Table 3.
Invasive Aspergillosis in COVID-19 patients (case reports and hematology patient case series excluded).
| Literature | Trial Design and Population | Diagnostic Criteria Used | CS Used | CS Length | Other IST | Comorbidities | IA Incidence | Time to IA Dx | Mortality |
|---|---|---|---|---|---|---|---|---|---|
| Alanio A. et al. [87] France | P, O, n = 27 ICU pts, 9/27 CAPA, med age 63 [IQR 56–71] | EORTC-MSGERC or IAPA + ser β-D-glucan and qPCR (serum or pulm specimens) | 6/9 pts: dexa IV 20 mg/d (D1–5) then 10 mg/d (D6–10). 2/9 pts on prev GCS |
10 ds | NM | HPN more frequent in IPA (7/9 vs. 6/18, p = 0·046) |
Probable IPAs: (4%) putative IPAs: 30% | NM | 4/9 |
| van Arkel A.E. et al. [88] Netherlands | O, n = 31 ICU pts on MV | A. fumigatus 5/6, A. Ag GM (+) BAL fluid: 3/6 | 3/6 pts: CS before IPA Dx, dose < 0.3 mg/kg/d |
<3 wks | No | 3/6 Pre-existing lung disease | 6/31 (19.35%) presumed IPA | Sx onset—IPA: med 11.5 ds (8–42). ICU admis–IPA: med 5 ds (3–28) | 66.7% died, med 12 ICU ds (11–20) |
| Bartoletti et al. [89] Italy |
P, MC, n = 822 | CAPA | MP 1 mg/kg | 5–7 ds | TOCI | 27.7% | Intub-CAPA: med 4ds (2–8). sx onset-CAPA: med 14ds (11–22) |
↑↑ ICU mortality after adj for age, RRT, admis severity scores | |
| Benedetti et al. [90] Argentina | n = 5 ICU pts | IAPA or EORTC-MSGERC serum markers, or AspICU | 5/5 CS (<0.3 mg/kg) | <3wks | No | 1/5 hematologic malignancy 2/5 diabetes |
Sx onset–CAPA: 22 ds (13–52). ICU admis-CAPA: med 12 ds |
1/5 died (rest still on MV) | |
| Delliere et al. [92] France | R, O, MC, n = 360 ICU pts; 108 pts sampled on deterioration. 1 SOT. 1 myeloma |
EORTC/MSGERC CAPA |
NM | NM | Sarilumab 1 pt, eculizumab 6 pts, toci 4 pts |
Azithromycin (>3 ds) and prob IPA (OR 3.1, 95% CI, 1.1–8.5, p = 0.02). HD dexa and IPA: 11.5% vs. 28.6%, (p = 0.08), cumul dose ≥100 mg and IPA (OR 3.7, 95% CI 1.0–9.7). | 5.7% in ICU pts 8.5% in MV pts 19.4% in deteriorated pts |
Sx onset- IPA: 16 ds (10–23) ICU admis—IPA: 6 ds (1–15) |
IPA pts vs. non-IPA: 71.4% vs. 36.8%, p < 0.01). |
| Dupont et al. [91] France |
R, 153 ICU pts screened for fungi; 106 PCR SARS-Co-V2 (+) | AspICU + serum/BAL GM | 37% CS | short time | NM | HTN 36.8%, DM 36.8%, TB/COPD/asthma 36.8% | 17.9% putative IPA | MV-CAPA: 6 ds | 42% |
| Fekkar A. et al. [24] France | R, SC, n = 145 COVID-19 ICU MV pts screened for fungal superinfection; 54% on ECMO | EORTC/MSGERC, Mycology lab (microscopy, cultures, PCR respir samples and serum for Aspergillus, PJP, mucorales, GMI, β-D-glucan |
Long-term (>3 wks) CS before COVID-19 and IFI (OR, 8.55; IQR, 6.8–10.3; p = 0.01), CS for COVID-19 (dexa 20 mg/d × 10 ds) no IFI |
10 ds | 6 Toci 3 saril 1 anti-IL1 |
100% MV, 68% ↑BW, 57% HTN, 32% DM, 14% preexisting immunosuppression |
4.8% prob/ putat IFI (1 fusarium case), 17.2% colonization |
ICU admis-IFI: med 7 ds (IQR, 2–56) | Survival 74.5% |
| Fortarezza et al. [94] Italy |
n = 45 COVID-19 autopsies | Histology | CS: 88% of CAPA vs. 54% non-CAPA CS: 12/28 pts 1st wave vs. 16/17 pts 2nd wave |
NM | No Toci No antiIL-1 | 7/9 ICU 7/9 HTN 3/9 COPD |
20% proven CAPA, 1st wave 2/28 vs. 2nd wave 7/17 | NM | NA |
| Janssen et al. [102] Belgium, Netherlands, France |
O, MC, 2 ICU cohorts: N1 = 512 N2 = 304 |
ECCM/ISHAM | CS use not more prevalent in CAPA groups vs. non-CAPA | NM | Other IST < 90 ds before ICU admis | CAPA vs. nonCAPA: COPD 19% vs. 8% (p = 0.042). HIV (AIDS) 7% vs. 0.4% (p = 0.011) |
