Tocilizumab administration in COVID-19 patients: Water on the fire or gasoline?

Deana, Cristian; Vetrugno, Luigi; Bassi, Flavio; Monte, Amato De

doi:10.1016/j.mmcr.2021.01.002

Cited by 15 publications

(10 citation statements)

References 14 publications

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“…Impaired host defences due to corticosteroid use, including LC3‐associated phagocytosis, have been reported more frequently in patients with CAPA who do not survive 24 . Tocilizumab use may also prevent Th17 responses favouring aspergillosis, and some authors suggest screening/early testing for CAPA in COVID‐19 patients being treated with this anti‐IL 6 antibody 53,62 . White et al reported mortality in 46.7% of patients with CAPA despite antifungal therapy which could be due to delayed diagnosis 39 .…”

Section: Discussionmentioning

confidence: 99%

Mortality in critically ill patients with coronavirus disease 2019‐associated pulmonary aspergillosis: A systematic review and meta‐analysis

Verma

Kanaujia

Chakrabarti

et al. 2021

Mycoses

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Reports of COVID‐19 associated pulmonary aspergillosis (CAPA) are rising, but the associated mortality and factors affecting it are not well‐characterised. We performed a systematic review including 20 peer‐reviewed English language studies reporting mortality in CAPA published till 18 February 2021from PubMed, Ovid SP, Web of Science, Embase and CINHAL. The pooled mortality in CAPA was 51.2% (95% CI: 43.1–61.1, I2 = 38%). The leave one out sensitivity analysis and influential case diagnostics revealed one outlier and its exclusion resulted in a mortality estimate of 54% (95% CI: 45–62). Higher odds of mortality: 2.83 (95% CI: 1.8–4.5) were seen in CAPA compared to controls. No significant difference in various subgroups according to the country of study, the continent of study, income category of country and quality of the included study was seen. None of the host risk factors, mycological test results, therapy for COVID‐19 and antifungal therapy affected mortality. Thus, patients with CAPA have a high probability of mortality and early diagnosis with prompt therapy must be ensured to optimally manage these patients. However, more prospective studies with global and multi‐centre coordination may help to address CAPA in a better way.

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Section: Discussionmentioning

confidence: 99%

Mortality in critically ill patients with coronavirus disease 2019‐associated pulmonary aspergillosis: A systematic review and meta‐analysis

Verma

Kanaujia

Chakrabarti

et al. 2021

Mycoses

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“…Adverse events were infrequent and mild. However, risk of secondary infections should always be considered [24].…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6

Flisiak

Jaroszewicz

Rogalska

et al. 2021

JCM

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Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08–0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.

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“…It explains the scarcity of data and supports the work of Koehler et al, who has explored COVID-19 as an independent risk factor of CAPA [ 3 ]. Another important risk factor for the development of CAPA is tocilizumab, which is an interleukin 6 (IL-6) inhibitor and is known to cause multiple co-bacterial and co-fungal infections in the ICU population [ 19 ]. In our cohort of CAPA cases, 54.1% had received tocilizumab, and all had received corticosteroids, which are known to cause immunosuppression and paves the way for the growth of Aspergillus and tissue invasion to cause CAPA [ 20 - 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Invasive pulmonary aspergillosis (IPA) is a fatal disease affecting immunosuppressed individuals with hematological malignancies and recipients of allogeneic bone marrow transplantation who develop acute graft versus host disease [1]. With the development of new treatment modalities and the emergence of novel diseases like influenza and coronavirus disease 2019 (COVID- 19), the spectrum of risk factors of IPA has enormously expanded. In a study by Schauwvlieghe et al, influenza was found to be an independent risk factor for IPA, especially in patients who require ICU care [2].…”

Section: Introductionmentioning

confidence: 99%

COVID-Associated Pulmonary Aspergillosis and Its Related Outcomes: A Single-Center Prospective Observational Study

Iqbal¹,

Ramzan²,

Akhtar³

et al. 2021

Cureus

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Background and objective Invasive pulmonary aspergillosis (IPA) is a frequent complication among neutropenic patients. It is increasingly being reported in critical coronavirus disease 2019 (COVID-19) patients requiring ICU admission and invasive mechanical ventilation (IMV) and is known as COVID-associated pulmonary aspergillosis (CAPA). We conducted this large prospective observational study to determine the frequency of CAPA and its outcomes in the ICU population. Methodology This was a prospective observational study. We recruited 307 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed cases of severe COVID-19 pneumonia requiring IMV. We excluded those who did not require IMV or had been transferred out to other hospitals. The Chi-square test was applied to find the association between categorical variables. A p-value of <0.05 was considered statistically significant. Results Out of the 307 cases of mechanically ventilated COVID-19 pneumonia, 61 had probable CAPA. The median age was 60 years. Malignancy and cirrhosis were significant risk factors associated with CAPA (p=<0.001, 0.001, respectively). Aspergillus fumigatus was detected in 78.7% of the cases. The median length of ICU stay was 11 days [interquartile range (IQR): 4-14]. Among CAPA cases, 70.5% developed septic shock and required ionotropic support. Among 61 probable cases of CAPA, 91.8% did not survive and there was a strong correlation between CAPA and ICU mortality (p=0.001). Conclusion We concluded that CAPA is a fatal complication of severe COVID-19 pneumonia and is associated with increased mortality.

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Tocilizumab administration in COVID-19 patients: Water on the fire or gasoline?

Cited by 15 publications

References 14 publications

Mortality in critically ill patients with coronavirus disease 2019‐associated pulmonary aspergillosis: A systematic review and meta‐analysis

Mortality in critically ill patients with coronavirus disease 2019‐associated pulmonary aspergillosis: A systematic review and meta‐analysis

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6

COVID-Associated Pulmonary Aspergillosis and Its Related Outcomes: A Single-Center Prospective Observational Study

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