key: cord-1042145-7u5hfqbq
authors: Diaz-Salazar, S.; Navas, R.; Sainz-Maza, L.; Fierro, P.; Maamar, M.; Artime, A.; Basterrechea, H.; Petitta, B.; Lamadrid, C.; Pedraja, L.; Gandara-Samperio, C.; Pini, S.; Olmos, J. M.; Ramos-Barron, C.; Pariente, E.; Hernandez, J. L.
title: Blood group O and post-COVID-19 syndrome
date: 2022-03-12
journal: nan
DOI: 10.1101/2022.03.10.22272197
sha: 63cbc85667ecf8f0364024f726f887f276210b8b
doc_id: 1042145
cord_uid: 7u5hfqbq

Objective The ABO system modulates the inflammatory response, and it has been involved in SARS-CoV-2 infection. There is increasing evidence of underlying immune-inflammatory mechanisms in post-COVID-19 syndrome (PCS). Blood group O seems to protect against COVID-19 infection, but there is no data on the relationship between blood group O and PCS. This study aimed to assess this potential association. Subjects and methods A case-control study including subjects who had suffered from mild COVID-19 in a community setting was designed. Cases were PCS+ patients, controls were PCS- subjects and the exposure variable was blood group O. Baseline epidemiological data (age, sex, BMI, smoking, comorbidities), and clinical and laboratory parameters (inflammatory markers and IgG anti-N antibodies) 3 months after the acute episode, were obtained. Five composite indices of inflammation were built, combining the upper ranges of the distributions of inflammatory markers. Blood group and Rh factor were obtained from the patient's medical history or capillary blood samples. Bivariate and multivariate analyses were performed. Results One-hundred and twenty-one subjects were analyzed (56.2% women). The mean age was 45.7 (16) years (range, 18-88 years). Blood group frequencies were 43.3% (group A), 7.7% (group B), 5.7% (group AB), and 43.3% (group O). Thirty-six patients were classified as PCS+ (25 women, 11 men; p=0.07). The most frequent symptom was fatigue (42.8%). There were no significant differences between PCS+ and PCS- subjects regarding age, BMI, smoking, or previous comorbidity. The prevalence of PCS was 43.2% (19/44) in the blood group O and 23.7% in non-O subjects (14/60) (p=0.036). The mean number of PCS symptoms was 0.82 (1) in the blood group O and 0.43 (0.9) in the non-O group (p=0.017). There were no significant differences between A, B, and AB groups (PCS+ and PCS-) regarding inflammatory markers. In contrast, blood group O PCS+ patients had significantly higher lymphocyte count, plasma CRP, fibrinogen levels, and higher percentages of C2, C3, and C4 composite indices than PCS- subjects. The blood group O had an increased risk of developing PCS compared to non-O subjects (adjusted OR=4.20 [95%CI, 1.2-14]; p=0.023). The variables that contributed the most to the predictive model were blood group O, lymphocyte count, neutrophil count, and female sex. R-squared was 0.46, and the area under the ROC curve was 0.807 [95% CI, 0.70-0.90] (p=0.0001). Conclusion An increased risk of PCS associated with blood group O has been observed. Slightly, albeit significant, raised levels of fibrinogen, CRP, and neutrophil and lymphocyte counts, not observed in the other ABO blood groups, have been demonstrated in blood group O. Further investigations are needed to confirm these results.

Blood groups A, B, AB, and O configure the ABO system, the most important blood group system in humans.

It is located on chromosome 9 (band 9q34.2) and is composed of proteins and oligosaccharides expressed on the surface of red blood cells. Blood groups play a relevant role in cardiovascular and oncological diseases, thromboembolic and hemorrhagic processes, as well as infectious diseases (parasitic, bacterial, and viral), acting sometimes as receptors or co-receptors that facilitate viral particles from entering the cells [1] . People with blood group O have a lower risk of diabetes mellitus, arteriosclerosis, and ischemic heart disease [2] , but a higher risk of tuberculosis, cholera, and Norovirus infections [3] .

