Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.

BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

Characteristics of chest pain among children presenting to the pediatric emergency department.

Chest pain in pediatric patients is a common concern in pediatric emergency departments (ED). In most cases, benign conditions are related to noncardiac causes, and only a minority of the cases are caused by heart disease. This research aimed to evaluate the causes and characteristics of chest pain among children in a pediatric emergency department. This retrospective study evaluated children younger than 14 years of age who presented to the emergency department of a general pediatric hospital in the Eastern area of Saudi Arabia with non-traumatic chest pain between 2017 and 2022. The data included socioeconomic information, physical examination findings, and the results of basic investigations, such as chest X-ray and electrocardiogram. The Chi-square test was performed to compare various etiologies, with a 5% significant level. The study evaluated 310 patients with a mean age of 9.1±2.7 years. The majority of children presenting with chest pain had normal physical examinations, except 3.3% who showed respiratory and cardiac findings. The diagnostic tests indicated pneumonia in 2.9% and arrhythmia in 2.1% of children. Most patients were discharged with a diagnosis of idiopathic or muscular chest pain. The majority of patients (95%) were treated symptomatically in outpatient settings, with just one patient requiring hospitalization. The most common cause of chest pain prompting a child to visit the ED was idiopathic chest pain. Therefore, this study highlights the significance of obtaining a comprehensive medical history and physical examination to reveal important clues and help avoid unnecessary tests.

Intussusception and COVID-19 in Children: A Systematic Review and Meta-Analysis.

Background: Intussusception (ISN) post-COVID-19 infection in children is rare but can occur. SARS-CoV-2 may play a role in the pathogenesis of ISN and trigger immune activation and mesenteric adenitis, which predispose peristaltic activity to "telescope" a proximal bowel segment into the distal bowel lumen. Objectives: To estimate the prevalence of SARS-CoV-2 infection in ISN children and analyze the demographic parameters, clinical characteristics and treatment outcomes in ISN pediatric patients with COVID-19 illness. Methods: We performed this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting on the incidence of ISN post-SARS-CoV-2 infection in children, published from 1 December 2019 until 1 October 2022, in PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS and NATURE, with a restriction to articles available in the English language, were included. Results: Of the 169 papers that were identified, 34 articles were included in the systematic review and meta-analysis (28 case report, 5 cohort and 1 case-series studies). Studies involving 64 ISN patients with confirmed COVID-19 (all patients were children) were analyzed. The overall pooled proportions of the ISN patients who had PCR-confirmed SARS-CoV-2 infection was 0.06% (95% CI 0.03 to 0.09, n = 1790, four studies, I2 0%, p = 0.64), while 0.07% (95% CI 0.03 to 0.12, n = 1552, three studies, I2 0%, p = 0.47) had success to ISN pneumatic, hydrostatic and surgical reduction treatment and 0.04% (95% CI 0.00 to 0.09, n = 923, two studies, I2 0%, p = 0.97) had failure to ISN pneumatic, hydrostatic and surgical reduction treatment. The median patient age ranged from 1 to 132 months across studies, and most of the patients were in the 1−12 month age group (n = 32, 50%), p = 0.001. The majority of the patients were male (n = 41, 64.1%, p = 0.000) and belonged to White (Caucasian) (n = 25, 39.1%), Hispanic (n = 13, 20.3%) and Asian (n = 5, 7.8%) ethnicity, p = 0.000. The reported ISN classifications by location were mostly ileocolic (n = 35, 54.7%), and few children experienced ileo-ileal ISN (n = 4, 6.2%), p = 0.001. The most common symptoms from ISN were vomiting (n = 36, 56.2%), abdominal pain (n = 29, 45.3%), red currant jelly stools (n = 25, 39.1%) and blood in stool (n = 15, 23.4%). Half of the patients never had any medical comorbidities (n = 32, 50%), p = 0.036. The approaches and treatments commonly used to manage ISN included surgical reduction of the ISN (n = 17, 26.6%), pneumatic reduction of the ISN (n = 13, 20.2%), antibiotics (n = 12, 18.7%), hydrostatic reduction of the ISN (n = 11, 17.2%), laparotomy (n = 10, 15.6%), intravenous fluids (n = 8, 12.5%) and surgical resection (n = 5, 7.8%), p = 0.051. ISN was recurrent in two cases only (n = 2, 3.1%). The patients experienced failure to pneumatic (n = 7, 10.9%), hydrostatic (n = 6, 9.4%) and surgical (n = 1, 1.5%) ISN treatment, p = 0.002. The odds ratios of death were significantly higher in patients with a female gender (OR 1.13, 95% CI 0.31−0.79, p = 0.045), Asian ethnicity (OR 0.38, 95% CI 0.28−0.48, p < 0.001), failure to pneumatic or surgical ISN reduction treatment (OR 0.11, 95% CI 0.05−0.21, p = 0.036), admission to ICU (OR 0.71, 95% CI 0.83−1.18, p = 0.03), intubation and placement of mechanical ventilation (OR 0.68, 95% CI 0.51−1.41, p = 0.01) or suffering from ARDS (OR 0.88, 95% CI 0.93−1.88, p = 0.01) compared to those who survived. Conclusion: Children with SARS-CoV-2 infection are at low risk to develop ISN. A female gender, Asian ethnicity, failure to ISN reduction treatment (pneumatic or surgical), admission to ICU, mechanical ventilation and suffering from ARDS were significantly associated with death following ISN in pediatric COVID-19 patients.

Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis.

Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06−8.17, I2 = 0% versus 5.31%, 95% CI 4.31−6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45−2.99, I2 = 0% versus 0.62%, 95% CI 0.00−1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70−4.34, I2 = 0% versus 4.91%, 95% CI 3.97−5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

Execution and Design of an Anti HPIV-1 Vaccine with Multiple Epitopes Triggering Innate and Adaptive Immune Responses: An Immunoinformatic Approach.

Human Parainfluenza Virus (HPIV) Type-1, which is an anti-sense ribonucleic acid (RNA) virus belonging to the paramyxoviridae family, induces upper and lower respiratory tract infections. The infections caused by the HPIV Type-1 virus are usually confined to northwestern regions of America. HPIV-1 causes infections through the virulence of the hemagglutinin-neuraminidase (HN) protein, which plays a key role in the attachment of the viral particle with the host's receptor cells. To the best of our knowledge, there is no effective antiviral drugs or vaccines being developed to combat the infection caused by HPIV-1. In the current study, a multiple epitope-based vaccine was designed against HPIV-1 by taking the viral HN protein as a probable vaccine candidate. The multiple epitopes were selected in accordance with their allergenicity, antigenicity and toxicity scoring. The determined epitopes of the HN protein were connected simultaneously using specific conjugates along with an adjuvant to construct the subunit vaccine, with an antigenicity score of 0.6406. The constructed vaccine model was docked with various Toll-like Receptors (TLRs) and was computationally cloned in a pET28a (+) vector to analyze the expression of vaccine sequence in the biological system. Immune stimulations carried out by the C-ImmSim Server showed an excellent result of the body's defense system against the constructed vaccine model. The AllerTop tool predicted that the construct was non-allergen with and without the adjuvant sequence, and the VaxiJen 2.0 with 0.4 threshold predicted that the construct was antigenic, while the Toxinpred predicted that the construct was non-toxic. Protparam results showed that the selected protein was stable with 36.48 instability index (II) scores. The Grand average of Hydropathicity or GRAVY score indicated that the constructed protein was hydrophilic in nature. Aliphatic index values (93.53) confirmed that the construct was thermostable. This integrated computational approach shows that the constructed vaccine model has a potential to combat laryngotracheobronchitis infections caused by HPIV-I.

The Molecular Characterization of Virulence Determinants and Antibiotic Resistance Patterns in Human Bacterial Uropathogens.

