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1.
Microorganisms ; 10(5)2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1834846

ABSTRACT

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.

2.
Swiss Med Wkly ; 151: w20550, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1350364

ABSTRACT

OBJECTIVES: Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS: In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation <93%, respiratory rate >30/min, C-reactive protein levels >75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS: Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS: In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351503.


Subject(s)
COVID-19 , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Cohort Studies , Humans , Prospective Studies , SARS-CoV-2
3.
Blood ; 136(Supplement 1):29-30, 2020.
Article in English | PMC | ID: covidwho-1338955

ABSTRACT

Background. COVID-19, caused by the SARS-CoV-2 virus, is a pandemic disease with high morbidity and mortality. Currently, available therapeutic options for COVID-19 are limited. Prior experience in epidemics with convalescent plasma (CP) containing antibodies to viruses has demonstrated variable indications of therapeutic efficacy for: Influenza, Argentine Hemorrhagic Fever, and SARS. Characterizing antibody titers to viruses has indicated correlation with therapeutic efficacy. Convalescent COVID-19 patients with potent SARS-CoV-2 antibody responses can serve as plasma donors for immune therapy. However, antibody responses are variable, many donors are first-time higher risk blood donors, and rapid assays to select optimal CP immune efficacy are limited. Pathogen inactivation (PI) of CP can reduce the risk of transfusion-transmitted infection by unrecognized pathogens. Objectives. This study characterized COVID-19 PI-CP activity;and evaluated efficacy and safety of PI CP transfusion in a case matched controlled cohort of acute COVID-19 patients. Methods. COVID-19 apheresis CP (650 - 1300 mL) was collected from nasopharyngeal PCR + outpatients following 2 PCR negative tests or 28 days after symptom resolution. Amotosalen-UVA PI of CP (INTERCEPT Blood System for Plasma) was performed, and antibody efficacy before and after PI was characterized by: VSV reporter pseudo-virus plaque neutralization (RVPN) NT-50 titer (Vitalant Research Institute, San Francisco), antibody to S and N virus proteins by agglutination-dependent antibody PCR (ADAP, Enable Biosciences, San Francisco), virus ACE-2 soluble receptor neutralization assay (Enable Biosciences), and SARS-CoV-2 antibody profile by coronavirus microarray (University of California, Irvine). Patient inclusion criteria were: confirmed SARS-CoV-2 infection, hospitalization, pulmonary infiltrates, availability of ABO compatible CP, and informed consent. CP patients were matched with control patients (CTRL) for disease severity at diagnosis by standardized clinical risk score (W. Liang et al JAMA Intern Med 2020) and concomitant Tocilizumab use. CP Patients received a total of 400 mL of PI CP from 2 donors over 48 hours and standard therapy. CTRL patients received standard COVID-19 therapy without CP. The primary outcome was in-hospital death to day 28. Secondary outcomes included: progression to intubation, admission to ICU, time to discharge, serious adverse events, NP viral clearance, plasma viral clearance, and humoral immune responses. Differences between CP and CTRL patients were assessed by the Mann-Whitney test for continuous variables, and by Fisher's exact test for categorical variables. Progression to ICU and intubation were analyzed as odds ratios calculated by conditional logistic regression. Results. 15 CP and 30 CTRL patients were enrolled. One CP patient was admitted in cardiogenic shock. Only 2 of 15 CP cohort patients had detectable IgG antibody to SARS CoV-2 S1 antigen at study entry. 3 of 15 PI CP donors had negligible SARS CoV-2 IgG antibodies to all antigens, and demonstrated poor neutralization efficacy. 12/15 CP had effective RVPN titers (>1:80), RVPN titers were correlated with ACE-2 neutralization antibody titers (r2 = 0.83), and had significant activity specific for S and RBD antigens by microarray profiling (Figure 1). SARS CoV-2 antibody levels were variable between CP donors, but not impacted by PI (Figure 1). Baseline characteristics of CP and matched CTRL patients were similar (Table 1). Sensitivity analysis was performed assessing mortality after exclusion of one CTRL patient admitted in cardiogenic shock and the 2 respective controls. In-hospital 28-day mortality was lower in the CP cohort (0/14) compared to 5/28 CTRL, p = 0.151, 2-sided Fisher's exact test. Progression to intubation, ICU admission, and days in hospital were not significantly different (Table 1). There was a trend toward decreased inflammatory response (CRP normalization) in CP patients. Conclusions. In hospital mortality of COVID-19 patients was lower in the PI-CP cohor , but not statistically significant. 15% of CP had ineffective antibody by multiple assays. However, PI did not impact CP anti-SARS-CoV-2 activity. PI of plasma provides reduced risk of transfusion transmitted infection from COVID-19 CP donors. In this study, PI CP was safe, and may be effective for early treatment of hospitalized COVID-19 patients.

4.
Swiss Med Wkly ; 151: w20572, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1332303

ABSTRACT

AIMS: The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland. METHODS: In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients’ characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality. RESULTS: During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53–76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45–2.26; p <0.001), male sex (aOR 1.68, 95% CI 1.00–2.82; p = 0.048), immunocompromising condition (aOR 2.09, 95% CI 1.01–4.33; p = 0.048) and chronic kidney disease (aOR 2.25, 95% CI 1.35–3.76; p = 0.002). CONCLUSION: In our study in-hospital mortality was 9.5%, 10.2% and 5.4% in the first, second and third waves, respectively. Age, immunocompromising condition, male sex and chronic kidney disease were factors associated with in-hospital mortality. Importantly, patients without any comorbidity had a very low in-hospital mortality regardless of age.


Subject(s)
COVID-19/diagnosis , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , SARS-CoV-2 , Aged , COVID-19/mortality , Cohort Studies , Comorbidity , Female , Humans , Kidney Diseases/epidemiology , Kidney Diseases/therapy , Length of Stay , Male , Middle Aged , Renal Replacement Therapy/adverse effects , Retrospective Studies , Risk Factors , Switzerland/epidemiology
5.
J Intensive Care ; 9(1): 10, 2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1067283

ABSTRACT

OBJECTIVES: SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. METHODS: We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. RESULTS: In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4-74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8-18) and time to bloodstream infection 14 days (IQR, 6-30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. CONCLUSIONS: Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

6.
Antimicrob Agents Chemother ; 64(9)2020 08 20.
Article in English | MEDLINE | ID: covidwho-639066

ABSTRACT

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.


Subject(s)
Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Hydroxychloroquine/pharmacokinetics , Lopinavir/pharmacokinetics , Pneumonia, Viral/drug therapy , Ritonavir/pharmacokinetics , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/blood , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Drug Administration Schedule , Drug Combinations , Female , Hospitals, University , Humans , Hydroxychloroquine/blood , Hydroxychloroquine/pharmacology , Length of Stay/statistics & numerical data , Lopinavir/blood , Lopinavir/pharmacology , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Ritonavir/blood , Ritonavir/pharmacology , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
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