Corpus overview


MeSH Disease

Human Phenotype


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    IgG seroprevalence SERO against SARS-CoV-2 in a cohort of 449 non-hospitalized, high-risk exposure individuals.

    Authors: Patricia Torres Martínez; Paula Diaque García; María Rubio Salas; Raquel Rodríguez Sánchez; Felipe García; Miguel Ángel Llamas; Paula Saz-Leal; CArlos del Fresno

    doi:10.21203/ Date: 2020-08-04 Source: ResearchSquare

    COVID-19 pandemic caused by SARS-CoV-2 led the Spanish government to impose a national lockdown in an attempt to control the spread of the infection MESHD. Mobility restrictions but also the requirement of a medical prescription to gain access to serological testing SERO for COVID-19 were included among the measures. Under this scenario, between April 15th to June 15th, 2020, we performed a seroprevalence SERO observational study including 449 individuals that fulfill prescription requirements: manifesting COVID-19 compatible symptoms, being in contact with a COVID-19 confirmed case TRANS or belonging to essential occupations including healthcare workers, firefighters or public safety personnel such as police. Importantly, none of the participants was hospitalized. Altogether, we studied this specific, non-commonly addressed cohort for SARS-CoV-2 seroprevalence SERO, uncovering intrinsic features of great demographic interest. The overall rate of IgG seropositivity was 33.69% (95% CI: 29.27 – 38.21). This seroprevalence SERO was comparable between different occupations performed by the participants. However, contacts with confirmed cases TRANS associated positively with IgG+ results, with stronger correlation if being a household member. The number of symptoms also correlated positively with IgG+ prevalence SERO. Ageusia/anosmia, pneumonia MESHD anosmia HP, pneumonia HP and cutaneous manifestations were the top-three symptoms that most strongly associated with IgG+ seroprevalence SERO. However, while pneumonia HP pneumonia MESHD and cutaneous manifestations were barely present in our cohort, fever HP fever MESHD, ageusia/anosmia MESHD anosmia HP and asthenia HP were the most frequently symptoms described within IgG+ subjects. Therefore, our data illustrate how specific cohorts display heterogeneous characteristics that should be taken into account when identifying population seroprevalence SERO against SARS-CoV-2 and key defining symptoms for COVID-19.

    Integration of heparin-binding protein and interleukin-6 in the early prediction of respiratory failure HP respiratory failure MESHD and mortality in pneumonia HP pneumonia MESHD by SARS-CoV-2 (COVID-19)

    Authors: Maria Saridaki; Simeon Metallidis; Sotiria Grigiropoulou; Emmanouil Vrentzos; Malvina Lada; Katerina Argyraki; Olga Tsachouridou; Anna Georgiadou; Anil Vasishta; Evangelos J. Giamarellos-Bourboulis

    doi:10.21203/ Date: 2020-08-03 Source: ResearchSquare

    Purpose Recent publications on the probable role of heparin-binding protein (HBP) as a biomarker in sepsis HP sepsis MESHD prompted us to investigate its diagnostic and prognostic performance SERO in severe COVID-19Methods HBP and IL-6 were measured by immunoassays SERO at admission and on day 7 in 178 patients with pneumonia HP pneumonia MESHD by SARS-CoV-2. Patients were classified into non- sepsis HP sepsis MESHD and sepsis HP sepsis MESHD as per the Sepsis HP-3 definitions and were followed-up for the development of severe respiratory failure HP respiratory failure MESHD ( SRF MESHD) and for outcome. Results were confirmed by multivariate analyses.Results HBP was significantly higher in patients classified as having sepsis HP sepsis MESHD and was negatively associated with the oxygenation ratio and positively associated with creatinine and lactate. Logistic regression analysis evidenced admission HBP more than 18 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for the development of SRP. Their integration prognosticated SRF MESHD with respective sensitivity SERO, specificity, positive predictive value SERO and negative predictive 59.1%, 96.3%, 83.9% and 87.8%. Cox regression analysis evidenced admission HBP more than 35 ng/ml and IL-6 more than 30 pg/ml as independent risk factors for 28-day mortality. Their integration prognosticated 28-day mortality with respective sensitivity SERO, specificity, positive predictive value SERO and negative predictive 69.2%, 92.7%, 42.9% and 97.5%. HBP remained unchanged over-time course. Conclusion A prediction score of the disposition of patients with COVID-19 is proposed taking into consideration admission levels of IL-6 and HBP. Using different cut-offs the score may predict the likelihood for SRF MESHD and for 28-day outcome. 

    SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic

    Authors: Jochen Schneider; Hrvoje Mijocevic; Kurt Ulm; Bernhardt Ulm; Simon Weidlich; Silvia Wuerstle; Kathrin Rothe; Matthias Treiber; Roman Iakoubov; Ulrich Mayr; Tobias Lahmer; Sebastian Rasch; Alexander Herner; Egon Burian; Fabian Lohöfer; Rickmer Braren; Marcus Makowski; Roland Schmid; Ulrike Protzer; Christoph Spinner; Fabian Geisler

    doi:10.21203/ Date: 2020-07-30 Source: ResearchSquare

    Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates HP with high sensitivity SERO, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR. Methods: IgM/IgG chemiluminescent immunoassay SERO was performed for 107 patients with confirmed (group A: PCR+; CT±) and 46 patients with suspected (group B: repetitive PCR-; CT+) COVID-19, admitted to a German university hospital during the pandemic’s first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia HP pneumonia MESHD was used to assess the probability of COVID-19. Results: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset TRANS (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p<0.01). Compared to hospitalized patients with a non-complicated course, seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 9%, 26%, 65%, 77% and 92% in group A, compared with 0%, 10%, 20%, 40% and 50% in group B (p<0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology >14 days after symptom onset TRANS (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity SERO of SARS-CoV-2 serology was superior to PCR >17d after symptom onset TRANS. Conclusions: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates HP in PCR negative patients. However, sensitivity SERO of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2 nd week following symptom onset TRANS.

    Overweight HP/ obesity HP obesity MESHD as the potentially most important lifestyle factor associated with signs of pneumonia HP pneumonia MESHD in COVID-19

    Authors: Vanessa Sacco; Barbara Rauch; Christina Gar; Stefanie Haschka; Anne L Potzel; Stefanie Kern-Matschilles; Friederike Banning; Irina Benz; Mandy Meisel; Jochen Seissler; Andreas Lechner

    doi:10.1101/2020.07.23.20161042 Date: 2020-07-24 Source: medRxiv

    Objective The occurrence of pneumonia HP pneumonia MESHD separates severe cases of COVID-19 from the majority of cases with mild disease. However, the factors determining whether or not pneumonia HP develops remain to be fully uncovered. We therefore explored the associations of several lifestyle factors with signs of pneumonia HP pneumonia MESHD in COVID-19. Methods Between May and July 2020, we conducted an online survey of 201 adults TRANS in Germany who had recently gone through COVID-19, predominantly as outpatients. Of these, 165 had a PCR-based diagnosis and 36 had a retrospective diagnosis by antibody testing SERO. The survey covered demographic information, eight lifestyle factors, comorbidities and medication use. We defined the main outcome as the presence vs. the absence of signs of pneumonia HP pneumonia MESHD, represented by dyspnea HP dyspnea MESHD, the requirement for oxygen therapy or intubation. Results Signs of pneumonia HP pneumonia MESHD occurred in 39 of the 165 individuals with a PCR-based diagnosis of COVID-19 (23.6%). Among the lifestyle factors examined, only overweight HP/ obesity HP obesity MESHD associated with signs of pneumonia HP pneumonia MESHD (odds ratio 2.68 (1.29 - 5.59) p=0.008). The observed association remained significant after multivariate adjustment, with BMI as a metric variable, and also after including the antibody SERO-positive individuals into the analysis. Conclusions This exploratory study finds an association of overweight HP/ obesity HP obesity MESHD with signs of pneumonia HP pneumonia MESHD in COVID-19. This finding suggests that a signal proportional to body fat mass, such as the hormone leptin, impairs the body's ability to clear SARS-CoV-2 before pneumonia HP develops. This hypothesis concurs with previous work and should be investigated further to possibly reduce the proportion of severe cases of COVID-19.


    Authors: Francesca Crovetto; Fatima Crispi; Elisa Llurba; Francesc Figueras; Maria Dolores Gomez-Roig; Eduard Gratacos

    doi:10.1101/2020.06.17.20134098 Date: 2020-06-19 Source: medRxiv

    Introduction: Case registries of pregnant women diagnosed with coronavirus disease MESHD (COVID-19) by polymerase chain reaction (PCR) have reported that the majority experienced mild infection MESHD, but up to 9% may require critical care. Most COVID-19 cases published were in the third trimester of pregnancy, which could reflect reporting bias, higher risk of infection TRANS risk of infection TRANS infection MESHD or increased disease severity in late pregnancy. Seroprevalence SERO studies may allow reliable estimates of the susceptibility to infection MESHD and clinical spectrum since they include asymptomatic TRANS and mild infections not tested for PCR. We evaluated the seroprevalence SERO and clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD in pregnant women in the first and third trimester. Methods: The study was approved by the Institutional Review Board at each institution and informed consent was obtained. We recruited 874 consecutive pregnancies attending for first trimester screening (10-16 weeks of gestation, n=372) or delivery (n=502) from April 14 to May 5. All women were interviewed with a structured questionnaire for COVID-19 symptoms two months prior to sampling. SARS-CoV-2 IgG and IgM/IgA antibodies were tested SERO (COVID-19 VIRCLIA Monotest, Vircell Microbiologist, Spain; reported sensitivity SERO 70% IgG and 89% IgM/IgA, and specificity 89% and 99% respectively). Indeterminate results were re-tested (VITROS Immunodiagnostic Products Anti-SARS-CoV2 Total Tests, Ortho Clinical Diagnostics, USA; 100% sensitivity SERO and specificity) and re-classified as positive or negative. Women with COVID-19 were diagnosed and managed according to standard protocols and guidelines3,4. Statistical differences were tested using the {chi}2 test or Student t-test as appropriate (p<0.05). Results: A total of 125 of 874 women (14.3%) were positive for either IgG or IgM/IgA SARS-CoV-2 antibodies SERO, 54/372 (14.5%) in the first and 71/502 (14.1%) in the third trimester. A total of 75/125 (60%) reported no symptoms of COVID-19 in the past 2 months, whereas 44 (35.2%) reported one or more symptoms, of which 31 (24.8%) had at least 3 symptoms or anosmia HP anosmia MESHD and 8 (6.4%) dyspnea HP dyspnea MESHD. Overall, 7 women (5.6%) were admitted for persistent fever HP fever MESHD despite paracetamol and dyspnea HP dyspnea MESHD, of which 3 had signs of pneumonia HP pneumonia MESHD on chest radiography. All 3 had criteria for severity (bilateral chest condensation, respiratory rate>30 and leukopenia HP leukopenia MESHD) and required oxygen support but not critical care or mechanical ventilation, and they were all discharged well. The rates of symptomatic infection MESHD, hospital admission or dyspnea HP dyspnea MESHD were significantly higher in third trimester women (Table and Figure). Discussion: The 14.3% seroprevalence SERO of SARS-COV-2 in pregnant women in this study was substantially larger than the contemporary rates of PCR positive cases (0.78%) reported for women 20-40y in Barcelona. The data confirm that COVID-19 is asymptomatic TRANS in the majority of pregnant women6 and illustrate the value of seroprevalence SERO studies to capture the high proportion of asymptomatic TRANS or mild infections MESHD. In this study, none of the 125 pregnant women with SARS-CoV-2 infection MESHD required critical care as compared to 9% reported in cases diagnosed with PCR. However, the proportion of infections MESHD with symptoms or dyspnea HP dyspnea MESHD was remarkably higher in the third trimester, and these results are in line with COVID-19 registries, reporting that 81% of hospitalized women were in late pregnancy or peripartum. These results provide reassuring information that, even in settings with a high prevalence SERO, SARS-CoV-2 infection MESHD in pregnancy mostly presents with asymptomatic TRANS or mild clinical forms. The susceptibility to infection seemed to be the same in the first and the third trimesters of gestation. The data further suggest that, as with other respiratory viruses, COVID-19 could be more severe and require increased surveillance in late pregnancy. These findings should be confirmed and extended with larger consecutive prevalence SERO studies in pregnancy.

