Impact of Co-infections in COVID-19: Predisposing Mechanisms and Interplay between Invasive Viral, Bacterial and Fungal Pathogens

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Coronaviruses".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 3310

Special Issue Editors

Dr. Sunil More
E-Mail Website
Guest Editor
Assistant Professor, Veterinary Pathobiology, Oklahoma State University, Stillwater, OK, USA
Interests: respiratory diseases and pathology
Dr. Telugu Akula Narasaraju
E-Mail Website
Guest Editor
Professor, Adichinchanagiri Institute of Medical Sciences, Adichunchanagiri University, BG Nagara, Karnataka, India
Interests: influenza; SARS-COV and bacterial pneumonia
Associate Professor, Infectious Diseases Translational Research Programme and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Interests: characterization of newly emerged viruses and hepatitis viruses; development of antibodies for diagnostic and therapeutic applications; protein engineering

Special Issue Information

Dear Colleagues,

COVID-19 patients with severe disease are highly prone to secondary superinfections with a wide range of viral, bacterial and fungal pathogens. Since the beginning of the pandemic, several clinical reports, as well as experimental animal models, have demonstrated how different microbial pathogens impact disease outcome in COVID-19. However, much remains to be explored regarding how other microbial pathogens interact with SARS-COV-2 and among themselves in the same infectious lung microenvironment. Further, the effect of co-infections or secondary superinfections on host immunity, tissue damage and recovery need to be understood.

This Special Issue will focus on the mechanisms by which various microbial pathogens contribute to COVID-19’s pathophysiology. We aim to discuss the signaling events involved in pathogen–pathogen and pathogen–host interactions and their influence on disease outcome in COVID-19.  We welcome clinical reports, epidemiology studies and work on animal models of co-infections, identification of novel signaling pathways in host defense and COVID-19-infected individuals’ susceptibility for further infections. Research conducted at the cellular level to explore the entry or co-existence of more than one pathogen, especially via respiratory epithelial cells, will be accepted. Further studies focused on understanding the mechanisms by which SARS-COV-2 infection predisposes individuals to secondary viral, bacterial or fungal infections and therapeutic interventions will also be discussed in this Special Issue.

Dr. Sunil More
Dr. Telugu Akula Narasaraju
Dr. Yee-Joo Tan
Guest Editors

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Keywords

  • SARS-COV-2
  • co-infections
  • bacterial superinfections
  • fungal infections
  • signaling pathways in co-infections
  • viral co-infections in COVID-19

Published Papers (4 papers)

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Research

12 pages, 1908 KiB  
Article
The Rapidly Changing Patterns in Bacterial Co-Infections Reveal Peaks in Limited Gram Negatives during COVID-19 and Their Sharp Drop Post-Vaccination, Implying Potential Evolution of Co-Protection during Vaccine–Virus–Bacterial Interplay
Viruses 2024, 16(2), 227; https://doi.org/10.3390/v16020227 - 31 Jan 2024
Viewed by 570
Abstract
SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types [...] Read more.
SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccination. Out of 389 isolates used in different aspects, 298 were examined before and during the pandemic (n = 149 before, n = 149 during). In this group, death rates were 32% during compared to only 7.4% before the pandemic with significant association (p-value = 0.000000075). However, the death rate was 34% in co-infected (n = 170) compared to non-co-infected patients (n = 128), indicating a highly significant value (p-value = 0.00000000000088). However, analysis of patients without other serious respiratory problems (n = 28) indicated that among the remaining 270 patients, death occurred in 30% of co-infected patients (n = 150) and only 0.8% of non-co-infected (n = 120) with a high significant p-value = 0.00000000076. The trending patterns of co-infections before, during, and after vaccination showed a significant decline in Staphylococcus aureus with concomitant peaks in Gram negatives n = 149 before/n = 149 during, including Klebsiella pneumonian = 11/49 before/during, E. coli n = 10/24, A. baumannii n = 8/25, Ps. aeruginosa n = 5/16, and S. aureus 13/1. Nevertheless, in the post-vaccination phase (n = 91), gender-specific co-infections were examined for potential differences in susceptibility. Methicillin-resistant S. aureus dominated both genders followed by E. coli in males and females, with the latter gender showing higher rates of isolations in both species. Klebsiella pneumoniae declined to third place in male patients. The drastic decline in K. pneumoniae and Gram negatives post-vaccination strongly implied a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry. Full article
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11 pages, 774 KiB  
Article
Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients
Viruses 2024, 16(1), 86; https://doi.org/10.3390/v16010086 - 05 Jan 2024
Cited by 1 | Viewed by 669
Abstract
COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of [...] Read more.
COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66–14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29–20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use. Full article
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11 pages, 587 KiB  
Article
Association between Pulmonary Aspergillosis and Cytomegalovirus Reactivation in Critically Ill COVID-19 Patients: A Prospective Observational Cohort Study
Viruses 2023, 15(11), 2260; https://doi.org/10.3390/v15112260 - 15 Nov 2023
Viewed by 840
Abstract
COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. [...] Read more.
COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. CAPA occurred in 96 patients (16.6%) of the 579 patients analyzed. Among the CAPA population, 40 (41.7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7–27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p = 0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21–4.48, p = 0.011). In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality. Full article
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13 pages, 290 KiB  
Article
Prevalence and Impact on Mortality of Colonization and Super-Infection by Carbapenem-Resistant Gram-Negative Organisms in COVID-19 Hospitalized Patients
Viruses 2023, 15(9), 1934; https://doi.org/10.3390/v15091934 - 15 Sep 2023
Cited by 1 | Viewed by 796
Abstract
Background: The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Methods: Herein, a [...] Read more.
Background: The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Methods: Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant Acinetobacter baumannii was assessed. Results: The incidence of KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24–1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18–12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43–9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40–0.72) were the features most strongly associated with in-hospital mortality. Conclusions: Although KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities. Full article
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