Co-infections: potentially lethal and unexplored in COVID-19

Cox, Michael J.; Loman, Nicholas J.; Bogaert, Debby; O’Grady, Justin

doi:10.1016/s2666-5247(20)30009-4

Cited by 350 publications

(382 citation statements)

References 5 publications

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“…During the COVID-19 pandemic, as well as other past viral outbreaks, respiratory viral infections are associated with co-infections with Streptococcus pneumoniae (Sp). As recently reported, 50% of COVID-19 patients who have died, also showed secondary bacterial infections, and fungal coinfections [35]. Thus, as a proof-of-concept, we designed a solid-phase immunoassay coating the plates with a library of seven structurally different CPS from S. pneumoniae (the seven most abundant serotypes worldwide as well as the ones included in pneumococcal conjugate-vaccines, PCV: Sp1, Sp5, Sp06B, Sp14, Sp18C, Sp19F and Sp23F) and determined the binding of SARS-CoV-2 spike protein as Fc-construct in our assay to quantify potential interactions.…”

Section: Figuresupporting

confidence: 57%

Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

Chiodo

Bruijns

Rodríguez

et al. 2020

Preprint

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The immediate call for translational research in the field of coronavirus disease (COVID-19) pandemic, needs new and unexplored angles to support and contribute to this important worldwide health problem. The aim of this study is to better understand the pathogenic mechanisms underlying COVID-19, deciphering the carbohydrate-mediated interactions of the SARS-CoV-2 spike protein. We studied the carbohydrate-binding receptors that could be important for viral entry and for immune-modulatory responses, and we studied the interactions of the spike protein with the host lung microbiota. Exploring solid-phase immunoassays, we evaluated the interactions between the SARS-CoV-2 spike protein and a library of 12 different human carbohydrate-binding proteins (C-type lectins and Siglecs) involved in binding, triggering and modulation of innate and adaptive immune-responses. We revealed a specific binding of the SARS-CoV-2 spike protein to the receptors DC-SIGN, MGL, Siglec-9 and Siglec-10 that are all expressed on myeloid immune cells. In addition, because the lung microbiota can promote or modulate viral infection, we studied the interactions between the SARS-CoV-2 spike protein and a library of Streptococcus pneumoniae capsular polysaccharides, as well as other bacterial glyco-conjugates. We show specific binding of the spike protein to different S. pneumoniae capsular polysaccharides (serotypes 19F and 23F but not to serotype 14). Moreover we demonstrated a specific binding of SARS-CoV-2 spike protein to the lipopolysaccharide from the opportunistic human pathogen Pseudomonas aeruginosa, one of the leading cause of acute nosocomial infections and pneumonia. Interestingly, we identified rhamnosylated epitopes as one of the discriminating structures in lung microbiota to bind SARS-CoV-2 spike protein. In conclusion, we revealed novel ACE2-independent carbohydrate-mediated interactions with immune modulating lectins expressed on myeloid cells, as well as host lung microbiota glycoconjugates. Our results identified new molecular pathways using host lectins and signalling, that may contribute to viral infection and subsequent immune exacerbation. Moreover we identified specific rhamnosylated epitopes in lung microbiota to bind SARS-CoV-2, providing a hypothetical link between the presence of specific lung microbiota and SARS-CoV-2 infection and severity.

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Section: Figuresupporting

confidence: 57%

Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

Chiodo

Bruijns

Rodríguez

et al. 2020

Preprint

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“…26,27,161 Despite the proven significance of co-infections in the severity of respiratory diseases, these kinds of infections during large outbreaks of respiratory infections are underdetermined. 162 For the precise diagnosis and evaluation of co-infections during the COVID-19 pandemic, samples must be taken longitudinally throughout the disease course via techniques independent of the culture for identifying mixed infections such as whole-genome metagenomics (WGMs). 162 Such works offer valuable monitoring findings on co-infection pathogens and drug-resistance infections resulting in improved antibiotic prescribing options.…”

