Exclusion of bacterial co-infection in COVID-19 using baseline inflammatory markers and their response to antibiotics

Abstract

Background: COVID-19 is infrequently complicated by bacterial co-infection, but antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in bacterial pulmonary infections, testing the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish bacterial co-infection from COVID-19.

Methods: Retrospective cohort study of CAP (lobar consolidation on chest radiograph) and COVID-19 (PCR detection of SARS-CoV-2) patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH), serving as independent discovery and validation cohorts. All CAP and >90% COVID-19 patients received antibiotics on hospital admission.

Results: We identified 106 CAP and 619 COVID-19 patients at RFH. Compared with COVID-19, CAP was characterized by elevated baseline white cell count (WCC) [median 12.48 (IQR 8.2-15.3) versus 6.78 (IQR 5.2-9.5) ×106 cells/mL, P < 0.0001], C-reactive protein (CRP) [median 133.5 (IQR 65-221) versus 86.0 (IQR 42-160) mg/L, P < 0.0001], and greater reduction in CRP 48-72 h into admission [median ΔCRP -33 (IQR -112 to +3.5) versus +14 (IQR -15.5 to +70.5) mg/L, P < 0.0001]. These observations were recapitulated in the independent validation cohort at BH (169 CAP and 181 COVID-19 patients). A multivariate logistic regression model incorporating WCC and ΔCRP discriminated CAP from COVID-19 with AUC 0.88 (95% CI 0.83-0.94). Baseline WCC >8.2 × 106 cells/mL or falling CRP identified 94% of CAP cases, and excluded bacterial co-infection in 46% of COVID-19 patients.

Conclusions: We propose that in COVID-19, absence of both elevated baseline WCC and antibiotic-related decrease in CRP can exclude bacterial co-infection and facilitate antibiotic stewardship efforts.

Figure 1.

Admission blood samples for all patients admitted to RFH. Violin plots represent distribution of values for CAP (n = 106), MR− COVID-19 (n = 589) and MR+ COVID-19 (n = 30) patients. Bold lines represent median values. Dotted lines represent IQR values. P values derived from two-tailed Mann–Whitney test. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 2.

Change in values between admission blood samples and those collected 48–72 h into admission at RFH. Violin plots represent distribution of difference (Δ) in investigation results between those collected on hospital admission and 48–72 h into admission in CAP (n = 53), MR− COVID-19 (n = 313) and MR+ COVID-19 (n = 18) patients. Bold lines represent median values. Dotted lines represent IQR values. P values derived from two-tailed Mann–Whitney test. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 3.

Accuracy of blood parameters to diagnose CAP in RFH cohorts of CAP and MR− COVID-19 patients. ROC curves generated from logistic regression models that incorporate combinations of WCC on admission and difference (Δ) in CRP between samples on admission and 48–72 h into admission in order to discriminate RFH patients diagnosed with CAP from those diagnosed with COVID-19. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.