The high rates of bacterial infections affect the economy worldwide by contributing to the increase in morbidity and treatment costs. The present cross-sectional study was carried out to evaluate the prevalence of bacterial infection in urinary tract infection (UTI) patients and to evaluate the antimicrobial resistance rate (AMR) in a Tertiary Care Hospital in Lahore, Pakistan. The study was conducted for the period of one year from January 2020 to December 2020. A total of 1899 different clinical samples were collected and examined for bacterial cultures using standard procedures. Samples were inoculated on different culture media to isolate bacterial isolates and for identification and susceptibility testing. A total of 1107/1899 clinical samples were positive for Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and other bacterial isolates. Methicillin-resistant S. aureus (MRSA) prevalence was 16.93% from these positive cases. MRSA strains were found to be highly resistant to amikacin, clindamycin, fusidic acid, gentamicin and tobramycin, while highest sensitivity was noted against vancomycin (100%) and linezolid (100%). MRSA and high rates of multidrug resistance (MDR) pose a serious therapeutic burden to critically ill patients. A systematic and concerted effort is essential to rapidly identify high-risk patients and to reduce the burden of AMR.

Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis.

BACKGROUND: Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. OBJECTIVES: To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. DESIGN: A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. METHODS: Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. RESULTS: Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger's tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important. CONCLUSION: The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.

Diabetic ketoacidosis in patients with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA). OBJECTIVES: To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA. DESIGN: A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. METHODS: Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient's final treatment outcome (survival or death). RESULTS: Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from < 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399-638 mg/dl], 11.4% [IQR 9.9-13.5%], 7.16 [IQR 7.00-7.22], 10 mmol/l [IQR 6.9-13 mmol/l], and 24.5 mEq/l [18-29.2 mEq/l]; respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27%; p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07-15.19; p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38-7.91; p = 0.007], and male gender [OR 2.61, 95% CI 1.37-5.17; p = 0.004] compared to those who survived. CONCLUSION: DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are individuals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level > 1000 mg/dl, and anion gap ≥ 30 mEq/l.

Coinfections with Bacteria, Fungi, and Respiratory Viruses in Patients with SARS-CoV-2: A Systematic Review and Meta-Analysis.

BACKGROUND: Coinfection with bacteria, fungi, and respiratory viruses in SARS-CoV-2 is of particular importance due to the possibility of increased morbidity and mortality. In this meta-analysis, we calculated the prevalence of such coinfections. METHODS: Electronic databases were searched from 1 December 2019 to 31 March 2021. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. RESULTS: Of the 6189 papers that were identified, 72 articles were included in the systematic review (40 case series and 32 cohort studies) and 68 articles (38 case series and 30 cohort studies) were included in the meta-analysis. Of the 31,953 SARS-CoV-2 patients included in the meta-analysis, the overall pooled proportion who had a laboratory-confirmed bacterial infection was 15.9% (95% CI 13.6-18.2, n = 1940, 49 studies, I2 = 99%, p < 0.00001), while 3.7% (95% CI 2.6-4.8, n = 177, 16 studies, I2 = 93%, p < 0.00001) had fungal infections and 6.6% (95% CI 5.5-7.6, n = 737, 44 studies, I2 = 96%, p < 0.00001) had other respiratory viruses. SARS-CoV-2 patients in the ICU had higher co-infections compared to ICU and non-ICU patients as follows: bacterial (22.2%, 95% CI 16.1-28.4, I2 = 88% versus 14.8%, 95% CI 12.4-17.3, I2 = 99%), and fungal (9.6%, 95% CI 6.8-12.4, I2 = 74% versus 2.7%, 95% CI 0.0-3.8, I2 = 95%); however, there was an identical other respiratory viral co-infection proportion between all SARS-CoV-2 patients [(ICU and non-ICU) and the ICU only] (6.6%, 95% CI 0.0-11.3, I2 = 58% versus 6.6%, 95% CI 5.5-7.7, I2 = 96%). Funnel plots for possible publication bias for the pooled effect sizes of the prevalence of coinfections was asymmetrical on visual inspection, and Egger's tests confirmed asymmetry (p values < 0.05). CONCLUSION: Bacterial co-infection is relatively high in hospitalized patients with SARS-CoV-2, with little evidence of S. aureus playing a major role. Knowledge of the prevalence and type of co-infections in SARS-CoV-2 patients may have diagnostic and management implications.

Knowledge of infection prevention and control among healthcare workers and factors influencing compliance: a systematic review.

