The virus SARS-CoV-2 commonly causes self-resolving, flu-like illnesses in most patients, but a critical illness can be seen in 5 per cent of cases – especially in the elderly population or in patients with multiple comorbidities. It causes significant cytopenia, mainly severe lymphopenia, and excessive exhaustion of CD8+ T cells, resulting in an immunocompromised state and cytokine storm. Furthermore, COVID-19 can commonly be complicated with acute thrombotic events, including venous thromboembolism, acute stroke, acute myocardial infarction, clotting of hemodialysis and extracorporeal membrane oxygenation (ECMO) catheters, and acute limb ischemia. This makes SARS-COV-2 a unique virus with an undiscovered pathophysiology.

 The most reported blood count abnormality is lymphopenia which occurs in 35-83 per cent of patients. In addition to a significant reduction in both CD4+ and CD8+ T lymphocyte subsets in COVID-19 patients, severe cases had much lower CD8+ lymphocytes and a subsequent increase positively correlated with improved clinical outcomes.

Related: COVID-19 risk avoidance and management in limited-resource countries

Mild thrombocytopenia has been reported in up to 20-36 per cent of COVID-19 cases however, severe thrombocytopenia is less frequent. Thrombocytopenia was independently predictive of the risk of admission to ICU, mechanical ventilation, or death. In addition, bone marrow hemophagocytosis can be a feature of severe COVID-19 and this has been observed in a small number of patients. The cytokine storm syndrome is also associated with the secondary Haemophagocytic lymphohistiocytosis (sHLH).

The diagnostic criteria of sHLH based on the H-score are fever, hepatomegaly and/or splenomegaly, 2 or 3 cytopenias, hypertriglyceridemia or hypofibrinogenaemia (or both), hyperferritinemia, serum aspartate aminotransferase elevation, hemophagocytosis on bone marrow aspirate and known immunosuppression. Laboratory tests such as elevated ferritin are useful predictors of fatality as shown in a recent retrospective, multicenter study of 150 confirmed COVID-19 cases in Wuhan, China. This report suggested that COVID-19 related mortality might be due to virally driven hyperinflammation. Neutrophil to lymphocyte ratio (NLR) has also been documented as a useful triage tool.

Related: Novel collaborative approach among public and private sectors

Patients affected with rheumatic diseases represent a particularly vulnerable group to present a severe COVID-19 associated to a sHLH, considering that they might be on immunosuppressive therapy.

In our hospital, we had a case of a 67-year-old lady; under a long-term immunosuppressive treatment (Methotrexate, Corticosteroids and Hydroxychloroquine) for her rheumatoid arthritis. She was asthmatic and hypertensive, so she had risk factors to develop a severe COVID-19 infection. Her H-Score for the diagnosis sHLH was evaluated at 200 and the probability of sHLH was 88 per cent.

Bone marrow aspiration findings were hypocellular and hemodiluted smears showed maturing myeloid and erythroid hematopoiesis, histiocytic cells with rare larger forms. No significant increase in blasts forms or dyserythropoiesis was seen. Non-hematological cells invading the bone marrow were not found.

Bone marrow biopsy yielded a very good length of evaluable marrow, which was slightly hypocellular in regard to the three cells lines with maturing trilineage hematopoiesis, relative erythroid hyperplasia and scattered macrophages (confirmed with CD68 immunohistochemical stains) showing evidence of hemophagocytosis. (Image 1)

The correlation of these findings with the clinical and laboratory tests, the negativity of blood cultures, urine culture, EBV and CMV serologies, and the H-Score at 200 points made the diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) highly probable.

Early recognition of sHLH, a task force involving multiple specialties (rheumatologists, hematologists, intensive care physicians, infectious disease specialists, and pulmonologists) should be involved in the treatment and the follow-up of the COVID-19 patients. 

Recent data emerging from the management of patients with COVID-19 suggests an increased thrombotic tendency. Approximately one-third of patients with COVID-19 had CT scan evidence of pulmonary embolism (PE) in a French study. Notably, two thirds of the patients without PE in this cohort also had elevated D-dimers with a higher cut off value of 2660 µg/L being more predictive of PE in this cohort. From a prognostic perspective, D-dimers appear to be the most useful coagulation parameter as progressive increase in D-Dimer level is associated with the development of severe disease and in-hospital mortality.

