Moderately Low Effectiveness of the Influenza Quadrivalent Vaccine: Potential Mismatch between Circulating Strains and Vaccine Strains.

The annual seasonal influenza vaccination is the most effective way of preventing influenza illness and hospitalization. However, the effectiveness of influenza vaccines has always been controversial. Therefore, we investigated the ability of the quadrivalent influenza vaccine to induce effective protection. Here we report strain-specific influenza vaccine effectiveness (VE) against laboratory-confirmed influenza cases during the 2019/2020 season, characterized by the co-circulation of four different influenza strains. During 2019-2020, 778 influenza-like illness (ILI) samples were collected from 302 (39%) vaccinated ILI patients and 476 (61%) unvaccinated ILI patients in Riyadh, Saudi Arabia. VE was found to be 28% and 22% for influenza A and B, respectively. VE for preventing A(H3N2) and A(H1N1)pdm09 illness was 37.4% (95% CI: 43.7-54.3) and 39.2% (95% CI: 21.1-28.9), respectively. The VE for preventing influenza B Victoria lineage illness was 71.7% (95% CI: -0.9-3), while the VE for the Yamagata lineage could not be estimated due to the limited number of positive cases. The overall vaccine effectiveness was moderately low at 39.7%. Phylogenetic analysis revealed that most of the Flu A genotypes in our dataset clustered together, indicating their close genetic relatedness. In the post-COVID-19 pandemic, flu B-positive cases have reached three-quarters of the total number of influenza-positive cases, indicating a nationwide flu B surge. The reasons for this phenomenon, if related to the quadrivalent flu VE, need to be explored. Annual monitoring and genetic characterization of circulating influenza viruses are important to support Influenza surveillance systems and to improve influenza vaccine effectiveness.

Evaluation of 34 Cytokines and Vitamin D Status Reveal A Sexually-Dimorphic Active Immune Response to SARS-CoV-2.

Background: Several observational studies have inconsistently demonstrated that vitamin D deficiency is a risk factor for coronavirus disease-19 (COVID-19) infection and severity. Discrepancies in results may partially be explained by the individuals' immune profiles, which are modulated, in varying degrees, by vitamin D status and sex hormones. Methods: In this study we evaluated the differences and associations of serum levels of 25(OH)D with 34 cytokines in 220 adults (82 controls (41 males; 41 females) and 138 SARS-CoV-2 patients (79 males and 59 females)) with and without COVID-19. Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 group than in the controls. Serum IP-10, MCP-1, CRP, IFNγ, IL-10, IL-13, IL-17α, IL-23, and IL-6 were significantly higher in COVID-19 patients compared to controls. Serum levels of VEGF, IFNγ, IL-13, and IL-5 were significantly higher in male patients than in females. 25(OH)D was significantly correlated with EFG (R = 0.39, p < 0.05) and IL-15 (R = 0.39, p < 0.05) in male patients, while it was inversely correlated with CRP (R = −0.51, p < 0.05) in female patients. Conclusions: Altered levels of cytokines, chemokines, and vitamin D were observed in SARS-CoV-2 adult patients. These expressions were sexually dimorphic and thus highlight the sex-specific nature of the active immune response following SARS-CoV-2 infection.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.

COVID-19 in the Gulf Cooperation Council Member States: An Evidence of Effective Response.

OBJECTIVES: The World Health Organization (WHO) published a global strategic response plan in February 2020 aiming to mitigate the impact of the novel coronavirus disease 2019 (COVID-19) outbreak. It identified immediate activities required for global preparedness and response to the outbreak and set eight priority areas (pillars) essential for scaling up countries' operational readiness and response. Despite a semi-annual progress report on implementing the Global Strategic Plan in June 2020, there is limited granular information available on the extent of the national plan's content and implementation, particularly in the Member States of the Gulf Cooperation Council (GCC). Therefore, we sought to review the preparedness and responsiveness towards the COVID-19 outbreak in the GCC in the first phase of the pandemic and to document lessons learned for improving the ongoing response efforts and preparedness for future pandemics. METHODS: A rapid appraisal was conducted in June 2020 according to the WHO Strategic Preparedness and Response Plan and the accompanying Operational Planning Guidelines. The survey was administered to public health professionals or/and infectious disease experts in the states. The findings were cross-triangulated with secondary data that was publicly available for each country. RESULTS: The preparedness and response efforts of Bahrain, Saudi Arabia, and the UAE were fully compliant with all 11 (100%) pillars of the modified strategic response measures. Kuwait, Oman, and Qatar complied with eight of the pillars. The component on conducting COVID-19 related research was the lowest-performing across all the six states. CONCLUSIONS: All GCC states demonstrated an effective response to the pandemic, enhanced existing infrastructures, and accelerated reforms that would have otherwise taken longer. The lessons learned through the early phase of the pandemic continue to steer the states in realigning their strategies and resetting their goals of controlling the outbreak, particularly in the current context of vaccine introduction and increasing preparedness capacities for future pandemics.

