A Case of Hyperhemolysis Syndrome in Sickle Cell Disease and Concomitant COVID-19

Background Hyperhemolysis syndrome (HHS) is an uncommon transfusion reaction described in several hematologic disorders, including sickle cell disease (SCD). HHS is characterized by a decline in hemoglobin (Hb) values below pre-transfusion levels following transfusion of red blood cells (RBCs), coupled with laboratory markers consistent with hemolysis. The proposed pathophysiologic mechanisms underlying HHS include increased phosphatidylserine expression, macrophage activation, and complement dysregulation. Many pathophysiologic mechanisms thought to contribute to HHS have been similarly described in cases of severe COVID-19. Case Report A 28-year-old male with a history of HbSS presented with shortness of breath, right-sided chest pain, and a two-day history of fever. Polymerase chain reaction (PCR) detected SARS-CoV-2 infection with the omicron variant. The patient required an RBC transfusion (pre-transfusion hemoglobin [Hb]5.8 g/dL) with an immediate post-transfusion Hb of 6.3 g/dL. However, Hb rapidly declined to 1.7 g/dL, and lactate dehydrogenase (LDH) rose to 8,701 u/L. The absolute reticulocyte count of 538×109/L correspondingly fell to 29×109/L. Despite additional RBC transfusions and initiation of immunosuppressive therapy, he expired on Day 9(D9). Conclusion Given the similarities in their proposed pathophysiology, patients with SCD and concomitant SARS-CoV-2 infection may be predisposed to developing HHS.

The Incidence of Long-Term Fatigue in Patients Who Achieved Remission From COVID-19 at King Abdulaziz Medical City.

Introduction Long-term fatigue is a common condition that involves both physical and psychiatric symptoms, and it affects multiple age groups and causes morbidity and disabling symptoms that range from mild to severe symptoms. Many patients are discharged following coronavirus disease 2019 (COVID-19) infection without proper follow-up and evaluation of long-term effects, resulting in the improper treatment of the long-term symptoms, which increases the burden on the patients and healthcare systems. Coronavirus disease 2019 (COVID-19) is a disease caused by the novel SARS-CoV-2. It results in a variety of symptoms, including fever, cough, respiratory distress, the loss of the sense of smell and taste, and long-term effects such as post-severe acute respiratory syndrome (SARS), which is characterized by chronic fatigue, sleep disturbances, myalgia, weakness, and depression. The aim of this study is to assess the incidence of long-term fatigue in patients who achieved remission from COVID-19 at King Abdulaziz Medical City (KAMC), National Guards Health Affairs, Riyadh. Methods We conducted a cross-sectional, non-probability convenience sampling study. All participants who were diagnosed with COVID-19 and achieved remission were approached in an outpatient department (OPD) setting and signed an informed consent form and were evaluated by standard questionnaires at clinics after remission from COVID-19 at King Abdulaziz Medical City in Riyadh, Saudi Arabia. A total of 343 subjects who fit the inclusion criteria of any patients who have been diagnosed with COVID-19 and achieved remission were included in the study. This study included patients from the National Guard Hospital, students, and staff members. The primary outcome variable was the incidence of long-term fatigue in patients who achieved remission from COVID-19 as measured by the Chalder fatigue scale (CFQ). The participants were approached in clinics and general OPD by one of the research teams. Results Based on the study design, 343 patients were selected from King Abdulaziz Medical City in Riyadh, the incidence of long-term fatigue in patients who achieved remission from COVID-19 was 55.7%, and the rest were normal (44.3%). The incidence of long-term fatigue was statistically significantly higher in females and those who had been diagnosed with COVID-19 and achieved remission for more than two months. The age of the participants ranged from 18 to more than 45, with a predominance of females (60.6%). Regarding body mass index (BMI), 39.9% were overweight, and 29.2% were obese. Additionally, the incidence of patients with associated chronic disease was 27.4%; among these chronic diseases, hypertension was the most common one (18.1%), followed by diabetes (17%) and thyroid diseases (14.9%). Conclusion To the best of our knowledge, this is one of the few studies that were carried out in Saudi Arabia that assess long-term fatigue post COVID-19 infection. In our study, we discovered that long-term fatigue was highly prevalent (55.7%). We found that among those participants, more than half of those who reported chronic fatigue had a COVID-19 diagnosis for longer than two months. Furthermore, females made up the majority of those who had long-term fatigue. We urge that additional longitudinal and standardized studies be carried out in order to thoroughly determine the severity of long-term fatigue in patients who obtained remission from COVID-19.

Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy.

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.

Malaysian Enhanced Movement Control Order (EMCO): a unique and impactful approach to combating pandemic COVID-19

Purpose - The paper highlights the process-handling during the Enhanced Movement Control Order (EMCO) in combating pandemic COVID-19 in Malaysia. Design/methodology/approach - Malaysia first issued an EMCO following a cluster that involved a religious gathering. The EMCO was issued to lockdown the area, undertake screening, treat positive cases and quarantine their close contacts. Active case detection and mass sampling were the main activities involving the population in both zones. Findings - One hundred ninety-three confirmed COVID-19 cases were identified from the total population of 2,599. Of these cases, 99.5% were Malaysians, 31.7% were aged >60 years and all four deaths (Case Fatality Rate, 2.1%) were elderly people with comorbidities. One hundred and one cases (52.3%) were asymptomatic, of which 77 (77%) were detected during mass sampling. The risk factors contributing to the outbreak were contacts that had attended the religious gathering, regular mosque congregants, wedding ceremony attendees and close household contacts. Malaysia implemented an effective measure in the form of the EMCO to contain the COVID-19 outbreak, where the last cases were reported 16 days before the EMCO was lifted. Originality/value - The residents' compliance and inter-agency cooperation were essential elements to the success of the EMCO. A targeted approach using an EMCO should be implemented in a future pandemic.

Learning management systems, education technology advancement, successes adoption of Delone-McLean model approaches

The education system has been greatly impacted due to the coronavirus disease 2019 (COVID-19) which was first reported on 3 0th January 2020 by World Health Organisation (WHO). This leads many to adopt and inculcate online learning and learning management systems for blended learning. The aim of this chapter is to study the success of using Moodle Learning Management System that is used among the students and lecturers in University Technology Brunei using the updated DeLone and McLean Information System Success Model. This study employs a mixed methods approach that comprises of both qualitative (through semi-structured interviews) and quantitative methods (collected using the adapted instruments from D&M 2003 Model). The outcome of the research shows support and validation of the adapted model and instruments. System quality and information quality were identified to be the constructs to determine the overall success. © 2023, IGI Global.

Experiences of online learning and teaching during the second phase of the COVID-19 pandemic: A study of in-service teachers at the Fiji National University

The current study investigated the experiences of in-service teachers' at Fiji National University (FNU) during the second phase of the COVID-19 pandemic. The research aimed to contribute to the evidence base of factors affecting the effectiveness of online learning for in-service teacher education in Fiji and identify strategies for improving student experiences in Fiji and similar contexts. The study involved an online questionnaire administered to 97 in-service teachers at FNU and a follow-up one-on-one interview with six questionnaire participants. The paper is structured into three sections: outlining the literature, context and methods used to gather the data;presentation of the results about online learning experiences of in-service teachers during the COVID-19 pandemic;discussion of the challenges faced by the in-service teachers in adapting to the online learning process during the COVID-19 pandemic. The main findings indicate that the FNU in-service teachers faced challenges in transitioning from face-to-face to online instruction, but, for at least some, the transition also brought benefits. The four main challenges included poor connectivity issues, unavailability of devices, inadequate technological skills and the demands of multiple roles. The benefits of online learning comprised improving students' technical skills, upskilling higher education staff and systems, staying connected during tough times, saving money and time, flexibility and convenience. The study reveals that adaptation should focus on improving the courses and accommodating the digital gap among in-service teachers by providing mobile-friendly, synchronous and asynchronous activities.

