In this retrospective study, it has been revealed that the fatality rate in critically ill Covid-19 patients with positive sputum bacterial culture was higher than that of the patients with negative results. The infectious hallmarks such as leukocyte, neutrophil, lymphocyte, NLR, CRP, and PCT were diverging evidently especially at the later stage of the hospitalization between the deceased and discharged patients. NLR, CRP, neutrophil, lymphocyte, leucocyte and PCT could be used to anticipate the fatality of critically ill patients with Covid-19. The patients with the values below the cutoff of leukocyte, neutrophil, NLR, and CRP, those with the value above the cutoff of lymphocyte, and those with negative sputum bacterial culture had higher cumulative overall survival rates, in comparison with the opposite. The positive sputum culture was positively correlated with infectious hallmarks including leukocyte, CRP, NLR and PCT. Sputum bacterial culture, CRP and NLR were independently correlated with the fatality of critically ill patients with Covid-19. The critically ill patients with severe Covid-19 who were complicated with secondary pulmonary bacterial infection may had an unfavorable outcome, in comparison with those who were not.
Being consistent with the statistical fatality rate among critically ill patients with Covid-19 being reported by Guan et al.2 and Bhatraju et al,8 the fatality rate of patients with critically severe Covid-19 in the ICUs of Wuhan Jinyintan Hospital is 46.2%. The reason for such high fatality consists in that this patient population represented the most severe cases at the early stage of the Covid-19 outbreak, ever since the blockade of Wuhan city. At that moment, Covid-19 was a newly emerging and contagiously uncharted disease, which had not been experienced before by any of the clinicians in Wuhan or those who reinforced Wuhan from all over the country, resulting in the unsatisfactory therapeutic response for critically ill patients. Besides, the unprepared medical resource was overwhelmed by the abrupt emergence of numerous patients with Covid-19 including a multitude of critically ill cases. In addition, there has been no efficacious iatreusis for Covid-19 to date, let alone at the incipient stage of the outbreak.
In the study of Dong, et al,6 cases who were complicated with a secondary bacterial pneumonia were more severe in comparison with those without it, being consistent with our study, in which secondary pulmonary bacterial infection is an independent factor for the fatality of critically ill patients with Covid-19. The results of the current study are also consistent with those in the study of Guan et al,2 Qin et al9 and Li et al,10 in which severe cases were prone to have lymphocytopenia and leukocytosis. Analogously, in the report of Qin et al,9 and Liu et al,11 an elevated NLR was frequently encountered in severe cases and was an independent risk factor for the in-hospital mortality of Covid-19 patients. The results of the present study are as well consistent with the study of Tan et al,12 and Wang et al,13 in which CRP was positively correlated with pulmonary lesion, disease development, and disease severity. To summarize, our study suggests that the Covid-19 patients with secondary bacterial infection and elevated infectious hallmarks such as leukocyte, NLR, CRP and PCT, have higher fatality rate by contrast with the opposite. Leukocytosis and elevated CRP as well as PCT have been already regarded as the hallmarks of bacterial infection,14–16 being confirmed once again by the positive correlation between sputum bacterial culture and serum infectious hallmarks in our study. Taken together, it strongly suggests that the secondary pulmonary bacterial infection is an adverse factor for the outcome of critically ill patients with Covid-19.
Although glucocorticoids may induce leukocytosis17 and secondary bacterial infection,18 since its usage rate were equal between the deceased and discharged patients, plus the uprising CRP and PCT in the deceased patients, it still indicated that the deceased patients with Covid-19 were more apt to supervene secondary pulmonary bacterial infection with time, in comparison with the discharged patients, despite Covid-19 is a viral infection at the initial stage of disease. Eventually, the discrepancy of positive incidence in sputum bacterial culture between the deceased and discharged patients answer for the anomaly in the serum infectious hallmarks. In addition, in view of the antibiotics usage rate were also equal between the deceased and discharged patients, the occurrence of secondary bacterial infection was not interfered by the antibiotic therapy. It was reported that secondary bacterial infections could be predisposed for patients with influenza viral infections. The mechanisms of secondary bacterial infections include multiple processes mediated by interactions amongst viruses, bacteria, and the immune system of host. Antiviral immune responses induced by viruses are associated with dysbiosis in the respiratory tract, which may subsequently compromise immunological function against secondary bacterial infection, or multiply the proliferation of underlying pathogenic bacterial loads.19 Meanwhile, the induced inflammation by influenza virus can mutate genome-wide nasal gene responses to the carriage of pneumococcus, besides the promoted level of cytokines by the viral infection.20 The current study verified that the analogue could likewise happen to the critically ill patients with Covid-19.
This study suffers from several limitations. First of all, it is a retrospective study due to the emergency nature of the Covid-19, resulting in unavoidable bias which may interfere with the results of study. Secondly, the sample size of this study is not considerable, since it was a single-centered study which only concerned the most critically ill patients with Covid-19. The last but not least, due to all patients we reviewed were unanimously critically ill ones, the conclusion may not be applicable to the patients with mild conditions.
In conclusion, we report through the present study that the critically ill patients with severe Covid-19 who are complicated with secondary pulmonary bacterial infection may have an unfavorable outcome, in comparison with those without it. Secondary pulmonary bacterial infection is an independent factor and a danger signal for the unfavorable outcome of critically ill patients with Covid-19. It may suggest that the implementation of potent antibiotic regimen could be of vital importance for the cure of critically ill Covid-19 patients with secondary pulmonary bacterial infection, despite Covid-19 is a disease caused by viral infection. Such findings may be helpfully informative for the prognostic assessment and therapeutic guidance in critically ill patients with severe Covid-19.