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2.
Infection ; 49(6): 1299-1306, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1482322

ABSTRACT

PURPOSE: Thorough knowledge of the nature and frequency of co-infections is essential to optimize treatment strategies and risk assessment in cases of coronavirus disease 2019 (COVID-19). This study aimed to evaluate the multiplex polymerase chain reaction (PCR) screening approach for community-acquired bacterial pathogens (CABPs) at hospital admission, which could facilitate identification of bacterial co-infections in hospitalized COVID-19 patients. METHODS: Clinical data and biomaterials from 200 hospitalized COVID-19 patients from the observational cohort of the Competence Network for community-acquired pneumonia (CAPNETZ) prospectively recruited between March 17, 2020, and March 12, 2021 in 12 centers in Germany and Switzerland, were included in this study. Nasopharyngeal swab samples were analyzed on hospital admission using multiplex real-time reverse transcription (RT)-PCR for a broad range of CABPs. RESULTS: In total of 200 patients Staphylococcus aureus (27.0%), Haemophilus influenzae (13.5%), Streptococcus pneumoniae (5.5%), Moraxella catarrhalis (2.5%), and Legionella pneumophila (1.5%) were the most frequently detected bacterial pathogens. PCR detection of bacterial pathogens correlated with purulent sputum, and showed no correlation with ICU admission, mortality, and inflammation markers. Although patients who received antimicrobial treatment were more often admitted to the ICU and had a higher mortality rate, PCR pathogen detection was not significantly related to antimicrobial treatment. CONCLUSION: General CABP screening using multiplex PCR with nasopharyngeal swabs may not facilitate prediction or identification of bacterial co-infections in the early phase of COVID-19-related hospitalization. Most patients with positive PCR results appear to be colonized rather than infected at that time, questioning the value of routine antibiotic treatment on admission in COVID-19 patients.


Subject(s)
COVID-19 , Coinfection , Community-Acquired Infections , Legionella pneumophila , Pneumonia , Cohort Studies , Coinfection/diagnosis , Coinfection/epidemiology , Community-Acquired Infections/diagnosis , Humans , Multiplex Polymerase Chain Reaction , Prospective Studies , SARS-CoV-2
3.
BMJ Open ; 11(9): e053819, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440827

ABSTRACT

INTRODUCTION: mHealth refers to digital technologies that, via smartphones, mobile apps and specialised digital sensors, yield real-time assessments of patient's health status. In the context of the COVID-19 pandemic, these technologies enable remote patient monitoring, with the benefit of timely recognition of disease progression to convalescence, deterioration or postacute sequelae. This should enable appropriate medical interventions and facilitate recovery. Various barriers, both at patient and technology levels, have been reported, hindering implementation and use of mHealth telemonitoring. As systematised and synthesised evidence in this area is lacking, we developed this protocol for a scoping review on mHealth home telemonitoring of acute COVID-19. METHODS AND ANALYSIS: We compiled a search strategy following the PICO (Population, Intervention, Comparator, Outcome) and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation for Scoping Reviews) guidelines. MEDLINE, Embase and Web of Science will be searched from 1 March 2020 to 31 August 2021. Following the title and abstract screening, we will identify, systematise and synthesise the available knowledge. Based on pilot searches, we preview three themes for descriptive evidence synthesis. The first theme relates to implementation and use of mHealth telemonitoring, including reported barriers. The second theme covers the interactions of the telemonitoring team within and between different levels of the healthcare system. The third theme addresses how this telemonitoring warrants the continuity of care, also during disease transition into deterioration or postacute sequelae. ETHICS AND DISSEMINATION: The studied evidence is in the public domain, therefore, no specific ethics approval is required. Evidence dissemination will be via peer-reviewed publications, conference presentations and reports to the policy makers.


Subject(s)
COVID-19 , Mobile Applications , Telemedicine , Adult , Humans , Pandemics , Review Literature as Topic , SARS-CoV-2 , Systematic Reviews as Topic
4.
Emerg Microbes Infect ; 10(1): 1515-1518, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1313723

ABSTRACT

We show a shift in the prevalence of respiratory viral pathogens in community-acquired pneumonia patients during the COVID-19 pandemic. Our data support the efficiency of non-pharmaceutical interventions on virus circulation except for rhinoviruses. The consequences of an altered circulation on subsequent winter seasons remain unclear and support the importance of systematic virological surveillance.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Respiratory Tract Infections/epidemiology , Adult , Aged , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , COVID-19/virology , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia/microbiology , Pneumonia/virology , Prevalence , Prospective Studies , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viruses/classification , Viruses/genetics , Viruses/isolation & purification , Young Adult
5.
Ann Am Thorac Soc ; 17(7): 879-891, 2020 07.
Article in English | MEDLINE | ID: covidwho-679536

ABSTRACT

There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features: 1) randomization, allowing robust causal inference; 2) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability; 3) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups; 4) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and 5) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).


