Identification of the novel HLA-B*53:69 allele by sequencing-based typing.

The HLA-B*53:69 allele differs from HLA-B*53:01:01:01 by two nucleotide changes in exon 3.

Combined effect of age and body mass index on postoperative mortality and morbidity in laparoscopic cholecystectomy patients.

Background: Previous studies have assessed the impact of age and body mass index (BMI) on surgery outcomes separately. This retrospective cohort study aimed to investigate the combined effect of age and BMI on postoperative mortality and morbidity in patients undergoing laparoscopic cholecystectomy. Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for laparoscopic cholecystectomy patients between 2008 and 2020 were analyzed. Patient demographics, functional status, admission sources, preoperative risk factors, laboratory data, perioperative variables, and 30-day postoperative outcomes were included in the dataset. Logistic regression was used to determine the association of age, BMI, and age/BMI with mortality and morbidity. Patients were stratified into different subcategories based on their age and BMI, and the age/BMI score was calculated. The chi-square test, independent sample t-test, and ANOVA were used as appropriate for each category. Results: The study included 435,052 laparoscopic cholecystectomy patients. Logistic regression analysis revealed that a higher age/BMI score was associated with an increased risk of mortality (adj OR 13.13 95% CI, 9.19-18.77, p < 0.0001) and composite morbidity (adj OR 2.57, 95% CI 2.23-2.95, p < 0.0001). Conclusion: Older age, especially accompanied by a low BMI, appears to increase the post-operative mortality and morbidity risks in laparoscopic cholecystectomy patients, while paradoxically, a higher BMI seems to be protective. Our hypothesis is that a lower BMI, perhaps secondary to malnutrition, can carry a greater risk of surgery complications for the elderly. Age/BMI is strongly and positively associated with mortality and morbidity and could be used as a new scoring system for predicting outcomes in patients undergoing surgery. Nevertheless, laparoscopic cholecystectomy remains a very safe procedure with relatively low complication rates.

Case Report: COVID-19 Infection of a Transplanted Heart Simulating Cellular Rejection.

Contemporary reports showed that solid organ transplantation patients who contract SARS-CoV-2 infection have a high mortality rate. There are sparse data about recurrent cellular rejections and the immune response to the SARS-CoV-2 virus in patients after heart transplantation. Herein, we report a case of a 61-year-old male post-heart transplant patient who tested positive for COVID-19 and developed mild symptoms 4 months after transplantation. Thereafter, a series of endomyocardial biopsies showed histologic features of acute cellular rejection despite optimal immunosuppression, good cardiac functions, and hemodynamic stability. Demonstration of SARS-CoV-2 viral particles by electron microscopy in the endomyocardial biopsy confirmed the presence of the virus in the foci of the cellular rejection, pointing to a possible immunologic reaction to the virus. To our knowledge, there is limited information regarding the pathology of COVID-19 infection in immunocompromised heart transplant patients, and there are no well-established guidelines for treating such patients. Based on the demonstration of SARS-CoV-2 viral particles within the myocardium, we concluded that myocardial inflammation visible on endomyocardial biopsy might be attributed to the host's immune response to the virus, which mimics acute cellular rejection in newly heart transplanted patients. We report this case to increase awareness of such events post-transplantation and to add to knowledge regarding the management of patients with ongoing SARS-CoV-2 infection that proved to be challenging.

Identification of the novel HLA-C*04:495 allele by sequencing-based typing.

The HLA-C*04:495 allele differs from HLA-C*04:01:01:31 by two nucleotide changes in the 5'UTR and exon 5.

Age/BMI is a Stronger Predictor of Death in COVID-19 Patients than Age Alone: A Pilot Study.

The objective of this study was to investigate the effect of age and BMI on the risk of death in patients with coronavirus disease 2019 (COVID-19). A cohort of 206 Saudi COVID-19 patients was included in this study. Data on age, BMI, hospitalization, comorbidities, and death were collected and analyzed. Descriptive, univariate, and multivariate logistic regression analyses were carried out. Out of the 206 studied patients, 28 died. Hypertension, cardiac disease, and hospital admission were predictors of death in univariate and multivariate logistic regression analysis. Moreover, age was a significant predictor of death, while increased BMI seemed to be protective at an older age. Therefore, a new score was suggested taking into consideration both factors, namely age/BMI score. Although older age was associated with death in univariate (OR, 1.09 [95% CI 1.05-1.12], p < 0.001) and multivariate analysis (OR, 1.05 [95% CI 1.02-1.09], p = 0.004), a higher age/BMI score was a stronger predictor of death than age alone, in both univariate (OR 4.42 [95% CI 2.50-7.80], p < 0.001) and multivariate analysis (OR 3.11 [95% CI 1.66-5.82], p < 0.001). Several factors appear to contribute to the risk of COVID-19 death. Interestingly, our new age/BMI score seems to carry a higher risk of death than age alone. This new score will be designated as the Hajeer score. Since this is a small cohort study, we recommend investigating this score in a larger cohort.

Identification of the novel HLA-A*74:03:03 allele by sequencing-based typing.

HLA-A*74:03:03 differs from A*74:03:01 by a synonymous mutation at nucleotide 1948 in exon 4.

Identification of the novel HLA-DQB1*03:483 allele by sequencing-based typing.

A single nucleotide change in exon 1 of HLA-DQB1*03:01:01:03 results in the novel HLA-DQB1*03:483 allele.

Correlation between ABO Blood Group Phenotype and the Risk of COVID-19 Infection and Severity of Disease in a Saudi Arabian Cohort.