Since the beginning of the SARS-CoV-2 pandemic, a higher prevalence of COVID-19 in blood group A subjects and lower susceptibility to acquiring the infection in those with blood group O was noted [4, 5] . This finding has been related to the anti-A antibodies presented in blood group O individuals. These antibodies bind themselves to the A-like antigens or to the spike protein expressed on the virus envelope, blocking its interaction with the ACE-2 receptor, which is an identified gateway for different coronaviruses to infect host cells [6] .

Regarding clinical outcomes, blood group A has been associated with a higher risk of hospitalization, mechanical ventilation, and death [6, 7] . These adverse outcomes have been related to higher levels of soluble circulating proteins linked to vascular adhesion in people with this group [8] . The studies are discordant concerning the clinical outcomes of group O patients [7, 8] . Thus, some have observed a better prognosis [9] , that has been related to lower circulating levels of factor VIII and von Willebrand factor -and a subsequently reduced risk of thrombotic phenomena-, and to lower angiotensin-converting enzyme (ACE) activity [10] . However, in other studies, group O has been related to serious outcomes [11] [12] [13] .

After COVID-19, a variable percentage of patients, even those with mild initial forms of the disease, report prolonged and recurrent symptoms for weeks or months. These symptoms include asthenia -the most frequent-, myalgia, dyspnea, anosmia/ageusia, autonomic dysregulation manifested as orthostatic hypotension, tachycardia, thermoregulation or gastrointestinal disturbances, attention deficit, memory loss, and cognition alterations, leading to a significant impact on the quality of life [14] [15] [16] . This condition, known as Long COVID or Post-COVID Syndrome (PCS) [17] , has certain similarities with the chronic profile of other epidemic coronavirus infections, such as SARS and MERS [18] .

A previous study by our group [19] has shown that in PCS, 3 months after the acute episode, there are slight but significant elevations of inflammatory markers, compared to controls who have had COVID-19 but not PCS, supporting the hypothesis of chronic low-grade inflammation underlying PCS pathogenesis [20, 21] .

On the other hand, the ABO system modulates endothelial function and influences the inflammatory response [8, 22] , although the mechanisms are not fully understood [8] . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ;  https://doi.org/10.1101/2022.03. 10 .22272197 doi: medRxiv preprint signs and symptoms that develop during or after an infection consistent with COVID-19, that last more than 12 weeks, and that are unexplained by an alternative diagnosis [17] .

Serum C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), fibrinogen and D-dimer levels, as well as neutrophil and lymphocyte counts, and neutrophil/lymphocyte ratio (NLR) were analyzed. CRP was measured in mg/dL, and the detection limit was 0.4 mg/dL. Low-grade inflammation has been defined by a serum CRP level >0.3 mg/dL and <1.0 mg/dL [25] . Normal ranges for LDH (U/L), ferritin (ng/mL), fibrinogen (mg/dL), D-dimer (ng/mL), neutrophil count, and lymphocyte count were 120-246, 22-322, 180 -500, 0-500, 1.4-7.5 (x10³/µL), and 1.2-5 (x10³/µL), respectively. Blood samples were obtained from an antecubital vein using the standard venipuncture procedure in the morning after a 12-hour fast. LDH and ferritin were analyzed by spectrophotometric assay on an Atellica CH analyzer (Siemens Healthcare Diagnostics Inc, Tarrytown, NY, USA). CRP was quantified by immunonephelometric assay on an Atellica CH analyzer (Siemens Healthcare Diagnostics Inc, Tarrytown, NY, USA). Hematologic cell counts were analyzed on a DXH900 (Beckman Coulter), and fibrinogen and Ddimer on an ACL TOP 750 (Werfen). Anti-N IgG was obtained by chemiluminescence (QLIA), expressing the result as positive or negative.

The blood group was determined in capillary blood when it was not available in the clinical chart. To do this, a blood sample was taken by puncturing the pad of the finger with a lancet. The visualization or not of the agglutination reaction allowed the identification of the blood group when confronting the sample with reagents of known specificity (Alden Reagents, Laboquimia, Spain)

After assessing normality with the Shapiro-Wilk test, quantitative variables were expressed as mean ± standard deviation (SD) or as median [interquartile range (IQR)]. Some variables have been expressed as dichotomous using the median or tertiles. Student's t-test and ANOVA were used as parametric tests and the median and Kruskal-Wallis test as non-parametric procedures. Categorical variables have been expressed as numbers and percentages and the chi-square test was used for their comparison. Correlation analyses have been performed using Spearman's Rho and the Phi coefficient for categorical variables. The strength of an association has been expressed as an odds ratio (OR) with its corresponding 95% confidence interval (CI). Given the small number of subjects in blood groups B and AB, they were classified as group O/non-O, group A/non-A, group B/non-B, and group AB/non-AB. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint After selecting the serum inflammatory markers that showed the highest correlations with PCS, the upper ranges of their distributions were combined to develop the inflammatory indices, which were designated correlatively as C1-C5 (Table 1) .

