Infection with SARS-CoV-2 primes immunological memory in human nasal-associated lymphoid tissue.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in considerable morbidity and mortality in humans. Little is known regarding the development of immunological memory following SARS-CoV-2 infection or whether immunological memory can provide long-lasting protection against reinfection. Urgent need for vaccines is a considerable issue for all governments worldwide. METHODS: A total of 39 patients were recruited in this study. Tonsillar mononuclear cells (MNCs) were co-cultured in RPMI medium and stimulated with the full-length SARS-CoV-2 spike protein in the presence and absence of a CpG-DNA adjuvant. An enzyme-linked immunosorbent assay (ELISA) was utilised to measure the specific antibody response to the spike protein in the cell culture supernatants. RESULTS: The SARS-CoV-2 spike protein primed a potent memory B cell-mediated immune response in nasal-associated lymphoid tissue (NALT) from patients previously infected with the virus. Additionally, spike protein combined with the CpG-DNA adjuvant induced a significantly increased level of specific anti-spike protein IgG antibody compared with the spike protein alone (p < 0.0001, n = 24). We also showed a strong positive correlation between the specific anti-spike protein IgG antibody level in a serum samples and that produced by MNCs derived from the same COVID-19-recovered patients following stimulation (r = 0.76, p = 0.0002, n = 24). CONCLUSION: Individuals with serological evidence of previous SARS-CoV-2 exposure showed a significant anti-spike protein-specific memory humoral immune response to the viral spike protein upon stimulation. Additionally, our results demonstrated the functional response of NALT-derived MNCs to the viral spike protein. CpG-DNA adjuvant combined with spike protein induced significantly stronger humoral immune responses than the spike protein alone. These data indicate that the S protein antigen combined with CpG-DNA adjuvant could be used as a future vaccine candidate.

MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has been recognized as a highly pathogenic virus to humans that infects the respiratory tract and is associated with high morbidity and mortality. Studies in animal models suggest that MERS-CoV infection induces a strong inflammatory response, which may be related to the severity of disease. Data showing the cytokine profiles in humans during the acute phase of MERS-CoV infection are limited. In this study, we have analyzed the profile of cytokine responses in plasma samples from patients with confirmed MERS-CoV infections (n = 7) compared to healthy controls (n = 13). The cytokine profiles, including T helper (Th) 1, Th2 and Th17 responses, were analyzed using cytometric bead array (CBA). A prominent pro-inflammatory Th1 and Th17 response was clearly seen in patients with MERS-CoV infection, with markedly increased concentrations of IFN-γ, TNF-α, IL-15 and IL-17 compared to controls. IL-12 expression levels showed no difference between patients with MERS-CoV infection and the healthy controls despite the significantly increased levels of IFN-α2 and IFN-γ (P < .01). No changes were observed in the levels of IL-2, IL-4, IL-5, IL-13, and TGF-α (P > .05). Our results demonstrate a marked pro-inflammatory cytokine response during the acute phase of MERS-CoV infection in humans.

Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses.

Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. An enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nose-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B cell responses to pH1N1, seasonal H1N1 (sH1N1), and avian H5N1 (aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1, and aH5N1 viruses. The 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity to not only H1N1 but also aH5N1 viruses. These findings may have important implications for future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells.

Pandemic H1N1 influenza virus triggers a strong T helper cell response in human nasopharynx-associated lymphoid tissues.

