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.

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.

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.

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.

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.

The combination of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection and other respiratory pathogens is a real challenge for health care systems in terms of diagnosis, treatment, and management. Most of the reported bacterial coinfections among SARS-CoV-2 patients are hospital-acquired infections that occurred after several days of hospitalization. Little is known about the incidence of community-acquired atypical bacterial coinfections with SARS-CoV-2. In this work, we report on a rare case of an elderly SARS-CoV-2 patient with underdiagnosed bacterial coinfections who received care in the medical ward for 23 days then was discharged home. Retrospective serological investigation revealed positivity for Legionella pneumophila and Mycoplasma pneumoniae, indicating double community-acquired atypical bacterial coinfections that were in agreement with clinical manifestations that patients showed at his admission to the hospital. Screening for possible community-acquired respiratory co-pathogens among elderly SARS-CoV-2 patients is critical for effective treatment and management.