Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19

Reyes, Luis Felipe; Rodríguez, Alejandro; Bastidas, Alirio; Parra-Tanoux, Daniela; Fuentes, Yuli V.; García-Gallo, Esteban; Moreno, Gerard; Ospina-Tascón, Gustavo Adolfo; Hernandez, Gleen; Silva, Edwin; Díaz, Ana María Álvarez; Jibaja, Manuel; Vera-Alarcon, Magdalena; Díaz, Emilio; Bodí, M.; Solé‐Violán, Jordi; Ferrer, Ricard; Albaya-Moreno, Antonio; Socías, Lorenzo; Estella, Ángel; Loza-Vázquez, Ana; Jorge-García, Ruth; Sancho, Isabel; Martín‐Loeches, Ignacio

doi:10.1016/j.jcrc.2022.154014

Cited by 27 publications

(25 citation statements)

References 25 publications

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“…These results highlight that fatality rates and treatments changed during the pandemic and differed for each country. Moreover, these data align with our results, showing that IMV was frequently used in LMIC and that many patients with severe COVID-19 were treated outside of ICU [ 8 , 26 ]. Notably, the impact of ICU admission on clinical outcomes was already explored in our cohort and published elsewhere [ 3 ].…”

Section: Discussionsupporting

confidence: 90%

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

et al. 2022

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Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

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Section: Discussionsupporting

confidence: 90%

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

et al. 2022

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“…Lower respiratory tract infections range from mild to severe, with varying degrees of systemic complications and COVID-19 is not the exception [ 8 , 24 , 25 ]. There are robust data linking older age, male sex, and obesity with a greater risk of developing severe COVID-19 [ 13 , 26 – 28 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study

et al. 2022

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Purpose The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. Material and methods This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. Results A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). Conclusions This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

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“…For this reason, early-stage treatment of glucocorticoids, when the viral load is high, is not recommended. Corticosteroids are also immunosuppressive and have been linked to a rise in life-threatening infections ( 186 – 188 ) and hyperglycemia ( 189 ).…”

Section: Clinical Efforts To Suppress Nlrp3-mediated Inflammationmentioning

confidence: 99%

The multifaceted roles of NLRP3-modulating proteins in virus infection

Harris

Borg

2022

Front. Immunol.

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The innate immune response to viruses is critical for the correct establishment of protective adaptive immunity. Amongst the many pathways involved, the NLRP3 [nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3)] inflammasome has received considerable attention, particularly in the context of immunity and pathogenesis during infection with influenza A (IAV) and SARS-CoV-2, the causative agent of COVID-19. Activation of the NLRP3 inflammasome results in the secretion of the proinflammatory cytokines IL-1β and IL-18, commonly coupled with pyroptotic cell death. While this mechanism is protective and key to host defense, aberrant NLRP3 inflammasome activation causes a hyperinflammatory response and excessive release of cytokines, both locally and systemically. Here, we discuss key molecules in the NLRP3 pathway that have also been shown to have significant roles in innate and adaptive immunity to viruses, including DEAD box helicase X-linked (DDX3X), vimentin and macrophage migration inhibitory factor (MIF). We also discuss the clinical opportunities to suppress NLRP3-mediated inflammation and reduce disease severity.

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Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19

Cited by 27 publications

References 25 publications

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study

The multifaceted roles of NLRP3-modulating proteins in virus infection

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