Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease. Razazi Keyvan,Arrestier Romain,Haudebourg Anne Fleur,Benelli Brice,Carteaux Guillaume,Decousser Jean-Winoc,Fourati Slim,Woerther Paul Louis,Schlemmer Frederic,Charles-Nelson Anais,Botterel Francoise,de Prost Nicolas,Mekontso Dessap Armand Critical care (London, England) BACKGROUND:Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. METHODS:We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). RESULTS:We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization. CONCLUSIONS:In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group. 10.1186/s13054-020-03417-0
    Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Rouzé Anahita,Martin-Loeches Ignacio,Povoa Pedro,Makris Demosthenes,Artigas Antonio,Bouchereau Mathilde,Lambiotte Fabien,Metzelard Matthieu,Cuchet Pierre,Boulle Geronimi Claire,Labruyere Marie,Tamion Fabienne,Nyunga Martine,Luyt Charles-Edouard,Labreuche Julien,Pouly Olivier,Bardin Justine,Saade Anastasia,Asfar Pierre,Baudel Jean-Luc,Beurton Alexandra,Garot Denis,Ioannidou Iliana,Kreitmann Louis,Llitjos Jean-François,Magira Eleni,Mégarbane Bruno,Meguerditchian David,Moglia Edgar,Mekontso-Dessap Armand,Reignier Jean,Turpin Matthieu,Pierre Alexandre,Plantefeve Gaetan,Vinsonneau Christophe,Floch Pierre-Edouard,Weiss Nicolas,Ceccato Adrian,Torres Antoni,Duhamel Alain,Nseir Saad, Intensive care medicine PURPOSE:Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI. METHODS:Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models. RESULTS:1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp. CONCLUSIONS:The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates. 10.1007/s00134-020-06323-9
    Clonal dispersion of Acinetobacter baumannii in an intensive care unit designed to patients COVID-19. Durán-Manuel Emilio Mariano,Cruz-Cruz Clemente,Ibáñez-Cervantes Gabriela,Bravata-Alcantará Juan Carlos,Sosa-Hernández Oscar,Delgado-Balbuena Laura,León-García Gregorio,Cortés-Ortíz Iliana Alejandra,Cureño-Díaz Monica Alethia,Castro-Escarpulli Graciela,Vélez-Reséndiz Juan Manuel,Bello-López Juan Manuel Journal of infection in developing countries INTRODUCTION:SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico. METHODOLOGY:Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done. RESULTS:Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus. CONCLUSIONS:Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients. 10.3855/jidc.13545
    Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs. Gamberini Lorenzo,Tonetti Tommaso,Spadaro Savino,Zani Gianluca,Mazzoli Carlo Alberto,Capozzi Chiara,Giampalma Emanuela,Bacchi Reggiani Maria Letizia,Bertellini Elisabetta,Castelli Andrea,Cavalli Irene,Colombo Davide,Crimaldi Federico,Damiani Federica,Fogagnolo Alberto,Fusari Maurizio,Gamberini Emiliano,Gordini Giovanni,Laici Cristiana,Lanza Maria Concetta,Leo Mirco,Marudi Andrea,Nardi Giuseppe,Ottaviani Irene,Papa Raffaella,Potalivo Antonella,Russo Emanuele,Taddei Stefania,Volta Carlo Alberto,Ranieri V Marco, Journal of intensive care BACKGROUND:A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. METHODS:This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. RESULTS:Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO/FiO ratio during the first 5 days of MV, respiratory system compliance (C) lower than 40 mL/cmHO during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. CONCLUSIONS:Age, SOFA score at ICU admission, C, PaO/FiO, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. TRIAL REGISTRATION:NCT04411459. 10.1186/s40560-020-00499-4
    Ventilator-associated bacterial pneumonia in coronavirus 2019 disease, a retrospective monocentric cohort study. Moretti Marco,Van Laethem Johan,Minini Andrea,Pierard Denis,Malbrain Manu L N G Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy INTRODUCTION:Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. METHODS:Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. RESULTS:Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. CONCLUSIONS:Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality. 10.1016/j.jiac.2021.01.011
