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1. Bloodstream Infections in a COVID-19 Non-ICU Department: Microbial Epidemiology, Resistance Profiles and Comparative Analysis of Risk Factors and Patients’ Outcome

Author

Efthymia Giannitsioti, Christina Louka, Vasiliki Mamali, Elisavet Kousouli, Lemonia Velentza, Vaia Papadouli, Georgios Loizos, Panagiotis Mavroudis, Georgios Kranidiotis, Nektaria Rekleiti, Alexandra Stamati, Ioannis Speggos, Ioannis Daniil, Panagiotis Kouvatsos, Chrysanthi Sidiropoulou, Garifallia Linardaki, Styliani Gerakari, Georgios Chrysos, Katina Themeli-Digalaki, and Olympia Zarkotou

Subjects
COVID-19, SARS-CoV-2 pneumonia, bloodstream infections, bacteremia, fungemia, catheter-related bloodstream infection, Biology (General), QH301-705.5
Abstract

Background: Bloodstream infections (BSI) caused by highly resistant pathogens in non-ICU COVID-19 departments pose important challenges. Methods: We performed a comparative analysis of incidence and microbial epidemiology of BSI in COVID-19 vs. non-COVID-19, non-ICU departments between 1 September 2020-31 October 2021. Risk factors for BSI and its impact on outcome were evaluated by a case-control study which included COVID-19 patients with/without BSI. Results: Forty out of 1985 COVID-19 patients developed BSI. The mean monthly incidence/100 admissions was 2.015 in COVID-19 and 1.742 in non-COVID-19 departments. Enterococcus and Candida isolates predominated in the COVID-19 group (p < 0.001 and p = 0.018, respectively). All Acinetobacter baumannii isolates were carbapenem-resistant (CR). In the COVID-19 group, 33.3% of Klebsiella pneumoniae was CR, 50% of Escherichia coli produced ESBL and 19% of Enterococcus spp. were VRE vs. 74.5%, 26.1% and 8.8% in the non-COVID-19 group, respectively. BSI was associated with prior hospitalization (p = 0.003), >2 comorbidities (p < 0.001), central venous catheter (p = 0.015), severe SARS-CoV-2 pneumonia and lack of COVID-19 vaccination (p < 0.001). In the multivariate regression model also including age and multiple comorbidities, only BSI was significantly associated with adverse in-hospital outcome [OR (CI95%): 21.47 (3.86–119.21), p < 0.001]. Conclusions: BSI complicates unvaccinated patients with severe SARS-CoV-2 pneumonia and increases mortality. BSI pathogens and resistance profiles differ among COVID-19/non-COVID-19 departments, suggesting various routes of pathogen acquisition.

Published
2022
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2. Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial

Author

Panteleimon Tsiamalos, Iro Rapti, Androniki Papapostolou, Thomas Nitsotolis, Chrysanthi Sidiropoulou, Haralampos Milionis, Konstantinos N. Syrigos, Antonios Tsakiris, Konstantina Katrini, Eleftherios Klouras, Evangelos J. Giamarellos-Bourboulis, Emmanouil Vrentzos, George Chrysos, Georgios Tsibris, Periklis Panagopoulos, Dimitra-Melia Myrodia, Vagia Zarkada, Theologia Gkavogianni, Garyphallia Poulakou, Evangelos Michelakis, Konstantinos Tsiakos, Maria Georgiopoulou, Christina Damoulari, Vasileios Petrakis, Maria Kosmidou, Sofia Artemi, Areti Gravvani, Panagiotis Koufargyris, Pantazis-Michael Voutsinas, Anastasios Ioannidis, and Athanassios Karageorgos

Subjects
Microbiology (medical), medicine.medical_specialty, business.industry, COVID-19, Odds ratio, medicine.disease, Gastroenterology, Th1, Th2, Infectious Diseases, Upper respiratory tract infection, Respiratory failure, Internal medicine, Clarithromycin, Lower respiratory tract infection, medicine, Clinical endpoint, Viral load, Respiratory system, business, medicine.drug, Original Research
Abstract

Introduction The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. Methods An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. Results The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1–92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. Conclusions Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. Trial Registration ClinicalTrials.gov, NCT04398004 Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00505-8.

