• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• coronavirus disease 2019 (COVID-19)
• hemolytic anemia
• oxidative stress
• severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

• Child
• Humans
• Anemia, Hemolytic/diagnosis
• Anemia, Hemolytic/etiology
• COVID-19/complications
• Glucosephosphate Dehydrogenase
• Glucosephosphate Dehydrogenase Deficiency/complications
• Glucosephosphate Dehydrogenase Deficiency/diagnosis
• SARS-CoV-2

• Androgen
• Coronavirus Disease 2019
• Noncritical
• Testosterone
• dehydroepiandrosterone Sulfate

• COVID-19
• G6PD
• Methemoglobinemia

• COVID-19
• biochemical parameters
• glucose-6-phosphate dehydrogenase (G6PD)
• hematological
• oxidative stress metabolism

• Antioxidative therapy
• COVID-19
• G6PD deficiency
• Oxidative stress
• Viral load

• COVID-19
• G6PD
• SARS-CoV-2
• absolute neutrophil count
• white blood cells

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common RBC abnormality, affecting 400 million people globally. Neonatal jaundice, hemolytic anemia, icteric skin, dark urine, and fever are usually the primary signs of this condition, which is generally diagnosed between the ages of infancy and 16 years old. Therefore, its first manifestation in old age is an unexpected phenomenon. Here, we present the case of a 70-year-old man with no past medical history of G6PD deficiency that was admitted to our hospital due to COVID-19 infection and developed acute hemolytic anemia while receiving hydroxychloroquine (HCQ) medication for COVID-19-related pneumonia.

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients.

• COVID-19
• G6PD deficiency
• genetic factor
• inflammation
• oxidative stress

• T-cells
• biomarkers
• immunity
• virotherapy
• viruses

• Bias
• COVID-19
• Humans
• Immunity, Innate
• Pandemics
• Th2 Cells
• Virus Diseases
• Zika Virus
• Zika Virus Infection

• 24321 Cancer Research UK
• G0902317 Medical Research Council
• 777682 (CANCER) Marie Curie
• C25574/A24321 Cancer Research UK

Glucose-6-phosphate dehydrogenase (G6PD) is the second rate-limiting enzyme of the pentose phosphate pathway. This enzyme is present in the cytoplasm of all mammalian cells, and its activity is essential for an adequate functioning of the antioxidant system and for the response of innate immunity. It is responsible for the production of nicotinamide adenine dinucleotide phosphate (NADPH), the first redox equivalent, in the pentose phosphate pathway. Viral infections such as SARS-CoV-2 may induce the Warburg effect with an increase in anaerobic glycolysis and production of lactate. This condition ensures the success of viral replication and production of the virion. Therefore, the activity of G6PD may be increased in COVID-19 patients raising the level of the NADPH, which is needed for the enzymatic and non-enzymatic antioxidant systems that counteract the oxidative stress caused by the cytokine storm. G6PD deficiency affects approximately 350–400 million people worldwide; therefore, it is one of the most prevalent diseases related to enzymatic deficiency worldwide. In G6PD-deficient patients exposed to SARS-CoV-2, the amount of NADPH is reduced, increasing the susceptibility for viral infection. There is loss of the redox homeostasis in them, resulting in severe pneumonia and fatal outcomes.

• COVID-19
• G6PD
• GSH
• SARS-CoV-2
• hydroxychloroquine
• reactive oxygen species

• COVID-19
• congenital anomalies
• disease incidence and association
• genetic diseases
• genetic susceptibility

• COVID-19
• China
• Comorbidity
• Humans
• Pandemics
• SARS-CoV-2/genetics

Glucose-6-phosphate dehydrogenase deficiency is a rarely recognized predisposing factor for rhabdomyolysis. Rhabdomyolysis with coronavirus disease 2019 has been increasingly seen during the pandemic. We report the uncommon occurrence of coronavirus disease 2019 pneumonia, severe rhabdomyolysis, and acute renal failure in the setting of glucose-6-phosphate dehydrogenase deficiency.

A 19-year-old African American male presented with myalgias, diaphoresis, and dark urine. Testing for severe acute respiratory syndrome coronavirus 2 was positive. He had severe rhabdomyolysis with creatine kinase levels up to 346,695 U/L. He was oliguric and eventually required hemodialysis. Progressive hypoxemia, methemoglobinemia, and hemolytic anemia occurred following one dose of rasburicase for hyperuricemia. Glucose-6-phosphate dehydrogenase deficiency was diagnosed. Full recovery followed a single volume exchange transfusion and simple packed red blood cell transfusions.

