Rhabdomyolysis in Critically Ill Patients With COVID-19: A Retrospective Study.

INTRODUCTION: The total number of ICU admissions for COVID-19 patients has increased steadily. Based on the research team's clinical observations, many patients developed rhabdomyolysis, but few cases were reported in the literature. This study explores the incidence of rhabdomyolysis and its outcomes, like mortality, the need for intubation, acute kidney injury, and the need for renal replacement therapy (RRT). METHODS: We retrospectively reviewed the characteristics and outcomes of patients admitted to the ICU at a COVID-19-designated hospital in Qatar between March and July 2020. Logistic regression analysis was used to determine factors associated with mortality. RESULTS: 1079 patients with COVID-19 were admitted to the ICU, and 146 developed rhabdomyolysis. Overall, 30.1% died (n = 44), and 40.4% developed Acute Kidney Injury (AKI) (n = 59), with only 19 cases (13%) recovering from the AKI. AKI was significantly associated with increased mortality rates among rhabdomyolysis patients. Moreover, significant differences were found between groups regarding the subject's age, calcium level, phosphorus level, and urine output. However, the AKI was the best predictor of mortality for those who got the COVID-19 infection and rhabdomyolysis. CONCLUSION: Rhabdomyolysis increases the risk of death in COVID-19 patients admitted to the ICU. The strongest predictor of a fatal outcome was acute kidney injury. The findings of this study emphasize the importance of early identification and prompt treatment of rhabdomyolysis in patients with severe COVID-19.

Immediate and contributory causes of death in patients hospitalized with COVID-19.

OBJECTIVES: Accurate determination of the immediate causes of death in patients with COVID-19 is important for optimal care and mitigation strategies. METHODS: All deaths in Qatar between March 01, 2020, and August 31, 2022, flagged for likely relationship to COVID-19 were reviewed by two independent, trained reviewers using a standardized methodology to determine the immediate and contributory causes of death. RESULTS: Among 749 flagged deaths, the most common admitting diagnoses were respiratory tract infection (91%) and major adverse cardiac event (MACE, 2.3%). The most common immediate causes of death were COVID-19 pneumonia (66.2%), MACE (7.1%), hospital-associated pneumonia (HAP, 6.8%), bacteremia (6.3%), disseminated fungal infection (DFI, 5.2%), and thromboembolism (4.5%). After COVID-19 pneumonia, MACE was the predominant cause of death in the first 2 weeks but declined thereafter. No death occurred due to bacteremia, HAP, or DFI in the first week after hospitalization, but became increasingly common with increased length of stay in the hospital accounting for 9%, 12%, and 10% of all deaths after 4 weeks in the hospital, respectively. CONCLUSION: Nearly one-third of patients with COVID-19 infection die of non-COVID-19 causes, some of which are preventable. Mitigation strategies should be instituted to reduce the risk of such deaths.

Influenza prevalence and vaccine efficacy among diabetic patients in Qatar.

Seasonal influenza viruses may lead to severe illness and mortality in patients with comorbidities, including Diabetes Mellitus (DM). Vaccination against influenza in DM patients may reduce influenza incidence and severity. Before the emergence of the COVID-19 pandemic, influenza infections were the most prevalent respiratory infections in Qatar. Still, reports about influenza prevalence and vaccine efficacy in DM patients have not been reported. This study aimed to analyze influenza prevalence among other respiratory infections and assess influenza vaccine efficacy in DM patients in Qatar. Statistical analysis was performed on data obtained from Hamad Medical Corporation (HMC) database for patients that visited the emergency department (ED) with respiratory-like illnesses. The analysis was done for the period between January 2016 to December 2018. Among 17,525 patients who visited HMC-ED with clinical symptoms of respiratory infections, 2611(14.9%) were reported to have DM. Among DM patients, influenza was the most prevalent respiratory pathogen at 48.9%. Influenza virus A (IVA) was the most circulating type, contributing to 38.4%, followed by IVB contributing to 10.4% of total respiratory infections. Among the typed IVA-positive cases, 33.4% were H1N1, and 7.7% were H3N2. A significant decrease in influenza infections was reported in vaccinated DM patients (14.5%) when compared to non-vaccinated patients (18.9%) (p-value = 0.006). However, there was no significant relaxation in the clinical symptoms among vaccinated DM patients compared to their non-vaccinated counterparts. In conclusion, influenza was the most common etiology for respiratory viral infection among diabetic patients at the leading healthcare provider in Qatar. Although vaccination reduced the incidence rate among DM patients, it was less effective in preventing symptoms. Further studies on a larger cohort and for a more extended period are required to investigate influenza prevalence and vaccine efficacy among DM patients.

