Association of viral variant and vaccination status with the occurrence of symptoms compatible with post-acute sequelae after primary SARS-CoV-2 infection

ImportanceDisentangling the effects of different SARS-CoV-2 variants and of vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and potentially reduce the future burden of PASC. ObjectiveTo determine the association of primary SARS-CoV-2 infection on the frequency of PASC symptoms by viral variant and vaccination status. DesignCross-sectional questionnaire and SARS-CoV-2 serology (May/June 2022) performed within a prospective healthcare worker cohort (SURPRISE study). SettingMulticenter study in nine healthcare networks from North-Eastern Switzerland. ParticipantsVolunteer sample of healthcare workers (HCW) from participating institutions. Of approximately 20000 eligible participants, 3870 registered for the cohort and 2912 were included in this analysis. ExposuresSARS-CoV-2 infection documented by positive nasopharyngeal swab (>4 weeks ago), stratified by viral variant and vaccination status at time of infection, compared to absence of documented infection (no positive swab, negative serology). Main OutcomeSum score of eighteen self-reported PASC symptoms. ResultsAmong 2912 participants (median age 44 years, 81.3% female), SARS-CoV-2 infection was reported by 1685 (55.9%) participants, thereof 315 (18.7%) during Wild-type, 288 (17.1%) during Alpha/Delta, and 1082 (64.2%) during Omicron circulation. Mean symptom number in previously infected participants significantly exceeded that of uninfected controls (0.39), but decreased with recency of the viral variant: 1.12 (p<0.001) for Wild-type (median time since infection 18.5 months), 0.67 (p<0.001) for Alpha/Delta (6.6 months), and 0.52 (p=0.005) for Omicron BA.1 (3.1 months) infected participants. After Omicron BA.1 infection, the mean symptom score was 0.49 (p=0.30) for those with [≥]3 prior vaccinations and 0.71 (p=0.028) with 1-2 previous vaccinations compared to 0.36 for unvaccinated individuals. Adjusting for confounders, Wild-type (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) showed significant associations with the outcome, whereas Omicron BA.1 infection (aRR 1.29, 95% CI 0.69-2.43) and vaccination before infection (aRR 1.27, 95% CI 0.82-1.94) did not. Conclusions and RelevancePrevious infection with pre-Omicron variants was the strongest risk factor for reporting PASC symptoms in this HCW cohort. A definite influence of prior vaccination on the prevention of PASC after Omicron BA.1 infection was not measurable.

Evolution of COVID-19 mortality over time: results from the Swiss hospital surveillance system (CH-SUR)

BackgroundWhen comparing the periods of time during and after the first wave of the ongoing SARS-CoV-2/COVID-19 pandemic in Europe, 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. MethodsWe investigated the trends in COVID-19 related mortality (in-hospital and in-intermediate/intensive-care) over time in Switzerland, from February 2020 to May 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. ResultsOur analysis included 16,030 episodes recorded in CH-SUR, with 2,320 reported deaths due to COVID-19 (13.0% of included episodes). We found that overall in-hospital mortality was lower during the second wave of COVID-19 compared to the first wave (HR 0.71, 95% CI 0.69 - 0.72, p-value < 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 to the first wave (HR 1.48, 95% CI 1.42 - 1.55, p-value < 0.001), with significant changes in the course of hospitalisation between the first and the second wave. ConclusionWe 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.

SARS-CoV-2/COVID-19 hospitalised patients in Switzerland: a prospective cohort profile

BackgroundSARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world causing several million victims in 213 countries. Switzerland was severely hit by the virus, with 43000 confirmed cases as of September 1st, 2020. AimIn cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19 in addition to their mandatory reporting system. MethodsPatients hospitalised for more than 24 hours with a positive PCR test, from 20 Swiss hospitals, are included. Data collection follows a custom Case Report Form based on WHO recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms started more than 5 days after the patients admission date. ResultsAs of September 1st, 2020, 3645 patients were included. Most patients were male (2168 - 59.5%),and aged between 50 and 89 years (2778 - 76.2%), with a median age of 68 (IQR 54-79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported: hypertension (1481 - 61.7%), cardiovascular diseases (948 - 39.5%), and diabetes (660 - 27.5%) being the most frequent in adults; respiratory diseases and asthma (4 -21.1%), haematological and oncological diseases (3 - 15.8%) being the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly for respiratory diseases (2470 - 93.2% in adults, 16 - 55.2% in children), renal (681 - 25.7%) and cardiac (631 - 23.8%) complication for adults. The second and third most frequent complications in children affected the digestive system and the liver (7 - 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989 - 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. 527 (14.5%) deaths were registered, all among adults. ConclusionThe surveillance system has been successfully initiated and provides a very representative set of data for Switzerland. We therefore consider it to be a valuable addition to the existing mandatory reporting, providing more precise information on the epidemiology, risk factors, and clinical course of these cases.