The pH1N1 belongs to influenza A family that is sometimes transmitted to humans via contact with pigs. Human tonsillar immune cells are widely used as in vitro models to study responses to influenza viruses. In the current study, human memory (M) and naïve (N) T cells responses in mononuclear cells of tonsil (TMCs) and peripheral blood (PBMCs) were stimulated by pH1N1/sH1N1, and then stained for estimation of T cells proliferation index. Individuals with an anti-pH1N1 hemagglutination (HA) inhibition (HAI) titer of forty or greater exhibited stronger HA-specific M-CD4+ T cells responses to pH1N1 in TMCs/PBMCs than those with an HAI titer of less than forty (P < 0.01). In addition, a positive correlation was observed between proliferation indices of M-CD4+ T cells induced by exposure to sH1N1/pH1N1 (p < 0.01). Moreover, a strong correlation (p < 0.001) was detected between subjects' age and their HA-specific M-CD4+ T cells induced by pH1N1 exposure, indicating that this response was age-dependent. Finally, stimulation of TMCs with pH1N1-HA resulted in a significant M-CD8+ T cells response (p < 0.05). In conclusion, pH1N1 HA elicits a strong M-CD4+ T cells response in TMCs. Additionally, this response correlates with the response to sH1N1 suggesting cross-reactivity in T cells epitopes directed against HAs of both viral strains.

Predicting immunogenicity of COVID-19 vaccines in hemodialysis patients with renal disease.

Individuals who are diagnosed with chronic kidney disease, particularly those receiving maintenance hemodialysis treatment, face a greater likelihood of suffering from severe symptoms and fatality due to COVID-19. This study aimed to explore the optimal vaccination approach for these individuals. The study used data analysis tasks such as data preprocessing, cleaning, and exploration, and machine learning models including linear regression, random forest, XGBoost, gradient boosting, AdaBoost, decision trees, Lasso, and ridge regression were used to construct the predictive model. The study found that the Lasso model performed the best overall in predicting anti-S IgG antibodies levels in response to COVID-19 vaccines for people with kidney failure with MAE of 8.81, RMSE of 19.59, and R2 value of 0.93. The adjusted R2 value for the Lasso model was also 0.93, indicating that the model's ability to explain the variance in the data was not affected by the number of predictors in the model. The Random Forest model best predicted the duration of immunogenicity, with R2 and adjusted R2 values of 0.71 and 0.69, respectively. The ensemble model that includes all eight models, i.e., Ridge, Lasso, Linear Regression, Random Forest, AdaBoost, Gradient Boosting, XGBoost, and Decision Tree, has the best performance with the lowest MAE, the lowest RMSE, the highest R2, and the highest adjusted R2 values of 3.91, 5.00, 0.73, and 0.72, respectively. However, further research is required to validate these models and extend their application to different populations and vaccine types, as well as considering other factors that may affect immune response to COVID-19 vaccines. These findings can be helpful in improving vaccination strategies and promoting public health.

Exploring professional identity and its predictors in health profession students and healthcare practitioners in Saudi Arabia.

The government of Saudi Arabia is making significant efforts to improve the quality of health education and healthcare services. Professional identity has been linked to the quality of healthcare services provided by practitioners, however, data concerning the professional identity of health profession students (HPS) and healthcare practitioners (HCP) are still lacking in Saudi Arabia. The current study aimed to assess the level of professional identity in HPS and HCP in Saudi Arabia and to investigate its predictors. Cross-sectional data were collected from 185 HPS and 219 HCP in Saudi Arabia using river sampling technique. Data related to the sample characteristics were collected; an adapted version of the Macleod Clark Professional Identity Scale was utilized to collect data about the level of professional identity. Total score of professional identity was later calculated for each participant. Median professional identity scores for HPS and HCP were 38.0 (34.0-41.0) and 41.0 (37.0-43.0), respectively, out of 45. Significantly higher median professional identity score was found among HCP as compared to HPS (p <0.001). Data obtained from the multiple linear regression analysis, using the backward elimination method technique indicated that only working status (HPS vs. HCP) significantly predicted the professional identity score in all models performed. In conclusion, high levels of professional identity were reported among HCP and HPS in Saudi Arabia. Changes related to professional identity should be monitored in public and private educational and healthcare organizations to enhance the quality of healthcare services provided in the country.

