Apoptosis inhibitor of macrophage differentiates bacteria from influenza or COVID-19 in hospitalized adults with community-acquired pneumonia

•AIM levels were higher in bacterial pneumonia compared to influenza pneumonia.•AIM levels were higher in bacterial pneumonia compared to COVID-19 pneumonia.•AIM might be a biomarker in distinguishing between bacterial and viral pneumonia. We read with interest the report by Li and colleagues in this journal who showed that serum smyloid A (SAA) was a biomarker of severe Coronavirus Disease and poor prognosis.1Li H. Xiang X. Ren H. Xu L. Zhao L. Chen X. et al.Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis.J Infect. 2020; 80: 646-655Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar Rapidly and accurately differentiating between viral and bacterial infections in community-acquired pneumonia (CAP) is critical for prescribing appropriate therapy, especially in epidemic contexts such as influenza or coronavirus disease 19 (COVID-19).2Chow E.J. Doyle J.D. Uyeki T.M. Influenza virus-related critical illness: prevention, diagnosis, treatment.Crit Care. 2019; 23: 214Crossref PubMed Scopus (85) Google Scholar, 3Orkin A.M. Gill P.J. Ghersi D. Campbell L. Sugarman J. Emsley R. et al.Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 pandemic and other extenuating circumstances: the CONSERVE 2021 statement.JAMA. 2021; 326: 257-265Crossref PubMed Scopus (51) Google ScholarWe have reported that apoptosis inhibitor of macrophage (AIM, also called CD5L) production was elevated after bacterial infection,4Gao X. Yan X. Yin Y. Lin X. Zhang Q. Xia Y. et al.Therapeutic targeting of apoptosis inhibitor of macrophage/CD5L in sepsis.Am J Respir Cell Mol Biol. 2019; 60: 323-334Crossref PubMed Scopus (11) Google Scholar, 5Gao X. Yan X. Zhang Q. Yin Y. Cao J. CD5L contributes to the pathogenesis of methicillin-resistant Staphylococcus aureus-induced pneumonia.Int Immunopharmacol. 2019; 72: 40-47Crossref PubMed Scopus (12) Google Scholar and it may predict mortality in the patients with sepsis.6Gao X. Liu Y. Xu F. Lin S. Song Z. Duan J. et al.Assessment of apoptosis inhibitor of macrophage/CD5L as a biomarker to predict mortality in the critically ill with sepsis.Chest. 2019; 156: 696-705Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Herein, we present evidence that AIM might be a biomarker in distinguishing between bacterial and viral infection in hospitalized adults with CAP.In the first cohort study, 765 adult patients with CAP were enrolled at the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Chongqing Medical University from September 2017 to January 2020. All enrolled patients had clinical signs and radiographic evidence of CAP.7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar Influenza patients were defined as those with a positive virus result detected on viral nucleic acid testing. Bacterial infections were confirmed by microbiological evidence of bacterial infection. We classified patients into two groups based on laboratory test results: I, pure bacterial infection (detection of any bacteria other than virus); II, pure influenza (detection of influenza viruses A and B without co-detection of bacteria). CAP caused by mixed influenza and bacterial infection were excluded from analysis. Finally, 683 CAP patients did not meet the criteria, and 51 CAP patients had pure bacterial infection and 31 had pure influenza (Table 1). 62 sex- and age-matched healthy volunteers were recruited as healthy controls.Table 1.Clinical characteristics of the study population.Characteristic2017–2019 cohort2020–2021 cohortBacterial (n = 51)Influenza (n = 31)Healthy (n = 62)P valueBacterial (n = 47)COVID-19 (n = 39)Healthy (n = 51)PvalueDemographicAge, median (IQR)58 (49–71)49 (35–67)52 (38–69)0.0961 (44–77)55 (33–74)52 (36–71)0.11Female, n (%)17 (33.3)15 (48.1)19 (30.6)0.2518 (38.3)18 (46.1)23 (45.1)0.55BMI, median (IQR)27.6 (22.1–36.5)24.0 (22.9–27.5)22.6 (21.1–24.3)0.3725.9 (21.5–31.6)24.9 (21.5–27.7)22.9 (20.4–24.0)0.76Temp, median (IQR)38.3 (37.7–39.3)38.0 (37.4–39.0)36.4 (36.0–36.9)0.2138.3 (37.6–39.4)38.2 (37.7–39.2)36.4 (36.0–36.9)0.81Chronic Comorbidities, n (%)Asthma7 (13.7)4 (12.9)0 (0)0.995 (10.6)4 (10.2)0 (0)>0.99COPD5 (9.8)3 (9.7)0 (0)>0.994 (8.5)2 (5.1)0 (0)0.38Diabetes14 (27.4)7 (22.6)0 (0)0.8015 (31.9)10 (25.6)0 (0)0.12Hypertension7 (13.7)5 (16.1)0 (0)0.755 (10.6)6 (15.4)0 (0)0.54Heart failure2 (3.9)2 (6.5)0 (0)0.141 (2.1)2 (5.1)0 (0)0.09Kidney disease4 (7.8)2 (6.6)0 (0)0.884 (8.5)2 (5.1)0 (0)0.10Liver disease3 (5.9)2 (6.5)0 (0)0.993 (6.4)2 (5.1)0 (0)0.63Neurological disease2 (3.9)0 (0)0 (0)0.111 (2.1)0 (0)0 (0)0.89Laboratory values, median (IQR)WBC (109/L)15 (8–21)8 (5–12)6 (5–8)<0.0114 (6–19)9 (5–12)6 (4–9)<0.01Neutrophils (109/L)8 (5–15)5 (2–10)3 (2–5)<0.018 (4–13)6 (4–9)3 (2–5)<0.01Lymphocytes (109/L)3 (2–5)1 (0.6–1.5)2 (1.5–2.5)<0.013 (2–5)0.8 (0.6–1.1)2 (1.5–2.5)<0.01CRP (mg/L)79 (47–350)55 (18–168)NA0.0170 (51–220)15 (4–120)NA<0.01PCT (ng/ml)1.1 (0.1–8.1)0.6 (0.02–2.9)NA<0.010.9 (0.3–6.1)0.05 (0.02–0.34)NA<0.01Severity of illness, median (IQR)SOFA5 (3–10)4 (2–8)NA0.576 (2–9)4 (2–10)NA0.22APACHE II14 (8–24)10 (6–19)NA0.0612 (5–22)9 (3–19)NA0.05In-hospital morbidity, n (%)Shock7 (13.7)3 (9.7)NA0.183 (6.3)1 (2.6)NA0.19Mechanical ventilation10 (19.6)5 (16.1)NA0.396 (12.8)4 (10.2)NA0.46In-hospital mortality, n(%)6 (11.8)3 (9.7)NA0.402 (4.3)0 (0)NA0.14Bacterial etiology, n (%)S.aureus12 (23.5)0 (0)NANA10 (21.3)0 (0)NANAP.aeruginosa10 (19.6)0 (0)NANA11 (23.4)0 (0)NANAH.influenzae9 (17.6)0 (0)NANA7 (14.9)0 (0)NANAE.coli8 (15.7)0 (0)NANA8 (17.0)0 (0)NANAS.pneumoniae6 (11.8)0 (0)NANA6 (12.8)0 (0)NANAK.pneumoniae5 (9.8)0 (0)NANA4 (8.5)0 (0)NANAM.catarrhalis3 (5.9)0 (0)NANA3 (6.4)0 (0)NANAS.pyogenes3 (5.9)0 (0)NANA3 (6.4)0 (0)NANASerratia1 (2.0)0 (0)NANA0 (0)0 (0)NANAViral etiology, n (%)Influenza0 (0)31 (100)NANA0 (0)0 (0)NANACOVID-19NANANANA0 (0)39 (100)NANADefinition of abbreviations: APACHE II=acute physiology and chronic health evaluation II; BMI=body mass index; COPD= chronic obstructive pulmonary disease; COVID-19=coronavirus disease 2019; CRP=C-reactive protein; NA=not applicable; PCT=procalcitonin; SOFA=sequential organ failure assessment; Temp=temperature; WBC= white blood cell.Differences in continuous variables were estimated using the Mann–Whitney U test. Differences in categorical variables were calculated using the Fisher's exact or the Chi square test as appropriate. P values indicate differences between bacterial and influenza or COVID-19 group. P<0.05 was considered statistically significant. Open table in a new tab In the second cohort study from February 2020 to January 2021, 39 hospitalized patients with pure COVID-19 from the Department of Laboratory Medicine of Chongqing Public Health Medical Center, 47 hospitalized patients with pure bacterial infection from Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Chongqing Medical University, and 51 healthy volunteers were enrolled (Table 1).The following base-line variables were also recorded at enrollment: Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, body temperature, white blood cells (WBC) count, serum levels of C-reactive protein (CRP) and procalcitonin (PCT), presence of shock, and the use of mechanical ventilation. The in-hospital mortality was also recorded. Serum levels of AIM were measured in duplicate using an enzyme-linked immunosorbent assay (ELISA) kit (Catalog# MBS064988; MyBioSource). This study was approved by the Research Ethics Committee of the First Affiliated Hospital of the Chongqing Medical University ((numbers 2021-187 and 2015–156).Differences in continuous variables were estimated using the Mann–Whitney U test. Differences in categorical variables were calculated using the Fisher's exact or the Chi square test as appropriate. The ability of biomarker levels to discriminate between bacterial and viral infections was investigated by means of receiver operating characteristic (ROC) curve analysis. Area under the curve (AUC) was calculated. Sensitivity, specificity, and likelihood ratio (LR) values were calculated using AIM cut-points of 368 ng/ml, 430 ng/ml, and 567 ng/ml.During the first study period, 51 CAP patients with pure bacterial infection and 31 with pure