Complement dysregulation is a predictive and therapeutically amenable feature of long COVID

Baillie, Kirsten; Davies, Helen E; Keat, Samuel B K; Ladell, Kristin; Miners, Kelly L; Jones, Samantha A; Mellou, Ermioni; Toonen, Erik J M; Price, David A; Morgan, B Paul; Zelek, Wioleta M

doi:10.1101/2023.10.26.23297597

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…5) contrasting observations from the acute phase 68,69 (Table 1). The complement system is also known for a complex relationship with long COVID 70 : complement dysregulation might even be predictive of long COVID 71 . The complement cascade directly associates with altered blood coagulation in COVID-19 pathology 20,72,73 , and blood coagulation, which in turn involves platelet activation.…”

Section: Discussionmentioning

confidence: 99%

Complex changes in serum protein levels in COVID-19 convalescents

Pushalkar,

Wu,

Maity

et al. 2024

Sci Rep

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The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst COVID-19 convalescents compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some alterations opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1S, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst COVID-19 convalescents. We speculate that some of these shifts might originate from a transient decrease in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and proteins related to cholesterol metabolism.

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Section: Discussionmentioning

confidence: 99%

Complex changes in serum protein levels in COVID-19 convalescents

Pushalkar,

Wu,

Maity

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…A complex interplay exists between increased Another hypothesis would be complement activation in a severe SARS-CoV-2 infection. In this sense, the chronic or persistent inflammatory response associated with the deregulation of the complement system, microthrombosis phenomena, and endothelial dysfunction [128] could trigger various manifestations in LC, according to some recent studies in which they were identified as reliable biomarkers (fractions Ba, iC3b, C5a, and TCC of the complement system) for the diagnosis of LC [129].…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

Ailioaie,

Litscher

2023

IJMS

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The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the “leaky gut” to the “leaky electron transport chain (ETC)” into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.

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“…Further, we observed significant decreases of levels for some proteins of the complement cascade amongst the COVID-19 convalescents (Figure 5) contrasting observations from the acute phase 68,69 ( Table 1C ). The complement system is also known for a complex relationship with long COVID 70 : complement dysregulation might even be predictive of long COVID 71 . The complement cascade directly associates with altered blood coagulation in COVID-19 pathology 20,72,73 , and blood coagulation, which in turn involves platelet activation.…”

Section: Discussionmentioning

confidence: 99%

Complex changes in serum protein levels in COVID-19 convalescents

Pushalkar

Maity

et al. 2022

Preprint

View full text Add to dashboard Cite

The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 recuperated COVID-19 patients and 29 age-, race-, and sex-matched healthy controls. Many proteins from pathways known to change upon acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst recuperated COVID-19 cases compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some changes opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst recuperated COVID-19 cases. We speculate that some of these changes might originate from transient decreases in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and cholesterol-metabolism-related proteins.

show abstract

Complement dysregulation is a predictive and therapeutically amenable feature of long COVID

Cited by 4 publications

References 42 publications

Complex changes in serum protein levels in COVID-19 convalescents

Complex changes in serum protein levels in COVID-19 convalescents

Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID

Complex changes in serum protein levels in COVID-19 convalescents

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