BACKGROUND: Knowledge of infection prevention and control (IPC) procedures among healthcare workers (HCWs) is crucial for effective IPC. Compliance with IPC measures has critical implications for HCWs safety, patient protection and the care environment. AIMS: To discuss the body of available literature regarding HCWs' knowledge of IPC and highlight potential factors that may influence compliance to IPC precautions. DESIGN: A systematic review. A protocol was developed based on the Preferred Reporting Items for Systematic reviews and Meta-Analysis [PRISMA] statement. DATA SOURCES: Electronic databases (PubMed, CINAHL, Embase, Proquest, Wiley online library, Medline, and Nature) were searched from 1 January 2006 to 31 January 2021 in the English language using the following keywords alone or in combination: knowledge, awareness, healthcare workers, infection, compliance, comply, control, prevention, factors. 3417 papers were identified and 30 papers were included in the review. RESULTS: Overall, the level of HCW knowledge of IPC appears to be adequate, good, and/or high concerning standard precautions, hand hygiene, and care pertaining to urinary catheters. Acceptable levels of knowledge were also detected in regards to IPC measures for specific diseases including TB, MRSA, MERS-CoV, COVID-19 and Ebola. However, gaps were identified in several HCWs' knowledge concerning occupational vaccinations, the modes of transmission of infectious diseases, and the risk of infection from needle stick and sharps injuries. Several factors for noncompliance surrounding IPC guidelines are discussed, as are recommendations for improving adherence to those guidelines. CONCLUSION: Embracing a multifaceted approach towards improving IPC-intervention strategies is highly suggested. The goal being to improve compliance among HCWs with IPC measures is necessary.

Antimicrobial susceptibility of gram-positive and gram-negative bacteria: a 5-year retrospective analysis at a multi-hospital healthcare system in Saudi Arabia.

BACKGROUND: Studying time-related changes in susceptible pathogens causing healthcare-associated infections (HAIs) is vital in improving local antimicrobial and infection control practices. OBJECTIVES: Describe susceptibility patterns to several antimicrobials in gram-positive and gram-negative pathogens isolated from patients causing HAIs at three private tertiary care hospitals in Saudi Arabia over a 5-year period. METHODS: Data on trends of antimicrobial susceptibility among bacteria causing HAIs events in children and adults at three tertiary private hospitals located in Riyadh and Qassim, Saudi Arabia, were collected retrospectively between 2015 and 2019 using the surveillance data datasets. RESULTS: Over a 5-year period, 38,624 pathogens caused 17,539 HAI events in 17,566 patients. About 9450 (53.8%) of patients who suffered HAIs were females and the average age was 41.7 ± 14.3 years (78.1% were adults and 21.9% were children). Gram-negative pathogens were 2.3-times more likely to cause HAIs compared to gram-positive bacteria (71.9% vs. 28.1%). The ranking of causative pathogens in decreasing order was: Escherichia coli (38%), Klebsiella species (15.1%), and Staphylococcus aureus (12.6%). Gram-positive isolates were mostly susceptible to linezolid (91.8%) whereas they were resistant to ampicillin (52.6%), cefoxitin (54.2%), and doxycycline (55.9%). Gram-negative isolates were mostly sensitive to tigecycline (95%) whereas they were resistant to cefotaxime (49.5%) and cefixime (59.6%). During the 5 years, there were relatively stable susceptibility patterns to all tested antimicrobials, except for cefotaxime which shown a susceptibility reduction by 41.4%, among Escherichia coli and Klebsiella species. An increase in the susceptibility of Acinetobacter and Enterobacter and Citrobacter species to all studied antimicrobials was observed except for colistin that had a slight sensitivity reduction in 2019 by 4.3% against Acinetobacter species. However, we noted reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin; and increased resistance of MRSA to linezolid and vancomycin. CONCLUSION: The observed increase in susceptibility of gram-positive and gram-negative bacteria to studied antimicrobials is important; however, reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin; and increased resistance of MRSA to linezolid and vancomycin is a serious threat and calls for effective antimicrobial stewardship programs.