COVID-19 signalome: Potential therapeutic interventions.

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development.

Two years efficacy and safety results from real world experience for cladribine tablets in management of relapsing multiple sclerosis in Qatar

Objectives: To study safety and efficacy of Cladribine tablets (Clad T) treatment in RMS patients over 2 years in a real-world clinical setting. Aim(s): To describe the efficacy and safety in Real-world experience in an Arab Population. Method(s): This is a retrospective single-centre observational study in Qatar. Medical records of Relapsing Multiple Sclerosis (RMS) patients who received at least one year treatment of Cladribine treatment between January 2018 through December 2021 were reviewed. Demographic and clinical aspects, EDSS, previous disease-modifying drugs (DMD) and annual relapse rate (ARR) were recorded. MRI data of patients who completed at least first-year course of Cladribine tablets were assessed as well adverse events. Result(s): A total of 49 RMS patients (46 RRMS, 3 SPMS) were included, from those 34 (69%) were females. Mean age at Clad T initiation was 32 (18-59), mean disease duration is 7.6 (1-25) years. 25 patients (51%) were treatment naive, and 24 patients (49%) had one or more disease modifying therapy (DMT) before treatment. The most common reason for treatment with cladribine was disease activity (68 %), pregnancy planning (11%), compliance (10%) and side effects (11%). Prior DMTs included DMF (40%), Fingolimod (16%), Teriflunomide (16%), Natalizumab (12%), Interferon Beta (12%) and Ocrelizumab (5%). By December 2021, 32 patients finished the two courses of the drug. The Median follow-up period of the total cohort was 32 months. 26/32 (81.25%) patients were relapse free post treatment compared to 25% pretreatment. Annualised relapse rate (ARR) was reduced by 92% (0.08 vs 0.97). 75% of patients were free of Gd+ T1 lesions post treatment compared to 37.5% at the baseline. Majority of MRI findings (7/8) were observed in the 1st year of treatment and only one patient experimented radiological activity after the second-year course. 31 patients (96.8%) had no 3 months confirmed EDSS progression. Only mild Adverse events were reported and single case of herpes zoster, urinary tract infection and oral candidiasis. All COVID-19 cases (n=12) were mild and didn't need hospitalization. Grade 3 lymphopenia was recorder for 5 patients (1.5%) and no grade 4 was observed. Conclusion(s): Our real-world experience confirms good efficacy, tolerability, and safety of cladribine tablets in consistency with data from phase 3 clinical trials and other real-life studies. Reported adverse events showed lower frequency of lymphocytopenia.

Home based peritoneal dialysis training during COVID-19 era: A single centre experience

Introduction: COVID-19 disease has been declared as a pandemic since February 2020. Resulting from this, home peritoneal dialysis training programme was implemented. However, infectious complications was one of our major concerns. Material(s) and Method(s): This is a single centre, observational, retrospective study. We recruited patients who were newly enrolled into the peritoneal dialysis programme from January 2020 until March 2021 and follow up them for 6 months duration. Patients' demographic data, baseline characteristic, clinical outcome were collected through electronic health record (eHIS) and data were analysed using SPSS version 23. Result(s): A total of 133 patients were enrolled into the peritoneal dialysis programme. The median age of the patients was 55(42-65) years old. Most of the patients were on CAPD, 87(65.4%), and 76(57.1%) of them were on self-care peritoneal dialysis (PD). During this observational period, 29(21.8%) patients underwent hospital based training, while a total of 104(78.2%) patients underwent home based training. The PD peritonitis rate for hospital based training was 1 episode per 55.8 patient months while home based training group was 1 episode per 25.4 patient month. The survival free to 1st PD peritonitis for home based training was 83.7% over 6 months. The exit site infection rate was 1 episode per 73.1 patient month. Conclusion(s): Home based PD training should be encouraged especially during Covid-19 pandemic period, but standardised training protocol should be implemented to improve the clinical outcome of our patients.