Antimicrobial resistance trends of non-fermenter Gram negative bacteria in Saudi Arabia: A six-year national study.

BACKGROUND: Antimicrobial resistance (AMR) of non-fermenting Gram-negative bacteria (NFGNB) is increasingly recognized as urgent healthcare threat. Trend data on AMR of NFGNB in Saudi Arabia are either old or limited. The objective was to estimate the prevalence and resistance trends of isolated NFGNB in Saudi Arabia. METHODS: A retrospective multicenter study involving seven tertiary care hospitals in Saudi Arabia was conducted between 2011 and 2016. Susceptibility testing for non-duplicate isolates was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines in College of American Pathologists accredited diagnostic microbiology laboratories in the participating hospitals. RESULTS: Out of 461,274 isolates, 100,132 (21.7%) were NFGNB which represented 30% of gram-negative pathogens. Pseudomonas aeruginosa was the most common (73.6%), followed by Acinetobacter baumannii (21.0%) and Stenotrophomonas maltophilia (5.3%). Resistance trends of P. aeruginosa were increasing for aztreonam (absolute increase during the study was 17.3%), imipenem (12.3%), and meropenem (11.6%). A. baumannii was fully resistant to several beta lactam drugs, and resistance trends were increasing for potential treatments such as tigecycline (25.1%) and tobramycin (15.5%). S. maltophilia was >90% resistant to trimethoprim/ sulfamethoxazole and ciprofloxacin by the end of the study. CONCLUSION: We are reporting high and/or increasing resistance of NFGNB to common treatment options. The current findings call for urgent actions to combat the increasing resistance of NFGNB. Large scale sharing of AMR data collected at different hospitals with the Saudi AMR committee would be critical to set priorities and monitor progress.

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.

OBJECTIVE: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.

Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality.

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.

Promoting cross-regional collaboration in antimicrobial stewardship: Findings of an infectious diseases working group survey in Arab countries of the Middle East.

BACKGROUND: Antimicrobial resistance is a significant global issue that presents an increasing threat to patients' wellbeing. Although a global concern, the emergence of multi-drug resistant organisms is of particular significance in the Middle East. In recent years, this region has seen an alarming increase in antimicrobial resistance presenting a major challenge to physicians managing various infectious diseases. METHODS: A Working Group comprising experts in infectious diseases from Arab countries of Middle East assembled to review similarities and differences in antimicrobial practices and management of multi-drug resistant organisms across the region and assess the barriers to achieving cross-regional collaboration. The Working Group conducted an anonymous online survey to evaluate current practice and understanding of management of multi-drug resistant organisms across the region. RESULTS: A total of 122 physicians from Arab countries of the Middle East responded to the survey. Their responses demonstrated heterogeneity between countries in awareness of local epidemiology, management of multi-drug resistant organisms and antimicrobial stewardship practices. The Working Group recognized similarities and differences in the management of multi-drug resistant organisms across the region, and these were validated by the data collected in the survey. Overall, the similarities across the region reflect several key issues that can have an impact on the management of multi-drug resistant organisms and the prevention of antimicrobial resistance. CONCLUSIONS: This paper highlights the urgency of addressing antimicrobial resistance in Arab countries of the Middle East. The Working Group identified key barriers to effective management which may guide the development of future coherent strategies to promote effective antimicrobial stewardship in the region. Here, we outline a call to action for the region, with a need to focus on training and education, capacity building, infrastructure, regional research, and regional surveillance.

Combination of (interferon beta-1b, lopinavir/ritonavir and ribavirin) versus favipiravir in hospitalized patients with non-critical COVID-19: A cohort study.

OBJECTIVES: Our study aims at comparing the efficacy and safety of IFN-based therapy (lopinavir/ritonavir, ribavirin, and interferon ß-1b) vs. favipiravir (FPV) in a cohort of hospitalized patients with non-critical COVID-19. METHODS: Single center observational study comparing IFN-based therapy (interferon ß-1b, ribavirin, and lopinavir/ritonavir) vs. FPV in non-critical hospitalized COVID-19 patients. Allocation to either treatment group was non-random but based on changes to national treatment protocols rather than physicians' selection (quasi-experimental). We examined the association between IFN-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate. RESULTS: The study cohort included 222 patients, of whom 68 (28%) received IFN-based therapy. Antiviral therapy was started at a median of 5 days (3-6 days) from symptoms onset in the IFN group vs. 6 days (4-7 days) for the FPV group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FPV (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.27 (0.08-0.88)). No difference in hospitalization duration between the 2 groups, 9 (7-14) days vs. 9 (7-13) days, P = 0.732 was found. IFN treated group required less use of systemic corticosteroids (57%) as compared to FPV (77%), P = 0.005 after adjusting for disease severity and other confounders. Patients in the IFN treated group were more likely to have nausea and diarrhea as compared to FPV group (13%) vs. (3%), P = 0.013 and (18%) vs. (3%), P<0.0001, respectively. CONCLUSION: Early IFN-based triple therapy was associated with lower 28-days mortality as compared to FPV.

Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study.

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses. CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Dual catastrophe of COVID-19: Massive pulmonary embolism and stroke in a previously healthy young patient: A case report.

We are reporting a 45-year-old woman with COVID-19 who presented to the Emergency Department with a transient loss of consciousness and was found to have a massive pulmonary embolism and an acute stroke. To our knowledge, this is the first reported case that calls for attention to the importance of vigilance for such a catastrophic presentation of COVID-19.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study.

OBJECTIVES: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. METHODS: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. RESULTS: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity. CONCLUSIONS: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specific neutralizing antibodies were detected for 6 years postinfection.

Effects of home quarantine during COVID-19 lockdown on physical activity and dietary habits of adults in Saudi Arabia.

Public health endorsements during the present COVID-19 pandemic has led the governments of largely affected countries to imply policies that restrict social mobility to slow COVID-19 spread. The study aimed to explore the effects of COVID-19 home quarantine on lifestyle and health behavior of Saudi residents. An online survey in Saudi Arabia was launched from May 11 to June 6, 2020. The survey was designed by multidisciplinary scientists and academics uploaded and shared through the Google platform in Arabic and English languages. Questions presented related to responses "before" and "during" COVID-19 home quarantine. A total of 1965 respondents participated and were included in the analysis [921 (47.0%) males and 1044 (53.0%) females]. Non-Saudis were more likely to increase their physical activity during quarantine [odds ratio (95% confidence interval 1.41 (1.11-1.79); p < 0.005]. Prevalence of participants walking daily for more than 4 times per week significantly decreased during pandemic (before vs during, 30.5% vs 29.1%) which was in parallel to the significant increase in the prevalence of participants who did not perform daily walking during the quarantine (21% vs 22.9%; p < 0.001). The prevalence of participants who often consume snacks between meals increased during quarantine (27.4% vs 29.4%, p < 0.001), while the prevalence of participants who never consumed fresh fruits and vegetables significantly increased during home quarantine (2.4% vs 3.7%; p = 0.019). The lockdown imposed in Saudi Arabia modestly but significantly impacted physical activity and dietary behaviors of several citizens and residents in an unhealthy way. Interventions to alleviate these acute adverse lifestyle behaviors during pandemic should be formulated.

Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics. METHODS: We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity. RESULTS: Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were ß-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤ .001; I2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis. CONCLUSIONS: This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with ß-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible.

Structural Mapping of Mutations in Spike, RdRp and Orf3a Genes of SARS-CoV-2 in Influenza Like Illness (ILI) Patients.

In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019-2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.

Multidrug-Resistant and Extensively Drug-Resistant Enterobacteriaceae: Prevalence, Treatments, and Outcomes - A Retrospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative bacteria (GNB) are a global public health threat, especially in intensive care units (ICU). This study explored the prevalence of drug-resistant Enterobacteriaceae infections in an ICU in Saudi Arabia. The appropriateness of the antibiotic therapies used and their ability to improve the clinical outcomes were also assessed. METHODS: A retrospective study was conducted from 2015 to 2018 in the different ICUs of a tertiary-care hospital in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Enterobacteriaceae, including Klebsiella pneumoniae, Escherichia coli, and Enterobacter sp., were included. The primary outcomes involved microbiological cure and 30 days in-hospital mortality rate, while the secondary outcome included the length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of the antibiotic therapy and clinical outcomes. RESULTS: Of the 227 Enterobacteriaceae cultures included in this study, 60% were either MDR (n= 130) or XDR (n= 8) infections; no PDR Enterobacteriaceae cultures were identified. Majority of the patients were female (54%), and the average age was 60.1 ± 17.7 years. MDR/XDR cultures primarily comprised E. coli (51.4%), followed by K. pneumoniae (33%) and Enterobacter sp. (16%). Most commonly used antibiotics were piperacillin/tazobactam (53%), carbapenems (47%), and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in only 85 of 138 (61.59%) patients. Microbiological cure rate was achieved in 40% of the cases, and in-hospital death rate was 84%. The average LOS was 27 days. Appropriateness of the antibiotic therapy prescribed could not predict any of the study outcomes. CONCLUSION: The study revealed a high prevalence of drug-resistant Enterobacteriaceae infections, which were associated with a high mortality rate. Therefore, it is essential to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices, particularly in critically ill patients.

Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. METHODS: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. RESULTS: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I2 = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I2 = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I2 = 43.38%). CONCLUSION: In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST.