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Background: ABO blood groups are associated with different risk of viral infections. In vitro studies demonstrated how anti-A and anti-B antibodies neutralized the infectious capacity of SARS-CoV-2. Therefore, here we describe the inflammatory response of COVID-19 patients in the context of the blood group aiming to assess the lower severity status found in group O patients. Methods: Prospective and consecutive study including blood samples from 108 adult patients diagnosed with COVID-19 and admitted to the “Hospital Clinico Universitario” Valladolid, Spain between March 24 and April 11 2020. Patients were divided according to their ABO blood group. Plasma aliquots were analyzed, in duplicate, for the quantification of 45 mediators by MAGPIX system (Luminex). Statistical analysis was performed using the R statistical package version 4.0.2 Findings: We found a lower risk (2.16 times) of mechanical ventilation or death in patients with blood group O [Log Rank: p=0.042, Hazard Ratio: 0.463, CI 95% (0.213-1.004), p=0.050]. Moreover, 15 cytokines were significantly over-expressed (and only one under-expressed) in blood group O. Last, a multivariate model found BDNF, IL-13 and IL-27 as the best cytokines able to differentiate the immune profile based on blood group. Interpretation: Our cohort showed how blood group O was associated with both lower rates of hospital admission and a lower risk of intubation or death. Indeed, these patients produced higher amounts of cytokines in response to SARS-CoV-2, hence mounting an effective immune response which allowed them to control the viral infection and therefore decrease the risk of further complications. Funding Statement: This research was funded by Instituto de Salud Carlos III, grant number COV20/00491. Declaration of Interests: Alvaro Tamayo-Velasco declares no conflict of interest. - Maria Jesus Penarrubia-Ponce declares no conflict of interest. - Francisco Javier Alvarez declares no conflict of interest. - Hugo Gonzalo-Benito declares no conflict of interest. - Ignacio de la Fuente declares no conflict of interest. - Sonia Perez Gonzalez declares no conflict of interest. - Lucia Rico declares no conflict of interest. - Maria Teresa Jimenez-Garcia declares no conflict of interest. - Alba Sanchez-Rodriguez declares no conflict of interest. - Milagros Hijas-Villaizan declares no conflict of interest. - Marta Martin Fernandez declares no conflict of interest. - Carlos Duenas declares no conflict of interest. - Esther Gomez-Sanchez declares no conflict of interest. - Maria Heredia-Rodriguez declares no conflict of interest. - Oscar Gorgojo-Galindo declares no conflict of interest. - Itziar Fernandez declares no conflict of interest. - Lourdes del Rio declares no conflict of interest. - Irene Carnicero-Frutos declares no conflict of interest. - Maria Fe Munoz-Moreno declares no conflict of interest. - Eduardo Tamayo declares no conflict of interest. - David Bernardo declares no conflict of interest. - Pedro Martinez-Paz declares no conflict of interest. Ethics Approval Statement: The study was approved by the Hospital's Clinical Ethics Committee (CEIm) and approval was obtained from all study participants (cod: PI 20-1717).

Summary Objectives Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. Methods Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. Results The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. Conclusions The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.

Purpose There is increasing evidence on the relationship between endogenously produced immunoglobulins and the clinical outcome in septic shock (SS). Materials and methods Levels of immunoglobulin G (IgG) subclasses, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E were measured in plasma from 42 patients with SS and in 36 patients with systemic inflammatory response syndrome at diagnosis. Association of immunoglobulins levels with disease severity and outcome was evaluated. Results Eighteen patients with SS finally died. Both patients with systemic inflammatory response syndrome and SS showed subnormal levels of total IgG, IgG2, and IgM. Patients with SS who died showed the lowest levels of total IgG and IgG1. Total IgG, IgG1, IgG2, IgG3, IgG4, and IgA correlated inversely with Acute Physiology and Chronic Health Evaluation II score in SS. Univariate Cox regression analysis showed that levels of IgG1, IgG2, IgG3, IgM, IgA, and total IgG were inversely associated to the probability of death at 28 days. Multivariate analysis showed that IgG1, total IgG, IgM, and IgA behaved as independent protective factors against mortality (hazard ratio, P ): 0.23, 0.026; 0.16, 0.028; 0.11, 0.042; 0.05, 0.010, respectively, whereas IgG3 showed a protective trend also. Conclusions Our study evidenced that, in addition to IgG1, other major endogenous immunoglobulins isotypes and subclasses seem to play a beneficial role in SS.

Summary Objective As reported by WHO in its most recent report, H5N1 influenza virus affects mostly children. Differences in morbidity depending on the age could be explained, at least in part, by the differences in the immune response between children and adults. The main objective of the study was to evaluate the effect of H5N1 influenza haemagglutinin on the cytokine secretion profiles of peripheral blood mononuclear cells (PBMCs) from both children and adult healthy donors. Materials and methods We compared the profiles of 19 cytokines and chemokines released after exposure to PBMCs obtained from 30 healthy children and 30 healthy adults to a recombinant glycosylated H5 haemagglutinin after 24 h of culture with this antigen, compared to untreated control cells. Results Donors had not been exposed previously to the virus, as evidenced by the absence of haemagglutination inhibition activity in their plasma samples. Direct contact of PBMCs from both children and adults with the haemagglutinin of H5N1 virus induced increased levels of IL-6, MCP-1 and MIP-1β in the culture supernatants compared to control. Supernatants of adult PBMCs also showed increased levels of IL-8 and IP-10. Conclusions The results of our study supports the idea that, in the absence of protective immunity, the haemagglutinin of the H5N1 virus is able to induce the release of pro-inflammatory mediators by direct contact with PBMCs. Some of these mediators (IL-6, MCP-1 and MIP-1β) are induced regardless of age and have been previously reported to be associated with a poor control of viral replication in severe patients and animal models.

Purpose Critical illness results in derangements of all components of the immune response. Nonetheless, most of the efforts evaluating immune status in critically ill patients have been done in the field of sepsis. Here we have evaluated the immunity status at intensive care unit (ICU) admission in a cohort of nonseptic critically ill patients and its influence on their outcome. Material and methods Ninety patients 18 years and older admitted to our ICU were studied for levels of immunoglobulin (Ig) G, IgM, IgA, CD3 + CD4 + T cells, CD3 + CD8 + T cells, B cells, natural killer (NK) cells, and C3 and C4 complement factors in peripheral blood in the next 24 hours after admission to the ICU. Patients with infection, sepsis, immunodeficiency, or concomitant immunosuppressive therapy were excluded. Results Levels of IgM, CD3 + T cells, CD4 + T cells, CD8 + T cells, and B lymphocytes correlated inversely with age. In turn, levels of CD3 + T cells, CD4 + T cells, CD8 + T cells, and C3 factor of the complement system correlated inversely with Acute Physiology and Chronic Health Evaluation II score. Multivariate Cox regression analysis censored at 28 days evidenced that levels of IgM played a protective role, whereas levels of NK cells behaved as a risk factor for mortality. Kaplan-Meier curves showed a cutoff of 58 mg/dL for IgM and 140 cells/mm 3 for NK cells. Conclusions In conclusion, our results demonstrate that IgM plays a protective role in critically ill patients with no sepsis, whereas NK cell counts seem to play a deleterious one. Aging and severity at admission affect levels of key factors of the immune system in the blood of these patients.