Evaluation of a surveillance system for Clostridioides difficile infections for Swiss hospitals.

AIMS: This study evaluated an approach to establishing a comprehensive nationwide surveillance system for Clostridioides difficile infection in Switzerland. We report the results of patient-related surveillance and calculate the incidence rate of C. difficile infection in Switzerland in 2022. METHODS: Initiated in 2017 by the National Centre for Infection Prevention (Swissnoso), in collaboration with the Swiss Centre for Antibiotic Resistance (ANRESIS), laboratory surveillance enables the automatic import of C. difficile infection laboratory data and is fully operational. However, the very limited number of participating laboratories impedes the generation of representative results. To address this gap, Swissnoso introduced patient-related surveillance, with a questionnaire-based survey used across Swiss acute care hospitals. RESULTS: This survey revealed an incidence of 3.8 (Poisson 95% CI: 3.2-4.5) C. difficile infection episodes per 10,000 patient-days, just above the mean rate reported by the European Centre for Disease Prevention and Control (ECDC). Additionally, we report substantial heterogeneity in laboratory tests, diagnostic criteria and infection control practices among Swiss hospitals. CONCLUSION: This study underscores the importance of a joint effort towards standardized surveillance practices in providing comprehensive insights into C. difficile infection epidemiology and effective prevention strategies in Swiss healthcare settings. The patient-related approach remains the gold standard for C. difficile infection surveillance, although it demands substantial resources and provides results only annually. The proposed implementation of nationwide automated laboratory-based surveillance would be pragmatic and efficient, empowering authorities and hospitals to detect outbreaks promptly and to correlate infection rates with antibiotic consumption.

Impact of the COVID-19 pandemic on antibiotic prescribing in high-prescribing primary care physicians in Switzerland.

OBJECTIVES: The aim of this study was to evaluate antibiotic prescribing of medium-to-high prescribing primary care physicians being followed up after the completion of a Swiss national intervention trial of antibiotic prescription audit and feedback in the first SARS-CoV-2 pandemic year. METHODS: We used health insurer based claims data to calculate monthly antibiotic prescription rates per 100 consultations (primary endpoint) and applying interrupted time series (ITS) analysis methods, we estimated the immediate (step change) and sustained effects (slope) of the SARS-CoV-2 epidemic in 2020 on antibiotic prescribing compared to the pre-pandemic trial period from 2017-2019. RESULTS: We analysed data of 2945 of 3426 physicians (86.0%) from the trial with over 4 million consultations annually, who were in 2020 still in practice. Consultations dropped by 43% during the first pandemic year compared with 2017. Median monthly antibiotic prescription rates per 100 consultations in 2017 were 8.44 (Interquartile range [IQ] 6.32-11.50) and 8.35 (6.34-11.74) in the intervention and control groups, respectively, and increased to 15.63 (10.69-23.81) and 16.31 (10.65-24.72) per 100 consultations in 2020. ITS-derived incidence rate ratios for overall antibiotic prescriptions were 2.32 (95% CI 2.07-2.59) for the immediate pandemic effect, and 0.96 (0.95-0.98) for the sustained effect (change in slope in 2020 compared with 2017-2019). DISCUSSION: The SARS-CoV-2 pandemic had a major impact on antibiotic prescription patterns in primary care in Switzerland. For future viral pandemics, intervention plans with timely activation steps to minimize unjustified antibiotic consumption in primary care should be prepared.

Association between the introduction of a national targeted intervention program and the incidence of surgical site infections in Swiss acute care hospitals.

