Editorial of Special Issue “The COVID-19 Pandemic and Bacterial Infections: Microbiological and Clinical Aspects”

The emergence in late 2019 of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the pandemic coronavirus disease 2019 (COVID-19), posed significant health challenges worldwide [1].

Overall, individuals infected by SARS-CoV-2 exhibited a wide range of clinical manifestations, primarily affecting the upper respiratory tract and necessitating admission to intensive care units (ICUs) in the most at-risk groups [2]. Hospitalized, severely ill COVID-19 patients can develop bacterial co-infections or super-infections, which could be associated with worse outcomes.

Most recent data from the literature suggest that although bacterial infections in COVID-19 occur with a low overall prevalence, some differences can be observed according to the patients’ population [3,4]; indeed, while the chance of bacterial co-infections is low in subjects with COVID-19 presenting in hospitals, a higher risk of secondary infections exists among patients admitted to ICUs [3].

The impact of bacterial infections on the severity of respiratory diseases, including the microbiological and clinical characteristics of such infections, remains understudied. As a consequence, knowledge gaps about the possible synergistic interactions between the SARS-CoV-2 infection and certain coinfecting bacteria or about the burden of antibiotic-resistant bacteria, considering the high antibiotics consumption observed among COVID-19 patients [3], exist.

This Special Issue on “The COVID-19 Pandemic and Bacterial Infections: Microbiological and Clinical Aspects” aims to broaden our understanding of the prevalence, incidence, and characteristics of bacterial infections in COVID-19 patients.

The research paper by Cohen et al. retrospectively assesses the rates and characteristics of pulmonary infections and the associated outcomes of ventilated COVID-19 patients (n = 93) using molecular syndromic assays [5]. The results show that most enrolled patients (68%) had ventilator-associated pneumonia (VAP), whose diagnosis was associated with poor patient outcomes, in contrast to community-acquired pneumonia (17%). Moreover, patients with VAP were older than those with community-acquired pneumonia (CAP) or those with no infection (68.5 vs. 57–59 years). Typical and expected organisms were associated with VAP (P. aeruginosa and S. aureus) and CAP (H. influenzae, S. pneumoniae, M. catarrhalis, and E. cloacae).

On the other hand, a rare case of pneumonia by Hafnia alvei was reported in a critically ill patient with a serious type 1 (hypoxemic) respiratory insufficiency, requiring extracorporeal membrane oxygenation [6]. In the former case report, Mendez et al. highlighted that owing to the immunocompromised status observed in COVID-19 disease, difficult-to-treat nosocomial respiratory co-infections by rare organisms could occur.

In this same line, Deghmane and Taha identified profound changes in the epidemiology of invasive bacterial infections following the emergence of the COVID-19 pandemic in France [7]. The results from this epidemiological investigation showed a drastic reduction in the circulation of H. influenzae and N. meningitidis, regardless of vaccine uptake, likely due to the implementation of strict social restrictions aimed at limiting the circulation of SARS-CoV-2.

Finally, in a retrospective observational cohort study, Ego et al. carried out a qualitative and quantitative analysis of sedative use in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) and in non-COVID patients who suffered from ARDS as a consequence of bacterial or viral infections and polytrauma [8]. Overall, COVID-19 patients with ARDS received a more frequent combination of multiple sedative drugs than non-COVID patients, resulting in a longer duration of mechanical ventilation and ICU stay.

In conclusion, the interplay between COVID-19 and bacterial co-infections and super-infections is complex in terms of both epidemiology and clinical impact. Certainly, despite the high rates of bacterial infections that have been reported in the most critically ill COVID-19 patients, the overall prevalence of bacterial infections in hospitalized COVID-19 patients remains low (4–6%) [9], strikingly contrasting with the high prevalence of antibiotic use reported by the same population (60–100% in most studies) [10,11]. This latter represents the clearest modifiable factor on which to intervene to reduce the unfavorable consequences of the COVID-19 pandemic on antibiotic resistance. Further efforts to mitigate this uncomfortable disproportion are warranted.

Conflicts of Interest

Outside the submitted work, D.R.G. reports investigator-initiated grants from Pfizer, Gilead Italia, and Shionogi, and speaker/advisor fees from Pfizer and Tillotts Pharma.