Mortality rate and associated risk factors in hospitalised COVID-19 patients with kidney disease

Introduction: COVID-19 still poses a high morbidity and mortality in chronic kidney disease. We aim to determine the risk factors for mortality amongst hospitalised COVID-19 patients with kidney disease. Material(s) and Method(s): This is an observational cohort study involving all COVID-19 patients with kidney disease in the first quarter of 2021. Relevant data was extracted from the electronic medical records and statistical analysis was conducted using SPSS version 26. Result(s): Of 414 COVID-19 patients, 165 (39.9%) had kidney disease [25.5% end stage kidney disease (ESKD), 4.2% chronic kidney disease (CKD) and 70.3% acute kidney injury (AKI)). 56 of them died, giving an inpatient mortality rate of 33.9% in patients with kidney disease compared to 17.1% from all COVID-19 admissions. ESKD had the highest mortality rate at 42.9% followed by AKI, 31% and CKD, 28.6% (p=0.365). Majority of patients with kidney disease who died, were older (66 +/- 10.4 vs 54 +/- 14.6, p<0.001), male (78.6% vs 61.5%, p=0.035) and had category 5 infection (28.6% vs 19.3%;p=0.009). 66.1% were on mechanical ventilation while 51.8% were managed in the intensive care unit. Multiple logistic regression predicted older age, premorbid CKD & ESKD, raised peak serum sodium, admission category of illness 4 & 5, mechanical ventilation and unknown epidemiology link to increase mortality risk in patients with COVID-19 infection with kidney disease. Conclusion(s): COVID-19 mortality rate remains high amongst those with ESKD, CKD and AKI. Future studies should evaluate the incidence and outcome post vaccination.

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.

Strategies to Minimise the Impact of COVID-19 on the Construction Industry: A Case Study of Construction Site Clusters in Malaysia

Malaysia has seen the third wave of infection since the start of the global COVID-19 pandemic, with approximately 103 construction sites involving over 14,677 workers reported from April 2020 to February 2021. This has led to limited progress in construction projects or a complete halt, resulting in late project delivery. The purpose of this paper is to investigate the factors influencing the spread of COVID-19 and the strategies taken by the affected construction sites to mitigate the spread of the outbreak. The researchers adopted a case study approach with a multiple-case design and discusses the use of an in-depth interviewing method to collect rich data on the studied phenomenon. Data collected from three construction sites. The sites were mixed development projects in nature and provided in-depth, rigorous, and robust information. Based on the results, two categories of factors influencing the spread of COVID-19 were established. These are primary and secondary factors, such as workers’ mobilisation, uncontrolled movement of workers, and the limited practice of social distancing. Furthermore, evidence suggests that the strategies adopted to control the effects of the pandemic were a combination of government enforcement and initiatives taken by construction companies. This paper concludes that an early identification of the causes of the spread will enable appropriate implementation strategies to control the outbreak. This study is an attempt to present the experiences of one developing country as an example of a means of dealing with unexpected pandemics or other intractable diseases that can affect project delivery. © 2022 by the author(s).

