Efficacy of Sotrovimab (SOT), Molnupiravir (MOL), and Nirmatrelvir/Ritponavir (N/R) and Tolerability of Molnupiravir in Outpatients at High Risk for Severe COVID-19.

OBJECTIVE: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. METHODS: We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606), or N/R (398/2606), patients were followed-up with regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. RESULT: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0-1.5). CONCLUSION: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R.

SARS-CoV-2 infections in "less visible" hospital staff: The roles and safety of environmental services and allied health professionals.

BACKGROUND: During the early SARS-CoV-2 pandemic, all healthcare workers had specific and essential functions. However, environmental services (e.g., cleaning staff) and allied health professionals (e.g., physiotherapists) are often less recognised inpatient care. The aim of our study was to evaluate SARS-CoV-2-infection rates and describe risk factors relevant to workplace transmission and occupational safety amongst healthcare workers in COVID-19 hospitals before the introduction of SARS-CoV-2-specific vaccines. METHODS: This cross-sectional study (from May 2020 to March 2021, standardised WHO early-investigation protocol) is evaluating workplace or health-related data, COVID-19-patient proximity, personal protective equipment (PPE) use, and adherence to infection prevention and control (IPC) measures, anti-SARS-CoV-2-antibody status, and transmission pathways. RESULTS: Out of n = 221 HCW (n = 189 cleaning/service staff; n = 32 allied health professionals), n = 17 (7.7 %) were seropositive. While even SARS-CoV-2-naïve HCW reported SARS-CoV-2-related symptoms, airway symptoms, loss of smell or taste, and appetite were the most specific for a SARS-CoV-2-infection. Adherence to IPC (98.6 %) and recommended PPE use (98.2 %) were high and not associated with seropositivity. In 70.6 %, transmission occurred in private settings; in 23.5 %, at the workplace (by interaction with SARS-CoV-2-positive colleagues [17.6 %] or patient contact [5.9 %]), or remained unclear (one case). CONCLUSIONS: Infection rates were higher in all assessed 'less visible' healthcare-worker groups compared to the general population. Our data indicates that, while IPC measures and PPE may have contributed to the prevention of patient-to-healthcare-worker transmissions, infections were commonly acquired outside of work and transmitted between healthcare workers within the hospital. This finding emphasises the importance of ongoing education on transmission prevention and regular infection screenings at work.

A retrospective analysis of clinical features of patients hospitalized with SARS-CoV-2 Omicron variants BA.1 and BA.2.

The causative agent of the ongoing Corona virus disease 2019 (COVID-19) pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has acquired a considerable amount of mutations, leading to changes in clinical manifestations and increased transmission. Recent studies based on animal disease models and data from the general population were reporting a higher pathogenicity of the BA.2 sublineage compared to BA.1. The aim of this study was to provide real world data on patients with the SARS-CoV-2 Omicron BA.1 and BA.2 subvariants treated at our center, highlighting similarities and differences in the clinical disease course. We retrospectively collected and analyzed the data of adult patients admitted with confirmed SARS-CoV-2 infection at the Department for Infectious Diseases and Tropical Medicine, Klinik Favoriten, Vienna, Austria. Patient characteristics including age, underlying diseases, vaccination status and outcome were compared between patients with the BA.1 and BA.2 subvariants. Between January 2022 and May 2022 we included 168 patients infected with Omicron BA.1 and 100 patients with BA.2. Patients admitted with BA.2 were significantly older, more often fully immunized and required less dexamethasone than patients with BA.1. No substantial differences were identified between patients infected with BA.1 and BA.2 regarding BMI, laboratory findings, need for supplemental oxygen, mortality and other evaluated comorbidities excepting active malignancies. The significantly larger percentage of fully immunized patients admitted with BA.2 is pointing to an increased transmissibility of this subvariant, while the comparable outcome of a somewhat older and sicker patient population might be indicative of reduced virulence.

Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome.

Background: Symptoms lasting longer than 12 weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs. Methods: Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors. Results: Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4+ and CD8+ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3+) and IL-4 were more abundant in PCS+. Conclusion: This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients.

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 µg/ml to 1.5 µg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.

Cardiopulmonary Long-Term Sequelae in Patients after Severe COVID-19 Disease.

We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2-11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6-16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03-17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05-1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05-2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction.

The Role of Bacterial and Fungal Superinfection in Critical COVID-19.

