The state of complement in COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Afzali B
PROVIDER: S-EPMC8672651 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
2021-06-08 | GSE175450 | GEO
Project description:To analyse gene expression pattern in different disease state of COVID-19 patients. Experimental workflow: 1) rRNA was removed by using RNase H method, 2) QAIseq FastSelect RNA Removal Kit was used to remove the Globin RNA, 3) The purified fragmented cDNA was combined with End Repair Mix, then add A-Tailing Mix, mix well by pipetting, incubation, 4) PCR amplification, 5) Library quality control and pooling cyclization, 6) The RNA library was sequenced by MGI2000 PE100 platform with 100bp paired-end reads. Analysis steps: 1) RNA-seq raw sequencing reads were filtered by SOAPnuke (Li et al., 2008) to remove reads with sequencing adapter, with low-quality base ratio (base quality < 5) > 20%, and with unknown base (’N’ base) ratio > 5%. 2) Reads aligned to rRNA by Bowtie2 (v2.2.5) (Langmead and Salzberg, 2012) were removed. 3) The clean reads were mapped to the reference genome using HISAT2 (Kim et al., 2015). Bowtie2 (v2.2.5) was applied to align the clean reads to the transcriptome. 4)Then the gene expression level (FPKM) was determined by RSEM (Li and Dewey, 2011). Genes with FPKM > 0.1 in at least one sample were retained.
2021-03-24 | E-MTAB-10298 | biostudies-arrayexpress
Project description:To analyse gene expression pattern in different disease state of COVID-19 patients. Experimental workflow: 1) Small RNA enrichment and purification, 2) Adaptor ligation and Unique molecular identifiers (UMI) labeled Primer addition, 3) RT-PCR, Library quantitation and pooling cyclization, 4) Library quality control, 5) Small RNAs were sequenced by BGI500 platform with 50bp single-end reads resulting in at least 20M reads for each sample. Analysis steps: 1) Small RNA raw sequencing reads with low quality tags (which have more than four bases whose quality is less than ten, or have more than six bases with a quality less than thirteen.), the reads with poly A tags, and the tags without 3’ primer or tags shorter than 18nt were removed. 2) After data filtering, the clean reads were mapped to the reference genome and other sRNA database including miRbase, siRNA, piRNA and snoRNA using Bowtie2 (Langmead and Salzberg, 2012). Particularly, cmsearch (Nawrocki and Eddy, 2013) was performed for Rfam mapping. 3) The small RNA expression level was calculated by counting absolute numbers of molecules using unique molecular identifiers (UMI, 8-10nt). MiRNA with UMI count lager than 1 in at least one sample were considered as expressed.
2021-03-24 | E-MTAB-10299 | biostudies-arrayexpress
Project description:Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.
| S-EPMC8242600 | biostudies-literature
Project description: Not available
| S-BSST563 | biostudies-other
Project description:Background: The complement system is made up of an abundance of unique plasma proteins that play an important role in innate immunity and inflammation, aiding in the fight against pathogenic microbes and viral diseases. The purpose of this study was to evaluate the serum complement C4 concentration in COVID-19 patients in Khartoum and compare them to healthy controls. Methods: A total of 100 samples were collected, 50 samples from COVID-19 patients who presented as cases and 50 samples from people who were evidently healthy. Overall, 33 (66%) the patient populations in the case group were not in the hospital's intensive care unit (ICU), compared to 17 (34%) who were. The concentrations of C4 in each serum sample were calculated in milligrams per deciliter. SPSS version (20) was used to analyze the data. Results: The means level of complement C4 (mg/dL) were 37.44 ±18.618, 23.90 ±10.229 in the case group and in the control group, respectively. There was a statistically significant difference in complement C4 level between case and control (p-values ≤0.01). In addition, the mean complement C4 level in the ICU and non-ICU case groups was 25.00±17.85 and 43.85±15.712 mg/dL, respectively. There was a statistically significant variance in complement C4 level between ICU and non-ICU (p-values ≤0.01). Furthermore, the cases were divided into four age groups: 20-40, 40-60, 60-80, and over 80 years old. The one-way ANOVA test showed no statistically significant differences between age categories in complement C4 level (P = 0.735) Conclusions: The case group had a higher mean level of complement C4 than the control group, which could be understood by the stimulation of the complement cascade during the COVID-19 illness. Furthermore, the complement C4 level in severe COVID-19 patients was lower than in non-severe COVID-19.
| S-EPMC10390792 | biostudies-literature
Project description:A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.
| S-EPMC7323084 | biostudies-literature
Project description:Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune signature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutro-phil immune suppression loss associated with fatal clinical outcome in severe patients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allele, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of my-eloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
2021-01-27 | GSE157344 | GEO
Project description: Not available
| S-BSST416 | biostudies-other
Project description:Complement is integral to a healthy functioning immune system and orchestrates various innate and adaptive responses against viruses and other pathogens. Despite its importance, the potential beneficial role of complement in immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been overshadowed by reports of extensive complement activation in severe coronavirus disease 2019 (COVID-19) patients. Here, we hypothesize that complement may also have a protective role and could function to enhance virus neutralization by antibodies, promote virus phagocytosis by immune cells, and lysis of virus. These functions might be exploited in the development of effective therapeutics and vaccines against SARS-CoV-2.
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