Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics.

BACKGROUND: Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published. OBJECTIVES: We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs. METHODS: A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge. RESULTS: A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (p-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (p-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) (p = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) (p = 0.799) remained as a predictor for an increase in 28 day survival. CONCLUSION: The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial.

PURPOSE: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. METHODS: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. RESULTS: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55). CONCLUSIONS: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.

Colorectal cancer in patients with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. OBJECTIVES: To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. METHODS: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient's final treatment outcome (survival or death). RESULTS: Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I2 94%, p < 0.01). The median patient age ranged from 51.6 years to 80 years across studies. The majority of the patients were male (n = 2243, 66.7%) and belonged to White (Caucasian) (n = 262, 7.8%), Hispanic (n = 156, 4.6%) and Asian (n = 153, 4.4%) ethnicity. The main source of SARS-CoV-2 infection in CRC patients was community-acquired (n = 2882, 85.7%; p = 0.014). Most of those SARS-CoV-2 patients had stage III CRC (n = 725, 21.6%; p = 0.036) and were treated mainly with surgical resections (n = 304, 9%) and chemotherapies (n = 187, 5.6%), p = 0.008. The odd ratios of death were significantly high in patients with old age (≥ 60 years) (OR 1.96, 95% CI 0.94-0.96; p < 0.001), male gender (OR 1.44, 95% CI 0.41-0.47; p < 0.001) CRC stage III (OR 1.54, 95% CI 0.02-1.05; p = 0.041), CRC stage IV (OR 1.69, 95% CI 0.17-1.2; p = 0.009), recent active treatment with chemotherapies (OR 1.35, 95% CI 0.5-0.66; p = 0.023) or surgical resections (OR 1.4, 95% CI 0.8-0.73; p = 0.016) and admission to ICU (OR 1.88, 95% CI 0.85-1.12; p < 0.001) compared to those who survived. CONCLUSION: SARS-CoV-2 infection in CRC patient is not uncommon and results in a mortality rate of 26.2%. Key determinants that lead to increased mortality in CRC patients infected with COVID-19 include older age (≥ 60 years old); male gender; Asian and Hispanic ethnicity; if SARS-CoV-2 was acquired from hospital source; advanced CRC (stage III and IV); if patient received chemotherapies or surgical treatment; and if patient was admitted to ICU, ventilated or experienced ARDS.

Outcome of Transplant Recipients Infected with Omicron BA.1 and BA.2: A Single-Center Retrospective Study in Saudi Arabia.

The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.

New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review.

BACKGROUND: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. OBJECTIVES: To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. 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 incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. RESULTS: Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. CONCLUSION: Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.

COVID-19 breakthrough infections in rheumatic diseases patients after vaccination.

BACKGROUND: Rheumatic diseases patients receiving Rituximab had severe COVID-19 disease. Although they had impaired humoral immune responses following COVID-19 vaccine, they had preserved cellular immune responses. Waning of COVID-19 antibody responses was observed within six months post vaccination among immunocompromised patients. Recent reports showed fatal outcome of breakthrough SARS-CoV-2 infections among vaccinated high-risk rheumatic diseases patients receiving Rituximab. SAR-CoV-2 serological tests were not performed. OBJECTIVE: Evaluation of COVID-19 vaccine humoral responses and breakthrough infections among low risk fully vaccinated rheumatic patients during the Delta Variant Era. METHODS: A case series of 19 fully vaccinated patients with rheumatic diseases were followed to determine post vaccine SARS-CoV-2 neutralizing antibody titers and to monitor the development of breakthrough infections up to eight months post vaccine at our tertiary care center in Jeddah, Saudi Arabia from 1st April until 30th November 2021. RESULTS: The mean age of patients was 49 years old. 10% of patients were receiving Rituximab. 73% of patients had positive SARS-CoV-2 serological testing post second vaccine. Two mild breakthrough COVID-19 infections were diagnosed six months post second dose of vaccine. Patients were less than 65 years, did not receive Rituximab, did not have interstitial lung diseases and had positive post vaccine serological testing. CONCLUSIONS: We demonstrated high SARS-CoV-2 neutralizing antibodies seroprevalence and self-limiting breakthrough infections in low risk rheumatic diseases patients during the Delta Era. Future studies are needed to study the outcome of rheumatic diseases patients in the Era of Omicron in view of viral immune escape responses.