influenza were collected (Table 1). CAP patients with proven bacterial infection and those with influenza virus infection were not different in terms of demographics and chronic comorbidities. The severity of CAP on hospital admission was comparable between groups, as indicated by similar SOFA and APACHE-II scores, as well as similar percentages of shock and mechanical ventilation requirement. As expected, the levels of WBC, neutrophils, lymphocytes, CRP, and PCT were significantly higher in CAP with pure bacterial infection than those in CAP with pure influenza.As shown in Fig. 1A, AIM concentrations were significantly elevated in the sera from CAP patients with influenza and those with bacterial infection than from healthy volunteers. Interestingly, serum AIM concentrations were significantly higher in bacterial group on the day of hospital admission when compared with influenza group. Next, we compared the AUC of AIM, PCT and CRP to differentiate bacterial infection from influenza by performing a ROC curve analysis (Fig. 1B), and the best AUC was observed for circulating AIM concentration at the day of hospital admission (0.90, 95% confidence interval [CI], 0.83–0.96). The AUC for PCT and CRP were, respectively 0.81 (95% CI, 0.71–90) and 0.73 (95% CI, 0.62–0.85). An AIM threshold of ≥430 ng/mL discriminated bacterial infection from influenza with a sensitivity of 80.6% (95% CI, 62.5%−92.5%) and specificity of 84.3% (95% CI, 71.4%–93.0%).Fig. 1Circulating AIM in adults hospitalized with community-acquired pneumonia and its utility to differentiate bacteria from influenza or COVID-19. (A) Levels of AIM in the serum from 51 CAP patients with pure bacterial infection, 31 CAP patients with pure influenza, and 62 healthy volunteers. Horizontal bars represent median values, and dots represent individual participants. P<0.01 when compared between groups denoted by horizontal bracket (Mann–Whitney U test). (B) Receiver operating characteristics curve for serum AIM, PCT and CRP in differentiating between bacterial infection and influenza in adults hospitalized with community-acquired pneumonia. AUC were 0.90 (95% CI, 0.83 to 0.96) for AIM, 0.81 (95% CI, 0.71 to 0.90) for PCT, and 0.73 (95% CI, 0.62 to 0.85) for CRP. Diagnostic test characteristics of AIM at selected cut-points (368 ng/ml, 430 ng/ml, 567 ng/ml) are displayed below. (C) Levels of AIM in the serum from 47 CAP patients with pure bacterial infection, 39 CAP patients with COVID-19, and 51 healthy volunteers. Horizontal bars represent median values, and dots represent individual participants. P<0.01 when compared between groups denoted by horizontal bracket (Mann–Whitney U test). (D) Receiver operating characteristics curve for serum AIM in differentiating between bacterial infection and COVID-19 in adults hospitalized with community-acquired pneumonia. AUC were 0.97 (95% CI, 0.95 to 1.00) for AIM. Abbreviations: AIM=apoptosis inhibitor of macrophage; AUC=area under the receiver operating characteristics curve; CI=confidence interval; COVID-19=coronavirus disease 19; CRP=C-reactive protein; LR=likelihood ratio; PCT=procalcitonin.View Large Image Figure ViewerDownload Hi-res image Download (PPT)The second cohort study included 39 CAP patients with pure COVID-19 infection and 47 CAP patients with pure bacterial infection (Table 1). There were no significance differences in demographics, chronic comorbidities, severity of illness, and in-hospital morbidity and mortality between bacterial group and COVID-19 group. With regard to circulating AIM as shown in Fig. 1C, AIM concentrations were significantly higher in bacterial infection compared to COVID-19. Analysis of AUC [95% CI] showed that serum AIM concentration (0.97 [95% CI, 0.95–1.00]) robustly discriminated bacterial infection from COVID-19 in the patients with CAP on day of hospital admission (Fig. 1D).PCT-guided therapy has successfully reduced antibiotics in selected populations of patients with respiratory infections.7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar,8Niederman M.S. Baron R.M. Bouadma L. Calandra T. Daneman N. DeWaele J. et al.Initial antimicrobial management of sepsis.Crit Care. 2021; 25: 307Crossref PubMed Scopus (18) Google Scholar However, some individual patients with bacterial pathogens did present to the hospital with low PCT levels,7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar and severe respiratory viral infection could induce PCT in the absence of bacterial pneumonia.9Gautam S. Cohen A.J. Stahl Y Valda Toro P. Young G.M. Datta R. et al.Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia.Thorax. 2020; 75: 974-981Crossref PubMed Scopus (18) Google Scholar Therefore, clinicians cannot rely on PCT alone to guide antibiotic treatment decisions.Our present findings are evidence of the value and accuracy of a rapid test for AIM in the blood to predict bacterial versus viral infection in the patients with CAP during influenza or COVID-19 epidemic. Higher levels of serum AIM at hospital admission were associated with increased probability of bacterial infections, suggesting suggest that AIM might be a useful adjunct in the etiologic assessment of patients hospitalized with CAP. Further study is required to evaluate its clinical utility in a larger cohort of pneumonia patients with suspected and proven infections.Ethics approval and consent to participateThis study was carried out according to the principles of the declaration of Helsinki and approved by the Research Ethics Committee of the First Affiliated Hospital of the Chongqing Medical University ((numbers 2021-187 and 2015-156). Informed consent was obtained from all patients or their relatives prior to inclusion in the study.Consent for publicationNot applicable.FundingThis study was supported by the National Natural Science Foundation of China grants (No. 81902134 to YG and No. 82070014 to JC). This funding body had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. We read with interest the report by Li and colleagues in this journal who showed that serum smyloid A (SAA) was a biomarker of severe Coronavirus Disease and poor prognosis.1Li H. Xiang X. Ren H. Xu L. Zhao L. Chen X. et al.Serum Amyloid A is a biomarker of severe Coronavirus Disease and poor prognosis.J Infect. 2020; 80: 646-655Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar Rapidly and accurately differentiating between viral and bacterial infections in community-acquired pneumonia (CAP) is critical for prescribing appropriate therapy, especially in epidemic contexts such as influenza or coronavirus disease 19 (COVID-19).2Chow E.J. Doyle J.D. Uyeki T.M. Influenza virus-related critical illness: prevention, diagnosis, treatment.Crit Care. 2019; 23: 214Crossref PubMed Scopus (85) Google Scholar, 3Orkin A.M. Gill P.J. Ghersi D. Campbell L. Sugarman J. Emsley R. et al.Guidelines for reporting trial protocols and completed trials modified due to the COVID-19 pandemic and other extenuating circumstances: the CONSERVE 2021 statement.JAMA. 2021; 326: 257-265Crossref PubMed Scopus (51) Google Scholar We have reported that apoptosis inhibitor of macrophage (AIM, also called CD5L) production was elevated after bacterial infection,4Gao X. Yan X. Yin Y. Lin X. Zhang Q. Xia Y. et al.Therapeutic targeting of apoptosis inhibitor of macrophage/CD5L in sepsis.Am J Respir Cell Mol Biol. 2019; 60: 323-334Crossref PubMed Scopus (11) Google Scholar, 5Gao X. Yan X. Zhang Q. Yin Y. Cao J. CD5L contributes to the pathogenesis of methicillin-resistant Staphylococcus aureus-induced pneumonia.Int Immunopharmacol. 2019; 72: 40-47Crossref PubMed Scopus (12) Google Scholar and it may predict mortality in the patients with sepsis.6Gao X. Liu Y. Xu F. Lin S. Song Z. Duan J. et al.Assessment of apoptosis inhibitor of macrophage/CD5L as a biomarker to predict mortality in the critically ill with sepsis.Chest. 