Glucose-6-phosphate dehydrogenase deficiency may predispose individuals to rhabdomyolysis due to severe acute respiratory syndrome coronavirus 2, presumably due to altered host responses to viral oxidative stress. Early screening for glucose-6-phosphate dehydrogenase deficiency can be useful for management of patients with rhabdomyolysis.

• Acute kidney injury
• COVID-19
• Case report
• G6PD deficiency
• Methemoglobinemia
• Rhabdomyolysis
• SARS-CoV-2

Methemoglobinemia (MetHb) is a rare, life-threatening condition that occurs when the body is exposed to oxidative stress. It is typically corrected through the glucose-6-phosphate dehydrogenase (G6PD)-dependent shunt. G6PD deficiency is the most common enzymatic deficiency worldwide. This genetic disorder makes patients susceptible to oxidative stress and reduces the expected life span of erythrocytes (red blood cells (RBCs)) among other cells. G6PD deficiency is asymptomatic in most cases unless exogenous stressors are introduced, whether they are dietary, iatrogenic, or infections, such as the highly transmissible serotype of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

We report a case of an 11-year-old male with known insulin-dependent diabetes mellitus (IDDM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, who was found to develop methemoglobinemia after being infected by the SARS-CoV-2 virus.

The direct effects of COVID-19 on children were reported to be lower than on adults. However, the effects of COVID-19 on children with comorbidities, such as G6PD deficiency in our patient, are understood only to a minimal extent. Moreover, identifying cases of G6PD deficiency prior to initiating treatment with methylene blue, hydroxychloroquine (HCQ), or other contraindicated agents is essential to prevent further deterioration in symptoms.

• COVID-19/complications
• COVID-19/epidemiology
• COVID-19/physiopathology
• Female
• Health Status Disparities
• Humans
• Hypothalamo-Hypophyseal System
• Male
• Pituitary-Adrenal System
• Public Health
• Sex Characteristics
• Post-Acute COVID-19 Syndrome

• CH/16/3/32406 British Heart Foundation
• RG/16/14/32397 British Heart Foundation

• 2019-nCoV
• COVID-19
• pandemic
• vaccines
• variants

Influenza virus infection induces oxidative stress in host cells by decreasing the intracellular content of glutathione (GSH) and increasing reactive oxygen species (ROS) level. Glucose-6-phosphate dehydrogenase (G6PD) is responsible for the production of reducing equivalents of nicotinamide adenine dinucleotide phosphate (NADPH) that is used to regenerate the reduced form of GSH, thus restoring redox homeostasis. Cells deficient in G6PD display elevated levels of ROS and an increased susceptibility to viral infection, although the consequences of G6PD modulation during viral infection remain to be elucidated. In this study, we demonstrated that influenza virus infection decreases G6PD expression and activity, resulting in an increase in oxidative stress and virus replication. Moreover, the down regulation of G6PD correlated with a decrease in the expression of nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor that regulates the expression of the antioxidant response gene network. Also down-regulated in influenza virus infected cells was sirtuin 2 (SIRT2), a NADPH-dependent deacetylase involved in the regulation of G6PD activity. Acetylation of G6PD increased during influenza virus infection in a manner that was strictly dependent on SIRT2 expression. Furthermore, the use of a pharmacological activator of SIRT2 rescued GSH production and NRF2 expression, leading to decreased influenza virus replication. Overall, these data identify a novel strategy used by influenza virus to induce oxidative stress and to favor its replication in host cells. These observations furthermore suggest that manipulation of metabolic and oxidative stress pathways could define new therapeutic strategies to interfere with influenza virus infection.

• G6PD
• NRF2
• SIRT2
• antioxidant response
• glutathione
• influenza virus
• oxidative stress
• redox state

• COVID-19
• Enteral nutrition
• Hepatic failure
• Parenteral nutrition
• SARS-CoV-2

• COVID-19
• immune response
• redox balance

• predictive medicine
• genetics research

• Africa South of the Sahara/epidemiology
• COVID-19/epidemiology
• COVID-19/genetics
• Chloroquine/adverse effects
• Databases, Genetic
• Genetic Variation/genetics
• Glucosephosphate Dehydrogenase/genetics
• Glucosephosphate Dehydrogenase Deficiency/drug therapy
• Glucosephosphate Dehydrogenase Deficiency/epidemiology
• Glucosephosphate Dehydrogenase Deficiency/genetics
• Humans
• Hydroxychloroquine/adverse effects
• Mutation, Missense/genetics
• Risk Factors
• COVID-19 Drug Treatment

