Analysis of SARS-CoV-2 genomic surveillance data during the Delta and Omicron waves at a Saudi tertiary referral hospital.

BACKGROUND: Studying the genomic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may help determine outbreak clusters and virus transmission advantages to aid public health efforts during the pandemic. Thus, we tracked the evolution of SARS-CoV-2 by variant epidemiology, breakthrough infection, and patient characteristics as the virus spread during the Delta and Omicron waves. We also conducted phylogenetic analyses to assess modes of transmission. METHODS: Nasopharyngeal samples were collected from a cohort of 900 patients with positive polymerase chain reaction (PCR) test results confirming COVID-19 disease. Samples underwent real-time PCR detection using TaqPath assays. Sequencing was performed with Ion GeneStudio using the Ion AmpliSeq™ SARS-CoV-2 panel. Variant calling was performed with Torrent Suite™ on the Torrent Server. For phylogenetic analyses, the MAFFT tool was used for alignment and the maximum likelihood method with the IQ-TREE tool to build the phylogenetic tree. Data were analyzed using SAS statistical software. Analysis of variance or t tests were used to assess continuous variables, and χ2 tests were used to assess categorical variables. Univariate and multivariate logistic regression analyses were preformed to estimate odds ratios (ORs). RESULTS: The predominant variants in our cohort of 900 patients were non-variants of concern (11.1 %), followed by Alpha (4.1 %), Beta (5.6 %), Delta (21.2 %), and Omicron (58 %). The Delta wave had more male than female cases (112 vs. 78), whereas the Omicron wave had more female than male cases (311 vs. 208). The oldest patients (mean age, 43.4 years) were infected with non-variants of concern; the youngest (mean age, 33.7 years), with Omicron. Younger patients were mostly unvaccinated, whereas elderly patients were mostly vaccinated, a statistically significant difference. The highest risk for breakthrough infection by age was for patients aged 30-39 years (OR = 12.4, CI 95 %: 6.6-23.2), followed by patients aged 40-49 years (OR = 11.2, CI 95 %: 6.1-23.1) and then 20-29 years (OR = 8.2, CI 95 %: 4.4-15.4). Phylogenetic analyses suggested the interaction of multiple cases related to outbreaks for breakthrough infections, healthcare workers, and intensive care unit admission. CONCLUSION: The findings of this study highlighted several major public health ramifications, including the distribution of variants over a wide range of demographic and clinical variables and by vaccination status.

Association of sexually transmitted infections and human papillomavirus co-infection with abnormal cervical cytology among women in Saudi Arabia.

Human papillomavirus (HPV) is a causative agent of cervical and other cancers. Sexually transmitted Infections (STIs) may play a crucial role in HPV persistence, leading to serious complications, including cervical cancer. This study investigated the association of HPV/STI co-infection in cervical samples with cervical dysplasia among women in Saudi Arabia. HPV-positive cervical samples (n = 142) were obtained from previous studies and newly collected samples (n = 209) were obtained from women aged 19-83 years. For HPV detection and genotyping, PCR and Genoflow HPV assay kits were used. STIs were detected using a Genoflow STD array kit. Of 351 samples, 94 (27%) were positive for STIs. Among HPV-positive samples, 36 (25%) were positive for STIs; the most common pathogens were Ureaplasma urealyticum/Ureaplasma parvu (13%) and Mycoplasma hominis (6%). A global significant correlation was detected between HPV and STIs with progression of abnormal cervical cytology (χ2 = 176, P < 0.0001). Associations between cervical cytology diagnosis and HPV status, STI types (opportunistic and pathogenic), and the presence of Ureaplasma spp., and Mycoplasma hominis were significant (P < 0.05). Our results suggest that additional study in a larger population is warranted to determine the association between HPV/STI co-infection and cervical neoplasia in Saudi women.

Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia.

The detection of HPV viral DNA is regularly conducted with cervical screening. However, using a molecular marker such as the viral load may serve as a predictor associated with disease detection and progression. The present study aimed to screen for and genotype HPV among women in Saudi Arabia, develop and validate sensitive quantitative polymerase chain reaction (qPCR) assays to detect viral load for the two most common HPV types, namely 16 and 18, and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed paraffin embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA using nested PCR. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed and validated in-house was used to determine viral load for HPV genotypes 16 (n = 80) and 18 (n = 45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P < 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3-82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl, 2.43-88.49). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2-54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest that integrating a viral load test into current clinical screening practices for HPV-positive women is warranted in Saudi Arabia.

Touch-less heartbeat detection and measurement-based cardiopulmonary modeling.

