Bacterial and fungal coinfections among patients with COVID-19 in Zanjan, Northwest of Iran; a single-center observational with meta-analysis of the literature
Abstract
Background and Objectives: There is a poor understanding about the prevalence and characteristics of secondary bacterial and fungal infections among Coronavirus diseases 2019 (COVID-19) superinfection in hospitalized patients.
Materials and Methods: Four hundred COVID-19-proven patients were enrolled in this study. Nasal swabs for molecular assay (Real-time PCR) and sputum samples for further microbiological assays were collected. Following a broad-spectrum search, a meta-analysis was performed using StatsDirect software (version 2.7.9) according to the DerSimonian and Laird method applying the random-effects models.
Results: Streptococcus spp. (21.5%) and Staphylococcus spp. (16.7%) had the highest prevalence of bacterial coinfection among the COVID-19 patients, while Acinetobacter spp. had the lowest prevalence (4.2%). Among fungal coinfections, Candida albicans was the most prevalent (6.7%), and Aspergillus spp. was the lowest (2%). Males, elderly patients, patients with a history of underlying diseases and drug use, patients who showed acute clinical symptoms, and patients with a prolonged hospital stay had a higher incidence of secondary infections (P-value <0.05). The pooled prevalence for bacterial and fungal coinfections was 33.52% (95% CI: 18.12 to 50.98; I2: 99.4%; P-value: <0.0001).
Conclusion: We suggest designing additional research with a larger target population and diagnostic molecular analyses to depict a more realistic view of the coinfection status.
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3. Chen X, Liao B, Cheng L, Peng X, Xu X, Li Y, et al. The microbial coinfection in COVID-19. Appl Microbiol Biotechnol 2020; 104: 7777-7785.
4. Carvalho-Schneider C, Laurent E, Lemaignen A, Beaufils E, Bourbao-Tournois C, Laribi S, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect 2021; 27: 258-263.
5. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe 2021; 2(8): e354-e365.
6. Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. Post-COVID-19 symptom burden: what is long-COVID and how should we manage it? Lung 2021; 199: 113-119.
7. Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 syndrome: the persistent symptoms at the post-viral stage of the disease. A systematic review of the current data. Front Med (Lausanne) 2021; 8: 653516.
8. Malayala SV, Mohan G, Vasireddy D, Atluri P. A case series of vestibular symptoms in positive or suspected COVID-19 patients. Infez Med 2021; 29: 117-122.
9. Baral PK, Yin J, James MNG. Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2. Int J Biol Macromol 2021; 186: 490-500.
10. García LF. Immune response, inflammation, and the clinical spectrum of COVID-19. Front Immunol 2020; 11: 1441.
11. Li M, Lei P, Zeng B, Li Z, Yu P, Fan B, et al. Coronavirus disease (COVID-19): spectrum of CT findings and temporal progression of the disease. Acad Radiol 2020; 27: 603-608.
12. Xu Z, Li S, Tian S, Li H, Kong L-Q. Full spectrum of COVID-19 severity still being depicted. Lancet 2020; 395: 947-948.
13. Hull JH, Wootten M, Moghal M, Heron N, Martin R, Walsted ES, et al. Clinical patterns, recovery time and prolonged impact of COVID-19 illness in international athletes: the UK experience. Br J Sports Med 2022; 56: 4-11.
14. Rawson TM, Moore LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020; 71: 2459-2468.
15. Rawson TM, Wilson RC, Holmes A. Understanding the role of bacterial and fungal infection in COVID-19. Clin Microbiol Infect 2021; 27: 9-11.
16. Abdoli A. Iran, sanctions, and the COVID-19 crisis. J Med Econ 2020; 23: 1461-1465.
17. Buehler PK, Zinkernagel AS, Hofmaenner DA, Wendel Garcia PD, Acevedo CT, Gómez-Mejia A, et al. Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients. Cell Rep Med 2021; 2: 100229.
18. Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect 2021; 27: 83-88.
19. Paley EL. Towards understanding COVID-19: Molecular insights, co-infections, associated disorders, and aging. J Alzheimers Dis Rep 2021; 5: 571-600.
20. Ripa M, Galli L, Poli A, Oltolini C, Spagnuolo V, Mastrangelo A, et al. Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors. Clin Microbiol Infect 2021; 27: 451-457.
21. Risa E, Roach D, Budak JZ, Hebert C, Chan JD, Mani NS, et al. Characterization of secondary bacterial infections and antibiotic use in mechanically ventilated patients with COVID-19. induced acute respiratory distress syndrome. J Intensive Care Med 2021; 36: 1167-1175.