Logistic regression was performed to determine the relationship between group O and PCS, after controlling for confounding variables. The confounding variables were selected according to the literature and the principle of parsimony. The model was validated using the determination coefficient R² and the area under the ROC curve (AUC). IBM SPSS 28.0 statistical package (Armonk, NY: IBM Corp) was used to perform the analyses. A p-value <0.05 was considered significant in all calculations.

The postulates of the Declaration of Helsinki were fulfilled. The study was approved by the Clinical Research Ethics Committee of Cantabria (Internal Code 2021.102).

One-hundred and thirty-four patients with confirmed COVID-19 were included, and 13 were discarded due to moderate or severe disease ( Figure 1 ). Thus, we finally included 121 subjects with mild COVID-19, 68 of them (56.2%) were women. The mean age was 45.7±16 years (range, 18-88 years). The frequencies of the blood groups were 43.3% (group A), 7.7% (group B), 5.7% (group AB) and 43.3% (group O). Tertiles of age distribution were <41, 41-53, >53 years and BMI, <23.8, 23.8-27.6, >27.6 Kg/m². Thirty-six subjects, 29.7% of the sample, were classified as PCS+; 25 were women (35.8%) and 11 men (20.8%) (p=0.07). The remaining 85 were classified as PCS-. The most frequent PCS symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%), myalgia (11.4%) and palpitations (11.4%). Table 2 shows the baseline characteristics of the PCS+ and PCS-participants. There were no significant differences between both groups concerning BMI, tobacco use, or previous comorbidities.

The prevalence of PCS according to the blood group was: 25% (group A) and 37.3% (non-A) (p=0. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint group) and 0.43±0.9 (non-O) (p=0.017); 0.59±0.9 (Rh+) and 0.60±1 (Rh-) (p=0.98). The symptoms analyzed were anosmia, dyspnea, palpitations, asthenia, telogen effluvium, ageusia, headache, leukonychia, myalgia, concentration difficulties, rhinitis, and cough. They were evaluated according to their presence in O and non-O subjects, with myalgia presenting a significant difference between both groups (Table 3) . When analyzing these patients, it has been observed that both group O subjects and patients with myalgia have presented a high frequency of positives in the C2 composite index (64.7% of group O vs 22.7% of non-O, p=0.007; 100% of subjects with myalgia vs 46.2% of subjects without myalgia, p=0.044).

Regarding biomarkers, fibrinogen levels in patients with and without myalgia were 510±82 mg/dL and 394.6±87, respectively (p=0.013).

Group O, fatigue, and serum CRP have shown to be related. In group O individuals, fatigue and raised serum CRP showed a positive correlation (Phi=0.372; p=0.022), while in non-O, fatigue and serum CRP were not correlated (Phi=0.03; p=0.80). In group A patients with fatigue, raised CRP was registered in 20%.

By contrast, in group O patients with fatigue, the percentage was 37.5% (p=0.021)

Ninety-eight persons (81%) had anti-SARS-CoV-2 IgG. IgG+ subjects had a mean age of 47.3±15 years, and IgG-subjects, 38.8±18 (p=0.030). IgG+ subjects presented 0.61±1 symptoms compared to 0.17±0.4 symptoms in IgG-subjects (p=0.044). No differences were observed between IgG+ and IgG-subjects regarding sex distribution, Charlson index, tobacco use, or serum inflammatory marker levels. Some 91.4% of subjects with PCS had IgG antibodies, compared to 76.5% of subjects without PCS (p=0.058).

