Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses — are we our own worst enemy?

Wong, Lok-Yin Roy; Perlman, Stanley

doi:10.1038/s41577-021-00656-2

Cited by 133 publications

(130 citation statements)

References 144 publications

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“…While COVID vaccination has tremendously improved the morbidity and mortality of the disease, secondary fungal infections were common and had worsened the morbidity during the full-blown pandemic until 2021 [114,118]. SARS-CoV-2 triggers host immune dysregulation, which has been postulated to contribute to fungal co-infections increasing the morbidity and mortality associated with COVID-19 [119]. Candidiasis is one of the major complications of severe COVID-19, concomitant with a longer stay in the intensive care unit, a greater usage of broad-spectrum of antibiotics, and a higher mortality rate [115,120,121].…”

Section: Candida and Other Fungal Infections In Covid-19mentioning

confidence: 99%

Fungal Colonization and Infections—Interactions with Other Human Diseases

2022

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Candida albicans is a commensal fungus that asymptomatically colonizes the skin and mucosa of 60% of healthy individuals. Breaches in the cutaneous and mucosal barriers trigger candidiasis that ranges from asymptomatic candidemia and mucosal infections to fulminant sepsis with 70% mortality rates. Fungi influence at least several diseases, in part by mechanisms such as the production of pro-carcinogenic agents, molecular mimicking, and triggering of the inflammation cascade. These processes impact the interactions among human pathogenic and resident fungi, the bacteriome in various organs/tissues, and the host immune system, dictating the outcomes of invasive infections, metabolic diseases, and cancer. Although mechanistic investigations are at stages of infancy, recent studies have advanced our understanding of host–fungal interactions, their role in immune homeostasis, and their associated pathologies. This review summarizes the role of C. albicans and other opportunistic fungi, specifically their association with various diseases, providing a glimpse at the recent developments and our current knowledge in the context of inflammatory-bowel disease (IBD), cancers, and COVID-19. Two of the most common human diseases where fungal interactions have been previously well-studied are cancer and IBD. Here we also discuss the emerging role of fungi in the ongoing and evolving pandemic of COVID-19, as it is relevant to current health affairs.

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Section: Candida and Other Fungal Infections In Covid-19mentioning

confidence: 99%

Fungal Colonization and Infections—Interactions with Other Human Diseases

2022

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“…While both acute and long-term immune perturbations in hospitalized COVID-19 patients have been reported 21,[44][45][46][47][48][49] , less is known regarding healthy recovered individuals with prior mild, non-hospitalized SARS-CoV-2 infection months after acute illness. Furthermore, most studies of post-COVID-19 have focused on adaptive and antigen-specific immunity.…”

Section: Discussionmentioning

confidence: 99%

Influenza vaccination and single cell multiomics reveal sex dimorphic immune imprints of prior mild COVID-19

Sparks¹,

Lau²,

Liu

et al. 2022

Preprint

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Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants including the recent rapid acceleration in infections. As the majority of COVID-19 patients experienced mild disease, here we use systems immunology approaches to comparatively assess the post-infection immune status (mean: 151 [5th - 95th percentile: 58 - 235] days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination (as an "immune challenge") in 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19, as compared to 40 age- and sex-matched healthy controls with no history of COVID-19. Sex-specific, temporally stable shifts in signatures of metabolism, T-cell activation, and innate immune/inflammatory processes suggest that mild COVID-19 can establish new post-infection immunological set-points. COVID-19-recovered males had an increase in CD71hi B-cells (including influenza-specific subsets) before vaccination and more robust innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of numerous innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes increased and moved away from their post-COVID-19 repressed state toward the pre-vaccination baseline of healthy controls, and these changes tended to persist to day 28 in females, hinting that the acute inflammatory responses induced by vaccination could partly reset the immune states established by prior mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19 could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

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“… 11 , 12 , 13 Evidence of viral replication has been found in lungs, central airways, central nervous system, heart, liver, kidney, and pancreas. 13 , 14 , 15 Ghodsizad and colleagues 16 found the COVID-19 PCR test was still positive 3 days postpneumonectomy, suggesting that there were potentially other sources of virus. While pneumonectomy is unlikely to lead to immediate clearance of virus, future investigations should examine whether pneumonectomy instead reduces a source of dysregulated immune response to SARS-CoV-2.…”

mentioning

confidence: 99%

“…While pneumonectomy is unlikely to lead to immediate clearance of virus, future investigations should examine whether pneumonectomy instead reduces a source of dysregulated immune response to SARS-CoV-2. 16 …”

mentioning

confidence: 99%