Secondary infections in critically ill patients with COVID-19: effects of intravenous IgM-enriched immunoglobulin therapy

Introduction: Critically ill patients with severe COVID-19 have an increased risk of bacterial and fungal superinfections due to a dysregulated immune response characterized by lymphopenia and low immunoglobulins levels. The intravenous immunoglobulins are involved in pathogen/toxin scavenging and inhibition of inflammatory mediators gene transcription with anti-apoptotic effects on immune system cells. This research aimed to describe the effects of intravenous IgM-enriched immunoglobulins in COVID-19 patients with sepsis due to secondary infections and low IgM levels. Method(s): We performed an observational retrospective study, including patients admitted to our intensive care unit (ICU) between March 2020 and February 2021 with severe COVID-19 and sepsis due to a superinfection (known or suspected) treated with intravenous IgM-enriched immunoglobulins. We collected demographic data and comorbidities. We noted hemodinamic data, antimicrobial and adiuvant therapies, laboratory results at ICU admission (T0), at the beginning (T1) and at the end (T2) of the IgM-enriched immunoglobulins infusion and at ICU discharge (T3). Result(s): In our cohort of 36 patients (Table 1) the prevalence of documented secondary infections was 83%. We observed a significant reduction of leukocytes from T0 to T3 (10.4 [8.3-14.5] x 103/ mmc vs 7.1 [4.8-11.2] x 103/ mmc, p < 0.01) and the SOFA score from T0 to T2 (7 [6-19] vs 5 [3-7], p < 0.01) and from T0 to T3 (7 [6-10] vs 4 [2-9], p < 0.01);from T1 to T2 (7 [6-9] vs 5 [3-7], p < 0.01) and from T1 to T3 (7 [6-9] vs 4 [2-9], p < 0.01). Cardiovascular SOFA showed a statistically significant reduction from T1 to T2 (4 [3-4] vs 0 [0-3], p < 0.01). Conclusion(s): The IgM-enriched immunoglobulins could improve organ function, as evidenced by the reduction of the SOFA score. Although the latest Surviving Sepsis Campaign guidelines suggest against using of IgM-enriched immunoglobulins, our study supports its use as an adjunctive therapy in COVID-19 patients with septic shock.

Mortality in patients with COVID-19-related ARDS treated with venovenous extracorporeal membrane oxygenation: a retrospective observational study

Introduction: Venovenous extracorporeal membrane oxygenation (VV ECMO) is a technique that provides blood oxygenation and CO2 removal, allowing a protective ventilation strategy until the resolution of respiratory failure. A delay in ECMO initiation could worsen the outcome and prolong the duration of treatment. The study aims to describe the incidence of mortality in our intensive care unit (ICU) in patients with severe COVID-19-related acute respiratory distress syndrome (ARDS) treated with VV ECMO. Method(s): We performed an observational retrospective study, including patients with severe COVID-19-related ARDS admitted to our ICU and treated with VV ECMO between February 2020 and February 2022. We collected data on demographic characteristics, comorbidities, mechanical ventilation, therapies, laboratory results, VV ECMO and ICU mortality. SOFA score, SAPS II and Charlson Comorbidity Index were calculated at ICU admission. Result(s): The average age of our cohort of 60 patients was 54.4 +/- 7.7 years and 51 (85%) were males. The mean value of the SOFA score at ICU admission was 7 +/- 2.3 points, and the median value of the SAPS II score was 41 [31-48] points. The incidence of mortality in the whole cohort was 48.3%. The differences between the two groups of patients, Survivors and Non-survivors, are presented in Table 1. Through a multivariate logistic regression model we found that age (OR 1.09 [95% CI 1.00-1.19], p = 0.03) and lymphocytes (OR 0.09 [95% CI 0.01-0.59], p = 0.01) were significantly associated with ICU mortality. Mechanical ventilation before ECMO placement higher than 10 days and superinfections at ICU admission were not significantly associated with the outcome in the same model. Conclusion(s): In patients with COVID-19-related ARDS treated with VV ECMO, advanced age and lymphopenia at ICU admission are risk factors for ICU mortality. A longer duration of mechanical ventilation before ECMO placement and traditional ICU prognostic scores seem not to be relevant for the prognosis.