This paper presents a system for touch-less heartbeat detection and a cardiopulmonary signal modeling approach. Using a vector network analyzer, a microwave system is tested for the detection of the heartbeat signal at a distance of 1 m from a person. The proposed system shows the ability of detecting the heartbeat signals with the possibility of tuning both frequency and power. Measurements are performed at 2.4, 5.8, 10, 16, and 60 GHz, as well as at different power levels between 0 and -27 dBm. Based on measurements performed for both respiration and heart beatings, a model of the measured signals representing the cardiopulmonary activity is presented. The heartbeat rate and the heart rate variability are extracted from the modeling signal using wavelet and classic filters, for SNR between 0 and -20 dB.

State selection in the noisy stabilized Kuramoto-Sivashinsky equation.

In this work, we study the one-dimensional stabilized Kuramoto Sivashinsky equation with additive uncorrelated stochastic noise. The Eckhaus stable band of the deterministic equation collapses to a narrow region near the center of the band. This is consistent with the behavior of the phase diffusion constants of these states. Some connections to the phenomenon of state selection in driven out of equilibrium systems are made.

Differential regulation of tumor necrosis factor-alpha-converting enzyme and angiotensin-converting enzyme by type I and II interferons in human normal and leukemic myeloid cells.

The transmembrane metalloproteases angiotensin-converting enzyme (ACE) and tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE/ADAM-17) have been associated with inflammation, cancer progression and angiogenesis. Few investigations into the regulation of these enzymes by physiological stimuli have been reported. In this study, we investigated the influence of interferons (IFNs) type I (alpha, beta) and II (gamma) on ACE and TACE expression of human leukemic NB4 cells and monocytes. We assessed the expression of proteases by reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence analyses. IFNgamma, but not type I IFNs, upregulated membrane ACE in a dose- and time-dependency and this was reflected by the increase of ACE enzymatic activity and ACE mRNA. ACE upregulation was dependent on protein synthesis. Treatment of the interferon responsive factor 1 (IRF1)-unresponsive HepG2 cell line with IFNgamma did not affect ACE expression, thus suggesting the participation of the IRF1 signaling pathway in IFNgamma-mediated ACE upregulation in myeloid cells. In contrast, both types of IFNs, in a dose- and time-dependent manner, downregulated surface TACE without affecting TACE transcript. Soluble TACE was not detected in the medium of IFN-treated cells. IFNgamma-mediated decrease of surface TACE in NB4 cells was reversible, and correlated with an increase in intracellular TACE, suggesting that cell surface TACE was internalized in response to IFNs. These findings, showing the presence of IFN-dependent controlled mechanisms by which ACE and TACE levels are regulated in human normal and leukemic myeloid cells, may have implications in the context of current investigations on the therapeutic potential of IFNs.

Long survival after splenic immunoblastic transformation of Waldenström's macroglobulinaemia.

Immunoblastic transformation of Waldenström's macroglobulinaemia is normally a preterminal event. We report a case in which the immunoblastic transformation appeared to be limited to the spleen. Splenectomy was more effective than cytotoxic chemotherapy in controlling the disease, and the patient remains free of disease 45 months later.

Long-term response in a patient with ITP following low dose anti-D immunoglobulin therapy.

A patient with chronic ITP relapsed after conventional therapy but following an infusion with low dose anti D (Rho) immunoglobulin, she entered a remission which has now lasted 10 months. This is difficult to explain on the basis of long term macrophage Fc receptor blockade and suggests an alternative mechanism of action.

Fanconi anemia. Oxymetholone hepatic tumors, and chromosome aberrations associated with leukemic transition.

Jaundice and hepatomegaly developed in a boy with Fanconi anemia after he had undergone treatment with oxymetholone for nine years. A liver scan showed patchy uptake consistent with the presence of space-occupying lesions. After oxymetholone treatment was stopped, the jaundice resolved, the liver size decreased, and the filling defects were no longer detectable on the liver scan. A year later, 5% of his white blood cells showed a consistent chromosomal abnormality. His leukocyte count increased and 85% of these cells showed the same chromosomal abnormality. The rapid replication of this abnormal clone suggests that it was leukemic. The significance of oxymetholone therapy and the occurrence of hepatic tumors and leukemia is discussed.

Acute leukaemia relapse presenting as ovarian tumour.

Relapse of acute lymphoblastic leukaemia is described in a woman with a leukaemic ovarian tumour from which reseeding of the bone marrow had occurred. It is proposed that irradiation of the ovaries with the initial leukaemic therapy may prevent this form of relapse.

Prolonged erythrocyte T-polyagglutination in two children with bowel disorders.

In vivo erythrocyte polyagglutination of microbial origin is usually a transient condition. In two children with bowel disorders, erythrocyte T-polyagglutination persisted for 12 months in one case and for seven months in the other. Both cultures required both transfusions to support surgery. Washed red cell concentrates were transfused instead of whole blood to prevent dangerous destruction of T-transformed erythrocytes by anti-T antibodies normally present in the plasma of blood donors.

G gamma delta beta thalassaemia and g gamma HPFH (Hb Kenya type): comparison of 2 new cases.

Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.