BACKGROUND: In Switzerland, the national surgical site infection (SSI) surveillance program showed a modest decrease in SSI rates for different procedures over the last decade. The study aimed to determine whether a multimodal, targeted intervention program in addition to existing SSI surveillance is associated with decreased SSI rates in the participating hospitals. METHODS: Prospective multicenter pre- and postintervention study conducted in eight Swiss acute care hospitals between 2013 and 2020. All consecutive patients > 18 years undergoing cardiac, colon, or hip/knee replacement surgery were included. The follow-up period was 30 days and one year for implant-related surgery. Patients with at least one follow-up were included. The intervention was to optimize three elements of preoperative management: (i) hair removal; (ii) skin disinfection; and (iii) perioperative antimicrobial prophylaxis. We compared SSI incidence rates (main outcome measure) pre- and postintervention (three years each) adjusted for potential confounders. Poisson generalized linear mixed models fitted to quarter-yearly confirmed SSIs and adjusted for baseline differences between hospitals and procedures. Adherence was routinely monitored through on-site visits. RESULTS: A total of 10 151 patients were included, with a similar median age pre- and postintervention (69.6 and IQR 60.9, 76.8 years, vs 69.5 and IQR 60.4, 76.8 years, respectively; P = 0.55) and similar proportions of females (44.8% vs. 46.1%, respectively; P = 0.227). Preintervention, 309 SSIs occurred in 5 489 patients (5.6%), compared to 226 infections in 4 662 cases (4.8%, P = 0.09) postintervention. The adjusted incidence rate ratio (aIRR) for overall SSI after intervention implementation was 0.81 (95% CI, 0.68 to 0.96, P = 0.02). For cardiac surgery (n = 2 927), the aIRR of SSI was 0.48 (95% CI, 0.32 to 0.72, P < 0.001). For hip/knee replacement surgery (n = 4 522), the aIRR was 0.88 (95% CI, 0.52 to 1.48, P = 0.63), and for colon surgery (n = 2 702), the aIRR was 0.92 (95% CI, 0.75 to 1.14, P = 0.49). CONCLUSIONS: The SSI intervention bundle was associated with a statistically significant decrease in SSI cases. A significant association was observed for cardiac surgery. Adding a specific intervention program can add value compared to routine surveillance only. Further prevention modules might be necessary for colon and orthopedic surgery.

Timing of Cefuroxime Surgical Antimicrobial Prophylaxis and Its Association With Surgical Site Infections.

Importance: World Health Organization guidelines recommend administering surgical antimicrobial prophylaxis (SAP), including cefuroxime, within 120 minutes prior to incision. However, data from clinical settings supporting this long interval is limited. Objective: To assess whether earlier vs later timing of administration of cefuroxime SAP is associated with the occurrence of surgical site infections (SSI). Design, Setting, and Participants: This cohort study included adult patients who underwent 1 of 11 major surgical procedures with cefuroxime SAP, documented by the Swissnoso SSI surveillance system between January 2009 and December 2020 at 158 Swiss hospitals. Data were analyzed from January 2021 to April 2023. Exposures: Timing of cefuroxime SAP administration before incision was divided into 3 groups: 61 to 120 minutes before incision, 31 to 60 minutes before incision, and 0 to 30 minutes before incision. In addition, a subgroup analysis was performed with time windows of 30 to 55 minutes and 10 to 25 minutes as a surrogate marker for administration in the preoperating room vs in the operating room, respectively. The timing of SAP administration was defined as the start of the infusion obtained from the anesthesia protocol. Main Outcomes and Measures: Occurrence of SSI according to Centers for Disease Control and Prevention definitions. Mixed-effects logistic regression models adjusted for institutional, patient, and perioperative variables were applied. Results: Of 538 967 surveilled patients, 222 439 (104 047 men [46.8%]; median [IQR] age, 65.7 [53.9-74.2] years), fulfilled inclusion criteria. SSI was identified in 5355 patients (2.4%). Cefuroxime SAP was administered 61 to 120 minutes prior to incision in 27 207 patients (12.2%), 31 to 60 minutes prior to incision in 118 004 patients (53.1%), and 0 to 30 minutes prior to incision in 77 228 patients (34.7%). SAP administration at 0 to 30 minutes was significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.85; 95% CI, 0.78-0.93; P < .001), as was SAP administration 31 to 60 minutes prior to incision (aOR, 0.91; 95% CI, 0.84-0.98; P = .01) compared with administration 61 to 120 minutes prior to incision. Administration 10 to 25 minutes prior to incision in 45 448 patients (20.4%) was significantly associated with a lower SSI rate (aOR, 0.89; 95% CI, 0.82-0.97; P = .009) vs administration within 30 to 55 minutes prior to incision in 117 348 patients (52.8%). Conclusions and Relevance: In this cohort study, administration of cefuroxime SAP closer to the incision time was associated with significantly lower odds of SSI, suggesting that cefuroxime SAP should be administrated within 60 minutes prior to incision, and ideally within 10 to 25 minutes.