COVID-19: more than a little flu? Insights from the Swiss hospital-based surveillance of Influenza and COVID-19

BackgroundCoronavirus disease 19 (COVID-19) has frequently been colloquially compared to the seasonal influenza, but comparisons based on empirical data are scarce. AimsTo compare in-hospital outcomes for patients admitted with community-acquired COVID-19 to patients with community-acquired influenza in Switzerland. MethodsPatients >18 years, who were admitted with PCR proven COVID-19 or influenza A/B infection to 14 participating Swiss hospitals were included in a prospective surveillance. Primary and secondary outcomes were the in-hospital mortality and intensive care unit (ICU) admission between influenza and COVID-19 patients. We used Cox regression (cause-specific models, and Fine & Gray subdistribution) to account for time-dependency and competing events with inverse probability weighting to account for confounders. ResultsIn 2020, 2843 patients with COVID-19 were included from 14 centers and in years 2018 to 2020, 1361 patients with influenza were recruited in 7 centers. Patients with COVID-19 were predominantly male (n=1722, 61% vs. 666 influenza patients, 48%, p<0.001) and were younger than influenza patients (median 67 years IQR 54-78 vs. median 74 years IQR 61-84, p<0.001). 363 patients (12.8%) died in-hospital with COVID-19 versus 61 (4.4%) patients with influenza (p<0.001). The final, adjusted subdistribution Hazard Ratio for mortality was 3.01 (95% CI 2.22-4.09, p<0.001) for COVID-19 compared to influenza, and 2.44 (95% CI, 2.00-3.00, p<0.001) for ICU admission. ConclusionEven in a national healthcare system with sufficient human and financial resources, community-acquired COVID-19 was associated with worse outcomes compared to community-acquired influenza, as the hazards of in-hospital death and ICU admission were [~]3-fold higher.

Characteristics of three different chemiluminescence assays for testing for SARS-CoV-2 antibodies

Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multi-group study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (n=145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e. healthy blood donors, n=191, and healthcare workers, n=1002). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of Epstein-Barr virus (EBV) (n=9), cytomegalovirus (CMV) (n=7) and endemic common cold coronavirus infections (n=12) taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers cut-offs, the sensitivities were 90%, 95% confidence interval,[84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8](CMIA) 99.7% [99.3,99,9] (LIA) and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

Temporal course of SARS-CoV-2 antibody positivity in patients with COVID-19 following the first clinical presentation

Knowledge of the sensitivities of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody tests beyond 35 days after the clinical onset of COVID-19 is insufficient. We aimed to describe positivity rate of SARS-CoV-2 assays employing three different measurement principles over a prolonged period. Two hundred sixty-eight samples from 180 symptomatic patients with COVID-19 and a reverse transcription polymerase chain reaction (RT-PCR) test followed by serological investigation of SARS-CoV-2 antibodies were included.. We conducted three chemiluminescence (including electrochemiluminscence, ECLIA), four enzyme linked immunosorbent assay (ELISA), and one lateral flow immunoassay (LFIA) test formats. Positivity rates, as well as positive (PPV) and negative predictive values (NPV) were calculated for each week after the first clinical presentation for COVID-19. Furthermore, combinations of tests were assessed within an orthogonal testing approach employing two independent assays and predictive values were calculated. Heat maps were constructed to graphically illustrate operational test characteristics. During a follow-up period of more than 9 weeks, chemiluminescence assays and one ELISA IgG test showed stable positivity rates after the third week. With the exception of ECLIA, the PPVs of the other chemiluminescence assays were [≥]95% for COVID-19 only after the second week. ELISA and LFIA had somewhat lower PPVs. IgM exhibited insufficient predictive characteristics. An orthogonal testing approach provided PPVs [≥]95% for patients with a moderate pretest probability (e.g., symptomatic patients), even for tests with a low single test performance. After the second week, NPVs of all but IgM assays were [≥]95% for patients with low to moderate pretest probability. The confirmation of negative results using an orthogonal algorithm with another assay provided lower NPVs than the single assays. When interpreting results from SARS-CoV-2 tests, the pretest probability, time of blood draw and assay characteristics must be carefully considered. An orthogonal testing approach increases the accuracy of positive, but not negative, predictions.