BACKGROUND: The range of reported rates of bacterial and fungal superinfections in patients with a severe course of COVID-19 is wide, suggesting a lack of standardised reporting. METHODS: The rates of bacterial and fungal superinfection were assessed using predefined criteria to differentiate between infection and contamination. RESULTS: Overall, 117 patients admitted to the Intensive Care Unit due to severe COVID-19 were included. Overall, 55% of patients developed a superinfection and 13.6% developed a fungal superinfection (5.9% candidemia and 7.7% CAPA). The rate of ventilator-associated pneumonia was 65.2%. If superinfection was detected, the length of hospital stay was significantly longer and the mortality was especially increased if candidemia was detected. An increased risk of superinfection was observed in patients with pre-existing diabetes mellitus or chronic heart failure. The presence of immunomodulating therapy did not seem to have an impact on the frequency of superinfections. CONCLUSION: Increased awareness of high superinfection rates, fungal infections in particular, in patients suffering from severe COVID-19 is necessary.

The systemic renin-angiotensin system in COVID-19.

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Early administration of remdesivir may reduce mortality in hospitalized COVID-19 patients : A propensity score matched analysis.

BACKGROUND: Remdesivir is the only antiviral agent approved for the treatment of hospitalized coronavirus disease 2019 (COVID-19) patients requiring supplemental oxygen. Studies show conflicting results regarding its effect on mortality. METHODS: In this single center observational study, we included adult hospitalized COVID-19 patients. Patients who were treated with remdesivir were compared to controls. Remdesivir was administered for 5 days. To adjust for any imbalances in our cohort, a propensity score matched analysis was performed. The aim of our study was to analyze the effect of remdesivir on in-hospital mortality and length of stay (LOS). RESULTS: After propensity score matching, 350 patients (175 remdesivir, 175 controls) were included in our analysis. Overall, in-hospital mortality was not significantly different between groups remdesivir 5.7% [10/175] vs. control 8.6% [15/175], hazard ratio 0.50, 95% confidence interval (CI) 0.22-1.12, p = 0.091. Subgroup analysis showed a significant reduction of in-hospital mortality in patients who were treated with remdesivir ≤ 7 days of symptom onset remdesivir 4.2% [5/121] vs. control 10.4% [13/125], hazard ratio 0.26, 95% CI 0.09 to 0.75, p = 0.012 and in female patients remdesivir 2.9% [2/69] vs. control 12.2% [9/74], hazard ratio 0.18 95%CI 0.04 to 0.85, p = 0.03. Patients in the remdesivir group had a significantly longer LOS (11 days vs. 9 days, p = 0.046). CONCLUSION: Remdesivir did not reduce in-hospital mortality in our whole propensity score matched cohort, but subgroup analysis showed a significant mortality reduction in female patients and in patients treated within ≤ 7 days of symptom onset. Remdesivir may reduce mortality in patients who are treated in the early stages of illness.

SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients-A Single-Center Experience.

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on the use of tixagevimab/cilgavimab and sotrovimab as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PrEP in immunocompromised patients, comparing the evolution of antibody levels and reporting the incidence of breakthrough infections. A retrospective, single-center analysis was conducted including 132 immunocompromised patients with inadequate vaccine response, who received COVID-PrEP at our clinic between January and June 2022. Initially, 95 patients received sotrovimab while 37 patients received tixagevimab/cilgavimab. Antibody levels after first PrEP with sotrovimab remain high for several months after infusion (median 10,058 and 7235 BAU/mL after 1 and 3 months, respectively), with higher titers than after tixagevimab/cilgavimab injection even 3 months later (7235 vs. 1647 BAU/mL, p = 0.0007). Overall, breakthrough infections were rare (13/132, 10%) when compared to overall infection rates during this period (over 30% of the Austrian population), with mild disease course and rapid viral clearance (median 10 days). Sotrovimab may be an additional option for SARS-CoV-2 PrEP.

Tocilizumab vs. baricitinib in hospitalized severe COVID-19 patients: results from a real-world cohort.