In a study comparing coagulation parameters in hospitalised COVID-19 patients, 15 (71.4 per cent) of no survivors met the International Society on Thrombosis and Haemostasias (ISTH) criteria for overt Disseminated Intravascular Coagulation (DIC) compared with 1 (0.6 per cent) of survivors.

With recent reports of thrombotic complications in patients with COVID-19, there is increasing recognition of a distinct coagulopathy associated with COVID-19. The underlying mechanism is likely to be multifactorial including direct endothelial damage from SARS-CoV-2 or immune cells, inflammatory cytokine-induced activation of the coagulation cascade, the development of antiphospholipid antibodies and an increase in acute phase pro-coagulants such as Factor VIII and fibrinogen. Consequently, the recently published ISTH interim guidance recommends prophylactic anticoagulation with low molecular weight heparin (LMWH) for all hospitalised patients with COVID-19.

A lot is still not known about the marked difference between immune responses to SARS-CoV-2 between individuals and it is likely that genetic and environmental factors also play a role. Of particular interest is the association between certain ABO blood group genotypes and the likelihood of severe COVID-19. In a recently published genome wide association study, Blood group A and a few other Single Nucleotide Polymorphisms (SNPs) were associated with an increased risk of COVID-19-induced respiratory failure (Blood group O was apparently protective). Interestingly, Blood group A has also been shown to be associated with increased odds of thromboembolic and cardiovascular events. These findings are hardly surprising because blood group A individuals (as well as other non-O blood groups) are known to have higher plasma Von Willebrand levels and ABO blood group antigens have innate immune functions

Recently, some cases of thrombosis were also reported with a COVID-19 vaccine, the International Society on Thrombosis and Haemostasias (ISTH) recommends that all eligible adults continue to receive their COVID-19 vaccinations. At this time, the small number of reported thrombotic events relative to the millions of administered COVID-19 vaccinations does not suggest a direct link, the ISTH believes that the benefits of COVID-19 vaccination strongly outweigh any potential complications even for patients with a history of blood clots or for those taking blood thinning medications.

Therefore, monitoring of hematological parameters such as the absolute lymphocyte count, neutrophil-to-lymphocyte ratio and D-dimers can offer prognostic insight in the management of COVID-19 and will help with early identification of the high-risk group of patients requiring more intensive care.

References available on request

Dr Kayane Mheidly

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

Introduction

We demonstrate how point-of-care testing (POCT) can help transition risk avoidance to risk management during the COVID-19 crisis by applying sound geospatial strategies to a “hotspot.” We use the example of a border province in Cambodia to illustrate principles of implementing COVID-19 POCT in a limited-resource setting.

Goals

Our goals are a) to strategize high volume of COVID-19 testing to detect outbreaks quickly and limit their spread in Cambodia, b) to analyse public accessibility to COVID-19 testing, and c) to enhance awareness of COVID-19 test performance over the entire range of prevalence.

Methods

We collected public health reports regarding testing, COVID-19 assay performance, and options from PubMed, the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the World Health Organization (WHO), the Phnom Penh Post, the Khmer Times, manufacturer fact sheets, and public domain sources in Cambodia.

We explored articles on COVID-19 outbreaks, geographic prevalence, and lockdowns in Cambodia. We analysed data using fundamental equations from Kost GJ, then visualised them with Desmos Graphing Calculator, Mathematica, Symbolab Math, and Wolfram Alpha Widgets. This work was approved by the Ethics Committee of the University of Puthisastra.

Results

High-resource countries, such as the United States, conducted ~1.5 million tests per one million population each day in end-May 2021, while Cambodia tested at least 20 times fewer people. Of numerous commercialised tests and diagnostic kits available globally, Cambodia is limited in testing capacity to sparsely placed real time-polymerase chain reaction (RT-PCR) assays and antigen rapid detection tests (Ag-RDTs).

There is no national standardisation nor uniform policy to guide rural healthcare facilities in use of rapid COVID-19 diagnosis or their quality control. RT-PCR is performed using the Biorad cfx 96, GeneXpert Dx, Cobas 6800, and Cobas Z480, while Ag-RDTs comprise the Panbio COVID-19 Ag RDT and the Roche Diagnostics SARS-CoV2 Rapid Antigen Test.

Testing sites are concentrated in metropolitan areas, while just a few are located in rural provinces. Ag RDT is officially permitted for use by private health facilities. PCR testing is available at national testing laboratories in Phnom Penh, Siemreap, Battambang, Sihanoukville, and Banteay Meanchey (Cambodia-Japan Friendship Mongkul Borey Provincial Hospital). Phnom Penh has 11 testing sites while most provinces have only one testing site located at the provincial referral hospital.