De-isolation of vaccinated COVID-19 health care workers using rapid antigen detection test.

BACKGROUND: COVID-19 de-isolation guidelines of health care workers (HCW) were formulated based on evidence describing the duration of infectious viral shedding of the wild SARS-CoV-2 virus. During the periods of COVID-19 vaccination and variants, a test-based approach was recommended to end isolation of HCW, based on emerging data describing the viral kinetics of COVID-19 variants. While Rapid antigen detection tests (RADT) are increasingly used in the diagnosis of COVID-19, their use is limited in de-isolation. METHODS: We described the use of RADT in the de-isolation of COVID-19 vaccinated HCW with mild infection who were asymptomatic on day 7 post diagnosis in a single center retrospective cohort study during the Omicron surge. RESULTS: Of the 480 HCWs, 173 (36%) had positive RADT. The positivity rate of RADT was not different in HCW who received two doses versus three doses of vaccine (34.4% versus 40.3%, p = 0.239). CONCLUSIONS: A symptom based, test-based approach using RADT is a useful tool in the de-isolation of HCW, with mild disease, in the era of Omicron. Further studies are required to evaluate the role of RADT in de-isolation of patients with severe COVID-19 disease.

Machine learning decision tree algorithm role for predicting mortality in critically ill adult COVID-19 patients admitted to the ICU.

BACKGROUND: Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic. METHODS: This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses. RESULTS: There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio. CONCLUSION: DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.

Active viral shedding in a vaccinated hospitalized patient infected with the delta variant (B.1.617.2) of SARS-CoV-2 and challenges of de-isolation.

In the era of SARS-CoV-2 variants and COVID-19 vaccination, the duration of infectious viral shedding and isolation in post vaccine breakthrough infections is challenging and depends on disease severity. The current study described a case of SARS-CoV-2 Delta variant pneumonia requiring hospitalization. The patient received two doses of BNT162b2 COVID-19 vaccines, and he had positive SARS-CoV-2 viral cultures 12 days post symptom onset. The time between the second dose of vaccine and the breakthrough infection was 6 months. While immunosuppression is a known risk factor for prolonged infectious viral shedding, age and time between vaccination and breakthrough infection are important risk factors that warrant further studies.

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.

Outcome of COVID19 in Patients With Osteogenesis Imperfecta: A Retrospective Multicenter Study in Saudi Arabia.

Background: Although genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI. Methodology: A retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients. Results: Twelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination. Conclusion: Patients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

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.

Outcome of SARS-CoV-2 variant breakthrough infection in fully immunized solid organ transplant recipients.

SARS-CoV-2 vaccination in solid organ transplant recipients is associated with suboptimal immune response and risk for breakthrough infection. It is not known whether they are at risk of severe post-vaccine breakthrough infections in the presence of SARSCoV-2 variant of concern. We describe a case series of four fully vaccinated solid organ transplant recipients who developed SARS-CoV-2 variants of concern breakthrough infections. Three patients received BNT162b2 mRNA (Pfizer-BioNTech) and one patient received ChAdOx1 (AZD12220) COVID-19 vaccines. The patients were infected with SARS-CoV-2 variants circulating in Saudi Arabia. Two patients were infected with Alpha variant and had severe pneumonia requiring intensive care admission and ventilatory support and subsequently died. The other two patients recovered; one patient was infected with Beta variant required low supplemental oxygen via nasal flow and the other patient was infected with Delta variant and required high supplemental oxygen nasal flow. Younger patients had a better outcome than older patients. Future large studies are required to confirm our observations and to compare the different vaccine efficacy among solid organ transplants in the era of SARS-CoV-2 variants of concern.

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.

Examining and investigating the impact of demographic characteristics and chronic diseases on mortality of COVID-19: Retrospective study.

