Epidemiological Characteristics and Outcomes Predictors for Intensive Care Unit COVID-19 Patients in Al-Madinah, Saudi Arabia. Retrospective Cohort Study.

Introduction: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) increased the demand for intensive care unit (ICU) services. Mortality and morbidity rates among ICU COVID-19 patients are affected by several factors, such as severity, comorbidities, and coinfections. In this study, we describe the demographic characteristics of COVID-19 patients admitted to an ICU in Saudi Arabia, and we determined the predictors for mortality and prolonged ICU length of stay. Additionally, we determined the prevalence of bacterial coinfection and its effect on the outcomes for ICU COVID-19 patients. Methods: We retrospectively studied the medical records of 142 COVID-19 patients admitted to the ICU at a tertiary hospital in Madinah, Saudi Arabia. Data on demographics, medical history, mortality, length of stay, and presence of coinfection were collected for each patient. Results: Neutrophil-to-Lymphocyte ratio (NLR) and intubation were reliable predictors of mortality and ICU length of stay among these ICU COVID-19 patients. Moreover, bacterial coinfections were detected in 23.2% of the patients and significantly (p < 0.001) prolonged their ICU length of stay, explaining the 10% increase in the length of stay for these patients. Furthermore, mortality reached 70% among the coinfected patients, and 60.8% of the isolated coinfecting pathogens were multidrug-resistant (MDR) strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. Conclusion: Increased NLR and intubation are predictors of mortality and prolonged length of stay in COVID-19 patients admitted to the ICU. Coinfection with MDR bacterial strains potentially results in complications and is a high-risk factor for prolonged ICU length of stay.

Acute Helicobacter pylori Infection Prevalence Among Renal Failure Patients and Its Potential Roles with Other Chronic Diseases: A Retrospective Cohort Study.

Background: Helicobacter pylori (H. pylori) infection is relevant to several chronic human diseases, from digestive diseases to renal, metabolic, and cancer diseases. H. pylori infections and chronic kidney diseases are in increasing, global records; if not well controlled in a specific population, these diseases might lead to more clinical complications. Methods: In this retrospective study, we investigated the prevalence of acute H. pylori infections among 127 dialysis patients via subjecting their serums to the enzyme-linked immunosorbent assay (ELISA) to detect the human Immunoglobulin M (IgM) against H. pylori infections. Samples were from dialysis patients in a single hemodialysis center in Medina, Saudi Arabia, from January to August 2021. Results: Our results indicated the significant prevalence of H. pylori acute infections among 33.1% of renal failure patients recruited in this study, chi-squared: 14.559, p-value: 0.0001. In addition, no significant occurrence of acute H. pylori infection among males and females, chi-squared: 1.823, p-value: 0.177. Furthermore, the prevalence of acute H. pylori infection was not significant in different age groups of renal failure patients. Chi-squared: 6.803, p-value: 0.147, despite H. pylori-infected cases predominantly represented in patients above 51 years. Moreover, we noticed that hypertension, followed by diabetes, was the most prevalent underlying medical condition among acute infected H. pylori and renal failure patients. Conclusion: We documented the significant prevalence of acute H. pylori infection among renal failure patients. We also highlighted and discussed the possible potential roles of H. pylori in renal failure and other chronic diseases. Routine screening and treatment for acute H. pylori infection for chronic kidney diseases, hypertension, and diabetes patients would positively reduce the bacterium's progressive effects on them. They might even improve the control of these diseases.

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).

Seroprevalence of community-acquired atypical bacterial pneumonia among adult COVID-19 patients from a single center in Al Madinah Al Munawarah, Saudi Arabia: A retrospective cohort study.

OBJECTIVES: To investigate the seroprevalence of the community-acquired bacterial that causes atypical pneumonia among confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) patients. METHODS: In this cohort study, we retrospectively investigated the seroprevalence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila among randomly selected 189 confirmed COVID-19 patients at their time of hospital presentation via commercial immunoglobulin M (IgM) antibodies against these bacteria. We also carried out quantitative measurements of procalcitonin in patients' serum. RESULTS: The seropositivity for L. pneumophila was 12.6%, with significant distribution among patientsolder than 50 years (χ2 test, p=0.009), while those of M. pneumoniae was 6.3% and C. pneumoniae was 2.1%, indicating an overall co-infection rate of 21% among COVID-19 patients. No significant difference (χ2 test, p=0.628) in the distribution of bacterial co-infections existed between male and female patients. Procalcitonin positivity was confirmed amongst 5% of co-infected patients. CONCLUSION: Our study documented the seroprevalence of community-acquired bacteria co-infection among COVID-19 patients. In this study, procalcitonin was an inconclusive biomarker for non-severe bacterial co-infections among COVID-19 patients. Consideration and proper detection of community-acquired bacterial co-infection may minimize misdiagnosis during the current pandemic and positively reflect disease management and prognosis.