Subject(s)
Community-Acquired Infections/therapy , Coronavirus Infections/therapy , Influenza, Human/therapy , Pneumonia, Viral/therapy , Pneumonia/therapy , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Evidence-Based Medicine , Humans , Pandemics , Point-of-Care Systems , SARS-CoV-2
6.
J Infect Dis ; 223(1): 56-61, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066345

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany. METHODS: SARS-CoV-2-specific-antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and human coronavirus NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors. RESULTS: The severity of COVID-19 increased with age, and male patients encountered more serious symptoms than female patients. Disease severity was correlated with the amount of SARS-CoV-2-specific immunoglobulin (Ig) G and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2-specific IgG antibodies decreased with time after polymerase chain reaction conformation of the infection, and antibodies directed against the nucleoprotein waned faster than spike protein-directed antibodies. In contrast, for the common flu coronavirus NL63, COVID-19 disease severity seemed to be correlated with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection. CONCLUSION: The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Humoral , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Cohort Studies , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Female , Germany , HEK293 Cells , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Male , Middle Aged , Young Adult
7.
Cells ; 9(11)2020 10 30.
Article in English | MEDLINE | ID: covidwho-921181

ABSTRACT

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is the cause of the current coronavirus disease 19 (COVID-19) pandemic. Protease inhibitors are under consideration as virus entry inhibitors that prevent the cleavage of the coronavirus spike (S) protein by cellular proteases. Herein, we showed that the protease inhibitor aprotinin (but not the protease inhibitor SERPINA1/alpha-1 antitrypsin) inhibited SARS-CoV-2 replication in therapeutically achievable concentrations. An analysis of proteomics and translatome data indicated that SARS-CoV-2 replication is associated with a downregulation of host cell protease inhibitors. Hence, aprotinin may compensate for downregulated host cell proteases during later virus replication cycles. Aprotinin displayed anti-SARS-CoV-2 activity in different cell types (Caco2, Calu-3, and primary bronchial epithelial cell air-liquid interface cultures) and against four virus isolates. In conclusion, therapeutic aprotinin concentrations exert anti-SARS-CoV-2 activity. An approved aprotinin aerosol may have potential for the early local control of SARS-CoV-2 replication and the prevention of COVID-19 progression to a severe, systemic disease.


Subject(s)
Aprotinin/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19/metabolism , Caco-2 Cells , Chlorocebus aethiops , Epithelial Cells/drug effects , Humans , Pandemics , SARS-CoV-2/physiology , Serine Proteinase Inhibitors/pharmacology , Vero Cells
8.
Infection ; 48(6): 971-974, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-631448

ABSTRACT

PURPOSE: The first SARS-CoV-2 cases in Europe were reported in January 2020. Recently, concern arose on unrecognized infections before this date. For a better understanding of the pandemic, we retrospectively analyzed patient samples for SARS-CoV-2 from the prospective CAPNETZ study cohort. METHODS: We used nasopharyngeal swab samples from a cohort of well characterized patients with community acquired pneumonia of the CAPNETZ study group, recruited from different geographic regions across Germany, Austria, the Netherlands, and Switzerland between 02nd December 2019 and 28th April 2020. Multiplex real-time RT-PCR for a broad range of respiratory pathogens and SARS-CoV-2 real-time RT-PCR were performed on all samples. RESULTS: In our cohort, respiratory pathogens other than SARS-CoV-2 were detected in 21.5% (42/195) of patients with rhinovirus as the most frequently detected pathogen. The detection rate increased to 29.7% (58/195) when SARS-CoV-2 was included. No SARS-CoV-2 positive sample was detected before end of March 2020. CONCLUSIONS: Respiratory viral pathogens accounted for a considerable number of positive results but no SARS-CoV-2 case was identified before the end of March 2020.


Subject(s)
COVID-19/epidemiology , Community-Acquired Infections/epidemiology , Pneumonia/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/virology , Cohort Studies , Community-Acquired Infections/diagnosis , Community-Acquired Infections/etiology , Community-Acquired Infections/history , Female , Germany , History, 21st Century , Humans , Male , Middle Aged , Multiplex Polymerase Chain Reaction , Pneumonia/diagnosis , Pneumonia/etiology , Pneumonia/history , SARS-CoV-2 , Young Adult
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