Safety and efficacy of Single-Pass Albumin Dialysis (SPAD), Prometheus, and Molecular Adsorbent Recycling System (MARS) liver haemodialysis vs. Standard Medical Therapy (SMT): meta-analysis and systematic review.

Introduction: Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned.Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction. Material and methods: PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment. Results: Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; p < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; p = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; p = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; p = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; p = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; p = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; p = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; p = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; p = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; p = 0.31, respectively). Conclusions: MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events.

Mucosal immunity in upper and lower respiratory tract to MERS-CoV.

Introduction: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a deadly pathogen with a mortality rate of up to 36.2%. MERS-CoV can cause severe respiratory tract disease and multiorgan failure. Therefore, therapeutic vaccines are urgently needed. This intensive review explores the human immune responses and their immunological mechanisms during MERS-CoV infection in the mucosa of the upper and lower respiratory tracts (URT and LRT, respectively). Objective: The aim of this study is to provide a valuable, informative, and critical summary of the protective immune mechanisms against MERS-CoV infection in the URT/LRT for the purpose of preventing and controlling MERS-CoV disease and designing effective therapeutic vaccines. Methods: In this review, we focus on the immune potential of the respiratory tract following MERS-CoV infection. We searched PubMed, Embase, Web of Science, Cochrane, Scopus, and Google Scholar using the following terms: "MERS-CoV", "B cells", "T cells", "cytokines", "chemokines", "cytotoxic", and "upper and lower respiratory tracts". Results: We found and included 152 studies in this review. We report that the cellular innate immune response, including macrophages, dendritic cells, and natural killer cells, produces antiviral substances such as interferons and interleukins to prevent the virus from spreading. In the adaptive and humoral immune responses, CD4+ helper T cells, CD8+ cytotoxic T cells, B cells, and plasma cells protect against MERS-CoV infection in URT and LRT. Conclusion: The human nasopharynx-associated lymphoid tissue (NALT) and bronchus-associated lymphoid tissue (BALT) could successfully limit the spread of several respiratory pathogens. However, in the case of MERS-CoV infection, limited research has been conducted in humans with regard to immunopathogenesis and mucosal immune responses due to the lack of relevant tissues. A better understanding of the immune mechanisms of the URT and LRT is vital for the design and development of effective MERS-CoV vaccines.

COVID-19 vaccine in hemodialysis patients: Time for a boost.

OBJECTIVES: To evaluate anti-spike immunoglobulin G (IgG) antibody levels of hemodialysis patients and correlate them with the patients' demographic data and to evaluate these patients' need for a coronavirus disease-19 (COVID-19) vaccine booster. METHODS: A cross-sectional multi-center study carried out at King Abdulaziz Kidney Center, Hasan Tahir Hemodialysis Center, and Hayat Organization Hemodialysis Center in Al-Madinah Al-Munawarah, Saudi Arabia. Patients (n=167) who received a minimum single dose of COVID-19 vaccine were recruited. The samples were collected between March 2022 and January 2023. Anti-spike IgG antibody levels were measured using enzyme-linked immunosorbent assays. RESULTS: A significantly higher proportion of patients who received 3 doses of COVID-19 vaccine had positive serostatus compared with patients who received one or 2 doses (3 doses: 87.2%, one dose: 0.0%, 2 doses: 77.3%; p=0.000). Compared with patients who received one dose, significantly higher IgG antibody levels were detected in patients who received 2 (p=0.013) and 3 doses (p=0.025; n=35). In contrast, there was no significant difference in IgG antibody levels between patients who received 2 or 3 doses (p=0.45). Significant IgG antibody levels were detected in patients who received 2 and 3 doses (p=0.0125) compared with those received one vaccine dose (p=0.0004). Furthermore, patients who received 3 doses had significantly higher IgG antibody levels than patients who received 2 doses (p=0.000). CONCLUSION: The results show a dose-dependent association between IgG antibody levels and the number COVID-19 vaccines received. The study highlights the need for booster COVID-19 vaccination for patients on hemodialysis.