A three-level model for therapeutic drug monitoring of antimicrobials at the site of infection.

The silent pandemic of bacterial antimicrobial resistance is a leading cause of death worldwide, prolonging hospital stays and raising health-care costs. Poor incentives to develop novel pharmacological compounds and the misuse of antibiotics contribute to the bacterial antimicrobial resistance crisis. Therapeutic drug monitoring (TDM) based on blood analysis can help alleviate the emergence of bacterial antimicrobial resistance and effectively decreases the risk of toxic drug concentrations in patients' blood. Antibiotic tissue penetration can vary in patients who are critically or chronically ill and can potentially lead to treatment failure. Antibiotics such as ß-lactams and glycopeptides are detectable in non-invasively collectable biofluids, such as sweat and exhaled breath. The emergence of wearable sensors enables easy access to these non-invasive biofluids, and thus a laboratory-independent analysis of various disease-associated biomarkers and drugs. In this Personal View, we introduce a three-level model for TDM of antibiotics to describe concentrations at the site of infection (SOI) by use of wearable sensors. Our model links blood-based drug measurement with the analysis of drug concentrations in non-invasively collectable biofluids stemming from the SOI to characterise drug concentrations at the SOI. Finally, we outline the necessary clinical and technical steps for the development of wearable sensing platforms for SOI applications.

An appeal for strengthening genomic pathogen surveillance to improve pandemic preparedness and infection prevention: the German perspective.

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.

Effect of Antibiotic Prescription Audit and Feedback on Antibiotic Prescribing in Primary Care: A Randomized Clinical Trial.

Importance: Antibiotics are commonly prescribed in primary care, increasing the risk of antimicrobial resistance in the population. Objective: To investigate the effect of quarterly audit and feedback on antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Design, Setting, and Participants: This pragmatic randomized clinical trial was conducted from January 1, 2018, to December 31, 2019, among 3426 registered primary care physicians and pediatricians in single or small practices in Switzerland who were among the top 75% prescribers of antibiotics. Intention-to-treat analysis was performed using analysis of covariance models and conducted from September 1, 2021, to January 31, 2022. Interventions: Primary care physicians were randomized in a 1:1 fashion to undergo quarterly antibiotic prescribing audit and feedback with peer benchmarking vs no intervention for 2 years, with 2017 used as the baseline year. Anonymized patient-level claims data from 3 health insurers serving roughly 50% of insurees in Switzerland were used for audit and feedback. The intervention group also received evidence-based guidelines for respiratory tract and urinary tract infection management and community antibiotic resistance information. Physicians in the intervention group were blinded regarding the nature of the trial, and physicians in the control group were not informed of the trial. Main Outcomes and Measures: The claims data used for audit and feedback were analyzed to assess outcomes. Primary outcome was the antibiotic prescribing rate per 100 consultations during the second year of the intervention. Secondary end points included overall antibiotic use in the first year and over 2 years, use of quinolones and oral cephalosporins, all-cause hospitalizations, and antibiotic use in 3 age groups. Results: A total of 3426 physicians were randomized to the intervention (n = 1713) and control groups (n = 1713) serving 629 825 and 622 344 patients, respectively, with a total of 4 790 525 consultations in the baseline year of 2017. In the entire cohort, a 4.2% (95% CI, 3.9%-4.6%) relative increase in the antibiotic prescribing rate was noted during the second year of the intervention compared with 2017. In the intervention group, the median annual antibiotic prescribing rate per 100 consultations was 8.2 (IQR, 6.1-11.4) in the second year of the intervention and was 8.4 (IQR, 6.0-11.8) in the control group. Relative to the overall increase, a -0.1% (95% CI, -1.2% to 1.0%) lower antibiotic prescribing rate per 100 consultations was found in the intervention group compared with the control group. No relevant reductions in specific antibiotic prescribing rates were noted between groups except for quinolones in the second year of the intervention (-0.9% [95% CI, -1.5% to -0.4%]). Conclusions and Relevance: This randomized clinical trial found that quarterly personalized antibiotic prescribing audit and feedback with peer benchmarking did not reduce antibiotic prescribing among primary care physicians in Switzerland with medium to high antibiotic prescription rates. Trial Registration: ClinicalTrials.gov Identifier: NCT03379194.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the adherence to hand hygiene practice in hospitals-Data from a Swiss national surveillance system.