BACKGROUND: Tocilizumab and baricitinib are recommended treatment options for hospitalized COVID-19 patients requiring oxygen support. Literature about its efficacy and safety in a head-to-head comparison is scarce. METHODS: Hospitalized COVID-19 patients requiring oxygen were treated with tocilizumab or baricitinib additionally to dexamethasone. Tocilizumab was available from February till the 19th of September 2021 and baricitinib from 21st of September. The primary outcome was in-hospital mortality. Secondary outcome parameters were progression to mechanical ventilation (MV), length-of-stay (LOS) and potential side effects. RESULTS: 159 patients (tocilizumab 68, baricitinib 91) with a mean age of 60.5 years, 64% male were included in the study. Tocilizumab patients were admitted 1 day earlier, were in a higher WHO category at the time of inclusion and had a higher CRP level on admission and treatment initiation. Patients receiving Tocilizumab were treated with remdesivir more often and only patients in the baricitinib group were treated with monoclonal antibodies. Other characteristics did not differ significantly. In-hospital mortality (18% vs. 11%, p = 0.229), progression to MV (19% vs. 11%, p = 0.173) and LOS (13 vs. 12 days, p = 0.114) did not differ between groups. Side effects were equally distributed between groups, except ALAT elevation which was significantly more often observed in the tocilizumab group (43% vs. 25%, p = 0.021). CONCLUSIONS: In-hospital mortality, progression to MV and LOS were not significantly different in patients treated with tocilizumab or baricitinib additionally to standard of care. Both drugs seem equally effective but further head-to-head trials are needed.

Comparison of clinical characteristics among patients infected with alpha vs. delta SARS-CoV-2 variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone different molecular changes, sprouting genetic variants of the original wildtype. Clinical comparisons between patients infected with alpha versus delta are scarce. METHODS: In this retrospective observational study, adult patients hospitalized with coronavirus disease 2019 (COVID-19) due to confirmed SARS-CoV­2 alpha or delta infection were included. Patient characteristics, virologic and laboratory parameters, as well as the clinical course were compared in patients infected with alpha vs. delta variants. RESULTS: A total of 106 patients infected with alpha and 215 patients infected with delta were included. Patients infected with the delta variant were admitted to hospital earlier after symptom onset (6 vs. 7 days, p < 0.001). Blood levels of C­reactive protein (43.3 vs. 62.9 mg/l, p = 0.02) and neutrophil count (3.81 vs. 4.53 G/l, p = 0.06) were lower in delta patients. Furthermore, at hospital admission cycle threshold (CT) values were significantly lower in patients infected with the delta variant (22.3 vs. 24.9, p < 0.001). Patients infected with the delta variant needed supplemental oxygen less often during disease course (50% vs. 64%, p = 0.02). Furthermore, there was a statistically non-significant trend towards a lower ICU admission rate among delta patients (16% vs. 24%, p = 0.08) CONCLUSION: Patients diagnosed with the delta variant were admitted to the hospital earlier, had a less severe course of disease and a higher viral replication on admission. This may provide a window of opportunity for antivirals in the hospital setting.

Treatment of persistent COVID-19 in two B-cell-depleted patients with the monoclonal antibody Sotrovimab.

Background: Patients having undergone B-cell-depletion with anti-CD20-antibodies have a higher risk of mortality, delayed viral clearance and prolonged infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report two cases of patients with persistent coronavirus disease 2019 (COVID-19) in association with B-cell-depletion that were treated with the monoclonal antibody Sotrovimab. Case presentation: Both patients presented with chronic symptoms of COVID-19 such as dyspnea, fatigue, and chest pain. Nasopharyngeal swabs remained positive months after the initial infection with fluctuating cycle threshold (Ct) values around 30. Both patients received a single infusion with the monoclonal SARS-CoV-2 antibody Sotrovimab, which resulted in a rapid improvement of symptoms and inflammation markers as well as negative SARS-CoV-2 swabs. A follow-up after a month showed ongoing improvement of symptoms, persistent negative SARS-CoV-2 swabs, and positive serum antibodies. Conclusion: Infusion with the monoclonal SARS-CoV-2 antibody led to rapid improvement in two patients with persistent COVID-19 after B-cell depletion.

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 μg/ml to 1.5 μg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.

Rapid Detection of Bacterial and Fungal Pathogens Using the T2MR versus Blood Culture in Patients with Severe COVID-19.