Live attenuated influenza vaccine induces broadly cross-reactive mucosal antibody responses to different influenza strains in tonsils.

Intranasal live attenuated influenza vaccine (LAIV) was used to stimulate tonsillar monocular cells (MNCs) following isolation. Haemagglutinin (HA) proteins of several influenza strains were used for the detection of HA-specific IgG, IgM and IgA antibodies using ELISA. Significant anti-sH1N1 HA IgG IgA and IgM antibody titres were detected in cell culture supernatants after stimulation (mean ± SE: 0.43 ± 0.09, mean ± SE: 0.23 ± 0.04 and mean ± SE: 0.47 ± 0.05 respectively, p < 0.01). LAIV stimulation of tonsillar MNCs induced significant IgG, IgA and IgM antibodies to the pH1N1 HA (mean ± SE:1.35 ± 0.12), (mean ± SE: 0.35 ± 0.06) and (mean ± SE: 0.58 ± 0.10) respectively, p < 0.01. Surprisingly, LAIV was shown to induce cross-reactive anti-aH5N1 HA antibodies (mean ± SE: 0.84 ± 0.20, p < 0.01) to avian influenza virus (aH5N1). Anti-H2N2 HA IgG antibody was also detected in the cell culture supernatants in a significant level after LAIV stimulation (mean ± SE: 0.93 ± 0.23, p < 0.01). High levels of anti-sH3N2 HA IgG antibody was discovered after LAIV stimulation of tonsillar MNCs, (mean ± SE: 1.2 ± 0.23p < 0.01). The current model of human nasal-associated lymphoid tissue (NALT) to evaluate B cells responses to LAIV was evident that it is a successful model to study future intranasal vaccines.

Impaired humoral immune response to hepatitis B vaccine in patients on maintenance hemodialysis.

Hepatitis B virus (HBV) infection is a worldwide health problem. We aimed in this study to investigate the humoral immune response derived to HBV vaccine following completing the vaccine series in Madinah. Two hundred and two Saudi hemodialysis (HD) patients were included in this cross-sectional study. Mean concentration of Hepatitis B surface antibody (anti-HBs) was significantly higher among patients who received the vaccination twice compared to patients who received the vaccination only after starting hemodialysis (252 ± 489 mIU/mL vs. 144 ± 327 mIU/mL, respectively, p = 0.008). Almost half of the study sample were non-protected and showed anti-HBs concentration < 10 mlU/mL. In contrast, 20.3% (n = 41) were identified as poor responders (10-100 mlU/mL) and only 28.2% (n = 57) were identified as good responders (10-100 mlU/mL). However, the latter two groups were accounted as protected (48.5%, n = 98). Patients sex was associated with anti-HBs concentration (non-responders; poor responders; good responders), where significantly higher proportion of good responders were females compared to males (p = 0.007). In conclusion, HBV vaccine is efficient to elicit humoral immune response in hemodialysis patients.

The Clinical Advances of Oncolytic Viruses in Cancer Immunotherapy.

A promising future for oncology treatment has been brought about by the emergence of a novel approach utilizing oncolytic viruses in cancer immunotherapy. Oncolytic viruses are viruses that have been exploited genetically to assault malignant cells and activate a robust immune response. Several techniques have been developed to endow viruses with an oncolytic activity through genetic engineering. For instance, redirection capsid modification, stimulation of anti-neoplastic immune response, and genetically arming viruses with cytokines such as IL-12. Oncolytic viral clinical outcomes are sought after, particularly in more advanced cancers. The effectiveness and safety profile of the oncolytic virus in clinical studies with or without the combination of standard treatment (chemotherapy, radiotherapy, or primary excision) has been assessed using response evaluation criteria in solid tumors (RECIST). This review will comprehensively outline the most recent clinical applications and provide the results from various phases of clinical trials in a variety of cancers in the latest published literature.