BACKGROUND: Epidemiological features characterization of COVID-19 is highly important for developing and implementing effective control measures. In Saudi Arabia mortality rate varies between 0.6% to 1.26%. The purpose of the study was to investigate whether demographic characteristics (age and gender) and non-communicable diseases (Hypertension and Diabetes mellitus) have a significant association with mortality in COVID-19 patients. METHODS: Prior to data collection, an expedite approval was obtained from Institutional Review Board (IRB Log No: RC. RC20.09.10) in Al Habib Research Center at Dr. Sulaiman Al-Habib Medical Group, Riyadh, Saudi Arabia. This is a retrospective design where we used descriptive and inferential analysis to analyse the data. Binary logistic regression was done to study the association between comorbidities and mortality of COVID-19. RESULTS: 43 (86%) of the male patients were non-survivors while 7 (14%) of the female patients were survivors. The odds of non-survivors among hypertensive patients are 3.56 times higher than those who are not having a history of Hypertension (HTN). The odds of non-survivors among diabetic patients are 5.17 times higher than those who are not having a history of Diabetes mellitus (DM). The odds of non-survivors are 2.77 times higher among those who have a history of HTN and DM as compared to those who did not have a history of HTN and DM. CONCLUSIONS: Those patients that had a history of Hypertension and Diabetes had a higher probability of non-survival in contrast to those who did not have a history of Diabetes and hypertension. Further studies are required to study the association of comorbidities with COVID-19 and mortality.

Examining the Clinical Prognosis of Critically Ill Patients with COVID-19 Admitted to Intensive Care Units: A Nationwide Saudi Study.

Backgroundand Objectives: COVID-19 is a novel infectious disease caused by a single-stranded RNA coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to conduct a nationwide multicenter study to determine the characteristics and the clinical prognostic outcome of critically ill COVID-19 patients admitted to intensive care units (ICUs). Materials and Methods: This is a nationwide cohort retrospective study conducted in twenty Saudi hospitals. Results: An analysis of 1470 critically ill COVID-19 patients demonstrated that the majority of patients were male with a mean age of 55.9 ± 15.1 years. Most of our patients presented with a shortness of breath (SOB) (81.3%), followed by a fever (73.7%) and a cough (65.1%). Diabetes and hypertension were the most common comorbidities in the study (52.4% and 46.0%, respectively). Multiple complications were observed substantially more among non-survivors. The length and frequency of mechanical ventilation use were significantly greater (83%) in the non-survivors compared with the survivors (31%). The mean Sequential Organ Failure Assessment (SOFA) score was 6 ± 5. The overall mortality rate of the cohort associated with patients that had diabetes, hypertension and ischemic heart disease was 41.8%. Conclusion: Age; a pre-existing medical history of hypertension, diabetes and ischemic heart disease; smoking cigarettes; a BMI ≥ 29; a long mechanical ventilation and ICU stay; the need of ventilatory support; a high SOFA score; fungal co-infections and extracorporeal membrane oxygenation (ECMO) use were key clinical characteristics that predicted a high mortality in our population.

Clinical Predictors of COVID-19 Mortality Among Patients in Intensive Care Units: A Retrospective Study.

OBJECTIVE: The ongoing pandemic of the coronavirus disease 2019 (COVID-19), which originated from Wuhan, China, has been identified to be caused by the novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been spreading rapidly worldwide within just a few months. Our aims were to analyze clinical and laboratory abnormalities in ICU patients with COVID-19, in order to define which predictors can distinguish between those who are at higher risk of developing fatal versus non-fatal forms of the disease. METHODS: A descriptive cross-sectional survey was used; demographics, comorbidities, symptoms, laboratory parameters at ICU admission, and clinical outcomes for the adult patients admitted to ICU were collected from five hospitals in Saudi Arabia. RESULTS: A total of 86 patients with COVID-19 admitted in ICU, 50 patients died, 23 recovered, and 13 were still admitted, with a mortality rate of 58.1%. Septic shock (OR (95% CI): 58.1 (5.97-7812.8), p < 0.001) and acute kidney injury (AKI) (OR (95% CI): 7.279 (1.191-65.43), p = 0.032) had a significant impact on mortality. Cox proportional-hazards regression analysis revealed that septic shock (HR (95% CI): 9.502 (2.958-30.524), p < 0.001) and neutrophil count (HR (95% CI): 1.053 (1.023-1.085), p < 0.001) were significant predictors for mortality. CONCLUSION: Septic shock, AKI, and high neutrophil count were found to be predictive of death in these patients. Further studies are needed to aid efficient recognition and management of severe COVID-19 patients in our population. .

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.