We identified 4999 patients with a confirmed diagnosis of SARS-CoV-2 infection who were admitted to West China Hospital between Dec 2nd, 2022, and Mar 15th, 2023. A total of 1472 patients were eligible for inclusion and 1287 patients(87.4%) received early antibiotic treatments(Fig. 1). Besides, the delayed-antibiotic use cohort and non-antibiotic use cohort include 149 patients and 36 patients respectively. Patients with early antibiotic use were defined as controls.
Baseline characteristics of three cohorts before 1:2 propensity-score matching are presented in Table 1. Before matching, the non-antibiotic use cohort had a significantly lower age(61.42 ± 19.00 vs. 71.24 ± 16.95, p < 0.001) than the controls. More than 50% of patients were male in all three cohorts. In comparison with the control cohort, the non-antibiotic use cohort had lower prevalence rates of diabetes, chronic kidney disease, chronic lung disease, and cardiovascular disease. Fewer patients with more than 2 types of comorbidities were found in patients with non-antibiotic use(28.2% vs 55.7%, p < 0.001) and delayed-antibiotic use cohort(38.9% vs 55.7%, p = 0.045) than controls. The proportion of patients belonged to severe COVID-19 and critical COVID-19 was identified to be 39.4% and 23.5% respectively in the early antibiotic use cohort, which was much higher than that of both delayed-antibiotic use cohort(p < 0.001) and non-antibiotic use cohort(p < 0.001).
Table 1
Baseline characteristics and laboratory parameters of patients hospitalized with COVID-19 before and after propensity score matching.
| Before 1:2 propensity-score matching | After 1:2 propensity-score matching |
Non-antibiotic use (n = 149) | Delayed-antibiotic use(n = 36) | Early antibiotic use (Controls(n = 1287)) | p* Value | p∆ Value | p* Value | p∆ Value |
Baseline covariates |
Age(years) | 61.42 ± 19.00 | 69.11 ± 21.34 | 71.24 ± 16.95 | < 0.001 | 0.557 | 0.388 | 0.944 |
Sex: | | | | 0.512 | 0.199 | 0.499 | 0.813 |
Female | 33.6%(50/149) | 41.7%(15/36) | 30.6%(394/1287) | | | | |
Male | 66.4%(99/149) | 58.3%(21/36) | 69.4%(893/1287) | | | | |
BMI | 23.82 ± 3.60 | 25.66 ± 3.11 | 23.39 ± 3.87 | 0.220 | 0.003 | 0.942 | 0.913 |
Current or former smoker | 16.8%(25/149) | 13.9%(5/36) | 22.5%(290/1287) | 0.117 | 0.235 | 0.512 | 0.744 |
Comorbid: | | | | | | | |
Diabetes | 18.8%(28/149) | 25.0%(9/36) | 27.8%(358/1287) | 0.019 | 0.851 | 1.000 | 0.613 |
Hypertension | 40.9%(61/149) | 47.2%(17/36) | 46.1%(593/1287) | 0.259 | 1.000 | 0.334 | 0.816 |
Chronic kidney disease | 16.1%(24/149) | 13.9%(5/36) | 26.4%(340/1287) | 0.007 | 0.122 | 0.586 | 0.681 |
Chronic hepatic disease | 5.4%(8/149) | 0.0%(0/36) | 7.2%(93/1287) | 0.499 | 0.106 | 1.000 | NA |
Chronic lung diseases | 8.1%(12/149) | 8.3%(3/36) | 21.5%(277/1287) | < 0.001 | 0.062 | 1.000 | 0.742 |
Cardiovascular disease | 11.4%(17/149) | 19.4%(7/36) | 27.7%(356/1287) | < 0.001 | 0.345 | 0.585 | 0.765 |
Immune system disease | 3.4%(5/149) | 0.0%(0/36) | 4.1%(53/1287) | 0.678 | 0.397 | 0.767 | NA |
Malignancy | 8.7%(13/149) | 13.9%(5/36) | 13.8%(177/1287) | 0.097 | 1.000 | 0.726 | 0.681 |