In >100,000 observations across Swiss acute-care hospitals, hand hygiene (HH) adherence significantly increased during the first coronavirus disease 2019 (COVID-19) wave. However, despite persisting COVID-19 activity, HH adherence returned to prepandemic levels over a 2-year observation period. These results indicate that training and support remains challenging.

Patients exposed to vancomycin-resistant enterococci during in-hospital outbreaks in a low endemic setting: a proposal for risk-based screening.

BACKGROUND: The optimal extent of screening of contact patients (CoPat) after exposure to patients infected or colonized with vancomycin-resistant enterococci (VRE) remains controversial. METHODS: We retrospectively developed a new risk stratification for screening patients exposed to VRE, based on data from three outbreaks-two with Enterococcus faecium vanB and one with Enterococcus faecium vanA involving 1096 CoPat-in a low endemic setting. We classified them into four risk groups: three on environmental exposure, one by healthcare exposure: high (sharing the same room/bathroom with a VRE-colonized patient), medium (hospitalization in the same room after a VRE-colonized patient's discharge until terminal disinfection including ultraviolet C (UVc)-disinfection), low (hospitalized in the same room within three weeks before the VRE-colonized patient), and "staff" (screening of patients having the same medical care team). RESULTS: VRE-transmission occurred in 7.9% in the high-risk group compared to 0.6% and 0% in the medium and low risk groups. There was a significant trend to higher rates of transmission by risk level of exposure (p < 0.001). In the "staff" group, VRE transmission rate was 2.3%. CONCLUSION: Based on this stratification, we recommend to focus screening of exposed CoPat on the high-risk and "staff" group, saving resources and costs, but larger studies will allow to further improve the yield of VRE screening in the outbreak setting.

Nosocomial transmission of a blaVIM-2 carbapenemase integron between isolates of two different Pseudomonas species.

We report the first documented in-hospital patient-to-patient-transmission of a blaVIM-2 integron between isolates of Pseudomonas alcaligenes and P. aeruginosa. Molecular typing looking only for difference within species may fail to detect nosocomial transmission of resistance genes.

Association Between Antimicrobial Prophylaxis With Double-Dose Cefuroxime and Surgical Site Infections in Patients Weighing 80 kg or More.

