Co-infections as Modulators of Disease Outcome: Minor Players or Major Players?

Abstract

Human host and pathogen interaction is dynamic in nature and often modulated by co-pathogens with a functional role in delineating the physiological outcome of infection. Co-infection may present either as a pre-existing pathogen which is accentuated by the introduction of a new pathogen or may appear in the form of new infection acquired secondarily due to a compromised immune system. Using diverse examples of co-infecting pathogens such as Human Immunodeficiency Virus, Mycobacterium tuberculosis and Hepatitis C Virus, we have highlighted the role of co-infections in modulating disease severity and clinical outcome. This interaction happens at multiple hierarchies, which are inclusive of stress and immunological responses and together modulate the disease severity. Already published literature provides much evidence in favor of the occurrence of co-infections during SARS-CoV-2 infection, which eventually impacts the Coronavirus disease-19 outcome. The availability of biological models like 3D organoids, mice, cell lines and mathematical models provide us with an opportunity to understand the role and mechanism of specific co-infections. Exploration of multi-omics-based interactions across co-infecting pathogens may provide deeper insights into their role in disease modulation.

Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever

“…Also, it was reported that a fatal case of rapidly progressed extrapulmonary tuberculosis was triggered by COVID-19 infection in poor-adherence HIV-1-infected patient (CD4# 105/μL at COVID-19 diagnosis) [ 13 ]. Immuno-modulating effects of COVID-19 on pre-existing infectious diseases, such as tuberculosis, have been analyzed by biological models like 3D organoids [ 14 ]. Taken together, it is possible that unmasking of latent tuberculosis infection occurred owing to a cytokine storm with COVID-19 infection, although multiple replicates should be considered to conclude it.…”

Parasite co-infection: an ecological, molecular and experimental perspective

“…However, in almost all cases, such studies cannot represent the context and setting of pathogen infections in the real world. In particular, pathogens rarely exist in isolation but rather enter hosts already harbouring a diversity of pre-existing commensal or pathogenic organisms, each imposing their own effects on the within-host environment and immune system [1][2][3]. Furthermore, the community of organisms within a host may be unstable or destabilized by the new ingression.…”

A spotlight on HCV and SARS-CoV-2 co-infection and brain function

“…Co-infection with pathogenic RNA viruses, including hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), can affect disease severity and clinical outcomes ( Devi et al, 2021 ). There are limited data on the effects of HCV infection on outcomes in individuals with coronavirus disease 2019 (COVID-19), and no data on outcomes in individuals with long-term symptoms associated with COVID-19 (long COVID syndrome; post-acute sequelae of SARS CoV-2 infection [PASC]).…”

“…Importantly, for HCV and SARS-CoV-2, the degree and nature of their interactions and the underlying mechanisms remain largely unexplored, although the potential for disease modulating effects of HCV infection on COVID-19 outcomes, including long COVID symptoms, is highlighted by evidence discussed in recent reviews ( Devi et al, 2021 ; da Mata et al, 2021 ). For example, one study suggests that among patients with HCV and hepatocellular carcinoma, those with undetectable HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection ( Guler-Margaritis et al, 2021 ).…”

“…The clinical consequences of COVID-19 and HCV co-infection require further attention, particularly concerning the impact of co-infection on neurologic and neuropsychiatric function. Research suggests that HCV can affect the progression of COVID-19, including disease severity and mortality ( Devi et al, 2021 ), which may be related to extrahepatic effects of HCV leading to enhanced ACE-2/TMPRSS mechanisms of SARS-CoV-2 viral entry, baseline cytokine-mediated pro-inflammation, and endothelial dysfunction/impact on BBB. Further study of these extrahepatic effects will aid in identifying the various neurologic and neuropsychiatric symptoms, long-lasting effects, and appropriate methods of treatment to improve viral clearance and mental health outcomes in individuals with HCV and COVID-19.…”