Complement Activation during Critical Illness: Current Findings and an Outlook in the Era of COVID-19.
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ABSTRACT:
SUBMITTER: Bosmann M
PROVIDER: S-EPMC7365374 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.
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Project description:We performed single cell transcriptomics in 13 acute and convalescent mild versus severe COVID-19 subjects, in healthy controls and in sujects with flu-like-illness and HBV infection to assess COVID-19-specific T cell populations und function.
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Project description:The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.
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Project description:ObjectiveRecent cohort studies have identified obesity as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). To further explore the relationship between obesity and critical illness in COVID-19, the association of BMI with baseline demographic and intensive care unit (ICU) parameters, laboratory values, and outcomes in a critically ill patient cohort was examined.MethodsIn this retrospective study, the first 277 consecutive patients admitted to Massachusetts General Hospital ICUs with laboratory-confirmed COVID-19 were examined. BMI class, initial ICU laboratory values, physiologic characteristics including gas exchange and ventilatory mechanics, and ICU interventions as clinically available were measured. Mortality, length of ICU admission, and duration of mechanical ventilation were also measured.ResultsThere was no difference found in respiratory system compliance or oxygenation between patients with and without obesity. Patients without obesity had higher initial ferritin and D-dimer levels than patients with obesity. Standard acute respiratory distress syndrome management, including prone ventilation, was equally distributed between BMI groups. There was no difference found in outcomes between BMI groups, including 30- and 60-day mortality and duration of mechanical ventilation.ConclusionsIn this cohort of critically ill patients with COVID-19, obesity was not associated with meaningful differences in respiratory physiology, inflammatory profile, or clinical outcomes.
| S-EPMC8014725 | biostudies-literature
Project description:ObjectivesTo evaluate the presence of chronic critical illness (CCI) in COVID-19 patients and compare clinical characteristics and prognosis of patients with and without CCI admitted to intensive care unit (ICU).MethodsIt was a retrospective, observational study at a university hospital ICU. Patients were accepted as CCI if they had prolonged ICU stay (≥14 days) and got ≥1 score for cardiovascular sequential organ failure assessment (SOFA) score and ≥2 score in other parameters on day 14 of ICU admission which was described as persistent organ dysfunction.Results131 of 397 (33%) patients met CCI criteria. CCI patients were older (p = 0.003) and frailer (p < 0.001). Their Acute Physiology and Chronic Health Evaluation (APACHE) II and SOFA scores were higher, PaO2/FiO2 ratio was lower (p < 0.001). Requirement of invasive mechanical ventilation (IMV), steroid use, and septic shock on admission were higher in the CCI group (p < 0.001). CCI patients had higher ICU and hospital mortality than other patients (54.2% vs. 19.9% and 55.7% vs. 22.6%, p < 0.001, respectively). Regression analysis revealed that IMV (OR: 8.40, [5.10-13.83], p < 0.001) and PaO2/FiO2 < 150 on admission (OR: 2.25, [1.36-3.71], p = 0.002) were independent predictors for CCI.DiscussionOne-third of the COVID-19 patients admitted to the ICU were considered as CCI with significantly higher ICU and hospital mortality.
| S-EPMC9996170 | biostudies-literature
Project description:Most patients who became critically ill following infection with COVID-19 develop severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of critically ill patients with COVID-19. Apart from the lung, the kidney is the second most common organ affected by COVID-19. Using immunohistochemistry for complement factors C1q, MASP-2, C3c, C3d, C4d, and C5b-9 we investigated the involvement of the complement system in six kidney biopsies with acute kidney failure in different clinical settings and three kidneys from autopsy material of patients with COVID-19. Renal tissue was analyzed for signs of renal injury by detection of thrombus formation using CD61, endothelial cell rarefaction using the marker E-26 transformation specific-related gene (ERG-) and proliferation using proliferating cell nuclear antigen (PCNA)-staining. SARS-CoV-2 was detected by in situ hybridization and immunohistochemistry. Biopsies from patients with hemolytic uremic syndrome (HUS, n = 5), severe acute tubular injury (ATI, n = 7), zero biopsies with disseminated intravascular coagulation (DIC, n = 7) and 1 year protocol biopsies from renal transplants (Ctrl, n = 7) served as controls. In the material clogging plasma adsorbers used for extracorporeal therapy of patients with COVID-19 C3 was the dominant protein but collectin 11 and MASP-2 were also identified. SARS-CoV-2 was sporadically present in varying numbers in some biopsies from patients with COVID-19. The highest frequency of CD61-positive platelets was found in peritubular capillaries and arteries of COVID-19 infected renal specimens as compared to all controls. Apart from COVID-19 specimens, MASP-2 was detected in glomeruli with DIC and ATI. In contrast, the classical pathway (i.e. C1q) was hardly seen in COVID-19 biopsies. Both C3 cleavage products C3c and C3d were strongly detected in renal arteries but also occurs in glomerular capillaries of COVID-19 biopsies, while tubular C3d was stronger than C3c in biopsies from COVID-19 patients. The membrane attack complex C5b-9, demonstrating terminal pathway activation, was predominantly deposited in COVID-19 biopsies in peritubular capillaries, renal arterioles, and tubular basement membrane with similar or even higher frequency compared to controls. In conclusion, various complement pathways were activated in COVID-19 kidneys, the lectin pathway mainly in peritubular capillaries and in part the classical pathway in renal arteries whereas the alternative pathway seem to be crucial for tubular complement activation. Therefore, activation of the complement system might be involved in the worsening of renal injury. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury.
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