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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333086

ABSTRACT

The recently emerged Omicron variant is the most antigenically distinct SARS-CoV-2 variant of concern to date. As the heavily mutated spike protein enables escape from neutralizing antibodies, we studied the neutralizing activities of sera after Omicron BA.1 and BA.2 infections of naïve and vaccinated individuals. We show that primary BA.1 infections yielded reduced neutralizing antibody titers against wildtype (WT), Delta, and BA.2, while serum samples from individuals after BA.2 infection showed no cross-neutralization against the other variants. Fully vaccinated individuals were still able to neutralize both Omicron sub-lineages up to three months after vaccination, and Omicron-breakthrough infections showed equal cross-neutralizing activities against WT, Delta, BA.1, and BA.2. Our data demonstrate that Omicron variants are able to enhance cross-neutralizing antibodies in pre-immune individuals. Primary infections with one of the Omicron sub-lineages, however, induced variant-specific neutralizing antibodies. In particular, BA.2 infections generated a sub-lineage-specific response, emphasizing its antigenic distance.

2.
Med Klin Intensivmed Notfmed ; 117(3): 177-186, 2022 Apr.
Article in German | MEDLINE | ID: covidwho-1763329

ABSTRACT

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.


Subject(s)
COVID-19 , Noninvasive Ventilation , Humans , Intensive Care Units , Noninvasive Ventilation/methods , Prone Position , Respiration, Artificial
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322903

ABSTRACT

Background: A significant portion of critically ill patients with COVID-19 are at high risk of developing 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. Previously it has been shown that PES can restore safe swallowing in orally intubated or tracheotomised 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 female patient with confirmed 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 post-extubation dysphagia (PED), as evaluated by bedside swallowing assessments using the Gugging Swallowing Screen (GUSS), 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 five 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 optimise their full recovery. Pharyngeal Electrical Stimulation 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.

4.
Wien Klin Wochenschr ; 2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1561051

ABSTRACT

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.

6.
Infect Dis (Lond) ; 53(11): 820-829, 2021 11.
Article in English | MEDLINE | ID: covidwho-1269478

ABSTRACT

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.


Subject(s)
COVID-19 , Critical Illness , COVID-19/therapy , Cohort Studies , Humans , Immunization, Passive , Male , Middle Aged , SARS-CoV-2
7.
Wien Klin Wochenschr ; 133(17-18): 902-908, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1269150

ABSTRACT

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.


Subject(s)
COVID-19 , Myoclonus , Critical Illness , Humans , Intensive Care Units , Myoclonus/chemically induced , Myoclonus/diagnosis , Myoclonus/drug therapy , SARS-CoV-2
8.
Infection ; 49(5): 907-916, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1226249

ABSTRACT

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.


Subject(s)
COVID-19 , Influenza, Human , Adolescent , Austria , Hospitalization , Humans , Influenza, Human/epidemiology , Pandemics , SARS-CoV-2
9.
J Clin Microbiol ; 59(5)2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195818

ABSTRACT

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Three hundred fifty-four blood samples longitudinally obtained from 81 IgG-seroconverting progressed coronavirus disease 2019 (CoVID-19) patients were quantified for spike 1 (S1), S2, and nucleocapsid protein (NCP)-specific IgM, IgA, IgG, and total Ig antibodies using a microarray, 11 different enzyme-linked immunosorbent assays (ELISAs)/chemiluminescence immunoassays (CLIAs), and 1 rapid test by seven manufacturers. The assays' specificity was assessed in 130 non-CoVID-19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th day post-symptom onset, all patients developed IgG responses against S1, S2, and NCP. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoassay/methods , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Kinetics , Phosphoproteins/immunology , SARS-CoV-2 , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
10.
Sci Immunol ; 6(57)2021 03 04.
Article in English | MEDLINE | ID: covidwho-1148101

ABSTRACT

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified nonsynonymous mutations in MHC-I-restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding in a cell-free in vitro assay. Reduced MHC-I binding of mutant peptides was associated with decreased proliferation, IFN-γ production and cytotoxic activity of CD8+ T cells isolated from HLA-matched COVID-19 patients. Single cell RNA sequencing of ex vivo expanded, tetramer-sorted CD8+ T cells from COVID-19 patients further revealed qualitative differences in the transcriptional response to mutant peptides. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through point mutations in MHC-I-restricted viral epitopes.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19 , Epitopes, T-Lymphocyte , HLA-A Antigens/immunology , Immunity, Cellular , Mutation , SARS-CoV-2 , CD8-Positive T-Lymphocytes/pathology , COVID-19/genetics , COVID-19/immunology , COVID-19/pathology , Cell Proliferation , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , High-Throughput Nucleotide Sequencing , Humans , Interferon-gamma/immunology , Peptides/genetics , Peptides/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology
11.
J Med Case Rep ; 15(1): 148, 2021 Mar 22.
Article in English | MEDLINE | ID: covidwho-1147316

ABSTRACT

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.


Subject(s)
COVID-19/therapy , Deglutition Disorders/therapy , Electric Stimulation Therapy/methods , Intubation, Intratracheal/adverse effects , Pharynx , Recovery of Function , Aged , Deglutition Disorders/etiology , Deglutition Disorders/physiopathology , Female , Humans , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
12.
SN Compr Clin Med ; 3(1): 263-268, 2021.
Article in English | MEDLINE | ID: covidwho-1018583

ABSTRACT

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.

13.
Front Med (Lausanne) ; 7: 592629, 2020.
Article in English | MEDLINE | ID: covidwho-954056

ABSTRACT

Disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from mild illness to severe respiratory disease and death. In this study, we determined the kinetics of viral loads, antibody responses (IgM, IgG, neutralization) and SARS-CoV-2-specific CD4 T cells by quantifying these parameters in 435 serial respiratory and blood samples collected from a cohort of 29 COVID-19 patients with either moderate or severe disease during the whole period of hospitalization or until death. Remarkably, there was no significant difference in the kinetics and plateau levels of neutralizing antibodies among the groups with different disease severity. In contrast, the dynamics of specific CD4 T cell responses differed considerably, but all patients with moderate or severe disease developed robust SARS-CoV-2-specific responses. Of note, none of the patients had detectable cross-reactive CD4 T cells in the first week after symptom onset, which have been described in 20-50% of unexposed individuals. Our data thus provide novel insights into the kinetics of antibody and CD4 T cell responses as well as viral loads that are key to understanding the role of adaptive immunity in combating the virus during acute infection and provide leads for the timing of immune therapies for COVID-19.

15.
Infection ; 49(1): 171-175, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-714361

ABSTRACT

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.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , SARS-CoV-2/immunology , Aged , COVID-19/immunology , COVID-19/virology , COVID-19 Testing , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity , Severity of Illness Index , Tomography, X-Ray Computed
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