Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Tarun Sahu, Henu Kumar Verma, Lakkakula V K S Bhaskar

Tarun Sahu, Department of Physiology, All India Institute of Medical Science, Raipur 492001,Chhattisgarh, India

Henu Kumar Verma, Department of Immunopathology, Institute of Lung Health and Immunity,Comprehensive Pneumology Center, Helmholtz Zentrum, Munich 85764, Germany

Lakkakula V K S Bhaskar, Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495001, Chhattisgarh, India

Abstract Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4+ T and CD8+ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of coinfections.

Key Words: COVID-19; Co-infection; Bacterial co-infection; Fungal co-infection

TO THE EDITOR

The first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in December 2019, and the World Health Organization declared it a pandemic in March 2019. Approximately onethird of patients experienced severe complications of COVID-19 and required hospitalization[1]. Recently, secondary bacterial/fungal infections or co-infections are another major concern in COVID-19 patients, impacting mortality but lacking attention. Less evidence of bacterial and fungal infection was documented in earlier coronavirus pandemics and epidemics, such as severe acute respiratory syndrome (SARS)-1 and Middle East respiratory syndrome[2]. Recently, we have seen a paper by Saeedet al[3] entitled “Bacterial co-infection in patients with SARS-CoV-2 in the Kingdom of Bahrain”[3] in your well-regarded journalWorld J Virol. We appreciate the work done by Saeedet al[3] as they reported the microbial infections in patients with COVID-19 in the Kingdom of Bahrain.

The most common bacterial species they reported wereK. pneumonia, P. aeruginosa, A. baumannii, E.coli, S. aureus, E. faecalis,andE. faecium. Among all of these, hospital-acquired (HAI)/nosocomial infection was higher (73.8%) than community-acquired infection. Similar results were reported by Mahmoudi[4] and Sharifipouret al[5] in the neighboring country Iran. Both authors reported the same species of bacterial strains, which are the most common. Later on, a descriptive study conducted in the United Arab Emirates found bacterial co-infection in patients with COVID-19 and especiallyKlebsiella pneumonia, Escherichia coli, Staphylococcus aureus,andAcinetobacter baumanniiwere most predominant strains[6]. The recent reviews and meta-analysis also show thatKlebsiella pneumonia, Haemophiles influenzae, Streptococcus pneumoniae,andStaphylococcus aureusare the most frequently identified bacteria among co-infected patients[7,8]. A unique case series from Saudi Arabia reported Middle East respiratory syndrome coronavirus co-infection in 12% of patients already suffering from severe acute respiratory syndrome coronavirus 2[9]. At the same time, another case series from Saudi Arabia by Shabrawishiet al[10] reported 7 cases of COVID-19 and tuberculosis co-infection[10]. The interesting results of Hashemiet al[11] showed influenza A (H1N1) virus, human metapneumovirus, bocavirus, adenovirus, respiratory syncytial virus (RSV), and parainfluenza viruses in 105 dead patients with COVID-19 in northeastern Iran[11].

Other than bacteria, fungal and viral co-infections are also severe issues with COVID-19 patients. In the present article, the authors reported fungal co-infection in about 10% of total microbial co-infection. The most common isolated fungi wereCandida galabrata, Candida tropicalis, Candida albicans,andAspergillus fumigatus. They also found that the death rates in patients with fungal co-infection were very high (70.4%)[3]. Studies from other different regions found aspergillosis or invasive candidiasis as the common fungal co-infections[12]. In contrast, influenza type A, type B, and RSV were the most common viral co-infections in patients with COVID-19[7]. These co-infections are associated with an increased probability of death. Most of the articles reported that microbial co-infections were HAI/nosocomial infections, similar to Saeedet al[3], who found 71% were HAI.

Further, the authors have described well different microbial co-infections in patients of COVID-19. Furthermore, the study has some limitations, such as the authors not providing any treatment or management options for COVID-19 infected patients. That is the most crucial concern for the patient’s benefit. In this context, we would like to draw your attention to the management and recommendations for the infection. Chedidet al[13] reviewed the most common antibiotics used by COVID-19 hospitalized patients, primarily in an intensive situation, by analyzing the use of antibiotics in different types of bacterial secondary and co-infection[13].

On the other hand, Sieswerdaet al[14] gave evidence-based recommendations for antibacterial therapy for secondary microbial and co-infection[14]. Wuet al[15] described the management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19[15]. For the treatment of fungal co-infections, Songet al[16] suggested the regimen, which is currently in an induction phase and includes amphotericin B deoxycholate and flucytosine, followed by (1) Fluconazole; alternative options for fluconazole + flucytosine or amphotericin B deoxycholate + fluconazole; (2) Consolidation phase for fluconazole; and (3) Maintenance (or secondary prophylaxis) phase for fluconazole[16].

Depending upon disease severity, patients with influenza A or B viral co-infection should be treated with oseltamivir or its substitute[17]. Treatment options for other viral co-infection, such as RSV, are restricted and beneficial only in specific circumstances, such as immunosuppression or hypogammaglobulinemia[18,19].

Patients with COVID-19 had elevated levels of inflammatory cytokines and a debilitated cellmediated immune response, with lower CD4+T and CD8+T cell counts, indicating vulnerability to various co-infections. Furthermore, COVID-19 patients who are immunocompromised, such as those with extended neutropenia, hematopoietic stem cell transplantation, hereditary or acquired immunodeficiencies, or tumor, are more likely to develop co-infection. Co-infection and superinfection of pathogens in COVID-19 patients is a critical issue as it is difficult to distinguish the associated complications. Specific diagnostic tests should be recommended for proper treatment and management of these infections to reduce morbidity and mortality.

FOOTNOTES

Author contributions:Sahu T, Verma HK, and Bhaskar LVKS wrote and revised the letter.

Conflict-of-interest statement:The authors declare no conflict of interest.

Open-Access:This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: http://creativecommons.org/Licenses/by-nc/4.0/

Country/Territory of origin:Germany

ORCID number:Tarun Sahu 0000-0002-2721-7432; Henu Kumar Verma 0000-0003-1130-8783; Lakkakula V K S Bhaskar 0000-0003-2977-6454.

S-Editor:Fan JR

L-Editor:Filipodia

P-Editor:Fan JR