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial.

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39-7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients' subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.

A new One Health Framework in Qatar for future emerging and re-emerging zoonotic diseases preparedness and response.

One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022-2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface.

Evaluation of mortality attributable to SARS-CoV-2 vaccine administration using national level data from Qatar.

Accurate determination of mortality attributable to SARS-CoV-2 vaccination is critical in allaying concerns about their safety. We reviewed every death in Qatar that occurred within 30 days of any SARS-CoV-2 vaccine administration between January 1, 2021 and June 12, 2022. Probability of association with SARS-CoV-2 vaccination was determined by four independent trained reviewers using a modified WHO algorithm. Among 6,928,359 doses administered, 138 deaths occurred within 30 days of vaccination; eight had a high probability (1.15/1,000,000 doses), 15 had intermediate probability (2.38/1,000,000 doses), and 112 had low probability or no association with vaccination. The death rate among those with high probability of relationship to SARS-CoV-2 vaccination was 0.34/100,000 unique vaccine recipients, while death rate among those with either high or intermediate probability of relationship to SARS-CoV-2 vaccination was 0.98/100,000 unique vaccine recipients. In conclusion, deaths attributable to SARS-CoV-2 vaccination are extremely rare and lower than the overall crude mortality rate in Qatar.

Multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19 mRNA vaccination - A case report from Qatar.

COVID-19 vaccines are generally proven safe in all population and are highly recommended. However, rare adverse events have been reported. We hereby present a case of an 18-year-old man who presented to emergency department with fever, meningitis like symptoms, shortness of breath, chest pain, skin rash, and extreme fatigue. He had cardiac manifestations including hypotension, elevated troponin, and reduced ejection fraction. High inflammatory markers were also noted. He was initially worked up for and treated as a possible infectious etiology, but the microbiological studies were negative and there was no response to treatment. Since he had recently received booster dose of Pfizer-BioNTech COVID-19 vaccination three weeks prior to onset of symptoms, a possibility of Multisystem inflammatory syndrome in children (MIS-C) was made. His presentation fulfilled all the diagnostic criteria. The possibility for MIS-C being related to vaccination was proposed after relevant serological tests showed that the antibodies, he had were due to COVID-19 vaccine, not to a prior infection. After he received appropriate immunomodulatory treatment (IVIG and methylprednisolone) as per the guideline, he showed marked clinical improvement. Our case report highlights the need to consider MIS-C as a potential differential in young patients who present with unexplained multisystem illness with increased inflammatory markers and negative microbiologic work-up. MIS-C can be secondary to COVID-19 vaccination as well as to prior COVID-19 infection.

Dilemma of Tocilizumab therapy for a patient with critical COVID-19 disease and neutropenia: Case report and review of the literature.

Infection following SARS-Co V-2 leading to COVID-19 disease is associated with significant morbidity and mortality. The clinical entity, COVID-19 cytokine storm syndrome (CSS) is a severe immunological manifestation of the disease associated with ominous consequences. Tocilizumab is interleukin-6 inhibitors that has been shown to hamper the catastrophic outcomes of CCS including the need for mechanical ventilation as well as reduce mortality, but the usage is limited by warnings of reactivation of potential latent infections or immune dysfunctions including severe neutropenia. We describe a case of 39-year-old Nepalese male patient with a background of scleritis maintained on azathioprine and rituximab therapy with normal baseline parameters including complete blood count who presented with acute COVID-19 infection including associated leukopenia as well as severe neutropenia (absolute neutrophil count of 300 cells/µl), then progressed to critical disease culminating into CSS. Based on risks and benefits evaluation, the patient was treated with tocilizumab reinforced with granulocytes-colony stimulating factor (G-CSF, Filgrastim) to full recovery and safe outcome including reversal of neutropenia.

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. METHODS AND FINDINGS: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. CONCLUSION: In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04425382.

Burden and disease pathogenesis of influenza and other respiratory viruses in diabetic patients.

