Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can

Tamayo-Velasco, Álvaro; Ponce, María Jesús Peñarrubia; Álvarez, Francisco; Gonzalo-Benito, Hugo; Fuente, Ignacio de la; Pérez-González, Sonia; Rico, Lucía; García, María Teresa Jiménez; Rodríguez, Alba Sánchez; Villaizan, Milagros Hijas; Martín-Fernández, Marta; Dueñas, Carlos; Gómez-Sánchez, Esther; Heredia-Rodríguez, María; Gorgojo-Galindo, Óscar; Fernández, Itziar; Río, Lourdes Del; Carnicero-Frutos, Irene; Muñoz-Moreno, María Fe; Tamayo, Eduardo; Bernardo, David; Martínez-Paz, Pedro

doi:10.3389/fimmu.2021.726283

Cited by 13 publications

(17 citation statements)

References 37 publications

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“…Some questions might be interesting to consider and could open future investigations in this area. The first is related to the exact mechanism by which natural antibodies from the ABO blood system avoid the interaction between the S protein of the virus and ACE2 on the cell surface ( 20 , 24 , 43 , 44 ). An experimental model is required to understand whether antibodies only block the S protein, perhaps together with SARS-CoV-2, to competitively inhibit ACE2 in host cells or whether both molecular mechanisms are possible.…”

Section: Discussionmentioning

confidence: 99%

“…For example, suppose our natural anti-A or -B antibodies would constantly bind or block ACE2. In that case, O blood group individuals could present persistent ACE2 downregulation, resulting in increased production of multiple inflammatory cytokines ( 44 ). Furthermore, these antibodies might be associated with protection against cardiovascular diseases, similar to ACE inhibitors, conferring a lower risk in the O blood group.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, natural anti-A or -B antibodies can directly bind to the ACE2 glycosylated region ( 43 ). In this case, possible competitive inhibition of ACE2 by both natural (anti-A/anti-B) antibodies and SARS-CoV-2 may induce early ACE2 downregulation in blood group O, increasing the production of multiple inflammatory cytokines ( 44 ) in the first step of the infection. Patients with the O blood group suffered a consequent cytokine drop during the hospital stay, while non-O patients maintained their cytokine levels associated with hyperinflammation.…”

Section: Relationship Between Abo Blood Group and Covid-19 Severity A...mentioning

confidence: 99%

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ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

et al. 2022

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The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Relationship Between Abo Blood Group and Covid-19 Severity A...mentioning

confidence: 99%

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ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

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“…The occurrence of thrombotic events is more frequently associated with advanced age, male sex, and the presence of TE risk factors [ 14 , 30 , 31 ]. These are essentially the same factors that are associated with severe COVID-19 [ 1 , 5 , 33 , 34 ]. Nevertheless, we observed a higher Charlson index, older age, and a higher proportion of males as well as poorer in-hospital meters in the TE group.…”

Section: Discussionmentioning

confidence: 99%

Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic

Tamayo-Velasco

Bombín-Canal

Cebeira

et al. 2022

JCM

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The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12–2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.

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“…In addition, cytokines, such as Hepatocyte Growth Factor (HGF), Interleukin (IL)-1α, and IL-27, appear to play an important role in severity or mortality risk [13]. In fact, recent publications have described the relationship between the O blood group and cytokine profile with lower rates of hospital admission and risk of intubation or death in COVID-19 patients [14].…”

Section: Introductionmentioning

confidence: 99%

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles

Gorgojo-Galindo

Martín-Fernández

Peñarrubia-Ponce³

et al. 2021

JCM

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Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. Methods: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. Results: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI—(1.28–42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. Conclusions: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

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Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can

Cited by 13 publications

References 37 publications

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points

Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles

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