10–15% | ICU admis to CAPA: 6 ds (IQR 3–9) | 43–52% |
| Lamoth et al. [109] Switzerland |
n = 80 ICU MV pts | IAPA | NM | NA | Toci—IPA Dx: 4 ds |
No pt had any predisposing factors acc to EORTC/MSG | 3.8% 1 probable 2 putative |
COVID dx- IPA: med 9 ds, ICU admis-IPA: 6 ds, MV start-IPA: med 5 ds |
1/3 died |
| Marr et al. [20] Spain, USA |
R, MC n = 20 CAPA |
Aspergillus recovery in BAS, sputum, BAL or GMI ≥ 1, imaging | NM Systemic and inh CS most common IST associated with CAPA |
NM | NM | Age HTN Pulm dis underlying immunosuppressive disease/drugs |
NA | Sx onset-CAPA: med 11 ds, ICU admis-CAPA: 9 ds |
NM |
| Meijer et al. [93] Netherlands |
SC, P, 1st wave: 33 MV ICU pts vs. 2nd wave: 33 MV ICU pts | 2020 ECMM/ISHAM | All CAPA pts in 2nd wave on CS: Dexa 6 mg | 10 ds | no | CVD 4/13 DM 3/13 HTN 2/13 COPD 1/13 ARF 1/13 |
1st vs. 2nd wave poss and prob CAPA: 15.2% vs. 25% (p = 0.36) In total: 19.7% |
NM | 40–50% mortality in both groups |
| Obata R. et al. [95] USA |
R, 226 COVID-19 hosp pts, 57 on CS vs. 169 no-CS | NM | Dexa (48/57), P (6/57), MP (1/57), MP + P 1/57, HC 1/57 |
Max 10ds | 20/57 Toci | NM | CAPA in CS vs. no-CS: 5.3% vs. 0.6% CAPA in toci vs. no-toci: 5% vs. 5.4% |
NM | NM |
| Prattes et al. [111] Europe, USA |
MC, P, MN 592 COVID-19 ICU pts | 2020 ECMM/ISHAM | Majority on GCS | NM | Toci | Age MV Toci |
Proven: 1.9%, Prob 13.5% poss: 3% No-CAPA: 81.6% |
ICU admis-CAPA: 8 ds (0–31) |
Survival in CAPA pts vs. non-CAPA: 29% vs. 57% |
| Rutsaert et al. [99] Belgium |
n = 20 MV pts med 66 yo (56–77) | AspICU | 1/7 CS (pemphigus) | NM | NM | 4/7 DL 2/7 obesity 3/7 DM 3/7 HTN |
7/20 (35%) proven IPA | Sx onset—IPA: 11–23 ds | 4/7 died |
| Van Biesen et al. [100] Netherlands |
42 MV ICU pts (9 IPA vs. 33 non-IPA) | AspICU + GMI ≥ 1 | No CS | NA | NM | 1/9 SOT COPD and asthma more common in IPA group |
9/42 | NM | 22% IPA vs. 15.1% non-IPA (p = 0.6) |
| White et al. [30] UK |
MC, P n = 137 ICU pts screened for IFI |
AspICU, IAPA, CAPA | 12/25 different CS | N/M | no | 12/25 CRD 8/25 HTN 6/25 DM 6/25 obesity 5/25 CA |
14.1% CAPA | ICU admiss- (+) Aspergillus tests: 8 ds (0–35) | CAPA mortality 57.9% depending on appropriate Tx |
admis = admission, ARF = Acute Renal Failure, BAS = Bronchial aspirate, BSI = Blood-stream infections, BW = body weight, CFR = Case Fatality Rate, CS = corticosteroids, CRD = Chronic Respiratory Disease, cumul = cumulative, CVD = cardiovascular disease, DL = dyslipidemia, Ds = days, dexa = dexamethasone, DM = diabetes mellitus, Dx = diagnosis, ECMO = Extra-corporeal membrane oxygenation, GM = galactomannan, GM = Galactomannan, GMI = galactomannan index, HD = high dose, HTN = Hypertension, IA = Invasive Aspergillosis, IFI = invasive fungal infection, intub = intubation, IST = immunosuppressive therapy, MC = Multicenter, med = median, MN = multi-national, MP = methylprednisolone, MV = mechanically ventilated, m = median, n = number of patients, NA = not applicable, NM = not mentioned, O = observational, OR = odds Ratio, P = Prospective, prev = previous, prob = probable, put = putative, R = Retrospective, resp sampl on deterior = respiratory sampling on deterioration, ROM = Rhino-orbital mucormycosis, saril = sarilumab, SC = single center, Sx = symptom, Toci = tocilizumab, unclass = unclassified.