A high rate of bacterial and fungal superinfections was reported in critically ill patients with COVID-19. However, diagnosis can be challenging. The aim of this study is to evaluate the sensitivity and the clinical utility of the point-of-care method T2 magnetic resonance (T2MR) with the gold standard: the blood culture. T2MR can potentially detect five different Candida species and six common bacteria (so-called "ESKAPE" pathogens including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinet`obacter baumanii, Pseudomonas aeruginosa, and Enterococcus faecium). If superinfection was suspected in patients with COVID-19 admitted to the intensive care unit, blood culture and two panels of T2MR were performed. Eighty-five diagnostic bundles were performed in 60 patients in total. T2MR detected an ESKAPE pathogen in 9 out of 85 (10.6%) samples, compared to BC in 3 out of 85 (3.5%). A Candida species was detected in 7 of 85 (8.2%) samples of T2MR compared to 1 out of 85(1.2%) in blood culture. The mean time to positive test result in samples with concordant positive results was 4.5 h with T2MR and 52.5 h with blood culture. The additional use of T2MR enables a highly sensitive and rapid detection of ESKAPE and Candida pathogens. IMPORTANCE Coronavirus disease 2019 (COVID-19) has led to a high number of deaths since the beginning of the pandemic worldwide. One of the reasons is the high number of bacterial and fungal superinfections in patients suffering from critical disease. However, diagnosis is often challenging. In this study we could show that the additional use of the culture-independent method T2MR did not only show a much higher detection rate of bacterial and fungal pathogens but also a significantly shorter time until detection and therapy change compared to the gold standard: the blood culture. The implementation of T2MRin the care of patients with severe course of COVID-19 might lead to an earlier sufficient antimicrobial therapy and as a result lower mortality and less use of broad-spectrum unnecessary therapy reducing the risk of resistance development.

A Rapid, Highly Sensitive and Open-Access SARS-CoV-2 Detection Assay for Laboratory and Home Testing.

RT-qPCR-based diagnostic tests play important roles in combating virus-caused pandemics such as Covid-19. However, their dependence on sophisticated equipment and the associated costs often limits their widespread use. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative nucleic acid detection method that overcomes these limitations. Here, we present a rapid, robust, and sensitive RT-LAMP-based SARS-CoV-2 detection assay. Our 40-min procedure bypasses the RNA isolation step, is insensitive to carryover contamination, and uses a colorimetric readout that enables robust SARS-CoV-2 detection from various sample types. Based on this assay, we have increased sensitivity and scalability by adding a nucleic acid enrichment step (Bead-LAMP), developed a version for home testing (HomeDip-LAMP), and identified open-source RT-LAMP enzymes that can be produced in any molecular biology laboratory. On a dedicated website, rtlamp.org (DOI: 10.5281/zenodo.6033689), we provide detailed protocols and videos. Our optimized, general-purpose RT-LAMP assay is an important step toward population-scale SARS-CoV-2 testing.

[Diagnosis and treatment of COVID-19 in intensive care units]. / Diagnostik und Therapie von COVID-19 auf der Intensivstation.

Treatment of coronavirus disease 2019 (COVID-19) is particularly challenging due to the rapid scientific advances and the often significant hypoxemia. Use of high-flow oxygen, noninvasive mask ventilation, and the technique of awake proning can sometimes avoid the need for intubation. Mechanical ventilation follows the principles of ventilation for acute respiratory distress syndrome (ARDS; lung protective ventilation) and is generally supplemented by consequent positioning therapy (with at least 16 h in prone position in multiple cycles). Antiviral therapy options such as remdesivir usually come too late for patients with COVID-19 in the ICU, the only exception being the administration of monoclonal antibodies for patients without seroconversion. The value of immunomodulatory therapy such as dexamethasone is undisputed. Interleukin­6 antagonists, on the other hand, are rather problematic for ICU patients, and for Janus kinase inhibitors, data and experience are still insufficient in this context.

Management of hospitalized influenza A patients during the season 2018/19 : Comparison of three medical departments and the effect on outcome and antibiotic usage.

BACKGROUND: Diagnosis and treatment of influenza patients are often provided across several medical specialties. We compared patient outcomes at an infectious diseases (ID), a rheumatology (Rheu) and a pulmonology (Pul) department. MATERIAL AND METHODS: In this prospective observational multicenter study we included all influenza positive adults who were hospitalized and treated at flu isolation wards in three hospitals in Vienna during the season 2018/2019. RESULTS: A total of 490 patients (49% female) with a median age of 73 years (interquartile range [IQR] 61-82) were included. No differences regarding age, sex and most underlying diseases were present at admission. Frequencies of the most common complications differed: acute kidney failure (ID 12.7%, Rheu 21.2%, Pulm 37.1%, p < 0.001), acute heart failure (ID 4.3%, Rheu 17.1%, Pulm 14.4%, p < 0.001) and respiratory insufficiency (ID 45.1%, Rheu 41.5%, Pulm 56.3%, p = 0.030). Oseltamivir prescription was lowest at the pulmonology flu ward (ID 79.6%, Rheu 90.5%, Pulm 61.7%, p < 0.001). In total 176 patients (35.9%) developed pneumonia. Antibiotic selection varied between the departments: amoxicillin/clavulanic acid (ID 28.9%, Rheu 63.8%, Pulm 5.9%, p < 0.001), cefuroxime (ID 28.9%, Rheu 1.3%, Pulm 0%, p < 0.001), 3rd generation cephalosporins (ID 4.4%, Rheu 5%, Pulm 72.5%, p < 0.001), doxycycline (ID 17.8%, Rheu 0%, Pulm 0%, p < 0.001). The median length of stay was significantly different between wards: ID 6 days (IQR 5-8), Rheu 6 days (IQR 5-7) and Pulm 7 days (IQR 5-9.5, p = 0.034). In-hospital mortality was 4.3% and did not differ between specialties. CONCLUSION: We detected differences in oseltamivir usage, length of in-hospital stay and antibiotic choices for pneumonia. Influenza-associated mortality was unaffected by specialty.