SARS-CoV-2 antigen tests in Cambodia will be most useful in settings of low prevalence, as shown by predictive value geometric mean-squared (PV GM2) visual logistics (Figure 1). Factors affecting antigen test performance include age (children), environmental stress (uncontrolled temperature), drive-through conditions, and expertise at swabbing. Additional challenges include environmental conditions and use of POCT in emergency settings.

Figure 1. Visual logistics — Understanding and using COVID-19 antigen tests.

Factors affecting antigen test performance shown as PV GM2 comprise age, environmental stress, drive-through conditions, and expertise at swabbing, as wells as testing at points of care and in emergency settings, as illustrated in this figure.

Smaller towns in Banteay Meachey Province, our focus region, deemed a COVID-19 “hotspot” by the MOH, are experiencing high COVID-19 infection rates (Figure 2). This province shares an international border with Thailand. Human migration adds to risk, contagion, and the need for rapid diagnosis. Rapid testing can be appropriately placed and easily accessible close to the border.

Among 72 available public health facilities in this province, only three main hospitals offer COVID-19 testing — Cambodia-Japan Friendship Mongkul Borey Provincial Hospital, Serey Sorphorn Referral Hospital, and Poipet Referral Hospital. The first one provides RT-PCR testing using the GeneXpert, and the others, rapid antigen testing (see Figure 2).

Figure 2. Banteay Meanchey Province, human migration, and spread of contagion in Cambodia — the role of rapid POC diagnostics.

Cambodians own Leung Ke market shops in Thailand. They make regular visits to Thai hospitals. That mingling brings COVID-19 contagion and other problems to bear on the healthcare small-world network of the neighboring province in Cambodia. 

From geospatial analysis, people must travel an average of 43 (SD 24) kilometres or about 85 (SD 48) minutes one way by motorcycle to obtain RT-PCR testing at Cambodia-Japan Friendship Mongkul Borey Provincial Hospital (Table 1). Queuing time, return trip, large families, and wages lost diminish motivation to make the trips. Figure 2 provides a medically and economically effective solution by moving testing closer to the actual sites of community need.

Discussion

Strategic risk management through quick access to COVID-19 testing will benefit the capital, Phnom Penh, and rural areas. COVID-19 waves in rural Thailand and daily human migration call for rapid antigen testing to avoid risk. Scaling up of rapid antigen tests at health facilities in rural and border areas identified by geospatial analysis will enhance early detection at points of need.

RT-PCR should be placed in Poipet Referral Hospital (see Figure 2) to identify infections near the border where residents cross to Thai markets, healthcare sites, and in better times, casinos. Rapid antigen testing made available in Phnom Srok, Preah Neth Preah, Malai Health Center, and others will facilitate care of non-COVID-19 emergencies (e.g., acute myocardial infarction and motor vehicle accidents). That is, rapid identification of SARS-CoV-2 infected patients will help keep healthcare personnel safe.

Several point-of-care strategies represent proven COVID-19 solutions — drive-through and walk-up sites, self-swabbing, and mobile vans for immigration, airports, residences, schools, sports, markets, factories, and numerous others — basically, wherever testing is needed. For example, mobile drive-thru testing implemented in Solano County, California, U.S. (Figure 3) represents a valuable solution that Cambodia can develop to promote resilience through rapid evidence-based decision-making directly at sites of need in communities.

Figure 3. Mobile van equipped with five types of COVID-19 tests used to detect and manage outbreaks in small communities in America.

Recommendations and future vision

With limited resources, Cambodia should carefully and urgently devise a national testing plan by employing geospatial analysis, transit time metrics, and strategic mappings to avoid and manage COVID-19 risk and outbreaks (Table 2).

Performance analysis with visual logistics for pattern recognition will help health providers to select appropriate test formats and optimize COVID-19 diagnostics in different settings, environmental conditions, and community prevalence.

Mobile, drive-through, and walk-up POCT will allow public health practitioners to detect outbreaks and limit their spread, especially in crowded places like markets, regions of human migration, and daily transits across borders.

As geographic needs transition from risk avoidance to risk management, national leadership should establish POCT policy, guidelines, and plans for highly infectious diseases to achieve equitable access to diagnostic tests as well as vaccinations, which go hand-in-hand to end the pandemic.