Importance: Many guidelines recommend a weight-adopted dose increase of cefuroxime for surgical antimicrobial prophylaxis (SAP). However, the evidence that this approach is associated with lower rates of surgical site infection (SSI) is limited. Objective: To assess whether double-dose cefuroxime SAP was associated with a decreased SSI rate in patients weighing at least 80 kg. Design, Setting, and Participants: This cohort study included adult patients (>18 years) weighing at least 80 kg who underwent 9 major surgical procedures with a cefuroxime SAP administration from the Swissnoso SSI surveillance system between January 2015 and December 2019 at 142 Swiss hospitals. The follow-up was 30 days for all surgical procedures and 1 year for implant-related operations. Exposures: Cefuroxime SAP dose (1.5 vs 3.0 g). Main Outcomes and Measures: Overall SSI. A mixed-effects logistic regression adjusted for institutional, epidemiological, and perioperative variables was applied. Results were stratified by weight categories as well as by wound contamination classes. Results: Of 41 076 eligible patients, 37 640 were included, with 22 625 (60.1%) men and a median (IQR) age of 61.9 (49.9-71.1) years. The outcome SSI was met by 1203 patients (3.2%). Double-dose cefuroxime was administered to 13 246 patients (35.2%) and was not significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.89; 95% CI, 0.78-1.02; P = .10). After stratification by weight category, double-dose SAP vs single-dose SAP was associated with lower SSI rates among 16 605 patients weighing at least 80 to less than 90 kg (aOR, 0.76; 95% CI, 0.61-0.97; P = .02) but not in the other weight categories (≥90 to <100 kg, 10 342 patients: aOR, 1.12; 95% CI, 0.87-1.47; P = .37; ≥100 to <120 kg, 8099 patients: aOR, 0.99; 95% CI, 0.76-1.30; P = .96; ≥120 kg, 2594 patients: aOR, 0.65; 95% CI, 0.42-1.04; P = .06). After stratification by contamination class, double-dose SAP was associated with lower SSI rates among 1946 patients with contaminated wounds (aOR, 0.49; 95% CI, 0.30-0.84; P = .008) but not those with clean wounds (25 680 patients; aOR, 0.92; 95% CI, 0.76-1.12; P = .44) or clean-contaminated wounds (10 014 patients; aOR, 0.90; 95% CI, 0.73-1.12; P = .37) compared with a single dose. Conclusions and Relevance: In this study, double-dose SAP with cefuroxime for patients weighing at least 80 kg was not consistently associated with a lower SSI rate.

Long-term antimicrobial effectiveness of a silver-impregnated foil on high-touch hospital surfaces in patient rooms.

BACKGROUND: The hospital environment has got more attention as evidence as source for bacterial transmission and subsequent hospital-acquired infection increased. Regular cleaning and disinfection have been proposed to lower the risk of infection, in particular for gram-positive bacteria. Auto-disinfecting surfaces would allow to decrease survival of pathogens, while limiting resource to achieve a safe environment in patient rooms. METHODS: A controlled trial to evaluate the antimicrobial effectiveness of a polyvinyl chloride foil containing an integrated silver-based agent (containing silver ions 2%) on high-touch surfaces in patient rooms. RESULTS: The overall log reduction of the mean values was 1.8 log10 CFU, the median 0.5 log10 CFU comparing bioburden of control vs antimicrobial foil (p < 0.01). Important pathogens were significantly less likely recovered from the foil, in particular enterococci. These effects were present even after 6 months of in-use. CONCLUSIONS: A foil containing an integrated silver-based agent applied to high-touch surfaces effectively results in lower recovery of important pathogens from such surfaces over a 6-month study period.

Handrub dispensers per acute care hospital bed: a study to develop a new minimum standard.

