Protection against COVID-19 hospitalisation conferred by primary-series vaccination with AZD1222 in non-boosted individuals: first vaccine effectiveness results of the European COVIDRIVE study and meta-regression analysis.

Background: Vaccine effectiveness (VE) studies with long-term follow-up are needed to understand durability of protection against severe COVID-19 outcomes conferred by primary-series vaccination in individuals not receiving boosters. COVIDRIVE is a European public-private partnership evaluating brand-specific vaccine effectiveness (VE). We report a prespecified interim analysis of primary-series AZD1222 (ChAdOx1 nCoV-19) VE. Methods: Seven Study Contributors in Europe collected data on individuals aged ≥18 years who were hospitalised with severe acute respiratory infection (June 1st, 2021-September 5th, 2022) and eligible for COVID-19 vaccination prior to hospitalisation. In this test-negative case-control study, individuals were defined as test-positive cases or test-negative controls (SARS-CoV-2 RT-PCR) and were either fully vaccinated (two AZD1222 doses, 4-12 weeks apart, completed ≥14 days prior to symptom onset; no booster doses) or unvaccinated (no COVID-19 vaccine prior to hospitalisation). The primary objective was to estimate AZD1222 VE against COVID-19 hospitalisation. A literature review and meta-regression were conducted to contextualise findings on durability of protection. Findings: 761 individuals were included during the 15-month analysis period. Overall AZD1222 VE estimate was 72.8% (95% CI, 53.4-84.1). VE was 93.8% (48.6-99.3) in participants who received second AZD1222 doses ≤8 weeks prior to hospitalisation, with spline-based VE estimates demonstrating protection (VE ≥ 50%) 30 weeks post-second dose. Meta-regression analysis (data from seven publications) showed consistent results, with ≥80% protection against COVID-19 hospitalisation through ∼43 weeks post-second dose, with some degree of waning. Interpretation: Primary-series AZD1222 vaccination confers protection against COVID-19 hospitalisation with enduring levels of VE through ≥6 months. Funding: AstraZeneca.

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.

COVID-19-associated myoclonus in a series of five critically ill patients.

BACKGROUND: In addition to respiratory symptoms, many patients with coronavirus disease 2019 (COVID-19) present with neurological complications. Several case reports and small case series described myoclonus in five patients suffering from the disease. The purpose of this article is to report on five critically ill patients with COVID-19-associated myoclonus. MATERIAL AND METHODS: The clinical courses and test results of patients treated in the study center ICU and those of partner hospitals are described. Imaging, laboratory tests and electrophysiological test results are reviewed and discussed. RESULTS: In severe cases of COVID-19 myoclonus can manifest about 3 weeks after initial onset of symptoms. Sedation is sometimes effective for symptom control but impedes respiratory weaning. No viral particles or structural lesions explaining this phenomenon were found in this cohort. CONCLUSION: Myoclonus in patients with severe COVID-19 may be due to an inflammatory process, hypoxia or GABAergic impairment. Most patients received treatment with antiepileptic or anti-inflammatory agents and improved clinically.

Adjunctive treatment with high-titre convalescent plasma in severely and critically ill COVID-19 patients - a safe but futile intervention. A comparative cohort study.

BACKGROUND: Convalescent plasma (CP) containing antibodies derived from coronavirus disease 2019 (COVID-19) survivors has been proposed as a promising therapeutic option for severe COVID-19. METHODS: In our intensive care unit (ICU), 55 patients (46 male, median age 61 years) with PCR-confirmed COVID-19 (35 = 63.6% on mechanical ventilation, 7 = 14.5% on high-flow nasal oxygen, 12 = 20% on non-invasive ventilation, 1 = 1.8% without respiratory support) were treated with high-titre CP (200 mL per dose, range 1-6 doses, median 3 doses per patient, minimum titre > 1:100, Wantai test). 139 COVID-19 patients treated in the same ICU who did not receive CP served as control group. In 27 patients, the effect of CP on the individual levels of SARS-CoV-2 IgG antibodies was assessed by ELISA in serum sample pairs collected before and after CP transfusion. RESULTS: The first CP dose was administered at a median of 8 days after symptom onset. 13 patients in the plasma cohort died (28-day mortality 24.1%), compared to 42 (30.2%) in the cohort who did not receive CP (p = 0.5, Pearson Chi-squared test). Out of the 27 individuals investigated for the presence of IgG antibodies, 8 did not have detectable IgG levels before the first CP transfusion. In this subpopulation, 3 patients (37.5%) died. Not a single confirmed adverse reaction to CP was noted. CONCLUSIONS: While adjunctive treatment with CP for severe and life-threatening COVID-19 was a very safe intervention, we did not observe any effect on mortality.