≥ 2 types of Comorbids | 28.2%(42/149) | 38.9%(14/36) | 55.7%(717/1287) | < 0.001 | 0.045 | 0.723 | 0.803 |
Disease severity for COVID-19: | < 0.001 | 0.001 | 0.296 | 0.296 |
Non-severe COVID-19 | 73.2%(109/149) | 63.9%(23/36) | 37.1%(478/1287) | | | | |
Severe COVID-19 | 24.2%(36/149) | 33.3%(12/36) | 39.4%(507/1287) | | | | |
Critical COVID-19 | 2.6%(4/149) | 2.8%(1/36) | 23.5%(302/1287) | | | | |
Laboratory parameters at admission |
Lymphocytes, 109 /L | 0.96 ± 0.46 | 0.93 ± 0.44 | 0.83 ± 0.92 | 0.090 | 0.508 | 0.807 | 0.782 |
PCT, ng/mL | 0.17 ± 0.44 | 0.10 ± 0.09 | 1.20 ± 4.36 | < 0.001 | < 0.001 | 0.069 | 0.077 |
CRP, mg/L | 40.49 ± 49.76 | 40.35 ± 50.56 | 75.91 ± 70.77 | < 0.001 | 0.013 | 0.034 | 0.311 |
IL-6, µg/L | 22.35 ± 42.51 | 28.51 ± 45.17 | 60.50 ± 105.44 | < 0.001 | 0.001 | 0.066 | 0.987 |
D-Dimer, mg/L | 1.22 ± 1.70 | 2.65 ± 5.09 | 3.85 ± 5.81 | < 0.001 | 0.229 | 0.079 | 0.849 |
CD4 + T cells, cell/µL | 389.50 ± 279.86 | 267 ± 227.84 | 213.19 ± 199.26 | 0.005 | 0.450 | 0.076 | 0.460 |
CD8 + T cells, cell/µL | 251.54 ± 183.97 | 161.38 ± 116.58 | 152.06 ± 124.93 | 0.015 | 0.834 | 0.052 | 0.493 |
p* Value: comparison between non-antibiotic use cohort and controls; p∆ Value: comparison between delayed-antibiotic use and controls; PCT: procalcitonin, CRP: C-reactive protein, IL-6: interleukin 6, NA: not applicated. |
Among patients with non-antibiotic use, several infectious indicators and inflammatory indicators(including serum PCT(0.17 ± 0.44 VS 1.20 ± 4.36, p < 0.001), CRP(40.49 ± 49.76 VS 75.91 ± 70.77, p < 0.001), IL-6 (22.35 ± 42.51 VS 60.50 ± 105.44, p < 0.001), D-dimer(1.22 ± 1.70 VS 3.85 ± 5.81, p < 0.001)) at admission were much lower than that of control cohort. Furthermore, immune indicators(CD4 + T cells(389.50 ± 279.86 VS 213.19 ± 199.26, p = 0.005) and CD8 + T cells count(251.54 ± 183.97 VS 152.06 ± 124.93, p = 0.015)) of patients with non-antibiotic use were observed to be greatly higher than controls. Compared with patients with early antibiotic use, similar lower serum PCT(p<0.001), CRP(p = 0.013), and IL-6(p = 0.001) levels were also seen in the delayed-antibiotic use cohort.
During the study period, 190 of the 1287 patients(14.8%) with early antibiotic use died, which was greatly higher than 3.1% of the non-antibiotic use cohort(0.194(95%CI:0.085–0.443), p < 0.001)(Table 2). What’s more, patients with non-antibiotic use were found to stay in the hospital for a significantly shorter time than controls(10.56 ± 5.89 VS 15.74 ± 10.15, p < 0.001). Among patients with non-antibiotic use, the risk of ICU admission(0.091(95%CI:0.022–0.369), p = 0.001), need for mechanical ventilation(0.149(95%CI:0.077–0.285), p < 0.001) and tracheal intubation(0.132(95%CI:0.032–0.541), p = 0.005) were identified to be much lower than controls. However, there was no significant difference in all-cause mortality, length of hospital stays, and the risk of tracheal intubation between the delayed-antibiotic use cohort and the early antibiotic use cohort. In comparison with the control cohort, a lower risk of ICU admission(p = 0.018) and mechanical ventilation(p = 0.006) were shown in the delayed-antibiotic use cohort.
