Association between markers of immune response at hospital admission and COVID‐19 disease severity and mortality: A meta‐analysis and meta‐regression

Khinda, Jaskaran; Janjua, Naveed Z.; Cheng, Shannon S.Y.; Heuvel, Edwin R. van den; Bhatti, Parveen; Darvishian, Maryam

doi:10.1002/jmv.26411

Cited by 52 publications

(55 citation statements)

References 116 publications

(201 reference statements)

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“…In our study, among acute-phase proteins, exosomal CRP resulted in 122-fold and 40-fold up-regulation in critical and non-critical patients, respectively. A preliminary analysis of hematological and inflammatory parameters was associated with elevated CRP, IL-6, and NLR values and with worse outcomes as well as a lack of response to treatment ( Montesarchio et al, 2020 ; Khinda et al, 2020 ). High C-reactive protein independently predicted the risk of mortality in a cohort of 183 COVID-19 patients ( Rolla et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Barberis

Vanella

Falasca

et al. 2021

Front. Mol. Biosci.

171

188

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Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes’ response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes’ involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19–associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers—such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component—were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes’ significant contribution to several processes—such as inflammation, coagulation, and immunomodulation—during SARS-CoV-2 infection. The study’s data are available via ProteomeXchange with the identifier PXD021144.

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Section: Discussionmentioning

confidence: 99%

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Barberis

Vanella

Falasca

et al. 2021

Front. Mol. Biosci.

171

188

View full text Add to dashboard Cite

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“…These findings underline that the early inflammatory host response to SARS-CoV-2 determines the course of disease more than pathogen factors such as initial SARS-CoV-2 RNA concentration [ 2 , 28 , 29 ]. A short duration of symptoms before admission possibly reflects a rapid increase of the level of inflammation and might serve as an easy to assess prognostic factor for clinical deterioration, a finding that merits further exploration [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

et al. 2021

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Purpose Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10–1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00–16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26–46.75, vs 18 days, IQR 16–46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6–15.5) for non-IMV and 49.5 days (IQR 36.8–82.5) for IMV patients. Conclusions Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19.

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“…The lactate dehydrogenase (LDH), a marker of tissue damage, was also associated with severe COVID-19 patients [ 14 , 25 , 26 ]. The mean value in patients with mild disease was 305.6 U/L versus 542.5 U/L in extremely severe ones.…”

Section: Methodsmentioning

confidence: 99%

“…In a recent meta-analysis, the biggest difference for severity was for ferritin at 423.13 ng/mL (281.4–582.85) [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It

Cappanera

Palumbo

Kwan

et al. 2021

JCM

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The “cytokine storm” (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes. We retrospectively analyzed 31 patients admitted to Infectious Disease Department in “St. Maria” Hospital in Terni with confirmed SARS-CoV-2 infections, and analyzed the “CS score” (CSs) and the severity of COVID-19. Then we conducted a prospective study of COVID-19 patients admitted after the definition of the CSscore. This is the first study that proposes and applies a new score to quickly identify COVID-19 patients who are in a hyperinflammation stage, to rapidly treat them in order to reduce the risk of intubation. CSs can accurately identify COVID-19 patients in the early stages of a CS, to conduct timely, safe, and effect administration of immunomodulators, corticosteroids, and cytokine antagonists, to prevent progression and reduce mortality.

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Association between markers of immune response at hospital admission and COVID‐19 disease severity and mortality: A meta‐analysis and meta‐regression

Cited by 52 publications

References 116 publications

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It

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