Over the past two decades, diabetes mellitus (DM) has been receiving increasing attention among autoimmune diseases. The prevalence of type 1 and type 2 diabetes has increased rapidly and has become one of the leading causes of death worldwide. Therefore, a better understanding of the genetic and environmental risk factors that trigger the onset of DM would help develop more efficient therapeutics and preventive measures. The role and mechanism of respiratory viruses in inducing autoimmunity have been frequently reported. On the other hand, the association of DM with respiratory infections might result in severe complications or even death. Since influenza is the most common respiratory infection, DM patients experience disease severity and increased hospitalization during influenza season. Vaccinating diabetic patients against influenza would significantly reduce hospitalization due to disease severity. However, recent studies also report the role of viral vaccines in inducing autoimmunity, specifically diabetes. This review reports causes of diabetes, including genetic and viral factors, with a special focus on respiratory viruses. We further brief the burden of influenza-associated complications and the effectiveness of the influenza vaccine in DM patients.

Remdesivir for COVID-19 pneumonia in patients with severe chronic kidney disease: A Case series and review of the literature.

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications.

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.

Prevalence of elevated anxiety symptoms among children in quarantine with COVID-19 infection in the State of Qatar: A cross-sectional study.

BACKGROUND: Children are particularly vulnerable to the psychological effects of the COVID-19 pandemic. The disruption in daily life has impacted children significantly. Moreover, the increased worrying associated with the probability of getting infected or becoming seriously unwell due to infection can potentially precipitate anxiety disorders among children. OBJECTIVE: This study aimed to determine rates of elevated anxiety symptoms in children with COVID-19 infection. It also explored whether there were any differences in terms of age, gender, and residency status. METHOD: A cross-sectional, questionnaire-based study with 88 participants (children aged 7-13 years, 54.5% males, 45.5% females) from two institutional quarantine centers. The Spence Children's Anxiety Scale and its validated Arabic version (self-reported questionnaires) were used to measure anxiety symptoms. RESULTS: 36.3% children reported elevated anxiety symptoms. A lower rate of 32.8% was reported in younger children (7-11 years) compared to 45.8% in older children (12 and 13 years). 70.4% and 57.9% children reported physical injury fears and separation anxiety respectively. A higher prevalence of overall anxiety was reported in children from expatriate families (40.6%) compared to native children (25%). The difference in the mean scores between the expatriate and native group of children was found statistically significant for obsessive-compulsive symptoms. CONCLUSIONS: The prevalence of elevated anxiety symptoms among children in quarantine with COVID-19 infection can be much higher than that reported in the general population. Older children can have elevated anxiety symptoms more commonly than their younger counterparts can. Expatriate children are likely to be more vulnerable to the psychological impact of the pandemic compared to children from local families. Our results suggest the crucial need of focusing on the psychological impact of COVID-19 pandemic on children. The prioritization and effective management of the mental health needs of children should be a vital component of the overall, global response to the pandemic.

Physical and Psychosocial Well-Being of Hospitalized and Non-Hospitalized Patients With COVID-19 Compared to the General Population in Qatar.

Background: Many studies have shown a high prevalence of depression, anxiety, and stress symptoms in COVID-19 patients and the general population. However, very few studies directly examined the potential impact on the health-related quality of life (HRQoL), and none compared HRQoL in COVID-19 patients to the general population amid the pandemic. Methods: We carried out a cross-sectional study comparing HRQoL (as measured using the RAND Short Form 36 or SF-36 Health Survey) in randomly selected individuals from three different groups: hospitalized COVID-19 patients, quarantined COVID-19 patients, and controls from the general population in Qatar. We constructed a multivariate analysis of covariance (MANCOVA) to compare the SF-36 scores between the three groups and control for various covariates. Results: Our sample consisted of 141 COVID-19 inpatients, 99 COVID-19 quarantined patients, and 285 healthy controls. Surprisingly, we found that HRQoL was higher in COVID-19 hospitalized than in COVID-19 non-hospitalized patients than in controls. The main components where COVID-patients scored higher than controls were physical functioning and role limitations due to emotional problems. In COVID-19 patients, the female gender, older age, and past psychiatric history were associated with lower HRQoL. Conclusions: It seems that COVID-19 patient's HRQoL might be better than expected. Our results can be explained by social support from family and friends, easy access to mental health screening and care, and a possible change of perspectives after recovery from COVID-19, resulting in psychological growth and enhanced resilience.

One Year of SARS-CoV-2: Genomic Characterization of COVID-19 Outbreak in Qatar.

Qatar, a country with a strong health system and a diverse population consisting mainly of expatriate residents, has experienced two large waves of COVID-19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global population's genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number of mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. These findings raise the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor the SARS-CoV-2 profile and re-emergence in Qatar.

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.

Ominous combination: COVID-19 disease and Candida auris fungemia-Case report and review of the literature.

The identification of Candida auris fungemia in critically ill COVID-19 patients is detrimental, with huge implications on patient mortality and infectious control measures.