Table 1.
Characteristics of pulmonary critically ill patients with COVID-19 and positive for fungi by metagenomic analysis.
| Characteristics | Patient #1 | Patient #2 | Patient #3 | Patient #4 | Patient #5 | Patient #6 | Patient #7 | Patient #8 | Patient #9 | Patient #10 |
|---|---|---|---|---|---|---|---|---|---|---|
| Demographics and clinical characteristics | ||||||||||
| Gender | M | M | F | M | M | F | M | M | M | M |
| Age (years) | 41 | 55 | 62 | 54 | 53 | 44 | 32 | 76 | 73 | 83 |
| Diagnosis for COVID-19 | PCR, mNGS | Antigen | PCR | PCR | Antigen | PCR, mNGS | PCR | PCR, mNGS | PCR | PCR, mNGS |
| Medical history | Hypertension, type 2 diabetes, kidney transplant status | Acute kidney injury, liver transplant status | Hypertension, nephritic syndrome | Hypertension, type 2 diabetes, liver abscess after percutaneous drainage | Thymoma B3 | Hypertension, kidney transplant status | No | Coronary atherosclerotic heart disease after PCI, liver cirrhosis, hypersplenism, old cerebral infarction, type 2 diabetes, hypertension | No | Hypertension, coronary heart disease |
| Current smoker | Yes | No | No | Yes | No | No | Yes | No | No | No |
| Underlying immunocompromising condition | Steroids, tacrolimus, mycophenolate | Tacrolimus, mycophenolate, sirolimus | Mycophenolate | No | Oxaliplatin + cyclophosphamide + doxorubicine chemotherapy | Steroids, tacrolimus, mycophenolate | No | No | No | No |
| Cause of admission to the ICU | ARDS | ARDS | ARDS | ARDS, cerebral infarction, cerebral hernia, septic shock | ARDS | ARDS | ARDS, acute pancreatitis | ARDS | ARDS | ARDS, cardiopulmonary arrest after cardiopulmonary resuscitation |
| Time from illness onset to ICU admission, days | 14 | 24 | 10 | 4 | 3 | 42 | 1 | 11 | 30 | 20 |
| ARDS | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| PaO2 (ICU admission) | 71 | 92 | 43 | 94 | 69 | 70 | 99 | 64 | 48 | 75 |
| FIO2 (ICU admission) | 0.90 | 0.95 | 0.61 | 0.41 | 0.7 | 0.60 | 0.41 | 0.81 | 1.00 | 0.80 |
| Horowitz Index (ICU admission) | 79 | 97 | 70 | 229 | 99 | 117 | 241 | 79 | 48 | 94 |
| Prone positioning | Yes | Yes | Yes | No | No | No | Yes | Yes | No | No |
| Tracheal intubation | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| SOFA score (ICU admission) | 7 | 8 | 4 | 7 | 6 | 7 | 4 | 7 | 9 | 8 |
| CURB-65 score (ICU admission) | 2 | 2 | 2 | 2 | 1 | 2 | 1 | 2 | 3 | 3 |
| APACHE II score (ICU admission) | 12 | 34 | 18 | 22 | 19 | 12 | 11 | 14 | 24 | 35 |
| CAPA classification | Probable | Possible | Probable | Probable | Possible | Probable | Probable | Probable | Possible | Possible |
| Laboratory findings | ||||||||||
| mNGS (first time after ICU admission) | ||||||||||
| Specimen | BALF & PB | BALF & PB | BALF | BALF | BALF | BALF | BALF | BALF | BALF | BALF |
| Fungus |
Aspergillus fumigatus (PB & BALF) Aspergillus niger (BALF) Pneumocystis jeroveci (BALF) |
Aspergillus flavus/Aspergillus oryzae(BALF) Aspergillus fumigatus (PB) |
Aspergillus fumigatus
Aspergillus flavus |
Aspergillus fumigatus | Aspergillus fumigatus |
Aspergillus flavus
Aspergillus fumigatus |
Aspergillus flavus/Aspergillus oryzae
Rhizopus oryzae |
Aspergillus flavus/Aspergillus oryzae
Aspergillus fumigatus |
Aspergillus flavus
Aspergillus terreus Clavispora lusitaniae |
Aspergillus fumigatus
Candida albicans |
| Bacteria |
Enterococcus faecium (BALF) Leuconostoc lactis (BALF) Tropheryma whipplei (BALF) |
Klebsiella pneumoniae (BALF & PB) Acinetobacter baumannii (BALF) |
No |
Klebsiella pneumoniae
Streptococcus pneumoniae Acinetobacter baumannii Enterococcus faecium |
Acinetobacter baumannii |