2019; 156: 696-705Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Herein, we present evidence that AIM might be a biomarker in distinguishing between bacterial and viral infection in hospitalized adults with CAP. In the first cohort study, 765 adult patients with CAP were enrolled at the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Chongqing Medical University from September 2017 to January 2020. All enrolled patients had clinical signs and radiographic evidence of CAP.7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar Influenza patients were defined as those with a positive virus result detected on viral nucleic acid testing. Bacterial infections were confirmed by microbiological evidence of bacterial infection. We classified patients into two groups based on laboratory test results: I, pure bacterial infection (detection of any bacteria other than virus); II, pure influenza (detection of influenza viruses A and B without co-detection of bacteria). CAP caused by mixed influenza and bacterial infection were excluded from analysis. Finally, 683 CAP patients did not meet the criteria, and 51 CAP patients had pure bacterial infection and 31 had pure influenza (Table 1). 62 sex- and age-matched healthy volunteers were recruited as healthy controls. Definition of abbreviations: APACHE II=acute physiology and chronic health evaluation II; BMI=body mass index; COPD= chronic obstructive pulmonary disease; COVID-19=coronavirus disease 2019; CRP=C-reactive protein; NA=not applicable; PCT=procalcitonin; SOFA=sequential organ failure assessment; Temp=temperature; WBC= white blood cell. Differences in continuous variables were estimated using the Mann–Whitney U test. Differences in categorical variables were calculated using the Fisher's exact or the Chi square test as appropriate. P values indicate differences between bacterial and influenza or COVID-19 group. P<0.05 was considered statistically significant. In the second cohort study from February 2020 to January 2021, 39 hospitalized patients with pure COVID-19 from the Department of Laboratory Medicine of Chongqing Public Health Medical Center, 47 hospitalized patients with pure bacterial infection from Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Chongqing Medical University, and 51 healthy volunteers were enrolled (Table 1). The following base-line variables were also recorded at enrollment: Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, body temperature, white blood cells (WBC) count, serum levels of C-reactive protein (CRP) and procalcitonin (PCT), presence of shock, and the use of mechanical ventilation. The in-hospital mortality was also recorded. Serum levels of AIM were measured in duplicate using an enzyme-linked immunosorbent assay (ELISA) kit (Catalog# MBS064988; MyBioSource). This study was approved by the Research Ethics Committee of the First Affiliated Hospital of the Chongqing Medical University ((numbers 2021-187 and 2015–156). Differences in continuous variables were estimated using the Mann–Whitney U test. Differences in categorical variables were calculated using the Fisher's exact or the Chi square test as appropriate. The ability of biomarker levels to discriminate between bacterial and viral infections was investigated by means of receiver operating characteristic (ROC) curve analysis. Area under the curve (AUC) was calculated. Sensitivity, specificity, and likelihood ratio (LR) values were calculated using AIM cut-points of 368 ng/ml, 430 ng/ml, and 567 ng/ml. During the first study period, 51 CAP patients with pure bacterial infection and 31 with pure influenza were collected (Table 1). CAP patients with proven bacterial infection and those with influenza virus infection were not different in terms of demographics and chronic comorbidities. The severity of CAP on hospital admission was comparable between groups, as indicated by similar SOFA and APACHE-II scores, as well as similar percentages of shock and mechanical ventilation requirement. As expected, the levels of WBC, neutrophils, lymphocytes, CRP, and PCT were significantly higher in CAP with pure bacterial infection than those in CAP with pure influenza. As shown in Fig. 1A, AIM concentrations were significantly elevated in the sera from CAP patients with influenza and those with bacterial infection than from healthy volunteers. Interestingly, serum AIM concentrations were significantly higher in bacterial group on the day of hospital admission when compared with