Burden of disease in patients hospitalised with COVID-19 during the first and second pandemic wave in Switzerland: a nationwide cohort study.

AIM OF THE STUDY: The first and second waves of the COVID-19 pandemic led to a tremendous burden of disease and influenced several policy directives, prevention and treatment strategies as well as lifestyle and social behaviours. We aimed to describe trends of hospitalisations with COVID-19 and hospital-associated outcomes in these patients during the first two pandemic waves in Switzerland. METHODS: In this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalised with COVID-19 in Switzerland between January 1st and December 31st, 2020. First, stratified by wave (first wave: January to May, second wave: June to December), we estimated incidence rates (IR) and rate differences (RD) per 10,000 person-years of COVID-19-related hospitalisations across different age groups (0-9, 10-19, 20-49, 50-69, and ≥70 years). IR was calculated by counting the number of COVID-19 hospitalisations for each patient age stratum paired with the number of persons living in Switzerland during the specific wave period. Second, adjusted odds ratios (aOR) of outcomes among COVID-19 hospitalisations were calculated to assess the association between COVID-19 wave and outcomes, adjusted for potential confounders. RESULTS: Of 36,517 hospitalisations with COVID-19, 8,862 (24.3%) were identified during the first and 27,655 (75.7%) during the second wave. IR for hospitalisations with COVID-19 was highest during the second wave and among patients above 50 years (50-69 years: first wave: 31.49 per 10,000 person-years; second wave: 62.81 per 10,000 person-years; RD 31.32 [95% confidence interval [CI]: 29.56 to 33.08] per 10,000 person-years; IRR 1.99 [95% CI: 1.91 to 2.08]; ≥70 years: first wave: 88.59 per 10,000 person-years; second wave: 228.41 per 10,000 person-years; RD 139.83 [95% CI: 135.42 to 144.23] per 10,000 person-years; IRR 2.58 [95% CI: 2.49 to 2.67]). While there was no difference in hospital readmission, when compared with the first wave, patients hospitalised during the second wave had a lower probability of death (aOR 0.88 [95% CI: 0.81 to 0.95], ARDS (aOR 0.56 [95% CI: 0.51 to 0.61]), ICU admission (aOR 0.66 [95% CI: 0.61 to 0.70]), and need for ECMO (aOR 0.60 [95% CI: 0.38 to 0.92]). LOS was -16.1 % (95% CI: -17.8 to -14.2) shorter during the second wave. CONCLUSION: In this nationwide cohort study, rates of hospitalisations with COVID-19 were highest among adults older than 50 years and during the second wave. Except for hospital readmission, the likelihood of adverse outcomes was lower during the second pandemic wave, which may be explained by advances in the understanding of the disease and improved treatment options.

Call, chosen, HA2T2, ANDC: validation of four severity scores in COVID-19 patients.

PURPOSE: To externally validate four previously developed severity scores (i.e., CALL, CHOSEN, HA2T2 and ANDC) in patients with COVID-19 hospitalised in a tertiary care centre in Switzerland. METHODS: This observational analysis included adult patients with a real-time reverse-transcription polymerase chain reaction or rapid-antigen test confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection hospitalised consecutively at the Cantonal Hospital Aarau from February to December 2020. The primary endpoint was all-cause in-hospital mortality. The secondary endpoint was disease progression, defined as needing invasive ventilation, ICU admission or death. RESULTS: From 399 patients (mean age 66.6 years ± 13.4 SD, 68% males), we had complete data for calculating the CALL, CHOSEN, HA2T2 and ANDC scores in 297, 380, 151 and 124 cases, respectively. Odds ratios for all four scores showed significant associations with mortality. The discriminative power of the HA2T2 score was higher compared to CALL, CHOSEN and ANDC scores [area under the curve (AUC) 0.78 vs. 0.65, 0.69 and 0.66, respectively]. Negative predictive values (NPV) for mortality were high, particularly for the CALL score (≥ 6 points: 100%, ≥ 9 points: 95%). For disease progression, discriminative power was lower, with the CHOSEN score showing the best performance (AUC 0.66). CONCLUSION: In this external validation study, the four analysed scores had a lower performance compared to the original cohorts regarding prediction of mortality and disease progression. However, all scores were significantly associated with mortality and the NPV of the CALL and CHOSEN scores in particular allowed reliable identification of patients at low risk, making them suitable for outpatient management.

SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot.

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna's mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme.

Long COVID 1 year after hospitalisation for COVID-19: a prospective bicentric cohort study.

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae ­ appearing or persisting after the typical convalescence period ­ of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00­1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04­1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94­1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis.

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech's BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1-31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination. The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections.

Comparison of characteristics, predictors and outcomes between the first and second COVID-19 waves in a tertiary care centre in Switzerland: an observational analysis.