    Risk factors for mortality of 557 adult patients with COVID 19 in Babol, Northern Iran: a retrospective cohort study. Javanian M,Bayani M,Shokri M,Sadeghi-Haddad-Zavareh M,Babazadeh A,Ghadimi R,Sepidarkish M,Bijani A,Yahyapour Y,Barary M,Hasanpour A H,Ebrahimpour S Bratislavske lekarske listy BACKGROUND:This study was aimed to investigate the risk factors for mortality in patients with COVID-19. METHODS:For this retrospective cohort study, we included 121 deceased and 436 discharged cases with COVID-19 in Babol, Northern Iran. The cases were between March 1 to April 1, 2020. RESULTS:Multivariate Poisson regression analysis revealed that older age (aRR: 1.03, 95% CI: 1.01, 1.05, p < 0.001), hospital length of stay (aRR: 0.94, 95% CI: 0.90, 0.97, p = 0.003), ICU admission (aRR: 4.34, 95% CI: 2.95, 6.37, p < 0.001), cerebrovascular disease (aRR: 1.96, 95% CI: 1.20, 3.19, p = 0.007), ventilator-associated pneumonia (VAP) (aRR: 2.09, 95% CI: 1.22, 3.55, p = 0.006), septic shock (aRR: 2.98, 95% CI: 1.44, 6.19, p = 0.003), acute respiratory distress syndrome (ARDS) (aRR: 3.80, 95% CI: 2.28, 6.31, p < 0.001), acute kidney failure (AKF) (aRR: 1.45, 95% CI: 1.12, 3.76, p = 0.021), acute heart failure (AHF) (aRR: 1.63, 95% CI: 1.01, 2.62, p = 0.043) and lymphocyte count (aRR: 3.01, 95% CI: 1.99, 4.57, p < 0.001) were associated with mortality. CONCLUSION:Findings showed that elderly with comorbidities such as cerebrovascular diseases had an increased risk of death. Some complications such as: pneumonia, septic shock, ARDS, AHF, and AKF played crucial roles as well death (Tab. 2, Ref. 25). 10.4149/BLL_2021_003
    Ventilator-associated pneumonia in critically ill patients with COVID-19. Maes Mailis,Higginson Ellen,Pereira-Dias Joana,Curran Martin D,Parmar Surendra,Khokhar Fahad,Cuchet-Lourenço Delphine,Lux Janine,Sharma-Hajela Sapna,Ravenhill Benjamin,Hamed Islam,Heales Laura,Mahroof Razeen,Solderholm Amelia,Forrest Sally,Sridhar Sushmita,Brown Nicholas M,Baker Stephen,Navapurkar Vilas,Dougan Gordon,Bartholdson Scott Josefin,Conway Morris Andrew Critical care (London, England) BACKGROUND:Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP). OBJECTIVES:To study the incidence of VAP and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients. METHODS:In this retrospective observational study, we compared the incidence of VAP and secondary infections using a combination of microbial culture and a TaqMan multi-pathogen array. In addition, we determined the lung microbiome composition using 16S RNA analysis in a subset of samples. The study involved 81 COVID-19 and 144 non-COVID-19 patients receiving invasive ventilation in a single University teaching hospital between March 15th 2020 and August 30th 2020. RESULTS:COVID-19 patients were significantly more likely to develop VAP than patients without COVID (Cox proportional hazard ratio 2.01 95% CI 1.14-3.54, p = 0.0015) with an incidence density of 28/1000 ventilator days versus 13/1000 for patients without COVID (p = 0.009). Although the distribution of organisms causing VAP was similar between the two groups, and the pulmonary microbiome was similar, we identified 3 cases of invasive aspergillosis amongst the patients with COVID-19 but none in the non-COVID-19 cohort. Herpesvirade activation was also numerically more frequent amongst patients with COVID-19. CONCLUSION:COVID-19 is associated with an increased risk of VAP, which is not fully explained by the prolonged duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the causative organisms of secondary pneumonia observed are similar to that seen in critically ill patients ventilated for other reasons. 10.1186/s13054-021-03460-5
    Epidemiology and microbiology of ventilator-associated pneumonia in COVID-19 patients: a multicenter retrospective study in 188 patients in an un-inundated French region. Blonz Gauthier,Kouatchet Achille,Chudeau Nicolas,Pontis Emmanuel,Lorber Julien,Lemeur Anthony,Planche Lucie,Lascarrou Jean-Baptiste,Colin Gwenhael Critical care (London, England) BACKGROUND:The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear. METHODS:We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture. FINDINGS:We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013). INTERPRETATION:Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional. REGISTRATION:As an observational study, this study has not been registered. 10.1186/s13054-021-03493-w
    Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study. Giacobbe Daniele Roberto,Battaglini Denise,Enrile Elisa Martina,Dentone Chiara,Vena Antonio,Robba Chiara,Ball Lorenzo,Bartoletti Michele,Coloretti Irene,Di Bella Stefano,Di Biagio Antonio,Brunetti Iole,Mikulska Malgorzata,Carannante Novella,De Maria Andrea,Magnasco Laura,Maraolo Alberto Enrico,Mirabella Michele,Montrucchio Giorgia,Patroniti Nicolò,Taramasso Lucia,Tiseo Giusy,Fornaro Giacomo,Fraganza Fiorentino,Monastra Luca,Roman-Pognuz Erik,Paluzzano Giacomo,Fiorentino Giuseppe,Corcione Antonio,Bussini Linda,Pascale Renato,Corcione Silvia,Tonetti Tommaso,Rinaldi Matteo,Falcone Marco,Biagioni Emanuela,Ranieri Vito Marco,Giannella Maddalena,De Rosa Francesco Giuseppe,Girardis Massimo,Menichetti Francesco,Viale Pierluigi,Pelosi Paolo,Bassetti Matteo Journal of clinical medicine The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were (27/77, 35%) and (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases. 10.3390/jcm10040555
    Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study. Luyt Charles-Edouard,Sahnoun Tarek,Gautier Melchior,Vidal Pauline,Burrel Sonia,Pineton de Chambrun Marc,Chommeloux Juliette,Desnos Cyrielle,Arzoine Jeremy,Nieszkowska Ania,Bréchot Nicolas,Schmidt Matthieu,Hekimian Guillaume,Boutolleau David,Robert Jérôme,Combes Alain,Chastre Jean Annals of intensive care BACKGROUND:The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons. RESULTS:Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42-56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8-16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups. CONCLUSIONS:Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung. 10.1186/s13613-020-00775-4
    Bacterial superinfection pneumonia in SARS-CoV-2 respiratory failure. Pickens Chiagozie O,Gao Catherine A,Cuttica Michael,Smith Sean B,Pesce Lorenzo,Grant Rogan,Kang Mengjia,Morales-Nebreda Luisa,Bavishi Avni A,Arnold Jason,Pawlowski Anna,Qi Chao,Budinger Gr Scott,Singer Benjamin D,Wunderink Richard G medRxiv : the preprint server for health sciences Background:Severe community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations. Methods:We obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care. Results:The 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive or species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days. Conclusions:With use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported. 10.1101/2021.01.12.20248588
    Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study. Xiong Qiutang,Xu Ming,Li Jiao,Liu Yinghui,Zhang Jixiang,Xu Yu,Dong Weiguo Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases OBJECTIVES:To describe the prevalence, nature and risk factors for the main clinical sequelae in coronavirus disease 2019 (COVID-19) survivors who have been discharged from the hospital for more than 3 months. METHODS:This longitudinal study was based on a telephone follow-up survey of COVID-19 patients hospitalized and discharged from Renmin Hospital of Wuhan University, Wuhan, China before 1 March 2020. Demographic and clinical characteristics and self-reported clinical sequelae of the survivors were described and analysed. A cohort of volunteers who were free of COVID-19 and lived in the urban area of Wuhan during the outbreak were also selected as the comparison group. RESULTS:Among 538 survivors (293, 54.5% female), the median (interquartile range) age was 52.0 (41.0-62.0) years, and the time from discharge from hospital to first follow-up was 97.0 (95.0-102.0) days. Clinical sequelae were common, including general symptoms (n = 267, 49.6%), respiratory symptoms (n = 210, 39%), cardiovascular-related symptoms (n = 70, 13%), psychosocial symptoms (n = 122, 22.7%) and alopecia (n = 154, 28.6%). We found that physical decline/fatigue (p < 0.01), postactivity polypnoea (p= 0.04) and alopecia (p < 0.01) were more common in female than in male subjects. Dyspnoea during hospitalization was associated with subsequent physical decline/fatigue, postactivity polypnoea and resting