Table 2
Comparison of outcomes parameters between patients with non-antibiotic use and early antibiotic use before and after propensity score matching.
| Before 1:2 propensity-score matching | After 1:2 propensity-score matching |
| Non-antibiotic use (n = 149) | Early antibiotic use (n = 1287) | Crude HR | 95%CI | p Value | Non-antibiotic use (n = 139) | Early antibiotic use (n = 278) | Crude HR | 95%CI | p Value |
Mechanical ventilation | 6.7%(10/149) | 32.6%(420/1287) | 0.149 | 0.077 | 0.285 | <0.001 | 5.0%(7/139) | 6.8%(19/278) | 0.723 | 0.296 | 1.763 | 0.476 |
Tracheal intubation | 1.3%(2/149) | 9.3%(120/1287) | 0.132 | 0.032 | 0.541 | 0.005 | 1.4%(2/139) | 1.1%(3/278) | 1.338 | 0.221 | 8.103 | 0.751 |
ICU admission | 1.3%(2/149) | 13.1%(168/1287) | 0.091 | 0.022 | 0.369 | 0.001 | 1.4%(2/139) | 3.2%(9/278) | 0.436 | 0.093 | 2.047 | 0.293 |
Length of hospital stay(days) | 10.56 ± 5.89 | 15.74 ± 10.15 | NA | NA | NA | <0.001 | 10.55 ± 5.81 | 13.88 ± 7.38 | NA | NA | NA | < 0.001 |
Mortality | 2.7%(4/149) | 14.8%(190/1287) | 0.159 | 0.058 | 0.435 | <0.001 | 2.2%(3/139) | 2.2%(6/278) | 1.000 | 0.246 | 4.06 | 1.000 |
NA: not applicated, ICU: Intensive Care Unit, HR: Hazard ratios, CI: Confidence interval |
After propensity score matching, our analysis included 139 patients with non-antibiotic use(with 278 matched controls) and 27 patients with delayed-antibiotic use(with 54 matched controls). The baseline characteristics of the case cohorts and matched control cohort were balanced with no significant difference(Table 1). The standard mean differences were greater than 0.1, indicating good balance. With the above methods, 332 patients with early antibiotic use(Appendix: Fig. 1 and Table 1) and 278 patients with antibiotic use(Appendix: Fig. 2 and Table 2) were successfully matched to 166 patients with non-early antibiotic use and 149 patients with non-antibiotic use respectively. After matching for baseline characteristics, laboratory parameters at admission in the delayed-antibiotic use cohort and non-antibiotic use cohort were found to be not significantly different from corresponding matched controls(except for lower serum CRP level in patients with non-antibiotic use).
Comparison of outcome parameters between patients with non-antibiotic use, delayed-antibiotic use, and matched controls
Further analysis was conducted in propensity-score-matched datasets and observed no evidence of improved outcome parameters in patients who received early antibiotics treatment. Compared with the non-antibiotic use cohort, matched controls did not have lower all-cause mortality(HR = 1.000(0.246–4.060), P = 1.000), lower risk of ICU admission(HR = 0.436(0.093–2.047), P = 0.293)), mechanical ventilation(HR = 0.723(0.296–1.763), P = 0.476)) and tracheal intubation (HR = 1.338(0.221–8.103), P = 0.751))(Table 2). Similar results were observed in the comparison of outcome parameters between patients with deferred-antibiotic use and matched controls(Table 3). However, patients with non-early antibiotic use, who had a less serious disease condition, tend to stay in the hospital for a significantly shorter time period than matched controls(10.55 ± 5.81 VS 13.88 ± 7.38, P < 0.001).
In propensity score matching cohorts analysis, log-rank test for comparison of survival curves in the non-antibiotic use cohort versus matched controls(HR = 1.522(95%CI: 0.339–7.109, p = 0.522), delayed-antibiotic use cohort versus matched controls(HR = 1.014(95%CI: 0.169–6.086), p = 0.988) had no statistical difference(Firgure2).
Comparison of outcome parameters between patients with and without early antibiotic use, and patients with and without antibiotic use.
Above comparison of outcome parameters was conducted between patients with and without early antibiotic use and patients with and without antibiotic use in propensity-score-matched cohorts. Similarly, both the non-early antibiotic use cohort(Appendix, Table 3) and the non-antibiotic use cohort(Appendix, Table 4) showed no statistical difference in all-cause mortality, the risk for ICU admission, mechanical ventilation and tracheal intubation from that of their respective matched controls.
Survival curves in Fig. 2 did not find any significant difference between patients with and without early antibiotic use(HR = 1.143(95%CI: 0.386–3.386), p = 0.387), patients with and without antibiotic use(HR = 1.281(95%CI: 0.393–4.171), p = 0.804).