Attitude towards donation of the excised foreskin after circumcision surgery for research: A study from Madinah, Saudi Arabia.

Studies have shown the possibility of using the part of the foreskin removed after circumcision in the field of scientific and therapeutic research. Donations of tissues and organs are always associated with ethical challenges posed by bioethicists and societies to ensure the appropriate use of these tissues/organs. The purpose of this study was to understand the attitudes and awareness of parents/guardians regarding donation of excised foreskin to research and medical use. The study was based on a questionnaire and included 133 parents/guardians who visited Uhud Children's Hospital in Madinah, Saudi Arabia for newborn male circumcision. The results showed a high willingness (61.7%) to donate the extracted foreskin to research. The willingness to donate the extracted foreskin to research associated with undergraduate degree (P = 0.018), male sex (P = 0.011), high income (P = 0.029), and participation in previous research studies (P = 0.002). About 41.8% were convinced that written informed consent should be obtained before circumcision surgery, 38.1% (n = 51) were convinced that written informed consent should be taken after surgery, while the remaining 19.4% reported that the timing of written informed consent is unimportant. Finally, fear of excision of excess tissue (74.5%), lack of confidence in the research (68.6%), and potential for commercial use (64.7%) were the main barriers to unwillingness to donate the excised foreskin for research. In conclusion, a reasonable portion of Saudis agreed to donate their foreskin for research purposes. There is an urgent need to enhance awareness and attitudes towards tissue donation for research and therapeutic use.

Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines.

Background: Kidney transplant recipients (KTRs) commonly suffer from impaired immunity. KTRs' compromised immune response to COVID-19 vaccines indicates urgent revision of immunisation policies. Methods: A cross-sectional study was conducted in Madinah, Saudi Arabia of 84 KTRs who had received at least one dose of a COVID-19 vaccine. ELISA was used to evaluate anti-spike SARS-CoV-2 IgG and IgM antibody levels in blood samples obtained one month and seven months after vaccination. Univariate and multivariate analyses were performed to identify associations between seropositive status and factors such as the number of vaccine doses, transplant age, and immunosuppressive therapies. Results: The mean age of KTRs was 44.3 ± 14.7 years. The IgG antibody seropositivity rate (n=66, 78.5%) was significantly higher than the seronegativity rate (n=18, 21.4%) in the whole cohort (p<0.001). In KTRs seroconverting after one month (n=66), anti-SARS-CoV-2 IgG levels declined significantly between one month (median [IQR]:3 [3-3]) and seven months (2.4 [1.7-2.6]) after vaccination (p<0.01). In KTRs with hypertension, IgG levels significantly decreased between one and seven months after vaccination (p<0.01). IgG levels also decreased significantly in KTRs with a transplant of >10 years (p=0.02). Maintenance immunosuppressive regimens (triple immunosuppressive therapy and steroid-based and antimetabolite-based regimens) led to a significant decrease in IgG levels between the first and second sample (p<0.01). KTRs receiving three vaccine doses showed higher antibody levels than those receiving a single dose or two doses, but the levels decreased significantly between one (median [IQR]: 3 [3-3]) and seven months (2.4 [1.9-2.6]) after vaccination (p<0.01). Conclusion: KTRs' humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.

Robust memory humoral immune response to SARS-CoV-2 in the tonsils of adults and children.

Background: Adaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood. Methods: Tonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs. Results: Strong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies. Conclusion: Our results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.

Unexpected Detection of Anti-SARS-CoV-2 Antibodies Before the Declaration of the COVID-19 Pandemic.