22. Chirico F, Nucera G, Magnavita N. COVID-19: protecting healthcare workers is a priority. Infect Control Hosp Epidemiol 2020; 41: 1117.
23. Alqahtani A, Alamer E, Mir M, Alasmari A, Alshahrani MM, Asiri M, et al. Bacterial Coinfections Increase Mortality of Severely Ill COVID-19 Patients in Saudi Arabia. Int J Environ Res Public Health 2022; 19: 2424.
24. Arastehfar A, Ünal N, Hoşbul T, Alper Özarslan M, Sultan Karakoyun A, Polat F, et al. Candidemia among Coronavirus Disease 2019 patients in Turkey admitted to intensive care units: a retrospective multicenter study. Open Forum Infect Dis 2022; 9: ofac078.
25. Bahçe YG, Acer Ö, Özüdoğru O. Evaluation of bacterial agents isolated from endotracheal aspirate cultures of Covid-19 general intensive care patients and their antibiotic resistance profiles compared to pre-pandemic conditions. Microb Pathog 2022; 164: 105409.
26. Ceparano M, Baccolini V, Migliara G, Isonne C, Renzi E, Tufi D, et al. Acinetobacter baumannii isolates from COVID-19 patients in a hospital intensive care unit: molecular typing and risk factors. Microorganisms 2022; 10: 722.
27. Chan XHS, O'Connor CJ, Martyn E, Clegg AJ, Choy BJK, Soares AL, et al. Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality. J Hosp Infect 2022; 124: 37-46.
28. Moradi N, Kazemi N, Ghaemi M, Mirzaei B. Frequency and antimicrobial resistance pattern of bacterial isolates from patients with COVID-19 in two hospitals of Zanjan. Iran J Microbiol 2021; 13: 769-778.
29. Moreno-Torres V, De Mendoza C, De la Fuente S, Sánchez E, Martínez-Urbistondo M, Herráiz J, et al. Bacterial infections in patients hospitalized with COVID-19. Intern Emerg Med 2022; 17: 431-438.
30. Papst L, Luzzati R, Carević B, Tascini C, Gorišek Miksić N, Vlahović Palčevski V, et al. Antimicrobial use in hospitalised patients with COVID-19: an international multicentre point-prevalence study. Antibiotics (Basel) 2022; 11: 176.
31. Scott H, Zahra A, Fernandes R, Fries BC, Thode HC Jr, Singer AJ. Bacterial infections and death among patients with Covid-19 versus non Covid-19 patients with pneumonia. Am J Emerg Med 2022; 51: 1-5.
32. Zhang H, Zhang Y, Wu J, Li Y, Zhou X, Li X, et al. Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerg Microbes Infect 2020; 9: 1958-1964.
33. Liu HH, Yaron D, Piraino AS, Kapelusznik L. Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors. Ann Clin Microbiol Antimicrob 2021; 20: 69.
34. Hughes S, Troise O, Donaldson H, Mughal N, Moore LS. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020; 26: 1395-1399.
35. De Santis V, Corona A, Vitale D, Nencini C, Potalivo A, Prete A, et al. Bacterial infections in critically ill patients with SARS-2-COVID-19 infection: results of a prospective observational multicenter study. Infection 2022; 50: 139-148.
36. Shafran N, Shafran I, Ben-Zvi H, Sofer S, Sheena L, Krause I, et al. Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients. Sci Rep 2021; 11: 12703.
37. Nasir N, Rehman F, Omair SF. Risk factors for bacterial infections in patients with moderate to severe COVID‐19: A case‐control study. J Med Virol 2021; 93:4564-4569.
38. Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ 2020; 11: 29.
39. McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz) 2011; 59: 203-213.
40. Cullen W, O'Brien S, O'Carroll A, O'Kelly FD, Bury G. Chronic illness and multimorbidity among problem drug users: a comparative cross sectional pilot study in primary care. BMC Fam Pract 2009; 10: 25.
41. White PL, Dhillon R, Healy B, Wise MP, Backs M. Reply to rodriguez et al and mastrangelo et al. Clin Infect Dis 2021; 73(9): e2839-e2841.
42. Vaseghi N, Sharifisooraki J, Khodadadi H, Nami S, Safari F, Ahangarkani F, et al. Global prevalence and subgroup analyses of Coronavirus disease (COVID‐19) associated Candida auris infections (CACa): A systematic review and meta‐analysis. Mycoses 2022; 65: 683-703.
43. Westblade LF, Simon MS, Satlin MJ. Bacterial coinfections in coronavirus disease 2019. Trends Microbiol 2021; 29: 930-941.