COVID-19 is not "just another flu": a real-life comparison of severe COVID-19 and influenza in hospitalized patients in Vienna, Austria.

BACKGROUND: COVID-19 is regularly compared to influenza. Mortality and case-fatality rates vary widely depending on incidence of COVID-19 and the testing policy in affected countries. To date, data comparing hospitalized patients with COVID-19 and influenza is scarce. METHODS: Data from patients with COVID-19 were compared to patients infected with influenza A (InfA) and B (InfB) virus during the 2017/18 and 2018/19 seasons. All patients were ≥ 18 years old, had PCR-confirmed infection and needed hospital treatment. Demographic data, medical history, length-of-stay (LOS), complications including in-hospital mortality were analyzed. RESULTS: In total, 142 patients with COVID-19 were compared to 266 patients with InfA and 300 with InfB. Differences in median age (COVID-19 70.5 years vs InfA 70 years and InfB 77 years, p < 0.001) and laboratory results were observed. COVID-19 patients had fewer comorbidities, but complications (respiratory insufficiency, pneumonia, acute kidney injury, acute heart failure and death) occurred more frequently. Median length-of-stay (LOS) was longer in COVID-19 patients (12 days vs InfA 7 days vs. InfB 7 days, p < 0.001). There was a fourfold higher in-hospital mortality in COVID-19 patients (23.2%) when compared with InfA (5.6%) or InfB (4.7%; p < 0.001). CONCLUSION: In hospitalized patients, COVID-19 is associated with longer LOS, a higher number of complications and higher in-hospital mortality compared to influenza, even in a population with fewer co-morbidities. This data, a high reproduction number and limited treatment options, alongside excess mortality during the SARS-CoV-2 pandemic, support the containment strategies implemented by most authorities.

Successful treatment of intubation-induced severe neurogenic post-extubation dysphagia using pharyngeal electrical stimulation in a COVID-19 survivor: a case report.

BACKGROUND: A significant portion of critically ill patients with coronavirus disease 2019 (COVID-19) are at high risk of developing intensive care unit (ICU)-acquired swallowing dysfunction (neurogenic dysphagia) as a consequence of requiring prolonged mechanical ventilation. Pharyngeal electrical stimulation (PES) is a simple and safe treatment for neurogenic dysphagia. It has been shown that PES can restore safe swallowing in orally intubated or tracheotomized ICU patients with neurogenic dysphagia following severe stroke. We report the case of a patient with severe neurogenic post-extubation dysphagia (PED) due to prolonged intubation and severe general muscle weakness related to COVID-19, which was successfully treated using PES. CASE PRESENTATION: A 71-year-old Caucasian female patient with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection developed neurogenic dysphagia following prolonged intubation in the ICU. To avoid aerosol-generating procedures, her swallowing function was evaluated non-instrumentally as recommended by recently published international guidelines in response to the COVID-19 pandemic. Her swallowing function was markedly impaired and PES therapy was recommended. PES led to a rapid improvement of the PED, as evaluated by bedside swallowing assessments using the Gugging Swallowing Screen (GUSS) and Dysphagia Severity Rating Scale (DSRS), and diet screening using the Functional Oral Intake Scale (FOIS). The improved swallowing, as reflected by these measures, allowed this patient to transfer from the ICU to a non-intensive medical department 5 days after completing PES treatment. CONCLUSIONS: PES treatment contributed to the restoration of a safe swallowing function in this critically ill patient with COVID-19 and ICU-acquired swallowing dysfunction. Early clinical bedside swallowing assessment and dysphagia intervention in COVID-19 patients is crucial to optimize their full recovery. PES may contribute to a safe and earlier ICU discharge of patients with ICU-acquired swallowing dysfunction. Earlier ICU discharge and reduced rates of re-intubation following PES can help alleviate some of the pressure on ICU bed capacity, which is critical in times of a health emergency such as the ongoing COVID-19 pandemic.