• U24 HG006941 NHGRI NIH HHS
• U54 AI110398 NIAID NIH HHS
• 1U54AI110398 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
• U54 HG003273 NHGRI NIH HHS
• 84177 National Research Foundation (NRF)
• U54 HG006938 NHGRI NIH HHS
• 099310/Z/12/Z Wellcome Trust (Wellcome)
• Wellcome Trust
• U54HG003273 U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)
• GlaxoSmithKline (GSK)
• Cell Biology Research Lab component: This work is based on the research supported by grants awards from the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council, a grantee of the Bill & Melinda Gates Foundation, and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (84177).
• The whole genome sequencing of the H3A Data was supported by a grant from the National Human Genome Research Institute, National Institutes of Health (NIH/NHGRI) U54HG003273.
• The Collaborative African Genetics Network (CAfGEN) is funded by the NIH/NHGRI (grant CAfGEN 1U54AI110398).
• The TrypanoGEN project was funded by the Wellcome Trust, study number 099310/Z/12/Z.

Coronavirus disease 2019 (COVID-19) has been associated with a spectrum of reported hematological complications ranging from immune cytopenias to thromboembolic manifestations of coagulopathy. Moreover, there have been documented cases of hemolytic anemia associated with COVID-19 infection which have been mainly attributed to development of autoantibodies. We report a case of an African-American patient who presented with hemolytic anemia in the second week after his COVID-19 diagnosis. Throughout this report, we explore the potential immune and non-immune etiologies that contributed to the patient’s hemolytic anemia in the setting of COVID-19 infection guided by a review of literature.

• Autoimmune hemolytic anemia
• COVID-19
• G6PD deficiency
• Hemolytic anemia

• epidemiology
• outcomes research
• respiratory signs and symptoms
• risk factors
• viral infection

• Acute Disease
• Adult
• Age Factors
• COVID-19/epidemiology
• COVID-19/metabolism
• COVID-19/pathology
• Comorbidity
• Critical Illness
• Female
• Glucose-6-Phosphatase/metabolism
• Glucosephosphate Dehydrogenase Deficiency/complications
• Humans
• Male
• Middle Aged
• SARS-CoV-2/pathogenicity

• 134 / 02-Mar-2021 Royal College of Surgeons in Ireland - Bahrain

Accumulating evidence recommends that infectious diseases including coronavirus disease 2019 (COVID-19) are often associated with oxidative stress and inflammation. Paraoxonase 1 (PON1, OMIM: 168,820), a member of the paraoxonase gene family, has antioxidant properties. Enzyme activity of paraoxonase depends on a variety of influencing factors such as polymorphisms of PON1, ethnicity, gender, age, and a number of environmental variables. The PON1 has two common functional polymorphisms, namely, Q192R (rs662) and L55M (rs854560). The R192 and M55 alleles are associated with increase and decrease in enzyme activity, respectively.

The present study was conducted to investigate the possible association of rs662 and rs854560 polymorphisms with morbidity and mortality of COVID-19.

Data for the prevalence, mortality, and amount of accomplished diagnostic test (per 10⁶ people) on 25 November 2020 from 48 countries were included in the present study. The Human Development Index (HDI) was used as a potential confounding variable.

The frequency of M55 was positively correlated with the prevalence (partial r = 0.487, df = 36, p = 0.002) and mortality of COVID-19 (partial r = 0.551, df = 36, p < 0.001), after adjustments for HDI and amount of the accomplished diagnostic test as possible confounders.

This means that countries with higher M55 frequency have higher prevalence and mortality of COVID-19.

• COVID-19
• SARS-CoV-2
• cytokine storm
• metabolic reprogramming
• post COVID disorders
• therapeutic target

Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus, Rhabdoviridae family, is a causative agent of high mortality in fish and has caused significant losses to the aquaculture industry. Currently, no effective vaccines, Food and Drug Administration-approved inhibitors, or other therapeutic intervention options are available against VHSV. α-Lipoic Acid (LA), a potent antioxidant, has been proposed to have antiviral effects against different viruses. In this study, LA (CC₅₀ = 472.6 μmol/L) was repurposed to exhibit antiviral activity against VHSV. In fathead minnow cells, LA significantly increased the cell viability post-VHSV infection (EC₅₀ = 42.7 μmol/L), and exerted a dose-dependent inhibitory effect on VHSV induced-plaque, cytopathic effects, and VHSV glycoprotein expression. The time-of-addition assay suggested that the antiviral activity of LA occurred at viral replication stage. Survival assay revealed that LA could significantly upregulated the survival rate of VHSV-infected largemouth bass in both co-injection (38.095% vs. 1.887%, P < 0.01) and post-injection manner (38.813% vs. 8.696%, P < 0.01) compared with the control group. Additional comparative transcriptome and qRT-PCR analysis revealed LA treatment upregulated the expression of several antiviral genes, such as IRF7, Viperin, and ISG15. Moreover, LA treatment reduced VHSV-induced reactive oxygen species production in addition to Nrf2 and SOD1 expression. Taken together, these data demonstrated that LA suppressed VHSV replication by inducing antiviral genes expression and reducing VHSV-induced oxidative stress. These results suggest a new direction in the development of potential antiviral candidate drugs against VHSV infection.

• Antiviral
• IFN response
• Oxidative stress
• Viral hemorrhagic septicemia virus (VHSV)
• α-Lipoic acid (LA)

• COVID-19
• pneumonia
• respiratory infection
• viral infection

• Age Distribution
• Age Factors
• Aged
• Air Pollution/analysis
• Benchmarking/methods
• COVID-19/ethnology
• COVID-19/therapy
• Comorbidity
• Crowding
• Ethnicity
• Female
• Follow-Up Studies
• Housing/standards
• Humans
• Male
• Middle Aged
• Multimorbidity
• Patient Admission
• Risk Assessment/methods
• Risk Factors
• SARS-CoV-2
• United Kingdom/epidemiology

• MR/L002736/1 Medical Research Council

• COVID-19
• SARS-CoV-2
• alpha-lipoic acid
• cardiovascular disease
• inflammation
• oxidative stress

• Angiotensin-Converting Enzyme 2/metabolism
• Animals
• Antioxidants/chemistry
• Antioxidants/therapeutic use
• COVID-19/complications
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/etiology
• Cytokine Release Syndrome/etiology
• Cytokine Release Syndrome/metabolism
• Endothelial Cells/metabolism
• Humans
• Thioctic Acid/chemistry
• Thioctic Acid/therapeutic use
• COVID-19 Drug Treatment

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10⁻⁵). The IL12RB2 gene (p-value: 2.18x10^-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.

Since the beginning of Zika virus outbreak in Brazil, five years ago, we still don’t understand the genetic factors associated with the small number of babies born with Congenital Zika Syndrome (CZS). Here, we focused on the host genetic susceptibility by studying the whole-exome of the CZS affected (n = 29) and healthy (n = 11) neonates, both born to ZIKV infected women from Brazil. We applied two strategies: 1) Determine whether cases individuals have pathogenic or harmful variants that explain the CZS outcomes (i.e. microcephaly) independently of ZIKV infection or not, 2) Exploring the common and rare variants association with CZS. We found that common and rare variants in genes like DISP3 and IL12RB2 could explain some level of the susceptibility to CZS. Moreover, by considering these and other candidate genes, we observed an over-representation of Gene Ontology terms related to neurological system, metabolism and microtubule-cytoskeleton organization.

• Brazil
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Humans
• Infant, Newborn
• Male
• Polymorphism, Single Nucleotide
• Pregnancy
• Pregnancy Complications, Infectious/genetics
• Pregnancy Complications, Infectious/virology
• Exome Sequencing
• Zika Virus/physiology
• Zika Virus Infection/congenital
• Zika Virus Infection/genetics

• FINEP
• H2020 European Institute of Innovation and Technology
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• FAPERJ
• Instituto Fernandes Figueira
• Eunice Kennedy Shriver National Institute of Child Health and Human Development
• RABICO/CAPES

This study was performed with the intention of comparing the clinical, laboratory, and chest computed tomography (CT) findings between severe and non-severe patients as well as between different age groups composed of pediatric patients with confirmed COVID-19.

This study was carried out on a total of 53 confirmed COVID-19 pediatric patients who were hospitalized in Namazi and Ali Asghar Hospitals, Shiraz, Iran. The patients were divided into two severe (n = 27) and non-severe (n = 28) groups as well as into other three groups in terms of their age: aged less than two years, aged 3–12 years and 13–17 years. It should be noted that CT scans, laboratory, and clinical features were taken from all patients at the admission time. Abnormal chest CT in COVID-19 pneumonia was found to show one of the following findings: ground-glass opacities (GGO), bilateral involvement, peripheral and diffuse distribution.