heart rate increases but not specifically with alopecia. A history of asthma during hospitalization was associated with subsequent postactivity polypnoea sequela. A history of pulse ≥90 bpm during hospitalization was associated with resting heart rate increase in convalescence. The duration of virus shedding after COVID-19 onset and hospital length of stay were longer in survivors with physical decline/fatigue or postactivity polypnoea than in those without. CONCLUSIONS:Clinical sequelae during early COVID-19 convalescence were common; some of these sequelae might be related to gender, age and clinical characteristics during hospitalization. 10.1016/j.cmi.2020.09.023
    Potential for Cognitive Communication Impairment in COVID-19 Survivors: A Call to Action for Speech-Language Pathologists. Ramage Amy E American journal of speech-language pathology Purpose Severe acute respiratory syndrome coronavirus 2 is the virus resulting in COVID-19 infections in nearly 4.3 million Americans with COVID-19 in the United States as of July 29, 2020, with nearly 150,000 deaths and hundreds of thousands of survivors (https://www.coronavirus.jhu.edu/map.html). This tutorial reviews (a) what has been reported about neurological insults in cases of COVID-19 infection, (b) what is known from similar conditions in other disorders, and (c) how that combined information can inform clinical decision making. Method PubMed and the Cochrane Central Register of Controlled Trials were searched for COVID-19 or other coronavirus infections, cognitive impairment observed following critical care, and disorders for which intermittent or chronic hypoxia is characteristic. These were combined with searches relating to cognition, brain, and communication. All searches were conducted between April 8 and May 23, 2020. Meta-analyses and randomized clinical trials addressing other critical illnesses were also included to extend findings to potential cognitive communication outcomes following COVID-19. Results COVID-19 infection results in a combination of (a) respiratory infection with mechanical ventilation secondary to inadequate oxygenation, (b) inflammatory system reactivity, and (c) increased blood clotting factors. These affect central nervous system function incurring long-term cognitive communication impairment in a proportion of survivors. Diagnostic and intervention approaches for such impairments are discussed. Conclusions The existing literature on cognitive sequela of COVID-19 infection is small to date, but much can be learned from similar viral infections and disorders. Although COVID-19 is novel, the speech-language pathology approaches to evaluation and intervention of other populations of critical care patients are applicable. However, speech-language pathologists have not routinely been involved in these patients' acute care. As such, this is a call to action to speech-language pathologists to address the unprecedented numbers of patients who will need their services early in the disease process and throughout recovery. 10.1044/2020_AJSLP-20-00147
    Axillary artery thrombosis resulting in upper limb amputation as a COVID-19 sequela. Ramachandran Riju,Vasudevan Pillai Anoop,Raja Suyambu,Sailesh Sailakshmi BMJ case reports Novel COVID-19 continues to intrigue medical professionals with its varied presentations. Though it affects the respiratory tract primarily, thrombogenesis has been the Achilles' heel. A 44-year-old man diagnosed with COVID-19 presented with upper limb pain at a local hospital and was found to have thrombosis of the right axillary artery. Despite a successful embolectomy at the local hospital, there was re-occlusion of the axillary artery and the limb became ischaemic. He was referred to our institution by which time the limb became gangrenous above the elbow and had to be amputated. Extensive sloughing of the nerves was also seen in the local area. Hypercoagulability presenting with various manifestations is common in COVID-19 and needs early anticoagulation. We present this asymptomatic patient who lost a limb to this COVID-19 sequelae. 10.1136/bcr-2020-240981