44. Casalini G, Giacomelli A, Ridolfo A, Gervasoni C, Antinori S. Invasive fungal infections complicating COVID-19: A narrative review. J Fungi (Basel) 2021; 7: 921.
45. Salehi M, Ahmadikia K, Badali H, Khodavaisy S. Opportunistic fungal infections in the epidemic area of COVID-19: a clinical and diagnostic perspective from Iran. Mycopathologia 2020; 185: 607-611.
2. Salimi R, Gomar R, Heshmati B. The COVID-19 outbreak in Iran. J Glob Health 2020; 10: 010365.
3. Chen X, Liao B, Cheng L, Peng X, Xu X, Li Y, et al. The microbial coinfection in COVID-19. Appl Microbiol Biotechnol 2020; 104: 7777-7785.
4. Carvalho-Schneider C, Laurent E, Lemaignen A, Beaufils E, Bourbao-Tournois C, Laribi S, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Clin Microbiol Infect 2021; 27: 258-263.
5. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe 2021; 2(8): e354-e365.
6. Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. Post-COVID-19 symptom burden: what is long-COVID and how should we manage it? Lung 2021; 199: 113-119.
7. Salamanna F, Veronesi F, Martini L, Landini MP, Fini M. Post-COVID-19 syndrome: the persistent symptoms at the post-viral stage of the disease. A systematic review of the current data. Front Med (Lausanne) 2021; 8: 653516.
8. Malayala SV, Mohan G, Vasireddy D, Atluri P. A case series of vestibular symptoms in positive or suspected COVID-19 patients. Infez Med 2021; 29: 117-122.
9. Baral PK, Yin J, James MNG. Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2. Int J Biol Macromol 2021; 186: 490-500.
10. García LF. Immune response, inflammation, and the clinical spectrum of COVID-19. Front Immunol 2020; 11: 1441.
11. Li M, Lei P, Zeng B, Li Z, Yu P, Fan B, et al. Coronavirus disease (COVID-19): spectrum of CT findings and temporal progression of the disease. Acad Radiol 2020; 27: 603-608.
12. Xu Z, Li S, Tian S, Li H, Kong L-Q. Full spectrum of COVID-19 severity still being depicted. Lancet 2020; 395: 947-948.
13. Hull JH, Wootten M, Moghal M, Heron N, Martin R, Walsted ES, et al. Clinical patterns, recovery time and prolonged impact of COVID-19 illness in international athletes: the UK experience. Br J Sports Med 2022; 56: 4-11.
14. Rawson TM, Moore LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020; 71: 2459-2468.
15. Rawson TM, Wilson RC, Holmes A. Understanding the role of bacterial and fungal infection in COVID-19. Clin Microbiol Infect 2021; 27: 9-11.
16. Abdoli A. Iran, sanctions, and the COVID-19 crisis. J Med Econ 2020; 23: 1461-1465.
17. Buehler PK, Zinkernagel AS, Hofmaenner DA, Wendel Garcia PD, Acevedo CT, Gómez-Mejia A, et al. Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients. Cell Rep Med 2021; 2: 100229.
18. Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M, et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect 2021; 27: 83-88.
19. Paley EL. Towards understanding COVID-19: Molecular insights, co-infections, associated disorders, and aging. J Alzheimers Dis Rep 2021; 5: 571-600.
20. Ripa M, Galli L, Poli A, Oltolini C, Spagnuolo V, Mastrangelo A, et al. Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors. Clin Microbiol Infect 2021; 27: 451-457.
21. Risa E, Roach D, Budak JZ, Hebert C, Chan JD, Mani NS, et al. Characterization of secondary bacterial infections and antibiotic use in mechanically ventilated patients with COVID-19. induced acute respiratory distress syndrome. J Intensive Care Med 2021; 36: 1167-1175.
22. Chirico F, Nucera G, Magnavita N. COVID-19: protecting healthcare workers is a priority. Infect Control Hosp Epidemiol 2020; 41: 1117.
23. Alqahtani A, Alamer E, Mir M, Alasmari A, Alshahrani MM, Asiri M, et al. Bacterial Coinfections Increase Mortality of Severely Ill COVID-19 Patients in Saudi Arabia. Int J Environ Res Public Health 2022; 19: 2424.
24. Arastehfar A, Ünal N, Hoşbul T, Alper Özarslan M, Sultan Karakoyun A, Polat F, et al. Candidemia among Coronavirus Disease 2019 patients in Turkey admitted to intensive care units: a retrospective multicenter study. Open Forum Infect Dis 2022; 9: ofac078.