Evaluation of Five Commercial SARS-CoV-2 Antigen Tests in a Clinical Setting.

BACKGROUND: Point-of-care antigen tests (AgTs) for the detection of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) enable the rapid testing of infected individuals and are easy-to-use. However, there are few studies evaluating their clinical use. OBJECTIVE: The present study aimed to evaluate and compare the clinical performance characteristics of various commercial SARS-CoV-2 AgTs. DESIGN: The sensitivity of five AgTs, comprising four rapid antigen tests (RAT; AMP Rapid Test SARS-CoV-2 Ag, NADAL COVID-19 Antigen Rapid Test, CLINITEST Rapid COVID-19 Antigen Test, and Roche SARS-CoV-2 Rapid Antigen Test) and one sandwich chemiluminescence immunoassay (CLIA; LIAISON SARS-CoV-2 Assay), were evaluated in 300 nasopharyngeal (NP) swabs. Reverse transcriptase (RT) polymerase chain reaction (PCR) was used as a reference method. PARTICIPANTS: NP swabs were collected from patients admitted to hospital due to COVID-19. KEY RESULTS: Sensitivities of the AgTs ranged from 64.9 to 91.7% for samples with RT-PCR cycle threshold (Ct) values lower than 30 and were 100% for cycle threshold (Ct) values lower than 20. The highest sensitivity was observed for CLINITEST Rapid COVID-19 Antigen Test, and Roche SARS-CoV-2 rapid antigen test. Multivariate analysis using time from symptom onset and the Ct value for AgT sensitivity showed an inverse correlation. Further, the female sex was an independent factor of lower RAT sensitivity. CONCLUSIONS: Antigen tests from NP swab samples show high sensitivity in patients with a Ct value < 20. The best clinical sensitivity can be obtained using AgTs within the first 6 days after symptom onset.

Detection of bacteria via multiplex PCR in respiratory samples of critically ill COVID-19 patients with suspected HAP/VAP in the ICU.

BACKGROUND: Critically ill Coronavirus disease 2019 (COVID-19) patients have high rates of bacterial superinfection. Multiplex polymerase chain reaction panels may be able to provide useful information about the incidence and spectrum of bacteria causing superinfections. METHODS: In this retrospective observational study we included all COVID-19 positive patients admitted to our intensive care unit with suspected hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) in whom the BioFire® Pneumonia Panel (PP) was performed from tracheal aspirate or bronchoalveolar lavage fluid for diagnostic purposes. The aim of our study was to analyze the spectrum of pathogens detected with the PP. RESULTS: In this study 60 patients with a median age of 62.5 years were included. Suspected VAP was the most frequent (48/60, 80%) indication for performing the PP. Tracheal aspirate was the predominant sample type (50/60, 83.3%). The PP led to a negative, monomicrobial and polymicrobial result in 36.7%, 35% and 28.3% of the patients, respectively. The three most detected bacteria were Staphylococcus aureus (13/60, 21.7%), Klebsiella pneumoniae (12/60, 20%) and Haemophilus influenzae (9/60, 15%). Neither atypical bacteria nor resistance genes were detected. Microbiological culture of respiratory specimens was performed in 36 (60%) patients concomitantly. The PP and microbiological culture yielded a non-concordant, partial concordant and completely concordant result in 13.9% (5/36), 30.6% (11/36) and 55.6% (20/36) of the analyzed samples, respectively. CONCLUSION: In critically ill COVID-19 patients with suspected HAP/VAP results of the PP and microbiological culture methods were largely consistent. In our cohort, S. aureus and K. pneumoniae were the most frequently detected organisms. A higher diagnostic yield may be achieved if both methods are combined.