Clinical and Angiographic Features in Three COVID-19 Patients with Takotsubo Cardiomyopathy. Case Report.

While coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has often been perceived as a predominantly respiratory condition, it is characterized by complications in multiple organ systems. Especially the involvement of the cardiovascular system, along with the possibly severe pulmonary injury, is crucial for prognosis. We identified three COVID-19 patients with takotsubo (TT) cardiomyopathy at our infectious diseases treatment center and present their clinical, laboratory, echocardiographic, electrocardiographic, and angiographic features. All patients were female (median age, 67 years); disease severity regarding COVID-19 ranged from asymptomatic to ARDS (adult respiratory syndrome) necessitating mechanical ventilation for 22 days. Angiography revealed normal coronary arteries in patient 1, severe three-vessel coronary artery disease (CAD) in patient 2, and insignificant bystander CAD in patient 3. All patients showed classic apical hypokinesia with basal hyperkinesia. In patient 3, TT cardiomyopathy resulted in transient cardiogenic shock. Twenty-eight-day mortality was 0% in this case series. In conclusion, takotsubo cardiomyopathy may be yet another clinical entity associated with SARS-CoV-2 infection.

Diagnosis of COVID-19 using multiple antibody assays in two cases with negative PCR results from nasopharyngeal swabs.

We report of two cases of progressed COVID-19 with negative PCR tests from nasopharyngeal swabs, in whom diagnosis was made by different antibody assays, including a lateral flow rapid test and multiple commercial ELISAs, finally confirmed by comprehensive serological assays. These cases highlight that commercial ELISAs and even rapid tests might significantly aid the diagnosis of COVID-19, particularly, if a combination of serological assays is used with a specific clinical question, in severely ill patients after seroconversion and when comprehensive serological methods are used for confirmation.

Hydroxychloroquine versus lopinavir/ritonavir in severe COVID-19 patients : Results from a real-life patient cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a high mortality. To date no trial comparing hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/RTV) has been performed. METHODS: Hospitalized patients ≥18 years old with severe coronavirus disease 2019 (COVID-19) were treated with either HCQ or LPV/RTV if they had either respiratory insufficiency (SpO2 ≤ 93% on room air or the need for oxygen insufflation) or bilateral consolidations on chest X­ray and at least 2 comorbidities associated with poor COVID-19 prognosis. Outcomes investigated included in-hospital mortality, intensive care unit (ICU) admission, length of stay, PCR (polymerase chain reaction) negativity and side effects of treatment. RESULTS: Of 156 patients (41% female) with a median age of 72 years (IQR 55.25-81) admitted to our department, 67 patients fulfilled the inclusion criteria (20 received HCQ, 47 LPV/RTV). Groups were comparable regarding most baseline characteristics. Median time from symptom onset to treatment initiation was 8 days and was similar between the groups (p = 0.727). There was no significant difference (HCQ vs. LPV/RTV) in hospital mortality (15% vs. 8.5%, p = 0.418), ICU admission rate (20% vs. 12.8%, p = 0.470) and length of stay (9 days vs. 11 days, p = 0.340). A PCR negativity from nasopharyngeal swabs was observed in approximately two thirds of patients in both groups. Side effects led to treatment discontinuation in 15% of patients in the LPV/RTV group. CONCLUSION: No statistically significant differences were observed in outcome parameters in patients treated with HCQ or LPV/RTV but patients in the LPV/RTV group showed a numerically lower hospital mortality rate. Additionally, in comparison to other studies we demonstrated a lower mortality in patients treated with LPV/RTV despite having similar patient groups, perhaps due to early initiation of treatment.