Footnotes

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References

1. Hu, B.; Guo, H.; Zhou, P.; Shi, Z.-L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol.; 2021; 19, pp. 141-154. [DOI: https://dx.doi.org/10.1038/s41579-020-00459-7] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33024307]

2. Wiersinga, W.J.; Rhodes, A.; Cheng, A.C.; Peacock, S.J.; Prescott, H.C. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA; 2020; 324, pp. 782-793. [DOI: https://dx.doi.org/10.1001/jama.2020.12839] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32648899]

3. Langford, B.J.; So, M.; Simeonova, M.; Leung, V.; Lo, J.; Kan, T.; Raybardhan, S.; Sapin, M.; Mponponsuo, K.; Farrell, A. et al. Antimicrobial Resistance in Patients with COVID-19: A Systematic Review and Meta-Analysis. SSRN Electron. J.; 2022; 5247, pp. 1-13. [DOI: https://dx.doi.org/10.2139/ssrn.4099404]

4. Langford, B.J.; So, M.; Raybardhan, S.; Leung, V.; Westwood, D.; MacFadden, D.R.; Soucy, J.P.R.; Daneman, N. Bacterial Co-Infection and Secondary Infection in Patients with COVID-19: A Living Rapid Review and Meta-Analysis. Clin. Microbiol. Infect.; 2020; 26, pp. 1622-1629. [DOI: https://dx.doi.org/10.1016/j.cmi.2020.07.016] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32711058]

5. Cohen, R.; Babushkin, F.; Finn, T.; Geller, K.; Alexander, H.; Datnow, C.; Uda, M.; Shapiro, M.; Paikin, S.; Lellouche, J. High Rates of Bacterial Pulmonary Co-Infections and Superinfections Identified by Multiplex PCR among Critically Ill COVID-19 Patients. Microorganisms; 2021; 9, 2483. [DOI: https://dx.doi.org/10.3390/microorganisms9122483] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34946086]

6. Méndez, L.; Ferreira, J.; Caneiras, C. Hafnia Alvei Pneumonia: A Rare Cause of Infection in a Patient with COVID-19. Microorganisms; 2021; 9, 2369. [DOI: https://dx.doi.org/10.3390/microorganisms9112369]

7. Deghmane, A.E.; Taha, M.K. Changes in Invasive Neisseria Meningitidis and Haemophilus Influenzae Infections in France during the COVID-19 Pandemic. Microorganisms; 2022; 10, 907. [DOI: https://dx.doi.org/10.3390/microorganisms10050907] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35630352]

8. Ego, A.; Peluso, L.; Gorham, J.; Diosdado, A.; Restuccia, G.; Creteur, J.; Taccone, F.S. Use of Sedatives and Neuromuscular-Blocking Agents in Mechanically Ventilated Patients with Covid-19 Ards. Microorganisms; 2021; 9, 2393. [DOI: https://dx.doi.org/10.3390/microorganisms9112393] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34835518]

9. Alshaikh, F.S.; Godman, B.; Sindi, O.N.; Seaton, R.A.; Kurdi, A. Prevalence of Bacterial Coinfection and Patterns of Antibiotics Prescribing in Patients with COVID-19: A Systematic Review and Meta-Analysis. PLoS ONE; 2022; 17, e0272375. [DOI: https://dx.doi.org/10.1371/journal.pone.0272375] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35913964]

10. Giacobbe, D.R.; Bassetti, M. Too Many Antibiotics for Patients with COVID-19 despite Low Bacterial Infections. Lancet Infect. Dis.; 2023; S1473-3099(22)00866-0. [DOI: https://dx.doi.org/10.1016/S1473-3099(22)00866-0]

11. Chen, J.Z.; Hoang, H.L.; Yaskina, M.; Kabbani, D.; Doucette, K.E.; Smith, S.W.; Lau, C.; Stewart, J.; Remtulla, S.; Zurek, K. et al. Efficacy and Safety of Antimicrobial Stewardship Prospective Audit and Feedback in Patients Hospitalised with COVID-19 (COVASP): A Pragmatic, Cluster-Randomised, Non-Inferiority Trial. Lancet Infect. Dis.; 2023; S1473-3099(22)00832-5. [DOI: https://dx.doi.org/10.1016/S1473-3099(22)00832-5]