Fever (79.2%) and dry cough (75.5%) were the most common clinical symptoms. Severe COVID-19 patients showed lymphocytosis, while the non-severe ones did not (P = 0.03). C-reactive protein (CRP) was shown to be significantly lower in patients aged less than two years than those aged 3–12 and 13–17 years (P = 0.01). It was shown also that O₂ saturation experienced a significant increase as did patients’ age (P = 0.01). Severe patients had significantly higher CT abnormalities than non-severe patients (48.0% compared to 17.9%, respectively) (P = 0.02).

Lymphocytosis and abnormal CT findings are among the factors most associated with COVID-19 severity. It was, moreover, showed that the severity of COVID-19, O₂ saturation, and respiratory distress were improved as the age of confirmed COVID-19 pediatric patients increased.

• COVID-19
• CT
• Children
• Clinical symptoms
• Laboratory findings
• Pediatrics
• SARS-CoV-2

Shortage of blood during the severe acute respiratory syndrome‐COV‐2 (SARs‐COV‐2) pandemic impacted transfusion practice. The primary aim of the study is to assess management of acute haemolytic crisis (AHC) in glucose‐6‐phosphate dehydrogenase(G6PD)‐ deficient children during SARs‐COV‐2 pandemic, and then to assess blood donation situation and the role of telemedicine in management.

Assessment of G6PD‐deficient children attending the Emergency Department (ER) with AHC from 1 March 2020 for 5 months in comparison to same period in the previous 2 years, in three paediatric haematology centres. AHC cases presenting with infection were tested for SARs‐COV‐2 using RT‐PCR. Children with Hb (50–65 g/L) and who were not transfused, were followed up using telemedicine with Hb re‐checked in 24 h.

A 45% drop in ER visits due to G6PD deficiency‐related AHC during SARs‐COV‐2 pandemic in comparison to the previous 2 years was observed. 10% of patients presented with fever and all tested negative for COVID‐19 by RT‐PCR. 33% of patients had Hb < 50 g/L and were all transfused. 50% had Hb between 50 and 65 g/L, half of them (n = 49) did not receive transfusion and only two patients (4%) required transfusion upon follow up. A restrictive transfusion strategy was adopted and one of the reasons was a 39% drop in blood donation in participating centres.

Fewer G6PD‐deficient children with AHC visited the ER during SARs‐COV‐2 and most tolerated lower Hb levels. Telemedicine was an efficient tool to support their families. A restrictive transfusion strategy was clear in this study.

• acute haemolytic crisis (AHC)
• glucose-6-phosphate dehydrogenase (G6PD)
• packed red blood cell transfusions (PRBCs)
• severe acute respiratory syndrome-COV-2 (SARs-COV-2)

• coronavirus
• covid-19
• glucose-6-phosphate dehydrogenase (g6pd)
• hemolytic anemia
• hydroxychloroquine
• methemoglobinemia
• sars-cov-2

• COVID-19
• Kawasaki Disease
• children
• multisystem inflammatory syndrome
• pediatrics

• COVID-19
• G6PD
• NADPH
• redox
• virus

• COVID-19/complications
• COVID-19/epidemiology
• COVID-19/genetics
• COVID-19/metabolism
• Disease Susceptibility
• Glucosephosphate Dehydrogenase/genetics
• Glucosephosphate Dehydrogenase/metabolism
• Glucosephosphate Dehydrogenase Deficiency/complications
• Glucosephosphate Dehydrogenase Deficiency/epidemiology
• Glucosephosphate Dehydrogenase Deficiency/genetics
• Glucosephosphate Dehydrogenase Deficiency/metabolism
• Homeostasis/physiology
• Humans
• Oxidation-Reduction
• Pandemics
• SARS-CoV-2/physiology
• Virus Diseases/epidemiology
• Virus Diseases/genetics
• Virus Diseases/metabolism

Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses.