Enterococcus faecium
Acinetobacter pittii |
Escherichia coli
Klebsiella pneumoniae |
Acinetobacter baumannii |
Klebsiella pneumoniae
Enterococcus faecium |
No |
| Virology1 | Epstein–Barr virus (PB) Human betaherpesvirus 5 (BALF) SARS-CoV-2 (BALF) |
Human alphaherpesvirus 1 (PB) Epstein–Barr virus (PB) |
No | Human alphaherpesvirus 1 Epstein–Barr virus |
Human betaherpesvirus 5 | Torque teno virus SARS-CoV-2 |
No | SARS-CoV-2 | No | SARS-CoV-2 |
| Serum galactomannan (µg/L) [<0.85]2 | 0.43 | 0.47 | 0.31 | 0.12 | 0.81 | 0.84 | 1.94 | 0.96 | NA | 0.28 |
| Serum β-D-glucan (pg/mL) [0-95] | <10 | <10 | <10 | 171.11 | <10 | 294.35 | 126.97 | <10 | NA | <10 |
| BALF galactomannan (pg/mL) [<1] | 0.48 | 0.36 | NA | NA | NA | 0.36 | 3.87 | 1.26 | NA | NA |
| Sputum culture | Negative | Acinetobacter baumannii | NA | Acinetobacter baumannii | Negative | Negative | Acinetobacter baumannii | Acinetobacter baumannii | NA | NA |
| BALF culture | Aspergillus flavus | Acinetobacter baumannii |
Aspergillus fumigatus
Aspergillus flavus |
Negative | Negative | Negative |
Escherichia coli
Aspergillus flavus |
Acinetobacter baumannii | Klebsiella pneumoniae | Negative |
| Pheripheral blood culture | Negative |
Enterococcus faecium
Klebsiella pneumoniae |
Negative | Negative | Negative | Negative | Negative | Negative | Enterococcus faecium | Candida albicans |
| Treatment | ||||||||||
| Steroids to treat pneumonia | Yes | Yes | No | Yes | Yes | Yes | No | Yes | Yes | No |
| Antifungal | Voriconazole, Amphotericin B, Sulfamethoxazole | Voriconazole, Amphotericin B | Voriconazole | Voriconazole | Voriconazole | Voriconazole | Isavuconazole Amphotericin B |
Voriconazole | No | No |
| Antiviral (besides COVID-19) | Penciclovir | Ganciclovir | No | No | No | Ganciclovir | No | No | No | No |
| Anti-COVID-19 | Azvudine, Paxlovid | Paxlovid | Azvudine, Paxlovid | No | No | Paxlovid | No | Azvudine, Paxlovid | Azvudine, Paxlovid | No |
| Antibacterial | Meropenem, Linezolid | Ceftazidime and Avibactam Sodium, Polymyxin B | Ceftizoxime | Meropenem, Ceftazidime, and Avibactam Sodium | Imipenem and cilastatin sodium, Teicoplanin | Biapenem, Linezolid | Imipenem and Cilastatin Sodium, Ceftazidime and Avibactam Sodium, Teicoplanin | Moxalactam Cefoperazone Sodium and Sulbactam Sodium | Cefoperazone Sodium and Sulbactam Sodium | Imipenem and Cilastatin Sodium |
| Outcomes | ||||||||||
| Acute renal failure | Yes | Yes | No | No | Yes | No | No | No | No | Yes |
| Renal replacement therapy | Yes | Yes | No | No | Yes | No | No | No | No | Yes |
| Vasopressor | Yes | Yes | No | Yes | Yes | No | Yes | No | No | Yes |
| ECMO | No | No | No | No | Yes(V-A) | No | Yes (V-V) | No | No | Yes (V-V) |
| Outcome | Died | Survived | Survived | Died | Died | Survived | Survived | Died | Died | Died |
APACHE, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; CAPA, COVID-19-associated pulmonary aspergillosis; CURB-65, Confusion, Urea, Respiratory rate, Blood pressure plus age ≥ 65 years; ECMO, extracorporeal membrane oxygenation; FIO2, fraction of inspiration oxygen; ICU, intensive care unit; mNGS, metagenomic next-generation sequencing; NA, not available; PaO2, partial pressure of oxygen; PB, peripheral blood; PCI, percutaneous coronary intervention; PCR, polymerase chain reaction; SOFA, Sequential Organ Failure Assessment; V-A, venoarterial; V-V, venovenous.
1In patient #2, #3, #4, #5, #7, and #9, only DNA sequencing was performed and no SARS-CoV-2 was detected.
2Normal reference range of our laboratory was given in square brackets. The same below.