Background: Limited information is currently available regarding the global incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections prior to the declaration of the coronavirus disease 2019 (COVID-19) pandemic, which may result in improper conclusions regarding the timing of viral transmission. Methods: We investigated the presence of specific antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in archived serum samples that were collected from 478 healthy blood donors and patients in Madinah, Saudi Arabia, between October 2019 and January 2020. Enzyme-linked immunosorbent assay (ELISA) was performed to measure SARS-CoV-2 IgM and IgG antibodies. In addition, rheumatoid factor (RF) and urea dissociation tests were performed in all samples, which showed seropositivity for the SARS-CoV-2 IgM antibody. Additionally, Chemiluminescence immunoassays (CLIA) targeting the RBD of the SARS-CoV-2 spike (S) protein were performed to confirm the seropositivity of the samples. Results: Overall, 20 (4.18%) serum samples were detected by ELISA to have SARS-CoV-2 IgG or IgM antibodies. Of these, 12 (2.51%) samples were positive for IgM antibody, and 8 (1.67%) were positive for IgG antibody. The 12 samples positive for SARS-CoV-2 IgM antibody were subjected to RF and urea dissociation tests, and all samples were RF-negative. The ELISA results were negative for 7 (58.33%) samples when subjected to urea dissociation prior to ELISA, whereas the other 5 (41.67%) samples remained positive. These 5 samples remained positive for the anti-S RBD IgG antibody in the CLIA. In addition, 3 of the 8 samples with IgG positivity according to the ELISA remained positive in the CLIA. After reviewing their data, we discovered that the 8 CLIA-confirmed positive samples were obtained from returned travellers who had visited China during the 4-week period immediately preceding blood donation. Conclusion: In conclusion, we found evidence to support the early circulation of SARS-CoV-2 among persons who visited China a few months prior to the pandemic declaration. These results can be used to better define the spread of SARS-CoV-2 infections before the COVID-19 pandemic declaration. The detection of SARS-CoV-2 antibodies in individuals before the pandemic was declared in China could rewrite the pre-pandemic timeline.

Rubella Humoral Immunity Among the Saudi Population of Madinah in the Western Region of Saudi Arabia.

Maintaining herd immunity against the rubella virus is important for controlling the spread and recurrence of rubella. Rubella vaccination for children has been affordable in Saudi Arabia since 1982. To assess the immune response derived from vaccination, we assessed the seroprevalence against the rubella virus among the population of the Madinah region. An indirect enzyme-linked immunosorbent assay (ELISA) was used to measure anti-rubella IgG antibodies in 791 serum samples obtained from 336 (42.5%) men and 455 (57.5%) women, ranging from 14 to 49 years in age. Among all participants, 94.2% were seropositive for rubella IgG antibodies, indicating a high degree of immunization. However, 5.8% of participants were seronegative, suggesting a population of either poor vaccine responders or the potential risk of waning vaccine-induced immunity. No significant difference or association with rubella seropositivity was identified according to age, sex, or pregnancy status. The median anti-rubella IgG antibody concentrations differed significantly between age groups (p < 0.001). Although a high percentage of the tested population in Madinah demonstrated anti-rubella IgG antibody seropositivity, a notable percentage of the population were seronegative, making them susceptible to infection.

Serostatus and Epidemiological Characteristics for Atypical Pneumonia Causative Bacteria among Healthy Individuals in Medina, Saudi Arabia, a Retrospective Study.