• anti-inflammatory
• antiviral
• glutathione (GSH)
• pro-GSH molecules
• redox signaling
• viral infection

• COVID-19
• Challenges
• HIV
• Impact
• Malaria
• TB

• Africa South of the Sahara/epidemiology
• COVID-19/epidemiology
• HIV Infections/epidemiology
• Humans
• Incidence
• Malaria/epidemiology
• Pandemics
• Syndemic
• Tuberculosis/epidemiology

• Azithromycin
• COVID-19
• Efficacy
• Hydroxychloroquine
• Respiratory failure
• SARS-CoV-2
• Safety

• COVID-19
• G6PD
• SARS-CoV-2
• cytokine storm
• disparities
• in-silico docking
• life style variables
• natural product
• risk factors

• Antiviral Agents/chemistry
• Antiviral Agents/therapeutic use
• Biological Products/chemistry
• Biological Products/therapeutic use
• COVID-19/epidemiology
• Glucosephosphate Dehydrogenase Deficiency/drug therapy
• Glucosephosphate Dehydrogenase Deficiency/epidemiology
• Humans
• SARS-CoV-2
• COVID-19 Drug Treatment

• 1R34AI143511 NIH HHS
• BDCS-2019-57 Commonwealth Scholarship Award
• CCTS Pilot Funds Center for Clinical and Translational Science (CCTS), University of Mississippi School of Pharmacy (UMSOP) & University of Mississippi Medical Center

• COVID-19
• G6PD deficiency
• Hemoglobin
• Hemolytic crisis
• Hydroxychloroquine

• COVID-19
• Plasmodium falciparum infection
• SARS–CoV-2
• Sub-Saharan Africa
• co-infection

• Africa South of the Sahara/epidemiology
• Basigin/immunology
• COVID-19/epidemiology
• COVID-19/immunology
• Humans
• Immunologic Memory
• Malaria, Falciparum/epidemiology
• Malaria, Falciparum/immunology
• Merozoites/immunology
• Plasmodium falciparum/immunology
• SARS-CoV-2/immunology
• Severity of Illness Index

• 205069/Z/16/Z Wellcome Trust
• MC_UP_1204/10 Medical Research Council

The severe pneumonia caused by the human coronavirus (hCoV)-SARS-CoV-2 has inflicted heavy casualties, especially among the elderly and those with co-morbid illnesses irrespective of their age. The high mortality in African-Americans and males, in general, raises the concern for a possible X-linked mediated process that could affect the viral pathogenesis and the immune system. We hypothesized that G6PD, the most common X-linked enzyme deficiency, associated with redox status, may have a role in severity of pneumonia. Retrospective chart review was performed in hospitalized patients with COVID19 pneumonia needing supplemental oxygen. A total of 17 patients were evaluated: six with G6PD deficiency (G6PDd) and 11 with normal levels. The two groups (normal and G6PDd) were comparable in terms of age, sex, co-morbidities, and laboratory parameters—LDH, IL-6, CRP, and ferritin, respectively. Thirteen patients needed ventilatory support ; 8 in the normal group and 5 in the G6PDd group (72% vs.83%). The main differences indicating increasing severity in normal vs. G6PDd groups included G6PD levels (12.2 vs. 5.6, P = 0.0002), PaO2/FiO2 ratio (159 vs. 108, P = 0.05), days on mechanical ventilation (10.25 vs. 21 days P = 0.04), hemoglobin level (10 vs. 8.1 P = 0.03), and hematocrit (32 vs. 26 P = 0.015). Only one patient with G6PDd died; 16 were discharged home. Our clinical series ascribes a possible biological role for G6PDd in SARS-CoV2 viral proliferation. It is imperative that further studies are performed to understand the interplay between the viral and host factors in G6PDd that may lead to disparity in outcomes.

• COVID19 studies show higher mortality in men, due to severe pneumonia and ARDS, indicating possible X-linked mediated differences

• G6PD, the most common X-linked enzymopathy, highly prevalent in African Americans and Italians, maintains redox homeostasis.

• Preclinical studies using G6PD deficient (G6PDd) cells infected with human coronavirus (hCoV), show impaired cellular responses, viral proliferation and worsening oxidative damage.

• Retrospective chart review in hospitalized patients with COVID19 pneumonia needing supplemental oxygen shows differences between the two groups (Normal and G6PDd) in hematological indices; the G6PDdgroup demonstrated prolonged PaO2/FiO2 ratio, and longer days on mechanical ventilation indicating the severity of the pneumonia.

• African American
• COVID19
• G6PD
• X-linked

• COVID-19
• Coronavirus
• Diabetes
• MERS
• Nutrition management
• SARS

• Asymptomatic
• COVID-19
• Clinical presentation
• Hospitalization
• SARS-CoV-2

• G6PD deficiency
• Glucose-6-phosphate dehydrogenase
• Hemolytic anemia
• Malaria