The prevalence of anti-N IgG+ was 77.3% in the blood group O and 90% in the non-O group (p=0.076). In the remaining groups, these figures were 88.9% (group A), 100% (group B), 83.3% (group AB), 84.8% (Rh+) and 84.0% (Rh-). The performance of biomarkers and composite indices of inflammation (C1 to C5), concerning PCS in each blood group, was also analyzed. Groups A, B, AB, and Rh-subjects did not present any significant difference between PCS+ and PCS-. Conversely, significant differences were observed in blood group O, in which PCS+ patients had a lymphocyte count, serum CRP and fibrinogen levels, and percentages of positivity in . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint C2, C3, and C4 indices, significantly higher than PCS-subjects (Table 5 and Figure 2 ). Compared to the Rh+ subjects without PCS, those Rh+ with PCS had higher percentage of serum CRP in the low-grade inflammation range (28.6% vs. 8.5%; p=0.031), and higher percentage of subjects meeting the C1 (76 % vs. 50%; p=0.030), C3 (82.6% vs. 54%; p=0.019) and C4 criteria (69.6 vs. 44%; p=0.042). Table 6 shows the crude and adjusted OR (aOR) associated with the different blood groups and the Rh factor. Although in the crude analysis, groups B, AB, O, and Rh-showed significant ORs, the association was canceled when adjusting for age and sex. However, the OR for the blood group O remains significant.

Additional adjustments for different clinical and laboratory confounders did not virtually modify this result. 

To our knowledge, this is the first study that found an independent association between blood group O and PCS. The relationships of blood group O with the PCS, inflammatory markers, fatigue, and myalgia are discussed below.

Compared to non-O subjects, group O had a significantly higher prevalence of PCS and a higher number of PCS symptoms. In these patients (group O and PCS+), 3 findings would simultaneously point to underlying low-grade inflammation: (i) slight but significant increase of the lymphocyte count, and serum fibrinogen and CRP levels, (ii) significant correlations of these same markers with the number of symptoms, and (iii) a higher percentage of individuals meeting the criteria of the composite indices C2, C3 and C4.

These results are in line with the current knowledge since there is increasing evidence of an excessive and dysregulated inflammatory/immune activation underlying PCS pathogenesis [14, 26] . However, the question of why PCS has been related to inflammatory markers in subjects with blood group O, and not in other groups of the ABO system, does not have a simple answer.

A genomic study by Naitza et al. has linked blood group O with increased levels of interleukin (IL) 6 (IL-6) [27] . IL-6 is a multifunctional proinflammatory cytokine involved in a wide range of immunomodulatory processes. It also has a relevant role in acute and chronic inflammation [28] , activating the adhesion of lymphocytes and endothelial cells and influencing the magnitude of the inflammatory response [8] . In is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint addition, it stimulates the synthesis of fibrinogen and CRP and regulates the recruitment of neutrophils and their subsequent controlled elimination [28] [29] [30] . Once the acute phase of COVID-19 is finished, IL-6 levels remain elevated in a variable percentage of patients, between 3.9% and 32.2% according to a recent review [14] .

In our study, the subjects with blood group O and PCS+ presented significantly elevated levels of fibrinogen and lymphocytes, and a CRP in the range of low-grade inflammation. Based on what is known, it can be speculated that after acute COVID-19, these patients maintained persistently high levels of IL-6, which could have promoted a prolonged inflammatory response through the synthesis of CRP and fibrinogen, among others.

The persistent fatigue was the most self-reported symptom by participants, in line with the published papers [31] . A systematic review has shown that the pooled proportion of subjects with fatigue 12 or more weeks after the COVID-19 diagnosis was 0.32 (95% CI 0.27-0.37; p<0.001; n=25268) [14] .

The exact mechanisms of chronic fatigue remain unraveled, but there is consensus in accepting 4 models: the oxidative stress and mitochondrial dysfunction, the hypothalamus-pituitary-adrenal axis, genetics and the inflammation [32] . Higher levels of circulating pro-inflammatory cytokines (tumor necrosis factor (TNF)- The results corroborate these findings. We found a significant association between fatigue, CRP in range of low-grade inflammation, and group O, not observed in the other blood groups.

Of note, in our previous work, gender showed to be a relevant variable in the relationship between fatigue and CRP, being significant only in men [19] . The correlation between fatigue and high CRP has been positive and quite similar in both subsamples (Phi=0.383; p=0.012, in men, and Phi=0.372; p=0.022 in group O).

