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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.
Virus Evol ; 8(1): veac002, 2022.
Article in English | MEDLINE | ID: covidwho-1746220

ABSTRACT

Transmission chains within small urban areas (accommodating ∼30 per cent of the European population) greatly contribute to case burden and economic impact during the ongoing coronavirus pandemic and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in a European urban area, Basel-City (Switzerland). We combined detailed epidemiological, intra-city mobility and socio-economic data sets with whole-genome sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44 per cent of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60 per cent of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare system burden (intensive care unit (ICU) occupancy). Transmissions were driven by socio-economically weaker and highly mobile population groups with mostly cryptic transmissions which lacked genetic and identifiable epidemiological links. Amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90 per cent transmission reduction and 70-90 per cent reduction of severe cases showed that prioritising mobile, socio-economically weaker populations for vaccination would effectively reduce case numbers. However, long-term ICU occupation would also be effectively reduced if senior population groups were prioritised, provided there were no changes in testing and prevention strategies. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area.

3.
Swiss Med Wkly ; 151: w30105, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1689912

ABSTRACT

BACKGROUND: When the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe are compared, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors. METHODS: We investigated the trends in COVID-19-related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to June 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk. RESULTS: Our analysis included 16,984 patients recorded in CH-SUR, with 2201 reported deaths due to COVID-19 (13.0%). We found that overall in-hospital mortality was lower during the second wave of COVID-19 than in the first wave (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.63- 0.78; p <0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared with the first wave (HR 1.25, 95% CI 1.05-1.49; p = 0.029), with significant changes in the course of hospitalisation between the first and the second wave. CONCLUSION: We found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.


Subject(s)
COVID-19 , Hospital Mortality , Hospitals , Humans , Pandemics , SARS-CoV-2 , Switzerland/epidemiology
4.
Antimicrob Resist Infect Control ; 11(1): 30, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1677540

ABSTRACT

BACKGROUND: Protecting healthcare workers (HCWs) from exposure to SARS-CoV-2 during patient care is central to managing the current pandemic. Higher levels of trust in personal protective equipment (PPE) and infection prevention and control (IPC) strategies have been previously related to lower levels of emotional exhaustion, yet little is known on how to achieve such a perception of safety. We thus sought to identify institutional actions, strategies and policies related to HCWs' safety perception during the early phase of the pandemic at a tertiary care center in Switzerland by interviewing HCWs from different clinics, professions, and positions. METHODS: For this qualitative study, 36 face-to-face semi-structured interviews were performed. Interviews were based on a guide that addressed the perception of institutional strategies and policies during the first phase of the pandemic in March 2020. The participants included doctors (n = 19) and nurses (n = 17) in senior and non-senior positions from eight clinics in the University Hospital Basel, Switzerland, all involved in patient care. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using qualitative content analysis and organized using MAXQDA (VERBI Software GmbH, Berlin). FINDINGS: Five recurring themes were identified to affect HCWs' perception of their safety during the SARS-CoV-2 pandemic: (1) transparency and clarity of information, (2) communication on the availability of PPE (with the provision of information alone increasing the feeling of safety even if supplies of PPE were reported as low), (3) uniformity and consistency of guidelines, (4) digital resources to support face-to-face teaching (although personal information transfer is still being considered superior in terms of strengthening safety perception) and (5) support and appreciation for the work performed. CONCLUSIONS: This study identifies institutional policies and actions influencing HCWs' safety perception during the first wave of the COVID-19 pandemic, the most important of which is the factor of transparent communication. This knowledge reveals potential areas of action critical to improving preparedness and management in hospitals faced with an infectious disease threat.


Subject(s)
COVID-19/prevention & control , Health Personnel , Pandemics , Personal Protective Equipment , Tertiary Care Centers , COVID-19/epidemiology , Humans , Infection Control/statistics & numerical data , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Patient Care , Personal Protective Equipment/standards , Qualitative Research , SARS-CoV-2 , Switzerland/epidemiology
5.
Swiss Med Wkly ; 151: w30105, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1542904

ABSTRACT

BACKGROUND: When the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe are compared, the associated COVID-19 mortality seems to have decreased substantially. Various factors could explain this trend, including changes in demographic characteristics of infected persons and the improvement of case management. To date, no study has been performed to investigate the evolution of COVID-19 in-hospital mortality in Switzerland, while also accounting for risk factors. METHODS: We investigated the trends in COVID-19-related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to June 2021, comparing in particular the first and the second wave. We used data from the COVID-19 Hospital-based Surveillance (CH-SUR) database. We performed survival analyses adjusting for well-known risk factors of COVID-19 mortality (age, sex and comorbidities) and accounting for competing risk. RESULTS: Our analysis included 16,984 patients recorded in CH-SUR, with 2201 reported deaths due to COVID-19 (13.0%). We found that overall in-hospital mortality was lower during the second wave of COVID-19 than in the first wave (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.63- 0.78; p <0.001), a decrease apparently not explained by changes in demographic characteristics of patients. In contrast, mortality in intermediate and intensive care significantly increased in the second wave compared with the first wave (HR 1.25, 95% CI 1.05-1.49; p = 0.029), with significant changes in the course of hospitalisation between the first and the second wave. CONCLUSION: We found that, in Switzerland, COVID-19 mortality decreased among hospitalised persons, whereas it increased among patients admitted to intermediate or intensive care, when comparing the second wave to the first wave. We put our findings in perspective with changes over time in case management, treatment strategy, hospital burden and non-pharmaceutical interventions. Further analyses of the potential effect of virus variants and of vaccination on mortality would be crucial to have a complete overview of COVID-19 mortality trends throughout the different phases of the pandemic.


