The presence of Pneumocystis jirovecii in critically ill patients with COVID-19

We read with interest the recent review on co-infections in coronavirus disease-2019 (COVID-19) patients1Lansbury L. Lim B. Baskaran V. W.S Co-infections people COVID-19: a systematic and meta-analysis.J Infect. 2020; 81: 266-275Abstract Full Text PDF PubMed Scopus (814) Google Scholar believe that fungal as evaluated from selected studies are underestimated. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is still spreading pandemically. Approximately 5–10% of COVID-19 patients may require intensive care unit (ICU) management 30% develop secondary pneumonia without identified etiology.2Huang C. Wang Y. Li X. Ren Zhao J. Hu et al.Clinical features infected 2019 novel Wuhan, China.Lancet. 395: 497-506Abstract (29360) Hospital-acquired bacterial or superinfections, described critically ill Influenza virus, can be suspected.3Schauwvlieghe A.F.A.D. Rijnders B.J.A. Philips N. Verwijs R. Vanderbeke Van Tienen al.Invasive aspergillosis admitted to severe influenza: retrospective cohort study.Lancet Respir Med. 2018; 6: 782-792Abstract (517) Since pneumocystosis usually reported T-cell immunodepression,4Alanio A. Hauser P.M. Lagrou K. Melchers W.J. Helweg-Larsen Matos O. al.ECIL guidelines for diagnosis Pneumocystis jirovecii haematological malignancies stem cell transplant recipients.J Antimicrob Chemother. 2016; 71: 2386-2396Crossref (160) less attention has been paid non-immunocompromised ICU although it accounts 7% those Influenza.5Beumer M.C. Koch R.M. van Beuningen D. OudeLashof A.M. de Veerdonk F.L. Kolwijck E. al.Influenza virus factors associated admission, pulmonary mortality.J Crit Care. 2019; 50: 59-65Crossref (74) Interestingly, lymphocytopenia distress (ARDS) requiring adjunctive steroids and/or immunomodulatory therapies, well-known susceptibility developing pneumocystosis.5Beumer designed this observational study investigate prevalence P. acid nucleic detection specimens sampled identify ICU. All consecutive between 2020/03/15 2020/05/01 positive SARS-CoV-2 PCR (Cobas? Test, Roche, France) ?1 sample (bronchoalveolar lavage (BAL), tracheal aspirate, sputum) sent mycology department. This was part COVID-ICU French registries. Our institutional ethics committee approved (IDRCB, 2020-A00256-33; CPP, 11-20-20.02.04.68737). When possible, signed informed consent obtained next kin. Whenever bronchoalveolar (BAL) performed middle lobe by trained pneumologist using at least 120 ml saline (yield, ?50%). Upon reception, including BAL fluids dTT-treated aspirations (dTT 1X 37 °C 15 min) were centrifuged, suspended 200µL water submitted extraction (whole acids extraction) GeneLead-VIII extractor-thermocycler™ (Precision System Science, Japan). reverse transcriptase quantitative (RTqPCR) amplify mtSSU mtLSU RNA DNA new R-DiaPnJ kit™ (Diagenode, Belgium). Serum ?-D-glucan tested Fungitell (Cape Cod Inc, US) recommended manufacturer. Data presented median [25th-75th percentiles] percentages appropriate. Comparisons Mann-Whitney exact Fisher tests required. P-values ?0.05 considered significant. One hundred-and-eight successive HIV-negative (Male/Female sex ratio, 4.4; age, 62 years [56–68]) usual risk presentation included (Table 1). except three intubated admission. Thirty-four (31.4%) who developed ARDS received one day corticosteroids before sampling. Respiratory samples 80 BALs (74.1%), 22 aspirates (20.4%), 4 sputa (3.7%) two bronchial aspiration (1.9%). In 10/108 (9.3%), RTqPCR positive. Median delay sampling admission 2days [1–2]. The cycle value 32.6 [30.8–34.7]. ?-d-glucan measured nine negative (>80pg/mL) seven patients.Table 1Characteristics according samples. medians percentiles]. (?) (*), appropriate.Total (N = 108)No 98)Detection 10)PMale gender, N (%)88 (81.5%)80 (81.6%)8 (80.0%)1*Age (years)62 [56–68]62 [56–68]59 [46–68]0.40?COVID-19 factorsPast hypertension, (%)64 (59.3%)58 (59.2%)6 (60.0%)1*Diabetes, (%)40 (37.0%)37 (37.8%)3 (30.0%)0.74*Obesity, (%)35 (32.4%)32 (32.7%)3 (30.0%)1*Coronary disease, (%)15 (13.9%)14 (14.3%)1 (10.0%)1*Body-mass index (kg/m2)28 [25–31]28 [27–32]0.61?Other remarkable comorbiditiesAsthma, (%)5 (4.6%)4 (4.1%)1 (10.0%)0.39*Chronic obstructive (%)2 (1.9%)2 (2.0%)0 (0.0%)1*Immunocompromised patient, (%)10 (9.3%)10 (10.2%)0 (0.0%)0.59*Long-term corticosteroids, (%)11 (10.2%)8 (8.2%)3 (30.0%)0.06*Biological data admissionPaO2/FiO2 (mmHg)137 [83–247]134 [83–239]177 [108–253]0.60?Serum creatinine (µmol/L)80 [64–111]80 [63–111]80 [67–104]0.99?Plasma d-dimer (ng/mL)2,2395 [1193–4635]2610 [1405- 4700]1270 [750–2390]0.03?Serum lactate dehydrogenase (IU/L)687 [540–901]687 [568–903]708 [436–893]0.65?Bronchoalveolar characteristics% macrophages28 [15–46]27 [14–42]51 [49–55]0.13?