Background: Community-acquired atypical pneumonia is generally a mild and self-limiting infection. Still, it may lead to hospitalization and progressive clinical complications in some cases, particularly among the elderly and individuals with chronic diseases. Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae are the community's main causative agents of atypical pneumonia. However, most published studies evaluated their incidence in the hospital setting, and little is known about their prevalence among healthy individuals. This work aims to assess the seroprevalence of these bacteria among healthy people to determine the status of immunity against these bacteria in the community. Methodology: Two hundred and eighty-three serum samples from a multicenter in Medina, Saudi Arabia, were collected in this study. Serum samples were subjected to indirect enzyme-linked immunosorbent assays (ELISAs) to detect IgG antibodies against C. pneumoniae, L. pneumophila, and M. pneumoniae to investigate the seroprevalence of these bacteria and their distribution among different genders and age groups of healthy people. Results: IgG seropositivity for at least one of the three atypical pneumonia-causative bacteria occurred in 85.8% (n= 243/283) of the sample population. IgG seropositivity for C. pneumoniae occurred in 80.6% (228/283) of the population, followed by 37.5% for L. pneumophila and 23% for M. pneumoniae (66/283). In addition, the IgG seropositivity rates for the three bacteria were observed predominantly among male participants. Furthermore, no significant difference in IgG seropositivity distribution occurred between different age groups of healthy people for C. pneumoniae, L. pneumophila and M. pneumoniae. Conclusions: The current study found that C. pneumoniae, L. pneumophila, and M. pneumoniae tended to be highly prevalent among healthy people and more common among males than females. Additionally, their pattern of distribution among healthy individuals seemed to be predominant among young adults (aged 20−40 years), which differs from their predominant distribution among elderly patients in hospital settings (>50 years).

Human Cytomegalovirus Seroprevalence Among Blood Donors in the Madinah Region, Saudi Arabia.

Background and objective Human cytomegalovirus (HCMV), a double-stranded DNA virus of the Herpesviridae family, can remain latent for long periods of time. HCMV may cause severe illness in immunocompromised patients and is associated with congenital anomalies. This study aimed to determine the anti-HCMV immunoglobulin G (IgG) and IgM antibody seroprevalence among blood-donating Saudi men in the Madinah region. Methods A total of 375 blood-donating Saudi men were recruited from the Central Blood Bank in Madinah, the Kingdom of Saudi Arabia (KSA), and stratified into three age groups: 18-30, 31-40, and 41-61 years. Anti-HCMV IgG and IgM antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Pearson's correlation coefficient was used to correlate antibody levels with variables. Results Most of the tested samples (95.73%, n=356) were positive for anti-HCMV IgG antibodies, but only 1.6% (n=6) were positive for both IgM and IgG antibodies, and all of them belonged to the age groups of 31-40 and 41-61 years. A strong inverse correlation was found between anti-HCMV IgG antibody levels and age (r=-0.51, p<0.0001). Additionally, there was an inverse correlation between anti-HCMV IgG antibody levels and body mass index (BMI) (r=-0.11, p=0.036). No correlations were found between anti-HCMV IgG levels and hemoglobin levels or blood groups of the participants. Conclusions Blood-donating Saudi men in Madinah had a high seroprevalence of anti-HCMV IgG antibodies, indicating previous viral exposure. Age and BMI might influence the humoral immunologic memory response against HCMV, which appears to be endemic in Madinah.

A Single Dose of SARS-CoV-2 Vaccine Primes a Strong Humoral Immune Response in COVID-19-Recovered Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), which has affected hundreds of millions of people globally. The development of safe and effective vaccines represents an urgent demand. A total of 136 participants were recruited in this study, including 75 men and 61 women. The participants were divided into two groups: those who were virus naïve (never infected) and those who had recovered from COVID-19. Each group included individuals who received either the Pfizer-BioNTech BNT162b2 mRNA or the Oxford-AstraZeneca ChAdOx1 COVID-19 vaccine. Enzyme-linked immunosorbent assay (ELISA) was used to measure anti-S IgG antibody concentrations in sequential serum samples obtained before vaccine administration, after the first vaccine dose, and after the second vaccine dose. We compared the antibody responses of individuals with confirmed prior COVID-19 infection with those of individuals without prior evidence of infection. All participants who were previously infected with SARS-CoV-2 who received one dose of either the Pfizer-BioNTech BNT162b2 mRNA or the Oxford-AstraZeneca ChAdOx1 COVID-19 vaccine showed significant anti-S IgG antibody levels. No sex-related differences were observed when we compared antibody levels between men and women. In infection-naïve participants ≥60 years, a second vaccine dose was necessary to achieve higher levels of antibody when comparing the IgG antibody levels after receiving the first and second dose.