BACKGROUND: Disease severity among patients infected with SARS-CoV-2 varies remarkably. Preliminary studies reported that the ABO blood group system confers differential viral susceptibility and disease severity caused by SARS-CoV-2. Thus, differences in ABO blood group phenotypes may partly explain the observed heterogeneity in COVID-19 severity patterns, and could help identify individuals at increased risk. Herein, we explored the association between ABO blood group phenotypes and COVID-19 susceptibility and severity in a Saudi Arabian cohort. METHODS: In this retrospective cohort study, we performed ABO typing on a total of 373 Saudi patients infected with SARS-CoV-2 and conducted association analysis between ABO blood group phenotype and COVID-19 infection severity. We then performed gender-stratified analysis by dividing the participating patients into two groups by gender, and classified them according to age. RESULTS: The frequencies of blood group phenotypes A, B, AB and O were 27.3, 23.6, 5.4 and 43.7%, respectively. We found that blood group phenotype O was associated with a lower risk of testing positive for COVID-19 infection (OR 0.76 95% CI 0.62-0.95, p = 0.0113), while blood group phenotype B was associated with higher odds of testing positive (OR 1.51 95% CI 1.17-1.93, p = 0.0009). However, blood group phenotype B was associated with increased risk in the mild and moderate group but not the severe COVID-19 infection group. Blood group phenotype O was protective in all severity groups. CONCLUSION: Our findings provide evidence that blood group phenotype B is a risk for COVID-19 disease while blood group phenotype O is protective from COVID-19 infection. However, further studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.

Association of KIR gene polymorphisms with COVID-19 disease.

BACKGROUND: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections. We investigated the association between KIR genes and COVID-19 disease severity. METHODS: 424 COVID-19 positive patients were divided according to their disease severity into mild, moderate and severe. KIR genes were genotyped using next generation sequencing (NGS). Association between KIR genes and COVID-19 disease severity was conducted and significant correlations were reported. RESULTS: In the COVID-19 patients, KIR Bx genotype was more common than AA genotype. The Bx genotype was found more frequently in patients with mild disease, while in severe disease the AA genotype was more common than the Bx genotype. The KIR2DS4 gene carried the highest risk for severe COVID-19 infection (OR 8.48, pc= 0.0084) followed by KIR3DL1 (OR 7.61, pc= 0.0192). CONCLUSIONS: Our findings suggest that KIR2DS4 and KIR3DL1 genes carry risk for severe COVID-19 disease.

Kinetics of antibody response in critically ill patients with Middle East respiratory syndrome and association with mortality and viral clearance.

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.

Characterization of the novel HLA-A*31:199 allele by sequencing-based typing.

A single nucleotide change in exon 4 of HLA-A*31:01:02:31 results in the novel HLA-A*31:199 allele.

Characterization of the novel HLA-A*68:277 allele by sequencing-based typing.

A single nucleotide change in exon 1 of HLA-A*68:01:01:02 results in the novel HLA-A*68:277 allele.

Characterization of the novel HLA-B*57:02:01:03 allele by sequencing-based typing.

Two-nucleotide changes in the 3' UTR of HLA-B*57:02:01:01 result in the novel HLA-B*57:02:01:03 allele.

Chances of Finding Matched Unrelated Donors for Saudi Patients in Need of Hematopoietic Stem Cell Transplantation.

Finding HLA-matched donors for patients in need of hematopoietic stem cell transplantation (HSCT) stands a better chance in their own ethnic group. This information led many nations to establish unrelated stem cell donor registries. We started our Saudi Stem Cell Donor registry (SSCDR) in 2011. The calculated donor pool size was nearly 1 million donors to find a matched donor for every patient. So far we have recruited 75,145 donors. In this exercise we attempted to investigate the chances of finding a matched donor for Saudi patients in need of HSCT. A total of 445 patients were recruited for this study. Donor searches were carried out locally and internationally using Prometheus software and World Marrow Donor Association Search and Match Service, respectively. Only 24% of the patients found a matched donor in our registry, 12% found a donor in other registries, making it a total of 36% of our patients who have the chance to find a full 10/10 HLA-matched donor. However, when we included 9/10 and 8/10 with the full matched donors, the chances go up to 83%. The top scoring registries for number of patients finding 10/10 matched donors were SSCDR (108), Deutsche Stammzellspenderdatei Nabelschnurblut (n = 52), King Faisal Specialist Hospital & Research Centre Stem Cell Donor Registry (n = 52), NMDP-National Marrow Donor Program/Be The Match (n = 43), TURKOK-Turkish Stem Cell Coordination Centre (n = 39), DKMS United Kingdom (n = 24), and Ezer Mizion Bone Marrow Donor Registry (n = 20). The patient who found the highest number of donors in international registries carried the European haplotype A1-B8-DR3; a total of 272 donors were found, and none of them were from our registry. Patients with the highest matched donor numbers in SSCDR carried haplotypes that were not common in international registries. Having a local registry increases the chances of finding a matched donor for our patients; however, international registries can still add to the chances of finding matched donors. Increasing our donor pool will increase chances of our patients finding a matched donor.

Identification of a novel HLA-A*31 variant, HLA-A*31:01:02:31, in a Saudi individual.

A single nucleotide change in the 5' UTR of A*31:01:02:01 results in the novel HLA-A*31:01:02:31 allele.

Identification of a novel HLA-B*18 variant, HLA-B*18:01:01:52, in a Saudi individual.

A single nucleotide change in the 3' UTR of HLA-B*18:01:01:01 results in the novel HLA-B*18:01:01:52 allele.

Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies.

OBJECTIVES: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. DESIGN: Prospective cohort study. SETTING: A tertiary care ICU in Riyadh, Saudi Arabia. PATIENTS: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1ß, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1ß, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). CONCLUSIONS: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.