% polymorphonuclear cells37 [26–81]46 [26–81]29 [18–32]0.54?% Lymphocytes13 [6–32]14 [5–34]13 [10–23]0.81?Specific anti-COVID-19 therapy, (%)Azithromycin, (%)34 (31.5%)30 (30.6%)4 (40.0%)0.72*Hydroxychloroquine, (40.0%)0.72*Hydroxychloroquine + Azithromycin, (%)29 (26.9%)26 (26.5%)3 (30.0%)1*Lopinavir-ritonavir, (%)16 (14.8%)12 (12.2%)4 (40.0%)0.04*Polyvalent immunoglobulins, (%)3 (2.8%)3 (3.1%)0 (0.0%)1*Sarilumab, (%)1 (0.9%)1 (1.0%)0 (0.0%)1*Eculizumab, (%)6 (5.6%)4 (4.1%)2 (20.0%)0.10*Tocilizumab, (%)4 (3.7%)4 (4.1%)0 (0.0%)1*Dexamethasone, (%)53 (49.1%)46 (46.9%)7 (70.0%)0.19*Dexamethasone cumulative dose >100 mg, (14.8%)15 (15.3%)1 (10.0%)1*Severity during hospitalization outcomeSAPS II admission37 [31–49]38 [31–51]34 [28–37]0.16?SOFA admission6 [3–8]6 [3–8]5 [2–7]0.43?Lowest PaO2/FiO2 (mmHg)71 [58–89]71 [59–89]65 [53–102]0.79?Vasopressors, (%)89 (82.4%)81 (82.7%)8 (80.0%)1*Renal replacement (%)38 (35.2%)35 (35.7%)3 (30.0%)1*ECMO, (9.3%)9 (9.2%)1 (10.0%)1*SAPS [28–37]0.16?ICU length stay (days)20 [12–32]20 [12–33]10 [6–19]0.03?Mortality, (%)47 (43.5%)44 (44.9%)3 (30.0%)0.51 *BAL, lavage; ECMO, extracorporeal membrane oxygenation; ICU, unit; SOFA, Sepsis-related Organ Failure Assessment; SAPS II, Simplified Acute Physiology Score II. Open table tab BAL, Clinical characteristics carrying did not significantly differ other lower plasma D-dimer (1270 ng/mL [750–2390] vs 2610 [1405–4700], P 0.03) more frequent lopinavir/ritonavir administration (40.0% 12.2%, 0.04), while long-term corticosteroid prescription tended (30.0% 8.2%, 0.06). Of note, among our 10 carriers, five concomitantly met criteria COVID-19-associated aspergillosis.6Alanio Dellière S. Fodil Bretagne Mégarbane B Prevalence putative invasive COVID-19.Lancet 8: e48-e49Abstract (282) Out these patients, four (40%) co-trimoxazole prophylaxis (80/400 mg once daily) whereas six rapidly improved not. co-trimoxazole-treated non-treated died remaining discharged. Mortality similar both groups. found an unexpectedly high proportion detected (10/108 patients; 9.3%), similarly previous findings influenza (3/45; ?7%).5Beumer presence healthy adult population oropharyngeal wash gargling examined conventional nested methods.7Medrano F.J. Montes-Cano M. Conde la Horra Respaldiza Gasch al.Pneumocystis general population.Emerg Infect Dis. 2005; 11: 245-250Crossref (180) However, experts agree (?20%) overestimated due technical issues such contamination amplicons responsible false positives.4Alanio center managing almost exclusively immunocompromised qPCR-positive load low ?13% (unpublished data), elsewhere.3Schauwvlieghe mostly exhibited marked lymphopenia alterations lymphocyte functions,8Liu Liu Liang H. al.Longitudinal responses cytokine profiles peripheral blood patients.EBioMedicine. 55102763Abstract (1053) likely explaining high-rate detection. serum advocated diagnosis,4Alanio we its concentrations RTqPCR-positive values (<120pg/mL) accordance loads lung alveoli.9Karageorgopoulos D.E. Qu J.M. Korbila I.P. Zhu Y.G. Vasileiou V.A. Falagas M.E Accuracy pneumonia: meta-analysis.Clin Microbiol 2013; 19: 39-49Abstract (139) out RTqPCR-negative higher B-D-glucan (450 500pg/ml) lead aspergillosis, another infection patients.6Alanio Although meta-analysis questioned sensitivity non-HIV patients,10Del Corpo Butler-Laporte G. Sheppard D.C. Cheng M.P. McDonald E.G. Lee T.C Diagnostic accuracy (1-3)-?-D-glucan (S1198-743X(20)30301-3)https://doi.org/10.1016/j.cmi.2020.05.024Abstract (46) widely used rule because predictive value. finding support hypothesis jirovecii, yet being per se. Thus, interesting context infections diagnosis, should interpreted caution when excluding pneumocystosis. Here, ten prophylactic regimen, based treating physician's decision. Whether result indication consider administering co-trimoxazole, dosage remains questionable. limitations include relatively small number bi-center setting, short period. best knowledge, first evaluating patients. Because focused determined. conclusion, jirovecii-positive observed Based findings, advocate systematically searching deep strategy useful limiting enhanced inflammation avoiding inter-patient transmission. registry conducted REACTing consortium (REsearch ACTion targeting emerging infectious diseases) directed INSERM (Institut national santé recherche médicale) ISARIC (International Emerging Infection Consortium). (N, IDRCB, Drs. Alanio, conceived study. Voicu, managed microbiological analysis. authors acquired, analyzed results. drafted manuscript. participated critical revision manuscript important intellectual content. Dr. Alanio full access all takes responsibility integrity analysis accuracy. publish.