Role of pH in Regulating Cancer Pyrimidine Synthesis.

Replication is a fundamental aspect of cancer, and replication is about reproducing all the elements and structures that form a cell. Among them are DNA, RNA, enzymes, and coenzymes. All the DNA is doubled during each S (synthesis) cell cycle phase. This means that six billion nucleic acids must be synthesized in each cycle. Tumor growth, proliferation, and mutations all depend on this synthesis. Cancer cells require a constant supply of nucleotides and other macromolecules. For this reason, they must stimulate de novo nucleotide synthesis to support nucleic acid provision. When deregulated, de novo nucleic acid synthesis is controlled by oncogenes and tumor suppressor genes that enable increased synthesis and cell proliferation. Furthermore, cell duplication must be achieved swiftly (in a few hours) and in the midst of a nutrient-depleted and hypoxic environment. This also means that the enzymes participating in nucleic acid synthesis must work efficiently. pH is a critical factor in enzymatic efficiency and speed. This review will show that the enzymatic machinery working in nucleic acid synthesis requires a pH on the alkaline side in most cases. This coincides with many other pro-tumoral factors, such as the glycolytic phenotype, benefiting from an increased intracellular pH. An increased intracellular pH is a perfect milieu for high de novo nucleic acid production through optimal enzymatic performance.

Low prevalence of community-acquired influenza coinfections among COVID-19 patients in Al-Madinah, Saudi Arabia: A retrospective cohort study.

BACKGROUND: Coinfections with respiratory viruses among SARS CoV-2 patients have been reported by several studies during the current COVID-19 pandemic. Most of these studies designated these coinfections as being hospital-acquired infections; however, there is inadequate knowledge about community-acquired respiratory coinfections among SARS CoV-2 patients. METHODS: In this retrospective cohort study, we investigated the seroprevalence of influenza A, influenza B, and parainfluenza-2 among newly hospitalized patients with confirmed COVID-19 infections (n = 163). The study was conducted during the early phase of the COVID-19 pandemic in Saudi Arabia (from April to October 2020). The patients' serum samples were subjected to commercial immunoglobulin M (IgM) antibody tests against the three aforementioned viruses. RESULTS: Seropositivity for influenza A and B and parainfluenza-2 occurred only in 4.2% (7/163) of COVID-19 patients, indicating simultaneous acute infections of these three viruses with SARS CoV-2 infection. All coinfection cases were mild and misdiagnosed during the care period in the hospital. CONCLUSION: This study highlights the low prevalence of community-acquired respiratory infections among COVID-19 patients in the current pandemic and we discussed the possible factors for this finding. During newly emerging epidemics or pandemics, considering other respiratory viruses circulating in the community is essential to avoid their misdiagnosis and account for their possible negative effects on pandemic disease management and prognosis.

COVID-19 with underdiagnosed influenza B and parainfluenza-2 co-infections in Saudi Arabia: Two case reports.

The emerging of the COVID-19 pandemic is currently challenging for the public health system globally. Beyond SARS-CoV-2 pathogenicity, co-infections with recycling respiratory pathogens, whether bacterial, viral, or fungal, might increase disease symptoms, morbidity, and mortality. In this study, we reported two COVID-19 cases in the early phase of the virus spread in Saudi Arabia with underdiagnosed respiratory viruses' co-infections, influenza B and Parainfluenza-2, detected retrospectively. Fortunately, both patients recovered and were discharged home. Underestimation of co-infection among COVID19 patients might lead to hospital stay prolongation and increases morbidity and mortality. Therefore, it is crucial to consider and screen for co-infecting pathogens among COVID-19 patients and those with risk factors.

Pathogenesis and Management of COVID-19.

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

Of mitochondrion and COVID-19.

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH.

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the "Warburg Effect". However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer.

Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism.

The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management.

Helicobacter pylori (HP) is a facultative anaerobic bacterium. HP is a normal flora having immuno-modulating properties. This bacterium is an example of a microorganism inducing gastric cancer. Its carcinogenicity depends on bacteria-host related factors. The proper understanding of the biology of HP inducing gastric cancer offers the potential strategy in the managing of HP rather than eradicating it. In this article, we try to summarize the biology of HP-induced gastric cancer and discuss the current pharmacological approach to treat and prevent its carcinogenicity.