    Evaluation of two commercial multiplex PCR tests for the diagnosis of acute respiratory infections MESHD in hospitalized children TRANS

    Authors: Le Wang; Shuo Yang; Xiaotong Yan; Teng Liu; Mengchuan Zhao; Dianping You; Guixia Li

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    Background Acute respiratory tract infections HP respiratory tract infections MESHD (ARTI), including the common cold, pharyngitis HP pharyngitis MESHD, sinusitis HP sinusitis MESHD, otitis media HP otitis media MESHD, tonsillitis HP tonsillitis MESHD, bronchiolitis HP bronchiolitis MESHD and pneumonia HP pneumonia MESHD are the most common diagnoses among pediatric patients and account for the majority of antibiotic prescriptions. A clear and rapid diagnosis is the key to preventing antibiotic abuse. Recently, based on different detection principles, many multi-target molecular analyses that can simultaneously detect dozens of pathogens have been developed, thereby greatly improving sensitivity SERO and shortening turnaround time. In this work, we conducted a head-to-head comparative study between melting curve analysis (MCA) and capillary electrophoresis assay (CE) in the detection of nine respiratory pathogens in sputum samples collected from hospitalized ARTI childre TRANS.Methods Through MCA and CE analysis, nine common respiratory pathogens were tested on hospitalized children TRANS under the age TRANS of 13 who met the ARTI criteria.Results A total of 237 children TRANS with sputum specimens were tested. For all the targets combined, the positive detection rate of XYRes-MCA was significantly higher than ResP-CE (72.2% vs. 63.7%, p = .002). Some pathogens were detected more often with MCA, such as parainfluenza virus, influenza B and coronavirus, and some pathogens do the opposite, such as adenovirus and influenza A (all p < .01). Very good kappa values for most of pathogens were observed, except for Influenza B and coronavirus (both κ = .39).Conclusions Multiplex melting curve and capillary electrophoresis assays performed similarly for the detection of common respiratory pathogens in hospitalized children TRANS, except for Influenza B and coronavirus. Higher sensitivity SERO was observed in the melting curve assay. By using this sensitive and rapid test SERO, it may improv patient prognosis and antimicrobial management.

    Kinetics of the humoral immune response to SARS-CoV-2: comparative analytical performance SERO of seven commercial serology tests

    Authors: Pauline H. Herroelen; Geert Antoine Martens; Dieter De Smet; Koen Swaerts; An-Sofie Decavele

    doi:10.1101/2020.06.09.20124719 Date: 2020-06-12 Source: medRxiv

    Background SARS-CoV-2 serology tests are clinically useful to document a prior SARS-CoV-2 infection MESHD in patients with no or inconclusive PCR results and suspected COVID-19 disease or sequelae. Data are urgently needed to select the assays with optimal sensitivity SERO at acceptable specificity. Methods A comparative analysis of analytical sensitivity SERO was performed of seven commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with PCR-confirmed SARS-CoV-2 infection MESHD, composed of 71 patients hospitalized for COVID-19 pneumonia HP pneumonia MESHD and 64 healthcare workers with paucisymptomatic infections. The kinetics of IgA/IgM/IgG seroconversion to viral N- and S-protein epitopes were studied from 0 to 54 days after symptom onset TRANS. Specificity was verified on 57 pre-pandemic samples. Results Wantai SARS-COV-2 Ab ELISA SERO and Orient Gene COVID-19 IgG/IgM Rapid Test SERO achieved a superior overall sensitivity SERO. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA also showed acceptable sensitivity SERO (>95%) versus the consensus result of all assays from 10 days post symptom onset TRANS. Optimal specificity (>98%) was achieved only by Wantai SARS-COV-2 Ab ELISA SERO, Elecsys Anti-SARS-CoV-2 assay and Innovita 2019-nCoV Ab rapid test SERO. LIAISON SARS-CoV-2 S1/S2 IgG showed a significantly lower sensitivity SERO as compared to all other assays. Lack of seroconversion by any test was seen in 1.4% of hospitalized and 4.7% of paucisymptomatic infections. Within 10 days from symptom onset TRANS, only the Wantai SARS-COV-2 Ab ELISA SERO has acceptable sensitivity SERO. Conclusions Wantai SARS-COV-2 Ab ELISA SERO and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific screening of a SARS-CoV-2 infection MESHD from 10 days after symptom onset TRANS.