Published
2021

3. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis

Author

Evdoxia Kyriazopoulou, Thomas Huet, Giulio Cavalli, Andrea Gori, Miltiades Kyprianou, Peter Pickkers, Jesper Eugen-Olsen, Mario Clerici, Francisco Veas, Gilles Chatellier, Gilles Kaplanski, Mihai G Netea, Emanuele Pontali, Marco Gattorno, Raphael Cauchois, Emma Kooistra, Matthijs Kox, Alessandra Bandera, Hélène Beaussier, Davide Mangioni, Lorenzo Dagna, Jos W M van der Meer, Evangelos J Giamarellos-Bourboulis, Gilles Hayem, Mihai G. Netea, Jos W.M. van der Meer, Evangelos J. Giamarellos-Bourboulis, Stefano Volpi, Maria Pia Sormani, Alessio Signori, Giorgio Bozzi, Francesca Minoia, Stefano Aliberti, Giacomo Grasselli, Laura Alagna, Andrea Lombardi, Riccardo Ungaro, Carlo Agostoni, Francesco Blasi, Giorgio Costantino, Anna Ludovica Fracanzani, Nicola Montano, Flora Peyvandi, Marcello Sottocorno, Antonio Muscatello, Giovanni Filocamo, Antonios Papadopoulos, Maria Mouktaroudi, Eleni Karakike, Maria Saridaki, Theologia Gkavogianni, Konstantina Katrini, Nikolaos Vechlidis, Christina Avgoustou, Stamatios Chalvatzis, Theodoros Marantos, Christina Damoulari, Georgia Damoraki, Sofia Ktena, Maria Tsilika, Panagiotis Koufargyris, Athanasios Karageorgos, Dionysia-Irene Droggiti, Aikaterini Koliakou, Garyfallia Poulakou, Konstantinos Tsiakos, Dimitra-Melia Myrodia, Areti Gravvani, Ioannis P. Trontzas, Konstantinos Syrigos, Ioannis Kalomenidis, Eleftheria Kranidioti, Periklis Panagopoulos, Vasileios Petrakis, Simeon Metallidis, Georgia Loli, Olga Tsachouridou, George N. Dalekos, Nikolaos Gatselis, Aggelos Stefos, Sarah Georgiadou, Vassiliki Lygoura, Haralampos Milionis, Maria Kosmidou, Ilias C. Papanikolaou, Karolina Akinosoglou, Efthymia Giannitsioti, Georgios Chrysos, Panagiotis Mavroudis, Chrysanthi Sidiropoulou, Georgios Adamis, Archontoula Fragkou, Aggeliki Rapti, Zoi Alexiou, Styliani Symbardi, Aikaterini Masgala, Konstantina Kostaki, Evangelos Kostis, Michael Samarkos, Petros Bakakos, Vassiliki Tzavara, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Vasileios Kotsis, George Tsoukalas, Ioannis Bliziotis, Michael Doumas, Aikaterini Argyraki, Ilias Kainis, Massimo Fantoni, Antonella Cingolani, Andrea Angheben, Chiara Simona Cardellino, Francesco Castelli, Francesco Saverio Serino, Emanuele Nicastri, Giuseppe Ippolito, Matteo Bassetti, Carlo Selmi, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Kyriazopoulou, E., Huet, T., Cavalli, Giulio., Gori, A., Kyprianou, M., Pickkers, P., Eugen-Olsen, J., Clerici, M., Veas, F., Chatellier, G., Kaplanski, G., Netea, M. G., Pontali, E., Gattorno, M., Cauchois, R., Kooistra, E., Kox, M., Bandera, A., Beaussier, H., Mangioni, D., Dagna, L., van der Meer, J. W. M., Giamarellos-Bourboulis, E. J., Hayem, G., Volpi, S., Sormani, M. P., Signori, A., Bozzi, G., Minoia, F., Aliberti, S., Grasselli, G., Alagna, L., Lombardi, A., Ungaro, R., Agostoni, C., Blasi, F., Costantino, G., Fracanzani, A. L., Montano, N., Peyvandi, F., Sottocorno, M., Muscatello, A., Filocamo, G., Papadopoulos, A., Mouktaroudi, M., Karakike, E., Saridaki, M., Gkavogianni, T., Katrini, K., Vechlidis, N., Avgoustou, C., Chalvatzis, S., Marantos, T., Damoulari, C., Damoraki, G., Ktena, S., Tsilika, M., Koufargyris, P., Karageorgos, A., Droggiti, D. -I., Koliakou, A., Poulakou, G., Tsiakos, K., Myrodia, D. -M., Gravvani, A., Trontzas, I. P., Syrigos, K., Kalomenidis, I., Kranidioti, E., Panagopoulos, P., Petrakis, V., Metallidis, S., Loli, G., Tsachouridou, O., Dalekos, G. N., Gatselis, N., Stefos, A., Georgiadou, S., Lygoura, V., Milionis, H., Kosmidou, M., Papanikolaou, I. C., Akinosoglou, K., Giannitsioti, E., Chrysos, G., Mavroudis, P., Sidiropoulou, C., Adamis, G., Fragkou, A., Rapti, A., Alexiou, Z., Symbardi, S., Masgala, A., Kostaki, K., Kostis, E., Samarkos, M., Bakakos, P., Tzavara, V., Dimakou, K., Tzatzagou, G., Chini, M., Kotsis, V., Tsoukalas, G., Bliziotis, I., Doumas, M., Argyraki, A., Kainis, I., Fantoni, M., Cingolani, A., Angheben, A., Cardellino, C. S., Castelli, F., Serino, F. S., Nicastri, E., Ippolito, G., Bassetti, M., and Selmi, C.