Subject(s)
COVID-19 , Hospital Mortality , Hospitals , Humans , Pandemics , SARS-CoV-2 , Switzerland/epidemiology
6.
J Clin Microbiol ; 59(12): e0138121, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1522904

ABSTRACT

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Testing , Cross-Sectional Studies , Humans , Immunoassay , Immunoglobulin G , Laboratories , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus
8.
Swiss Med Wkly ; 151: w30094, 2021 10 11.
Article in English | MEDLINE | ID: covidwho-1485323

ABSTRACT

BACKGROUND: Long-term symptoms after acute COVID-19 are highly debated. Nevertheless, data on long-term symptoms of COVID-19 in healthcare workers are scarce. METHODS: We assessed frequency and risk factors of persisting symptoms in a retrospective cohort of healthcare workers infected with SARS-CoV-2. RESULTS: Persistent symptoms at 3 and 12 months were reported by 26.5% and 13.5% of participants, respectively. Most commonly reported symptoms were fatigue, impaired sense of taste or smell and general weakness. A history of depression or state of exhaustion, pre-existing lung disease and older age were associated with persisting symptoms. CONCLUSION: Our study shows that a relevant proportion of healthcare workers with mild COVID-19 report persisting symptoms over 3 and 12 months. Although in the majority of cases symptoms are mild, this study highlights the need for further research into causes and therapy.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Cohort Studies , Health Personnel , Humans , Retrospective Studies
9.
Clin Pharmacol Ther ; 111(3): 579-584, 2022 03.
Article in English | MEDLINE | ID: covidwho-1396859

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) may experience a cytokine storm with elevated interleukin-6 (IL-6) levels in response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). IL-6 suppresses hepatic enzymes, including CYP3A; however, the effect on drug exposure and drug-drug interaction magnitudes of the cytokine storm and resulting elevated IL-6 levels have not been characterized in patients with COVID-19. We used physiologically-based pharmacokinetic (PBPK) modeling to simulate the effect of inflammation on the pharmacokinetics of CYP3A metabolized drugs. A PBPK model was developed for lopinavir boosted with ritonavir (LPV/r), using clinically observed data from people living with HIV (PLWH). The inhibition of CYPs by IL-6 was implemented by a semimechanistic suppression model and verified against clinical data from patients with COVID-19, treated with LPV/r. Subsequently, the verified model was used to simulate the effect of various clinically observed IL-6 levels on the exposure of LPV/r and midazolam, a CYP3A model drug. Clinically observed LPV/r concentrations in PLWH and patients with COVID-19 were predicted within the 95% confidence interval of the simulation results, demonstrating its predictive capability. Simulations indicated a twofold higher LPV exposure in patients with COVID-19 compared with PLWH, whereas ritonavir exposure was predicted to be comparable. Varying IL-6 levels under COVID-19 had only a marginal effect on LPV/r pharmacokinetics according to our model. Simulations showed that a cytokine storm increased the exposure of the CYP3A paradigm substrate midazolam by 40%. Our simulations suggest that CYP3A metabolism is altered in patients with COVID-19 having increased cytokine release. Caution is required when prescribing narrow therapeutic index drugs particularly in the presence of strong CYP3A inhibitors.


Subject(s)
COVID-19/complications , Cytochrome P-450 CYP3A/metabolism , Cytokine Release Syndrome/virology , Lopinavir/pharmacokinetics , Midazolam/pharmacokinetics , Ritonavir/pharmacokinetics , Adult , COVID-19/drug therapy , COVID-19/metabolism , Cytochrome P-450 CYP3A/pharmacokinetics , Cytochrome P-450 CYP3A Inhibitors/pharmacokinetics , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/metabolism , Cytokines/metabolism , Humans , Metabolic Clearance Rate/drug effects , Middle Aged , Models, Biological
10.
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
11.
Swiss Med Wkly ; 150: w20281, 2020 May 04.
Article in English | MEDLINE | ID: covidwho-1348747
12.
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.

13.
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
15.
Microorganisms ; 9(5)2021 May 19.
Article in English | MEDLINE | ID: covidwho-1234778

ABSTRACT

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima's D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.

16.
J Med Virol ; 93(4): 2374-2384, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217387

ABSTRACT

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively. CONCLUSION: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/methods , SARS-CoV-2/isolation & purification , Adult , Bronchoalveolar Lavage , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , COVID-19 Testing , Disease Transmission, Infectious/prevention & control , Female , Genome, Viral , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Pandemics , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Switzerland/epidemiology , Viral Load
17.
PLoS Pathog ; 17(3): e1009374, 2021 03.
Article in English | MEDLINE | ID: covidwho-1143300

ABSTRACT

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.


Subject(s)
COVID-19/diagnosis , Contact Tracing/methods , Crowding , Genome, Viral , Mutation , SARS-CoV-2/genetics , Adult , COVID-19/epidemiology , COVID-19/genetics , Female , Humans , Longitudinal Studies , Male , Mass Screening , Middle Aged , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Switzerland/epidemiology
18.
Antimicrob Resist Infect Control ; 10(1): 44, 2021 02 27.
Article in English | MEDLINE | ID: covidwho-1105744

ABSTRACT

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Aged , COVID-19/epidemiology , COVID-19/transmission , COVID-19 Testing/economics , COVID-19 Testing/methods , Cost-Benefit Analysis , Female , Humans , Male , Mass Screening/economics , Mass Screening/methods , Middle Aged , Switzerland/epidemiology
20.
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.

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