Subjects with blood group O had a significant association with post-COVID myalgia, a relationship that remained significant after adjusting for gender. A potential role of fibrinogen can be suggested as a pathophysiological marker. Thus, as previously said, blood group O has been associated with raised levels of IL-6, which is an important regulator of fibrinogen synthesis [39] . Secondly, apart from being involved in atherogenesis, thrombogenesis, and inflammation [40], fibrinogen is closely related to chronic pain [41, 42] .

In this context, fibrinogen has shown high sensitivity to changes in the activity of polymyalgia rheumatica is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint and, therefore, it is used as a marker of the disease [43] . Along with other proteins, it has also been involved in the intensity of pain in fibromyalgia [44] . Finally, a proteomics study [45] has shown that at least 2 months after acute COVID-19, raised levels of inflammatory molecules, such as α2-antiplasmin, chains of fibrinogen, and serum amyloid A (SAA) were present in the blood serum of subjects with PCS. Taking into account all these considerations, the role of fibrinogen in the relationship between blood group O and PCS myalgia is biologically plausible.

Hyperimmune plasma from convalescent COVID-19 donors has been a therapeutic option since the beginning of the pandemic. This has opened the option to assess a potential relationship between antibody titers and the ABO system, although the results of these studies have been controversial. Thus, on a sample of 232 plasma donors, Hayes et al. [46] observed that blood group O donors had lower titers than the other groups. Prevalences of high titers were 60%, 58%, 65%, and 35% for A, B, AB, and O, respectively. In the same line, Bloch et al. [47] analyzed 202 donors and reported that in blood group B there was a significantly higher number of subjects with high titers of neutralizing antibodies when compared with blood group O.

Also, Madariaga et al. [48] that donors with blood group AB had higher levels of anti-spike and anti-receptorbinding domain (RBD) antibodies than subjects with blood group O.

However, other studies have not confirmed these observations. Žiberna et al. [49] analyzed plasma samples from 3185 convalescent donors with 3 serological tests and a neutralizing antibody test. No difference between ABO groups with any of the tests was found. Similar results have been reported in other studies [50] [51] . According to these authors, the discrepancies in the results could be explained by the lack of representation of all ethnicities, the heterogeneity of the donors, the severity of the disease, the associated comorbidity, the small sample sizes in the studies carried out at the beginning of the pandemic, and the different sensitivity of the serological tests [50] [51] [52] .

It is known that high SARS-CoV-2 antibody titers are associated with male gender, older age, and severe acute COVID-19 [47, 48] , while tobacco use is associated with lower titers [53] and that there is a rapid loss of anti-RBD antibodies in mild COVID-19 [54] .

Accordingly, in our study, a higher mean age (p=0.03) was observed in IgG+ subjects. However, the mean age of the study participants was 45.7±16 years, and all had suffered from mild COVID-19 disease. These two factors could explain the relatively low prevalence of IgG antibodies in our population. Noteworthy, in IgG+ patients we found a higher number of PCS symptoms (p=0.044), as reported in other studies [55] .

Persistently high antibody titers, due to over-activation of the immune system, have been suggested as a risk factor for PCS [55, 56] . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 

The implications of these results deserve a brief comment. Blood O group has been associated with a 4.2fold increased risk of prevalent PCS compared to non-O subjects, after adjusting for confounders. Group O, lymphocyte and neutrophil counts, and female sex, were the variables that contributed the most in the predictive PCS model. The R² value (0.46) indicates a good fit and a moderate to strong effect size [57] , and the AUC of 0.807, an adequate discriminatory ability of the model [58] .

In our study, participants with blood group A, with a higher risk of acquiring the disease and developing a worse clinical outcome, according to previous reports, did not show any association with PCS. In contrast, blood group O could play a dual role in SARS-CoV-2 infection; as a protector factor against SARS-CoV-2 infection and, unexpectedly, according to our results, as a consistent risk factor for developing PCS.