Clinical features and prognostic factors of intensive and non-intensive 1014 COVID-19 patients: an experience cohort from Alahsa, Saudi Arabia.

BACKGROUND: COVID-19 is a worldwide pandemic and has placed significant demand for acute and critical care services on hospitals in many countries. OBJECTIVES: To determine the predictors of severe COVID-19 disease requiring admission to an ICU by comparing patients who were ICU admitted to non-ICU groups. METHODS: A cohort study was conducted for the laboratory-confirmed COVID-19 patients who were admitted to six Saudi Ministry of Health's hospitals in Alahsa, between March 1, 2020, and July 30, 2020, by reviewing patient's medical records retrospectively. RESULTS: This cohort included 1014 patients with an overall mean age of 47.2 ± 19.3 years and 582 (57%) were males. A total of 205 (20%) of the hospitalized patients were admitted to the ICU. Hypertension, diabetes and obesity were the most common comorbidities in all study patients (27.2, 19.9, and 9%, respectively). The most prevalent symptoms were cough (47.7%), shortness of breath (35.7%) and fever (34.3%). Compared with non-ICU group, ICU patients had older age (p ≤ 0.0005) and comprised a higher proportion of the current smokers and had higher respiratory rates (p ≤ 0.0005), and more percentage of body temperatures in the range of 37.3-38.0 °C (p ≥ 0.0005); and had more comorbidities including diabetes (p ≤ 0.0005), hypertension (p ≥ 0.0005), obesity (p = 0.048), and sickle cell disease (p = 0.039). There were significant differences between the non-ICU and ICU groups for fever, shortness of breath, cough, fatigue, vomiting, dizziness; elevated white blood cells, neutrophils, alanine aminotransferase and alkaline aminotransferase, lactate dehydrogenase, and ferritin, and decreased hemoglobin; and proportion of abnormal bilateral chest CT images (p < 0.05). Significant differences were also found for multiple treatments (p < 0.05). ICU patients group had a much higher mortality rate than those with non-ICU admission (p ≤ 0.0005). CONCLUSION: Identifying key clinical characteristics of COVID-19 that predict ICU admission and high mortality can be useful for frontline healthcare providers in making the right clinical decision under time-sensitive and resource-constricted environment.

Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: A systematic review and meta-analysis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs). AIMS: To re-assess the association between PPIs use and SBP incidence with larger and better-quality data. METHOD: The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity. RESULTS: A total of twenty-three studies: seven case-control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chi2p = 57.68; I2 = 74%). For case-control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger's test confirmed asymmetry suggesting publication bias (intercept = - 0.05, SE = 0.27, P = 0.850 two-tailed). CONCLUSION: This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.

A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma.

BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency accounts for about 4% of severe combined immunodeficiency diseases. PNP deficiency is a variable disease with recurrent infections and neurodevelopmental delay. Autoimmunity and malignancy can still occur in one-third of patients. METHODS: Case report. CASE PRESENTATION: An 8-year-old Saudi female who was apparently healthy presented at the age of 7 years with confirmed systemic lupus erythematosus (SLE) and lupus nephritis that were poorly controlled with conventional therapy. She also had frequent sinopulmonary and varicella infections. Preliminary immunological workup showed severe lymphopenia and depressed lymphocyte proliferation assay. The uric acid was within normal levels at 179 µmol/L (normal range, 150 to 350 µmol/L) 6 weeks after blood transfusion. Genetic study revealed a homozygous missense mutation c.265G>A in the PNP gene, resulting in a substitution of glutamic acid to lysine at amino acid 89 of the encoded protein (E89K). The PNP serum level was 798 nmol/h/mg (normal level 1354 ± 561 nmol/h/mg) 6 weeks after blood transfusion. Hematopoietic stem cell transplantation (HSCT) was planned from a matched unrelated donor; however, she developed an EBV and varicella meningoencephalitis. Atypical malignant cells suggestive of lymphoma were discovered, likely induced by EBV, and suspicious lesions were shown on brain MRI and PET scan. Unfortunately, she passed away before HSCT due to multiorgan failure. CONCLUSION: This report emphasizes the challenges in recognizing PNP deficiency in a patient suffering from SLE.