Long term follow-up of patients admitted to ICU for acute respiratory failure from SARS-CoV-2 infection

Introduction: The clinical features and acute complications of patients with severe COVID-19 have long been described. However, little information is available about the quality of life and long-term persistent symptoms after discharge from ICU [1]. The purpose of this study is to describe the symptoms, the neurological, functional and psychological status 6 months after discharge from ICU. Methods: We performed an observational prospective monocentric study. We considered patients admitted to ICU for acute respiratory failure from SARS-CoV-2 infection from March 2020 to March 2021 and discharged alive. Patients underwent a telephone interview 6 months after discharge. We asked for residual symptoms. Neurological, psychological and functional status was assessed using validated questionnaires. Results: Of the 111 eligible patients, 6 (5.4%) died after discharge and 35 (31,5%) were lost to follow-up. Demographic characteristics of the population are presented in Table 1. At 6 months after discharge, 9 (12.8%) patients reported no symptoms. Dyspnoea was present in 45 (64.3%) patients, asthenia in 39 (55.7%). 32 patients (45.7%) reported memory deficit, 28 (40%) peripheral neuropathy, 17 (24.3%) artrhalgias and 6 (8.6%) dysphagia. Palpitations were present in 16 (22.8%) patients and 10 (14.3%) patients experienced insomnia or agitation. The PC-PTSD-5 was positive in 21 (30%) patients. Based on PCFS Scale, 13 (18.6%) patients reported no functional limitations, 14 (20%) negligible functional limitations, 24 (34.3%) slight functional limitations, 5 (7.1%) moderate functional limitations and 14 (20%) severe functional limitations. The GOS-E score was 6 [5-8] and it was inversely correlated with the number of hypoxia episodes (Spearman rho = - 0.25, CI 95% - 0.47 to - 0.01, p = 0.03). Conclusions: At 6 months after ICU discharge, only a few patients reported no symptoms or functional limitations. Dyspnoea, asthenia and neurological symptoms were the most frequently described. (Table Presented).

Impact of steroid therapy on bacterial and fungal superinfections in patients with severe COVID-19 admitted to ICU

Introduction: Patients with severe COVID-19 admitted to ICU have an increased risk of bacterial and fungal superinfections [1,2]. Steroid therapy with dexamethasone is one of the recommended treatments for patients on oxygen therapy. The aim of this study is to evaluate the incidence of superinfections in patients treated with steroids. Methods: We performed an observational retrospective study, including patients with severe COVID-19 admitted to our ICU between March 2020 and February 2021. Data on bacterial and fungal superinfections and steroid therapy were collected. Results: Among the 152 patients enrolled, 82 (53.9%) received steroid therapy before admission to ICU, 50 (32.9%) did not receive steroids, for 20 (13.2%) the steroid treatment was not known. The clinical characteristics of the two groups of patients at admission are presented in Table 1. Comparing patients receiving steroids and those not receiving steroids, the incidence of superinfections due to fungi was respectively 29.6% vs 12.2% (RR 2.41, CI 95%: 1.06-5.50). The incidence of Gram- and Gram + superinfections was respectively 56% vs 55% (RR 1.03, CI 95%: 0.75-1.41) and 54% vs 38% (RR 1.40, CI 95% 0.93-2.09). Among Gram- superinfections, we observed a significant association between steroid therapy and Acinetobacter spp. superinfection (19.7% in patients on steroids and 6.1% in patients who did not receive steroids, p = 0.03). The duration of steroid therapy was directly correlated with the number of superinfections for each patient (Spearman's rho = 0.34, CI 95% 0.18-0.48, p < 0.001). Conclusions: In patients with severe COVID-19 admitted to ICU, steroid therapy seems to be a risk factor for fungal superinfections and associated with Acinetobacter spp. superinfections. The duration of the steroid therapy is directly correlated to the number of superinfections for each patient. (Table Presented).

Microvascular dysfunction in pediatric patients with SARS-COV-2 pneumonia: Report of three severe cases☆☆☆

The coronavirus 19 (COVID-19) pandemic has affected hundreds of millions of people worldwide: in most of cases children and young people developed asymptomatic or pauci-symptomatic clinical pictures. However authors have showed that there are some categories of childhood more vulnerable to COVID-19 infection such as newborns or children with comorbidities. We report for the first time to the best of our knowledge about microvascular dysfunction in three pediatric clinical cases who developed COVID-19 infections with need of pediatric critical care. We found that sublingual microcirculation is altered in children with severe COVID-19 infection. Our findings confirmed most of data already observed by other authors in adult population affected by severe COVID-19 infection, but with distinct characteristics than microcirculation alterations previous observed in a clinical case of MIS-C. However we cannot establish direct correlation between microcirculation analysis and clinical or laboratory parameters in our series, by our experience we have found that sublingual microcirculation analysis allow clinicians to report directly about microcirculation dysfunction in COVID-19 patients and it could be a valuable bedside technique to monitor thrombosis complication in this population.