Even with the protection of group O subjects from contracting COVID-19, it may imply a high prevalence of PCS in geographic areas with a predominance of this blood group. In the clinical setting, it may be helpful for PCS risk stratification in acute COVID-19. In addition, it can be useful for the diagnosis of a patient with a clinical suspicion of PCS in the post-acute phase. PCS is a challenge for clinicians, as there are no welldefined criteria to define this condition, patient-reported symptoms can be complex, changing and fluctuating, and complementary tests may be of little diagnostic value [59] This study has some limitations. Firstly, its design allows defining associations, but it does not establish causality. Secondly, it is a single-center study, on a Caucasian population, and the results may not be extrapolated to other populations. The frequencies of the ABO groups in the studied population are a confounding factor since geographical variations constitute potential bias [6] . In our case, the blood group proportions have been very similar to those in Spain (43.3% group A, 43.3% group O, and 13.4% groups B+AB). The main strength in this study is the well-characterized sample and the control group with subjects that came from the same population as the cases, and did not differ from them in any characteristics except for the PCS. Biomarkers have shown slight elevations, without exceeding the upper limit of normality ( Figure   2 ), in a similar way to our previous study [19] . Besides, the use of composite indices of inflammation has increased the ability to detect parameters with values in the upper ranges of their distribution.

We have found an increased risk of prevalent PCS associated with blood group O. Slightly, albeit significant, is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.10.22272197 doi: medRxiv preprint

Human ABO Blood Groups and Their Associations with Different Diseases

Correlation between ABO blood groups, major risk factors, and coronary artery disease

ABO research in the modern era of genomics

Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19

Blood type and outcomes in patients with COVID-19

ABO blood group association and COVID-19. COVID-19 susceptibility and severity: a review

ABO blood group and COVID-19: a review on behalf of the ISBT COVID-19 Working Group

or Truly Important Relationships? A Reasoned Review of Available Data. Viruses

The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19

Influence of ABO genotype and phenotype on angiotensinconverting enzyme plasma activity

Associations between blood type and COVID-19 infection, intubation, and death

Susceptibility of ABO blood group to COVID-19 infections: clinico-hematological, radiological, and complications analysis. Medicine (Baltimore)

Does ABO Blood Groups Affect Outcomes in Hospitalized COVID-19 Patients?

Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis

Meeting the challenge of long COVID

Immune determinants of COVID-19 disease presentation and severity

Postacute COVID-19: An Overview and Approach to Classification

Post-COVID-19 syndrome, lowgrade inflammation and inflammatory markers: a cross-sectional study

Long-Term Elevated Inflammatory Protein Levels in Asymptomatic SARS-CoV-2 Infected Individuals. Front Immunol

Covid-19: Middle aged women face greater risk of debilitating long term symptoms

Association between ABO and Duffy blood types and circulating chemokines and cytokines

World Health Organization (WHO) Publications: Clinical management of COVID-19: living guidance (2 nd version) 25

Low grade inflammation is negatively associated with physical Health-Related Quality of Life in healthy individuals: Results from The Danish Blood Donor Study (DBDS)

Serum Metabolic Profile in Patients With Long-Covid (PASC) Syndrome: Clinical Implications. Front Med (Lausanne)

A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation

Whole blood gene expression and interleukin-6 levels

Regulation of a lymphocyte-endothelial-IL-6 trans-signaling axis by fever-range thermal stress: hot spot of immune surveillance

IL-6 regulates neutrophil trafficking during acute inflammation via STAT3

More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep

Biological mechanisms of chronic fatigue

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin

Blood group O convalescent plasma donations have significantly lower levels of SARS-CoV-2 IgG antibodies compared to blood group A donations

ABO blood group and SARS-CoV-2 antibody response in a convalescent donor population

Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial

ABO blood group does not influence the level of anti-SARS-CoV-2 antibodies in convalescent plasma donors. Transfusion

Demographic and Clinical Factors Associated with Reactivity of Anti-SARS-CoV-2 Antibodies in Serbian Convalescent Plasma Donors

Absence of correlation between ABO Rh(D) blood group and neutralizing antibody titers in SARS-CoV-2 convalescent plasma donors

Loss of Anti-SARS-CoV-2 Antibodies in Mild Covid-19

Humoral Immune Response to SARS-CoV-2 in Iceland

Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19

Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients

Post-COVID syndrome. A case series and comprehensive review

An effect size primer: A guide for clinicians and researchers

Receiver operating characteristic curve in diagnostic test assessment

Characterizing Long COVID: Deep Phenotype of a Complex Condition