AIM OF THE STUDY: To compare admission characteristics, predictors and outcomes of patients with confirmed coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the first and second waves of the pandemic. METHODS: This retrospective observational analysis included adult patients with  severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection confirmed by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen test and hospitalised at the Cantonal Hospital Aarau from 26 February to 30 April 2020 (first wave) and from 1 October to 31 December 2020 (second wave). The primary endpoint was all-cause in-hospital mortality. The secondary endpoints were transfer to the intensive care unit (ICU) and length of hospital stay (LOS). RESULTS: Overall, 486 patients (mean age 65.9 years ± 14.7 SD, 65% male) were included. Ninety-two patients (19%) died during the hospital stay and 92 patients (19%) were transferred to the ICU. Admission characteristics, including comorbidities and frailty, were similar for patients of the first (n = 100) and second wave (n = 386). However, during the second wave the median time from symptom onset to presentation to the emergency department (ED) was shorter (7 days, interquartile range [IQR] 4–9 vs 8 days, IQR 4–11; p = 0.02). In the second wave, most patients received high-dose glucocorticoid treatment (0% vs 76%, p <0.01). In-hospital mortality was similar among COVID-19 patients in the first (19/100, 19%) and second wave (73/386, 19%); this finding persisted after full adjustment in multiple regression models (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI] 0.49–2.80; p = 0.71). Risk for ICU admission was also similar (24% vs 18%; aOR 0.98, 95% CI 0.46–2.06; p = 0.95). More patients were transferred to rehabilitation facilities in the second wave (18% vs 31%; aOR 2.06, 95% CI 1.04–4.07; p = 0.04) and LOS was 2.5 days shorter (9.0 vs 6.5 days; adjusted difference −2.53 days, 95%-CI −4.51 to −0.54; p = 0.01). Main predictors for in-hospital death were patient age (aOR 1.07, 95% CI 1.02–1.11; p <0.01), male sex (aOR 2.41, 95% CI 1.05–5.55; p = 0.04) and the age-adjusted Charlson comorbidity index (aOR 1.27, 95% CI 1.09–1.48 p <0.01). CONCLUSION: Despite differing treatment regimens, mortality and ICU admission remained largely unchanged for COVID-19 patients admitted during the second wave of the pandemic in our tertiary care hospital. However, discharge processes were optimised with patients leaving the hospital earlier and going to rehabilitation facilities more often.  .

Activation of Vasopressin System During COVID-19 is Associated With Adverse Clinical Outcomes: An Observational Study.

BACKGROUND: Activation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular, and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured levels of copeptin on admission and after days 3/4, 5/6, and 7/8 in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and acute or chronic bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Median admission copeptin levels in COVID-19 patients were almost 4-fold higher in nonsurvivors compared with survivors (49.4 pmol/L [iterquartile range (IQR) 24.9-68.9 pmol/L] vs 13.5 pmol/L [IQR 7.0-26.7 pmol/L]), resulting in an age- and gender-adjusted odds ratio of 7.0 (95% confidence interval [CI] 1.2-40.3), p < 0.03 for mortality. Higher copeptin levels in nonsurvivors persisted during the short-term follow-up. Compared with the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels. CONCLUSIONS: A pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections.

Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Lung Assessment with Point-of-Care Ultrasound in Respiratory Coronavirus Disease (COVID-19): A Prospective Cohort Study.

Lung ultrasound (LUS) has shown promising diagnostic potential in different pulmonary conditions. We evaluated the diagnostic accuracy of LUS for pulmonary COVID-19. In this prospective cohort study at a Swiss tertiary care center, patients hospitalized with suspected COVID-19 were scanned using a 12-zone protocol. Association of a summation score (0-36 points) with the final diagnosis was tested using the area under the receiver operating characteristic curve and sensitivity and specificity at different cutoff points. Of the 49 participants, 11 (22%) were later diagnosed with COVID-19. LUS score showed excellent diagnostic performance, with an odds ratio of 1.30 per point (95% confidence interval [CI], 1.09-1.54, p = 0.003) and an area under the curve of 0.85 (95% CI, 0.71-0.99). At a cutoff of 8/36 points, 10 of 11 participants later diagnosed with COVID-19 were correctly predicted (sensitivity 91%, 95% CI, 59%-100%), and 29 of the 38 who were not diagnosed with COVID-19 were correctly ruled out (specificity 76%, 95% CI, 60%-89%). LUS demonstrated promising discriminatory potential in people hospitalized with suspected COVID-19.

Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19.

OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.

Characteristics, predictors and outcomes among 99 patients hospitalised with COVID-19 in a tertiary care centre in Switzerland: an observational analysis.

AIMS OF THE STUDY: To describe admission characteristics, risk factors and outcomes of patients with coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the early phase of the pandemic. METHODS: This retrospective cohort study included adult patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) testing and hospitalised at the cantonal hospital Aarau (Switzerland) between 26 February 2020 and 30 April 2020. Our primary endpoint was severe COVID-19 progression defined as a composite of transfer to the intensive care unit (ICU) and in-hospital mortality. RESULTS: A total of 99 patients (median age 67 years [interquartile range 56–76], 37% females) were included and 35% developed severe COVID-19 progression (24% needed ICU treatment, 19% died). Patients had a high burden of comorbidities with a median Charlson comorbidity index of 3 points and a high prevalence of hypertension (57%), chronic kidney disease (28%) and obesity (27%). Baseline characteristics with the highest prognostic value for the primary endpoint by means of area under the receiver operating characteristic curve were male gender (0.63) and initial laboratory values including shock markers (lactate on ambient air 0.67; lactate with O2 supply 0.70), markers of inflammation (C-reactive protein 0.72, procalcitonin 0.80) and markers of compromised oxygenation (pO2 0.75 on ambient air), whereas age and comorbidities provided little prognostic information. CONCLUSION: This analysis provides insights into the first consecutively hospitalised patients with confirmed COVID-19 at a Swiss tertiary care hospital during the initial period of the pandemic. Markers of disease progression such as inflammatory markers, markers for shock and impaired respiratory function provided the most prognostic information regarding severe COVID-19 progression in our sample.