influenza group. Next, we compared the AUC of AIM, PCT and CRP to differentiate bacterial infection from influenza by performing a ROC curve analysis (Fig. 1B), and the best AUC was observed for circulating AIM concentration at the day of hospital admission (0.90, 95% confidence interval [CI], 0.83–0.96). The AUC for PCT and CRP were, respectively 0.81 (95% CI, 0.71–90) and 0.73 (95% CI, 0.62–0.85). An AIM threshold of ≥430 ng/mL discriminated bacterial infection from influenza with a sensitivity of 80.6% (95% CI, 62.5%−92.5%) and specificity of 84.3% (95% CI, 71.4%–93.0%). The second cohort study included 39 CAP patients with pure COVID-19 infection and 47 CAP patients with pure bacterial infection (Table 1). There were no significance differences in demographics, chronic comorbidities, severity of illness, and in-hospital morbidity and mortality between bacterial group and COVID-19 group. With regard to circulating AIM as shown in Fig. 1C, AIM concentrations were significantly higher in bacterial infection compared to COVID-19. Analysis of AUC [95% CI] showed that serum AIM concentration (0.97 [95% CI, 0.95–1.00]) robustly discriminated bacterial infection from COVID-19 in the patients with CAP on day of hospital admission (Fig. 1D). PCT-guided therapy has successfully reduced antibiotics in selected populations of patients with respiratory infections.7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar,8Niederman M.S. Baron R.M. Bouadma L. Calandra T. Daneman N. DeWaele J. et al.Initial antimicrobial management of sepsis.Crit Care. 2021; 25: 307Crossref PubMed Scopus (18) Google Scholar However, some individual patients with bacterial pathogens did present to the hospital with low PCT levels,7Self W.H. Balk R.A. Grijalva C.G. Williams D.J. Zhu Y. Anderson E.J. et al.Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia.Clin Infect Dis. 2017; 65: 183-190Crossref PubMed Scopus (122) Google Scholar and severe respiratory viral infection could induce PCT in the absence of bacterial pneumonia.9Gautam S. Cohen A.J. Stahl Y Valda Toro P. Young G.M. Datta R. et al.Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia.Thorax. 2020; 75: 974-981Crossref PubMed Scopus (18) Google Scholar Therefore, clinicians cannot rely on PCT alone to guide antibiotic treatment decisions. Our present findings are evidence of the value and accuracy of a rapid test for AIM in the blood to predict bacterial versus viral infection in the patients with CAP during influenza or COVID-19 epidemic. Higher levels of serum AIM at hospital admission were associated with increased probability of bacterial infections, suggesting suggest that AIM might be a useful adjunct in the etiologic assessment of patients hospitalized with CAP. Further study is required to evaluate its clinical utility in a larger cohort of pneumonia patients with suspected and proven infections. Ethics approval and consent to participateThis study was carried out according to the principles of the declaration of Helsinki and approved by the Research Ethics Committee of the First Affiliated Hospital of the Chongqing Medical University ((numbers 2021-187 and 2015-156). Informed consent was obtained from all patients or their relatives prior to inclusion in the study. This study was carried out according to the principles of the declaration of Helsinki and approved by the Research Ethics Committee of the First Affiliated Hospital of the Chongqing Medical University ((numbers 2021-187 and 2015-156). Informed consent was obtained from all patients or their relatives prior to inclusion in the study. Consent for publicationNot applicable. Not applicable. FundingThis study was supported by the National Natural Science Foundation of China grants (No. 81902134 to YG and No. 82070014 to JC). This funding body had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish. This study was supported by the National Natural Science Foundation of China grants (No. 81902134 to YG and No. 82070014 to JC). This funding body had no role in study design, data collection and analysis, preparation of the manuscript, or the decision to publish.