Section: Bacterial Co-infection With Coronaviruses and Covid-19mentioning

confidence: 99%

“…162 For the precise diagnosis and evaluation of co-infections during the COVID-19 pandemic, samples must be taken longitudinally throughout the disease course via techniques independent of the culture for identifying mixed infections such as whole-genome metagenomics (WGMs). 162 Such works offer valuable monitoring findings on co-infection pathogens and drug-resistance infections resulting in improved antibiotic prescribing options. 162 Zhou et al 163 found that in the current COVID-19 pandemic, 50% of patients who died from Covid-19 had bacterial co-infections.…”

Section: Bacterial Co-infection With Coronaviruses and Covid-19mentioning

confidence: 99%

Bacterial co‐infections with SARS‐CoV‐2

et al. 2020

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The pandemic coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID‐19 are underway. Respiratory viral infections, such as influenza, predispose patients to co‐infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co‐infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS‐CoV‐2). Although antibiotics do not directly affect SARS‐CoV‐2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co‐infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co‐infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID‐19. Also, the antibiotic‐resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co‐infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID‐19.

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“…Furthermore, a strong immune suppression of both the arms of the immune responses by the regulatory cells causes an apparent clearance of the virus but the virus can persist at very low levels until the immune cells are suppressed enough (compare Fig S5E, Fig S5F) for the resurgence of the virus (Fig 5D). This scenario of immuno-compromised state can allow other opportunistic pathogens to infect the lungs (47), thus further complicating the situation. These analyses suggest that although the regulatory T cells have the capability of resolving cytokine mediated immunopathology, overactivation of the same can enhance non-clearance of the virus and facilitate other infections.…”

Section: Fig 5 Effect Of Regulatory Cells On Clinical Phenotypes A)mentioning

confidence: 99%

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

Sahoo

Hari

Jhunjhunwala

et al. 2020

Preprint

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The disease caused by SARS-CoV-2 is a global pandemic that threatens to bring long-term changes worldwide. Approximately 80% of infected patients are asymptomatic or have mild symptoms such as fever or cough, while rest of the patients have varying degrees of severity of symptoms, with 3-4% mortality rate. Severe symptoms such as pneumonia and Acute Respiratory Distress Syndrome can be caused by tissue damage mostly due to aggravated and unresolved innate and adaptive immune response, often resulting from a cytokine storm. However, the mechanistic underpinnings of such responses remain elusive, with an incomplete understanding of how an intricate interplay among infected cells and cells of innate and adaptive immune system can lead to such diverse clinicopathological outcomes. Here, we use a dynamical systems approach to dissect the emergent nonlinear intra-host dynamics among virally infected cells, the immune response to it and the consequent immunopathology. By mechanistic analysis of cell-cell interactions, we have identified key parameters affecting the diverse clinical phenotypes associated with COVID-19. This minimalistic yet rigorous model can explain the various phenotypes observed across the clinical spectrum of COVID-19, various co-morbidity risk factors such as age and obesity, and the effect of antiviral drugs on different phenotypes. It also reveals how a fine-tuned balance of infected cell killing and resolution of inflammation can lead to infection clearance, while disruptions can drive different severe phenotypes. These results will help further the case of rational selection of drug combinations that can effectively balance viral clearance and minimize tissue damage simultaneously. Significance StatementThe SARS-CoV-2 pandemic has already infected millions of people, and thousands of lives have been lost to it. The pandemic has already tested the limits of our public healthcare systems with a wide spectrum of clinicopathological symptoms and outcomes. The mechanistic underpinnings of the resultant immunopathology caused by the viral infection still remains to be elucidated. Here we propose a minimalistic but rigorous description of the interactions of the virus infected cells and the core components of the immune system that can potentially explain such diversity in the observed clinical outcomes. Our proposed framework could enable a platform to determine the efficacy of various treatment combinations and can contributes a conceptual understanding of dynamics of disease pathogenesis in SARS-CoV-2 infections.

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Co-infections: potentially lethal and unexplored in COVID-19

Cited by 350 publications

References 5 publications

Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

Novel ACE2-Independent Carbohydrate-Binding of SARS-CoV-2 Spike Protein to Host Lectins and Lung Microbiota

Bacterial co‐infections with SARS‐CoV‐2

Mechanistic modeling of the SARS-CoV-2 and immune system interplay unravels design principles for diverse clinicopathological outcomes

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