    Acute Exacerbation of Interstitial Lung Disease as a Sequela of COVID-19 Pneumonia. Fonseca Mario,Summer Ross,Roman Jesse The American journal of the medical sciences 10.1016/j.amjms.2020.08.017
    Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations. Guadarrama-Ortiz Parménides,Choreño-Parra José Alberto,Sánchez-Martínez Claudia Marisol,Pacheco-Sánchez Francisco Javier,Rodríguez-Nava Alberto Iván,García-Quintero Gabriela Frontiers in neurology The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002-2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host- and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field. 10.3389/fneur.2020.01039
    Neurological consequences of COVID-19: what have we learned and where do we go from here? Jarrahi Abbas,Ahluwalia Meenakshi,Khodadadi Hesam,da Silva Lopes Salles Evila,Kolhe Ravindra,Hess David C,Vale Fernando,Kumar Manish,Baban Babak,Vaibhav Kumar,Dhandapani Krishnan M Journal of neuroinflammation The coronavirus disease-19 (COVID-19) pandemic is an unprecedented worldwide health crisis. COVID-19 is caused by SARS-CoV-2, a highly infectious pathogen that is genetically similar to SARS-CoV. Similar to other recent coronavirus outbreaks, including SARS and MERS, SARS-CoV-2 infected patients typically present with fever, dry cough, fatigue, and lower respiratory system dysfunction, including high rates of pneumonia and acute respiratory distress syndrome (ARDS); however, a rapidly accumulating set of clinical studies revealed atypical symptoms of COVID-19 that involve neurological signs, including headaches, anosmia, nausea, dysgeusia, damage to respiratory centers, and cerebral infarction. These unexpected findings may provide important clues regarding the pathological sequela of SARS-CoV-2 infection. Moreover, no efficacious therapies or vaccines are currently available, complicating the clinical management of COVID-19 patients and emphasizing the public health need for controlled, hypothesis-driven experimental studies to provide a framework for therapeutic development. In this mini-review, we summarize the current body of literature regarding the central nervous system (CNS) effects of SARS-CoV-2 and discuss several potential targets for therapeutic development to reduce neurological consequences in COVID-19 patients. 10.1186/s12974-020-01957-4
    Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD? Imam Sarah A,Lao Wilson P,Reddy Priyanka,Nguyen Shaun A,Schlosser Rodney J World journal of otorhinolaryngology - head and neck surgery Background:The SARS-CoV-2 virus continues to spread rapidly across the globe afflicting many with Coronavirus Disease 2019 (COVID-19). As the infection rates rise, a growing number of SARS-CoV-2 positive individuals have been reported to complain of olfactory disturbances at an alarming rate. Postviral olfactory dysfunction (PVOD) is a well-known phenomenon that may explain the olfactory dysfunction reported by SARS-CoV-2 infected individuals. Methods:A scoping literature review was performed to identify studies that investigated the mechanisms of postviral olfactory dysfunction. Studies demonstrating pathophysiological, histological, immunochemical, and epidemiological outcomes of PVOD were included. Results:Fourteen studies were included in addition to one international news article. Three studies reported destruction of the olfactory epithelium following intranasal inoculation of various viral strains in mice. Three studies isolated pathogenic, anosmia inciting viruses (Parainfluenza virus, Human Coronavirus, Rhinovirus) through nucleic acid amplification. Eleven studies demonstrated female predilection in patients with PVOD and COVID-19 associated olfactory dysfunction, of which the majority were over 50 years old. Conclusions:PVOD and COVID-19 associated olfactory dysfunction demonstrates considerable similarities in epidemiological trends and disease sequela of other viruses to suggest identical pathophysiological mechanisms. Further studies such as intranasal inoculation and histological biopsies are needed to support our hypothesis. 10.1016/j.wjorl.2020.05.004