Unusual Presentation of Acute Myeloid Leukemia (AML-M2): A Case Report

Context: Acute myeloid leukemia (AML) is rarely presented with thrombocytosis and marked thrombocytosis with a platelet count over 1.0×1012/L is an extremely rare phenomenon. Objective: A case of de novo AML with unusual presentation by extreme thrombocytosis. Design: A case report. Setting: Hematology Unit at the Oncology Center Mansoura University, Egypt. Patient: A 37-year-old male patient with a history of sleeve gastrectomy in 2020, presented with oral mucositis, recurrent abscess, fever, and bilateral axillary lymphadenopathy. Initial complete blood count (CBC) showed a Hb level of 6 g/dL, a platelet count of 1.685×109/L, and a white blood cell (WBC) count of 19×109/L. Diagnosis of de novo AML (FAB-M2 AML) was confirmed by bone marrow aspiration, biopsy, and immunophenotyping. Cytogenetic study showed negative t(8;21)/inv 16/ t(9;22). A molecular study showed positive FLT-3 mutation and negative BCP/ABL1, JAK2, V617F, and CALR exon 9 mutations excluding blast transformation on top of myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS). Interventions: The patient received induction chemotherapy including a course of 7-day-cytarabine along with 3-day-anthracycline on September 20th, 2021 but the patient was refractory as BMA showed blast cells 75%. The patient started salvage HAM (high-dose cytosine arabinoside and mitoxantrone) + Sorafenib on November 6th, 2021. Again, he could not achieve a response and received FLAG (high-dose cytosine arabinoside, fludarabine, and granulocyte colony-stimulating factors) + Sorafenib on December 18th, 2021, after recovery from COVID-19 infection. Main Outcome Measures: To shed light on fact that myeloid neoplasms as MPN, MDS, and de novo AML can share overlapping features. Results: On January 25th, 2022, the last CBC showed a Hb level of 8.4 g/dL, a platelet Count of 395×109/L, and a WBC Count of 2.41×109/L with a differential Neutrophil count of 0.24×109/L. The patient lost follow-up since then. Conclusions: Only a few AML cases have been reported with thrombocytosis. Detailed molecular studies are mandatory to confirm the diagnosis of de novo AML patients with unusual presentation. Careful follow-up of those cases could help in establishing management guidelines for better outcomes as those patients usually have a poor prognosis.

Emergence and spread of two SARS-CoV-2 variants of interest in Nigeria. (preprint)

Identifying the dissemination patterns and impacts of a virus of economic or health importance during a pandemic is crucial, as it informs the public on policies for containment in order to reduce the spread of the virus. In this study, we integrated genomic and travel data to investigate the emergence and spread of the B.1.1.318 and B.1.525 variants of interest in Nigeria and the wider Africa region. By integrating travel data and phylogeographic reconstructions, we find that these two variants that arose during the second wave emerged from within Africa, with the B.1.525 from Nigeria, and then spread to other parts of the world. Our results show how regional connectivity in downsampled regions like Africa can often influence virus transmissions between neighbouring countries. Our findings demonstrate the power of genomic analysis when combined with mobility and epidemiological data to identify the drivers of transmission in the region, generating actionable information for public health decision makers in the region.

Detection of erythroid progenitors and erythrocytopathies in patients with severe COVID-19 disease.

OBJECTIVES: To assess the effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on erythropoiesis and red blood cells (RBC) surface markers by evaluating erythroid progenitor cells (CD [cluster of differentiation]71+/CD235a+) and RBC surface markers (CD235a and CD36), together with various hematological parameters. METHODS: This case-control study includes 47 participants recruited in the study: 30 patients with coronavirus disease 2019 (COVID-19) and 17 healthy individuals. The COVID-19 patients were recruited from the intensive care unit (ICU) of various hospitals in Makkah, Saudi Arabia. Blood samples were collected during July and September 2021. Red blood cells indices were measured using a CBC analyzer. The expression of CD235a, CD71, and CD36 was obtained using flow cytometry technique. The unpaired t-test was conducted to evaluate the differences in these markers in COVID-19 patients and healthy individuals. RESULTS: The data showed that more than half of the COVID-19 patients were anemic (64%). Expansion of erythroid progenitors (CD71+/CD235a+) was detected in the COVID-19 patients. Analysis of the expression of RBC surface markers, such as CD235a and CD36, showed that SARS-CoV-2 was associated with significantly higher expression of these markers in COVID-19 patients. CONCLUSION: Severe acute respiratory syndrome coronavirus-2 promoted the expansion of erythroid progenitors in the peripheral blood of COVID-19 patients. In addition, the expression of RBC surface markers was higher in COVID-19 patients. The expansion of erythroid progenitors and alteration of RBC surface markers can contribute to erythrocytopathies observed in severe COVID-19 patients and can therefore be used as prognostic factors.