BACKGROUND: Accessibility to alcohol-based handrub (ABHR) dispenser is crucial to improve compliance to hand hygiene (HH), being offered as wall-mounted dispensers (ABHR-Ds), and/or pocket bottles. Nevertheless, information on the distribution and density of ABHR-Ds and their impact on HH have hardly been studied. Institutions such as the World Health Organisation or the Centers for Disease Control and Prevention do not provide guidance. The Robert-Koch-Institute (RKI) from Germany recommends an overall density of > 0.5 dispensers per patient bed. We aimed to investigate current conditions in hospitals to develop a standard on the minimal number of ABHR-D. METHODS: Between 07 and 09/2019, we applied a questionnaire to 178 hospitals participating in the Swissnoso National Surveillance Network to evaluate number and location of ABHR-Ds per bed in acute care hospitals, and compared the data with consumption and compliance with HH. RESULTS: 110 of the 178 (62%) hospitals provided data representing approximately 20,000 hospital beds. 83% hospitals provided information on both the total number of ABHR-Ds and patient beds, with a mean of 2.4 ABHR-Ds per bed (range, 0.4-22.1). While most hospitals (84%) had dispensers located at the room entrance, 47% reported also locations near or at the bed. Additionally, pocket-sized dispensers (100 mL) are available in 97% of hospitals. CONCLUSIONS: Swiss hospitals provide 2.4 dispensers per bed, much more than governmental recommendation. The first study on the number of ABHR-Ds in hospitals may help to define a minimal standard for national and international recommendations.

Antibiotic prescription monitoring and feedback in primary care in Switzerland: Design and rationale of a nationwide pragmatic randomized controlled trial.

INTRODUCTION: Antibiotic consumption is highest in primary care, and antibiotic overuse furthers antimicrobial resistance. In our recently published pilot-RCT, we used monthly aggregated claims data to provide personalized antibiotic prescription feedback to general practitioners (GPs). The pilot-RCT has shown that personalized prescription feedback is a feasible and promising low-cost intervention to reduce antibiotic prescribing. Here, we describe the rationale and design of the follow-up RCT with 3426 GPs in Switzerland. We now have access to pseudonymized patient-level data from routinely collected health insurance data of the three largest health insurers in Switzerland. METHODS AND ANALYSIS: 1713 GPs randomized to the intervention group received once evidence-based treatment guidelines at the beginning, including region-specific antibiotic resistance information from the community and personalized feedback of their antibiotic prescribing, followed by quarterly personalized prescription feedback for two years. The first and the last mailings were sent out in December 2017 and September 2019, respectively. The 1713 GPs randomized to the control group were not notified about the study and they received no guidelines and no prescription feedback. The personalized prescription feedbacks and the analyses of the primary and secondary outcomes are entirely based on pseudonymized patient-level data from routinely collected health insurance data. The primary outcome is prescribed antibiotics per 100 patient consultations during the second year of intervention. The secondary outcomes include antibiotic use during the entire two-year trial period, use of broad-spectrum antibiotics, hospitalization rates (all-cause and infection-related), and antibiotic use in different age groups. If the feedback intervention proves to be efficacious, the intervention could be continued systemwide. ETHICS AND DISSEMINATION: The trial is publicly funded by the Swiss National Science Foundation (SNSF, grant number 407240_167066). The trial was approved by the ethics committee "Ethikkommission Nordwest-und Zentralschweiz" (EKNZ Project-ID 2017-00888). Results will be disseminated in peer-reviewed journals and international conferences.

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

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.

A review of recommendations for infective endocarditis prevention in patients undergoing transcatheter aortic valve implantation.

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is a new disease entity. The rate of IE after TAVI is similar to that after surgical aortic valve replacement (SAVR), but mortality and prevalence of Enterococcus spp. as causing pathogens are significantly higher. Guidelines on infection prevention measures before TAVI procedures are currently lacking. We performed a structured review of the available data to provide interim recommendations based on guidelines to prevent infections issued by the World Health Organization as well as guidelines by professional societies from Europe and the USA. Such interim recommendations based on expert opinions are probably justified until large randomised trials provide strong evidence for infection control in TAVI, because IE after TAVI is often related to the TAVI procedure itself and the associated mortality rate is high. Antibiotic prophylaxis should be adapted from an intravenous cephalosporin to, e.g., amoxicillin/clavulanic acid, to cover enterococci. In addition, infection control should follow operating room standards as far as is reasonable, even if the evidence for this recommendation is very low. These recommendations are endorsed by the International Society for Cardiovascular Infectious Diseases (ISCVID).

Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures.

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.