam loading dose at the start of treatment (aHR = 0.16, 95% CI = 0.02-1.10, p = 0.064). The high mortality of KPC and NDM-K.p. BSIs in COVID-19 patients may be reduced by an early and appropriate antibiotic therapy. Further efforts should be made to develop antimicrobial stewardship and infection control programs in COVID-19 wards.

3.
JAC Antimicrob Resist ; 4(3): dlac064, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1961072

ABSTRACT

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE). Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-ß-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality. Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) (n = 64, 52%), followed by urinary-tract infections (UTI) (n = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) (n = 28, 22.8%), intra-abdominal infections (n = 2, 1.6%) and skin infections (n = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P = 0.002) were predictors of 30 day mortality. Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients.

4.
Clin Infect Dis ; 73(11): e4031-e4038, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559750

ABSTRACT

BACKGROUND: Prolonged QTc intervals and life-threatening arrhythmias (LTA) are potential drug-induced complications previously reported with antimalarials, antivirals, and antibiotics. Our objective was to evaluate the prevalence and predictors of QTc interval prolongation and incidences of LTA during hospitalization for coronavirus disease 2019 (COVID-19) among patients with normal admission QTc. METHODS: We enrolled 110 consecutive patients in a multicenter international registry. A 12-lead electrocardiograph was performed at admission, after 7, and at 14 days; QTc values were analyzed. RESULTS: After 7 days, 15 (14%) patients developed a prolonged QTc (pQTc; mean QTc increase 66 ± 20 msec; +16%; P < .001); these patients were older and had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, and lower platelet counts. The QTc increase was inversely proportional to the baseline QTc level and leukocyte count and directly proportional to the basal heart rate (P < .01).We conducted a multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate, and dual antiviral therapy; age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; P < .05), basal heart rate (OR, 1.07; 95% CI, 1.02-1.13; P < .01), and dual antiviral therapy (OR, 12.46; 95% CI, 2.09-74.20; P < .1) were independent predictors of QT prolongation.The incidence rate of LTA during hospitalization was 3.6%. There was 1 patient who experienced cardiac arrest and 3 with nonsustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of the mortality rate. CONCLUSIONS: After 7 days of hospitalization, 14% of patients with COVID-19 developed pQTc; age, basal heart rate, and dual antiviral therapy were found to be independent predictors of pQTc. Life-threatening arrhythmias have an incidence rate of 3.6%, and were associated with a poor outcome.


Subject(s)
COVID-19 , Long QT Syndrome , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/etiology , Electrocardiography , Hospitalization , Humans , Male , Registries , SARS-CoV-2
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