Our study showed that only 1.0% of COVID-19 patients presenting at a general hospital experienced a clinically relevant bacteraemia, compared to 4.0% in influenza A patients and 3.0% in influenza B patients. E. coli and S. pneumoniae were most frequently isolated from positive blood cultures in COVID-19 patients. The same pathogens were also common in influenza A and B patients. We reported a 30-day all-cause mortality of 28.3% in COVID-19 patients, which was statistically significantly higher than the 30-day all-cause mortality of 7.1 and 6.4% found in respectively influenza A and B patients.
Our results are consistent with findings in a recent study of Sepulveda et al. . They performed a large multicentre cohort analysis on patients with COVID-19 in New York. The authors reported a true bacteraemia rate of 1.6%. The most common causative microorganisms of bacteraemia in their study population were E. coli, S. aureus, K. pneumoniae and Enterobacter cloacae complex. A study of Hughes et al. also described similar findings . The authors reported an occurrence of bacteraemia of 3.2%. This percentage consisted of both hospital- and community-acquired infections. We only reported on community-acquired infections, which may explain the difference. Their most frequently isolated community-acquired pathogens were Enterobacterales, Streptococcus spp., S. aureus and Enterococcus spp. A recent study of Goyal et al. noted a bacteraemia rate of 5.6% in COVID-19 patients . This is significantly higher than the 1.0% that our study reported. Like Hughes et al., these authors examined both hospital-acquired and community-acquired infections, which may explain the higher rate of bacteraemia.
We reported a blood culture contamination rate of 89.1% amongst COVID-19 patients. This percentage is fairly consistent with other studies [17, 18]. This high percentage may be explained by the high workload and the recruitment of more inexperienced health care workers during the pandemic.
We found a 30-day all-cause mortality of 28.3% in our COVID-19 cohort. This number is relatively high compared to recent reports from Europe that describe 30-day all-cause mortality rates ranging from 19.7 to 21.5% [20, 21]. This disparity may be attributed to the higher risk of severe disease in our study population. During the first wave of COVID-19, family doctors in our region were asked to refer only severe cases to the overloaded hospitals. Furthermore, we only included patients with COVID-19 and analysed blood cultures. The required collection of blood cultures suggests these patients experienced severe febrile illness which indicates more severe disease.
Our findings on bacteraemia in influenza patients are consistent with prior studies [22, 23]. We reported a slightly lower rate of bacteraemia in influenza B patients in comparison to influenza A patients. This is in agreement with the assertion that influenza B often leads to milder disease and less co-infections when compared to influenza A [24, 25]. The 30-day all-cause mortality rate amongst influenza patients in our cohort was comparable to mortality rates mentioned in other literature [20, 26].
Our findings support current guidelines on antibiotic management that do not recommend the use of empiric antibiotics in patients with COVID-19 unless there is a clear suspicion of an accompanying bacterial infection . However, differentiating between viral disease and a bacterial co-infection can be a challenge for physicians. Procalcitonin levels may be of assistance in determining the likelihood of bacterial co-infection and a potential adverse outcome . When a bacterial co-infection is suspected and empiric antibiotics are administered, we advise to regularly collect blood cultures and respiratory samples. The antibiotic therapy may then be de-escalated or completely terminated based on the microbiological results. These recommendations will help in preventing overuse and the occurrence of potential side-effects from antibiotics.
A major strength of our study is the inclusion of over 1300 patients from two different hospitals in the Netherlands. This large sample size increases the accuracy and reliability of our results. In addition, we reported on community-acquired infections. Most studies on bacterial co-infections in COVID-19 failed to report on the setting of their study and possibly investigated hospital-acquired infections as well, which negatively affects the interpretability of their results [17, 28,29,30]. Finally, we did not experience any missing data, which minimizes the potential risk of information bias.
Some limitations should be mentioned. We did not collect data on prior antibiotic use, which may have led to an underestimation of the actual occurrence of bacteraemia in COVID-19 and influenza patients. Although the sample size of this study was of a reasonably large magnitude, the actual number of patients experiencing relevant bacteraemia was quite low, subgroup analyses of the 30-day all-cause mortality are therefore unreliable. In addition, we only reported on patients with bacteraemia and did not investigate other manifestations of bacterial co-infections. Thus, these results do not represent the entirety of bacterial co-infections in influenza and COVID-19 patients.
In conclusion, the proportion of clinically relevant community-acquired bacteraemia in COVID-19 patients was very low in comparison to influenza patients. These results justify the prudent use of empiric antibiotics in COVID-19 patients, when there is insufficient evidence of a bacterial co-infection.