    Leukoencephalopathy Associated with Severe COVID-19 Infection: Sequela of Hypoxemia? Lang M,Buch K,Li M D,Mehan W A,Lang A L,Leslie-Mazwi T M,Rincon S P AJNR. American journal of neuroradiology There is increasing evidence to suggest that complications of coronavirus disease 2019 (COVID-19) infection are not only limited to the pulmonary system but can also involve the central nervous system. Here, we report 6 critically ill patients with COVID-19 infection and neuroimaging findings of leukoencephalopathy. While these findings are nonspecific, we postulate that they may be a delayed response to the profound hypoxemia the patients experienced due to the infection. No abnormal enhancement, hemorrhage, or perfusion abnormalities were noted on MR imaging. In addition, Severe Acute Respiratory Syndrome coronavirus 2 was not detected in the CSF collected from the 2 patients who underwent lumbar puncture. Recognition of COVID-19-related leukoencephalopathy is important for appropriate clinical management, disposition, and prognosis. 10.3174/ajnr.A6671
    SARS-CoV-2 Aiming for the Heart: A Multicenter Italian Perspective About Cardiovascular Issues in COVID-19. Briguglio Matteo,Porta Mauro,Zuffada Francesca,Bona Alberto R,Crespi Tiziano,Pino Fabio,Perazzo Paolo,Mazzocchi Marco,Giorgino Riccardo,De Angelis Giuseppe,Ielasi Alfonso,De Blasio Giuseppe,Turiel Maurizio Frontiers in physiology The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the high fatality rate of coronavirus disease 2019 (COVID-19) have been putting a strain on the world since December 2019. Infected individuals exhibit unpredictable symptoms that tend to worsen if age is advanced, a state of malnutrition persists, or if cardiovascular comorbidities are present. Once transmitted, the virus affects the lungs and in predisposed individuals can elicit a sequela of fatal cardiovascular consequences. We aim to present the pathophysiology of COVID-19, emphasizing the major cellular and clinical manifestations from a cardiological perspective. As a roaming viral particle or more likely the Trojan horse route, SARS-CoV-2 can access different parts of the body. Cardiovascular features of COVID-19 can count myocardial injuries, vasculitis-like syndromes, and atherothrombotic manifestations. Deviations in the normal electrocardiogram pattern could hide pericardial effusion or cardiac inflammation, and dispersed microthrombi can cause ischemic damages, stroke, or even medullary reflex dysfunctions. Tailored treatment for reduced ejection fraction, arrhythmias, coronary syndromes, macrothrombosis and microthrombosis, and autonomic dysfunctions is mandatory. Confidently, evidence-based therapies for this multifaceted nevertheless purely cardiological COVID-19 will emerge after the global assessment of different approaches. 10.3389/fphys.2020.571367
    A 67-Year-Old Woman with Sudden Hearing Loss Associated with SARS-CoV-2 Infection. Lamounier Pauliana,Franco Gonçalves Victória,Ramos Hugo Valter Lisboa,Gobbo Débora Aparecida,Teixeira Racine Procópio,Dos Reis Paulo César,Bahmad Fayez,Cândido Costa Claudiney The American journal of case reports BACKGROUND Few reports have described the association between coronavirus disease 2019 (COVID-19) and sudden hearing loss. The precise pathophysiological mechanism causing this symptom is unknown. This report describes a case of sudden hearing loss in a patient with COVID-19 pneumonia due to SARS-CoV-2 infection. CASE REPORT A 67-year-old woman with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing from nasopharyngeal and oropharyngeal swabs, was examined. She experienced sudden hearing loss in her right ear and disabling tinnitus. She underwent combined corticosteroid therapy (oral and intratympanic), resulting in an isolated improvement of 250 kHz in the right ear (from 60 dB, the threshold became 15 dB) and of 4, 6, and 8 kHz in the left ear (from 35 dB, 20 dB, and 35 dB, the thresholds became 15 dB, 5 dB and 20 dB, respectively). CONCLUSIONS Although rare, hearing loss appears to be a possible sequela to SARS-CoV-2 infection and deserves attention because it is a medical emergency requiring immediate clinical treatment. Additional studies are needed to assess the pathophysiological mechanisms involved in and the long-term characteristics of this type of hearing loss. 10.12659/AJCR.927519