    SARS-CoV-2 Serology Results in the First COVID-19 Case in California: A Case Report and Recommendations for Serology Testing and Interpretation

    Authors: Richard B. Lanman, MD; Todd H. Lanman

    doi:10.21203/ Date: 2020-06-12 Source: ResearchSquare

    Background: As countries in COVID-19 pandemic lockdown begin relaxation of shelter-in-place mitigation strategies, the role of serology testing escalates in importance. However, there are no clear guidelines as to when to use qualitative rapid diagnostic serology tests (RDTs) vs. SARS-CoV-2 viral RNA load (PCR) tests as an aid in acute diagnosis of patients presenting with flu-like symptoms, nor how to interpret serology test results in asymptomatic TRANS individuals or those with atypical COVID-19 symptomatology. Here we describe, in the context of the likely first case of COVID-19 in California, with an atypical presentation and not tested acutely, who nearly 3 months later was found to be IgM- and IgG+ positive for SARS-CoV-2 antibodies SERO, highlighting the role of RDT- based serology testing SERO and interpretation in retrospective diagnosis.Case Presentation: A 62-year-old male TRANS practicing neurosurgeon had onset of flu-like symptoms on January 20 with fatigue HP fatigue MESHD, slight cough HP only on deep inspiration, intermittent pleuritic chest pain MESHD chest pain HP unrelated to exertion, dyspnea HP dyspnea MESHD, and night sweats HP but without fever HP fever MESHD, sore throat or rhinorrhea HP rhinorrhea MESHD. He had recently traveled TRANS abroad but not to China. CT scan revealed right lower lobe infiltrate and effusion. Because of atypical symptoms, and low prevalence SERO of COVID-19 in January, community acquired pneumonia HP pneumonia MESHD was diagnosed and one week of doxycycline was prescribed without relief, followed by a second week of azithromycin with symptom remission. Three months later the physician-patient (author THL), tested positive for SARS-CoV-2 antibodies SERO by a serology point-of-care rapid diagnostic test (RDT).Conclusions: Serology testing may be an aid in acute diagnosis of COVID-19, especially in patients with atypical presentations, as well as in assessment of asymptomatic TRANS higher-risk persons such as healthcare workers for prior infection MESHD. Recommendations for serology testing and interpretation are explicated.

    A case of COVID - 19 with Imported Falciparum Malaria Infection MESHD is Reported

    Authors: Mingchao Zhu; Ya Zhu; Jue Zhang; Weiping Liu

    doi:10.21203/ Date: 2020-06-01 Source: ResearchSquare

    Background During the COVID − 19 outbreak, limited medical resources in the short term and inadequate experience in dealing with major new public health events may lead to the neglect of some other infectious diseases MESHD, such as malaria MESHD, leading to the risk of the spread of infectious diseases MESHD.Therefore, it is particularly important to formulate classified guidance, take scientific prevention and control measures in a comprehensive manner, strengthen the screening of malaria MESHD patients and provide access to medical treatment during the outbreak.Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for a falciparum malaria infection MESHD patient with laboratory-confirmed COVID − 19 pneumonia HP pneumonia MESHD .Results Patient's serum SERO novel coronavirus antibody tested SERO positive for IgG and weakly positive for IgM that were positive for severe acute respiratory syndrome MESHD coronavirus 2 [SARS-CoV-2],the blood SERO samples were classified as plasmodium falciparum by RT-PCR.Conclusions The patient when workers infected with p. falciparum in Africa, malaria MESHD recurrence after back to China, after antimalarial treatment in tianmen city first people's hospital, after an outbreak in wuhan will be coronavirus, and symptoms of COVID − 19, but soon be cured patients, to explore the diagnosis and treatment of antimalarial drugs in COVID − 19 patients with the role, for further in-depth study of COVID − 19 treatment provides a good example.

    A systems approach to inflammation MESHD identifies therapeutic targets in SARS-CoV-2 infection MESHD

    Authors: Frank L. van de Veerdonk; Nico A.F. Janssen; Inge Grondman; Aline H. de Nooijer; Valerie A.C.M. Koeken; Vasiliki Matzaraki; Collins K. Boahen; Vinod Kumar; Matthijs Kox; Hans J.P.M. Koenen; Ruben L. Smeets; Irma Joosten; Roger J.M. Brüggemann; Ilse J.E. Kouijzer; Hans G. van der Hoeven; Jeroen A. Schouten; Tim Frenzel; Monique Reijers; Wouter Hoefsloot; Anton S.M. Dofferhoff; Angèle P.M. Kerckhoffs; Marc J.T. Blaauw; Karin Veerman; Coen Maas; Arjan H. Schoneveld; Imo E. Hoefer; Lennie P.G. Derde; Loek Willems; Erik Toonen; Marcel van Deuren; Jos W.M. van der Meer; Reinout van Crevel; Evangelos J. Giamarellos-Bourboulis; Leo A.B. Joosten; Michel M. van den Heuvel; Jacobien Hoogerwerf; Quirijn de Mast; Peter Pickkers; Mihai G. Netea

    doi:10.1101/2020.05.23.20110916 Date: 2020-05-24 Source: medRxiv

    Background Infection with SARS-CoV-2 manifests itself as a mild respiratory tract infection HP respiratory tract infection MESHD in the majority of individuals, which progresses to a severe pneumonia HP pneumonia MESHD and acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) in 10-15% of patients. Inflammation plays a crucial role in the pathogenesis of ARDS MESHD, with immune dysregulation HP in severe COVID-19 leading to a hyperinflammatory response. A comprehensive understanding of the inflammatory process in COVID-19 is lacking. Methods In this prospective, multicenter observational study, patients with PCR-proven or clinically presumed COVID-19 admitted to the intensive care unit (ICU) or clinical wards were included. Demographic and clinical data were obtained and plasma SERO was serially collected. Concentrations of IL-6, TNF-, complement components C3a, C3c and the terminal complement complex (TCC) were determined in plasma SERO by ELISA SERO. Additionally, 269 circulating biomarkers were assessed using targeted proteomics. Results were compared between ICU and non ICU patients. Findings A total of 119 (38 ICU and 91 non ICU) patients were included. IL-6 plasma SERO concentrations were elevated in COVID-19 (ICU vs. non ICU, median 174.5 pg/ml [IQR 94.5-376.3 vs. 40.0 pg/ml [16.5-81.0]), whereas TNF- concentrations were relatively low and not different between ICU and non ICU patients (median 24.0 pg/ml [IQR 16.5-33.5] and 21.5 pg/ml [IQR 16.0-33.5], respectively). C3a and terminal complement complex (TCC) concentrations were significantly higher in ICU vs. non ICU patients (median 556.0 ng/ml [IQR 333.3-712.5]) vs. 266.5 ng/ml [IQR 191.5-384.0 for C3a and 4506 mAU/ml [IQR 3661-6595 vs. 3582 mAU/ml [IQR 2947-4300] for TCC) on the first day of blood SERO sampling. Targeted proteomics demonstrated that IL-6 (logFC 2.2), several chemokines and hepatocyte growth factor (logFC 1.4) were significantly upregulated in ICU vs. non ICU patients. In contrast, stem cell factor was significantly downregulated (logFC -1.3) in ICU vs. non ICU patients, as were DPP4 (logFC -0.4) and protein C inhibitor (log FC -1.0), the latter two factors also being involved in the regulation of the kinin-kallikrein pathway. Unsupervised clustering pointed towards a homogeneous pathogenetic mechanism in the majority of patients infected with SARS-CoV-2, with patient clustering mainly based on disease severity. Interpretation We identified important pathways involved in dysregulation of inflammation MESHD in patients with severe COVID-19, including the IL-6, complement system and kinin-kallikrein pathways. Our findings may aid the development of new approaches to host-directed therapy.

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MeSH Disease
Human Phenotype

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