25. Bahçe YG, Acer Ö, Özüdoğru O. Evaluation of bacterial agents isolated from endotracheal aspirate cultures of Covid-19 general intensive care patients and their antibiotic resistance profiles compared to pre-pandemic conditions. Microb Pathog 2022; 164: 105409.
26. Ceparano M, Baccolini V, Migliara G, Isonne C, Renzi E, Tufi D, et al. Acinetobacter baumannii isolates from COVID-19 patients in a hospital intensive care unit: molecular typing and risk factors. Microorganisms 2022; 10: 722.
27. Chan XHS, O'Connor CJ, Martyn E, Clegg AJ, Choy BJK, Soares AL, et al. Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality. J Hosp Infect 2022; 124: 37-46.
28. Moradi N, Kazemi N, Ghaemi M, Mirzaei B. Frequency and antimicrobial resistance pattern of bacterial isolates from patients with COVID-19 in two hospitals of Zanjan. Iran J Microbiol 2021; 13: 769-778.
29. Moreno-Torres V, De Mendoza C, De la Fuente S, Sánchez E, Martínez-Urbistondo M, Herráiz J, et al. Bacterial infections in patients hospitalized with COVID-19. Intern Emerg Med 2022; 17: 431-438.
30. Papst L, Luzzati R, Carević B, Tascini C, Gorišek Miksić N, Vlahović Palčevski V, et al. Antimicrobial use in hospitalised patients with COVID-19: an international multicentre point-prevalence study. Antibiotics (Basel) 2022; 11: 176.
31. Scott H, Zahra A, Fernandes R, Fries BC, Thode HC Jr, Singer AJ. Bacterial infections and death among patients with Covid-19 versus non Covid-19 patients with pneumonia. Am J Emerg Med 2022; 51: 1-5.
32. Zhang H, Zhang Y, Wu J, Li Y, Zhou X, Li X, et al. Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerg Microbes Infect 2020; 9: 1958-1964.
33. Liu HH, Yaron D, Piraino AS, Kapelusznik L. Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors. Ann Clin Microbiol Antimicrob 2021; 20: 69.
34. Hughes S, Troise O, Donaldson H, Mughal N, Moore LS. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020; 26: 1395-1399.
35. De Santis V, Corona A, Vitale D, Nencini C, Potalivo A, Prete A, et al. Bacterial infections in critically ill patients with SARS-2-COVID-19 infection: results of a prospective observational multicenter study. Infection 2022; 50: 139-148.
36. Shafran N, Shafran I, Ben-Zvi H, Sofer S, Sheena L, Krause I, et al. Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients. Sci Rep 2021; 11: 12703.
37. Nasir N, Rehman F, Omair SF. Risk factors for bacterial infections in patients with moderate to severe COVID‐19: A case‐control study. J Med Virol 2021; 93:4564-4569.
38. Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ 2020; 11: 29.
39. McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz) 2011; 59: 203-213.
40. Cullen W, O'Brien S, O'Carroll A, O'Kelly FD, Bury G. Chronic illness and multimorbidity among problem drug users: a comparative cross sectional pilot study in primary care. BMC Fam Pract 2009; 10: 25.
41. White PL, Dhillon R, Healy B, Wise MP, Backs M. Reply to rodriguez et al and mastrangelo et al. Clin Infect Dis 2021; 73(9): e2839-e2841.
42. Vaseghi N, Sharifisooraki J, Khodadadi H, Nami S, Safari F, Ahangarkani F, et al. Global prevalence and subgroup analyses of Coronavirus disease (COVID‐19) associated Candida auris infections (CACa): A systematic review and meta‐analysis. Mycoses 2022; 65: 683-703.
43. Westblade LF, Simon MS, Satlin MJ. Bacterial coinfections in coronavirus disease 2019. Trends Microbiol 2021; 29: 930-941.
44. Casalini G, Giacomelli A, Ridolfo A, Gervasoni C, Antinori S. Invasive fungal infections complicating COVID-19: A narrative review. J Fungi (Basel) 2021; 7: 921.
45. Salehi M, Ahmadikia K, Badali H, Khodavaisy S. Opportunistic fungal infections in the epidemic area of COVID-19: a clinical and diagnostic perspective from Iran. Mycopathologia 2020; 185: 607-611.
| Files | ||
| Issue | Vol 14 No 5 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i5.10955 | |
| Keywords | ||
| COVID-19; Secondary infection; Nosocomial infection | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Morovati H, Eslami S, Farzaneh Bonab H, Kord M, Darabian S. Bacterial and fungal coinfections among patients with COVID-19 in Zanjan, Northwest of Iran; a single-center observational with meta-analysis of the literature. Iran J Microbiol. 2022;14(5):624-635.
