Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

Abstract

Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

Mortality in critically ill COVID-19 patients with fungal infections: a comprehensive systematic review and meta-analysis

“…After excluding the articles for pre-specified reasons, the final 38 papers were included in the systematic review (Table 2 and Supplementary Table 1). All of the papers were observational in design (n=38), of which 10 were prospective [15][16][17]19,24,36,40,41,44,48] and 26 retrospective studies [18,[20][21][22][23][25][26][27][28][29][30][31][32][33][34][35][37][38][39]42,43]. Among them, 8 studies were classified as case-series [18,21,22,27,37,40,45,47].…”

“…By implementing NOS, we assessed 30 analytical studies (the remaining 8 studies were descriptive in design). Overall, we identified 12 studies of "good" quality [15,22,27,28,36,41,45,46,48,[50][51][52] and 18 studies of "poor" quality [16][17][18][19][20][21][23][24][25][26][29][30][31][32][33][34][35][37][38][39][40][42][43][44]47,49]. The majority of studies were deemed to be lacking in terms of "Comparability" criterion, as the aforementioned 26 studies did not control for any confounding factors (Supplementary Table 2).…”

“…The number of patients who developed any fungal infection over the course of COVID-19 disease was 1182 and accounted for 6.7% of all patients. The mean or median age of patients with fungal infection in 19 studies was above 65 years [15,16,19,21,23,26,27,29,31,33,34,[37][38][39][40][41][45][46][47] whereas in the remaining 15, below 65 years [13,14,17,18,20,22,24,30,32,35,36,42,43,48,49]. Information regarding age was absent in four studies [23,28,44,50].…”

“…Organ failure scores were assessed in 16 studies, of which the SOFA score was the most common (n=9), the score varying from 3 to 12 points (median=6). The number of studies which reported the frequency of mechanical ventilation of patients with fungal infection (either invasive or non-invasive) was 27 while the frequency of mechanical ventilation varied from 37 to 100% (median=100%; IQR 87-100%) [13,14,[17][18][19][20][21][22]24,26,27,[29][30][31][32][33][34][37][38][39][40][41][42][43][47][48][49]. The mean or the median ICU length of stay was reported in 18 studies and varied from 7 to 41 days (median=21 days; IQR 13-29 days) [13][14][15][16][17]20,21,23,26,31,33,34,[37][38][39]42,43,46].…”

“…was 32 (of which 20 focused only on Aspergillus spp. [13,15,17,19,[21][22][23]30,31,[34][35][36][40][41][42][43]46,47,49,50] and 12 focused on various fungal infections [14,18,20,25,[27][28][29]37,38,45,48]). All Aspergillus spp.…”