Subjects
medicine.medical_specialty, Anakinra, business.industry, Secondary infection, [SDV]Life Sciences [q-bio], Immunology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Odds ratio, Articles, Placebo, law.invention, Rheumatology, Randomized controlled trial, law, Meta-analysis, Fraction of inspired oxygen, Internal medicine, Clinical endpoint, Immunology and Allergy, Medicine, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

Contains fulltext : 237989.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO(2)/FiO(2). In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.

Published
2021
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4. Long Term Immune and Epigenetic Dysregulation Following COVID-19: The Impact of Anti-IL-1 Treatment in the Post-Acute COVID Syndrome

Author

Chrysanthi Sidiropoulou, Evangelos Giamarellos-Bourboulis, Garyfallia Poulakou, Maria Tsilika, Spyros Foutadakis, Vassiliki Evangelopoulou, George Adamis, Aggeliki Rapti, Efthymia Giannitsioti, Styliani Symbardi, Nikoletta Charalampaki, Paraskevi Chra, Konstantinos Tsiakos, Giannis Vatsellas, Mervan Damadoglou, Petros Bakakos, Georgia Damoraki, Theologia Gkavogianni, Leda Efstratiou, Christina Damoulari, Konstantinos Leventogiannis, Achilleas Laskaratos, Anna Strikou, Panagiotis Koufargyris, Konstantina Katrini, Vassiliki Rapti, Aglaia Galanopoulou, Karolina Akinosoglou, Haralampos Milionis, Archontoula Fragkou, Dimitris Thanos, Periklis Panagopoulos, Zoi Alexiou, George N. Dalekos, Konstantinos N. Syrigos, Athanasios Ziogas, Rob ter Horst, Jos W.M. van der Meer, Mihai G. Netea, and Evdoxia Kyriazopoulou

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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5. Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial

Author

Panteleimon Tsiamalos, Maria Kosmidou, Areti Gravvani, Evangelos Michelakis, Panagiotis Koufargyris, Pantazis Voutsinas, Vasileios Petrakis, George Chrysos, Periklis Panagopoulos, Dimitra-Melia Myrodia, Theologia Gkavogianni, Sofia Artemi, Emmanouil Vrentzos, Androniki Papapostolou, Evangelos J. Giamarellos-Bourboulis, Thomas Nitsotolis, Anastasios Ioannidis, Konstantinos N. Syrigos, Konstantinos Tsiakos, Maria Georgiopoulou, Iro Rapti, Garyphallia Poulakou, Athanassios Karageorgos, Vagia Zarkada, Chrysanthi Sidiropoulou, Christina Damoulari, Gerorgios Tsibris, Haralampos Milionis, Antonios Tsakiris, Konstantina Katrini, and Eleftherios Klouras

Subjects
medicine.medical_specialty, business.industry, Odds ratio, medicine.disease, Upper respiratory tract infection, Respiratory failure, Lower respiratory tract infection, Clarithromycin, Internal medicine, medicine, Clinical endpoint, Respiratory system, business, Viral load, medicine.drug
Abstract

BackgroundTo study the efficacy of oral clarithromycin in moderate COVID-19.MethodsAn open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end-of-treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection; and as at least 50% decrease of the respiratory symptoms score the without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells, and safety were assessed.ResultsThe primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p: 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported.ConclusionsEarly clarithromycin treatment provides most of clinical improvement in moderate COVID-19 (Trial Registration: ClinicalTrials.gov, NCT04398004)

Published
2020
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