Acknowledgements

This work was supported by the Point-of-Care Testing Center for Teaching and Research (POCT•CTR), School of Medicine, UC Davis; by Dr. Kost, Director; and by a Fulbright Scholar Award (GK) 2020-2022, ASEAN Program. Figures and tables were provided courtesy and permission of Knowledge Optimization, Davis, California, which reserves all rights to this work and grants Omnia Health Magazine the one-time permission to publish this work digitally as a proceedings report of the Medlab Middle East presentation by Dr. Kost, which rendition does not preclude publication in a medical journal. 

References

Kost GJ. Designing and interpreting Coronavirus Disease 2019 (COVID-19) diagnostics: Mathematics, visual logistics, and low prevalence. Arch Pathol Lab Med. 2021;145(3):291-307. doi: 10.5858/arpa.2020-0443-SA. [open access]

 Kost GJ. The impact of increasing prevalence, false omissions, and diagnostic uncertainty on Coronavirus Disease 2019 (COVID-19) test performance. Arch Pathol Lab Med. 2021 Mar 8. doi: 10.5858/arpa.2020-0716-SA. Epub ahead of print. [open access]

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

Fear, worry, and stress are normal responses when we are faced with uncertainty or the unknown. So, it is understandable that people are experiencing fear in the context of the COVID-19 pandemic.

Faced with new realities of working from home, temporary unemployment, home-schooling of children, and lack of physical contact with other family members, friends and colleagues, the World Health Organisation (WHO) highlight that it is essential that we look after our mental, as well as our physical, health.

Related: COVID-19 has shifted the focus from mental illness to mental wellness in family medicine

Omnia Health Insights spoke to Sneha John, who is a clinical psychologist at Medcare's Camali Clinic Child & Adult Mental Health in the United Arab Emirates, about how the pandemic is affecting the mental health and wellbeing of patients and how they are coping with the significant changes to our daily lives.

As the virus continues to spread and many countries continue to go in and out of lockdown, how do you think this will continue to impact mental health in general?

The pandemic has caused a significant impact on mental health globally. Quarantine and self-isolation lead to boredom, stress, uncertainty and low mood.

Related: How COVID-19 is affecting nurses’ mental health, and what to do about it

In the long term, mood and trauma-related disorders may be prevalent. The pandemic has also laid the foundation for a worldwide increase in suicide rates due to job loss, economic pressure, job insecurity, unemployment and social isolation. 

Substance abuse has become rampant, with people relying on substances to cope with the uncertainty and disappointment linked to the pandemic. 

Prolonged school closures have impacted the mental health and social anxiety levels of children and adolescents. Schools have an essential role in shaping friendships, socio-emotional development. The switch to online learning has impacted social interactions with their peers and teachers. This has resulted in some students becoming more withdrawn, isolated, anxious, de-motivated, irritable and depressed. 

What are the gender differences in mental health effects of COVID-19?

The gender differences in mental health effects of Covid-19 are two-fold. The gender gap arises because men and women experience situations differently. Women are taking on more roles at home, centred on taking care of the family. Working mothers may be most affected by this, as taking care of the housework and children simultaneously would interrupt their work-time. Research shows that women find it challenging to stay positive during the pandemic compared to men. This could be due to their work being impacted by the pandemic and care burden at home. 

Men may have concerns addressing their mental health. Their intimate emotions and thoughts may not be validated. Men have been seen as the providers, seen as strong and dependable. However, they too have experienced isolation, anxiety, stress and depression alone. The societal stigma around men’s mental health is still prevalent. This may cause men to avoid being open and vulnerable about themselves.

How can clinicians use this information to treat their patients better?

Healthcare providers should assess mental health needs along with physical health during patient check-ups. This could be done in the form of a quick mental health screening assessment and consequent referral to Psychiatry or Psychology. 

Very often, patients are reluctant to share mental health concerns due to fear of being stigmatised. Taking the effort to form a rapport with the patient where the Physician asks questions about their emotional wellbeing would allow them to open up. 

The assessment could also include coping methods to stress and uncertainty, which will help determine whether they are at risk of self-neglect. The provision of low-cost psychology services would also make services easily accessible. With the advancement of telemedicine, patients can be encouraged to schedule mental-health check-ups from the comfort of their homes as they cope with the new normal. 

Suicide prevention training should be widely endorsed among companies, healthcare sectors and the public in general. As time and resources permit, frontline workers should have training on basic psychosocial care principles and psychological first aid. Online training may be used if it is not possible to train staff in person due to remote or distributed work, limited time and concerns about infection risk. 

Emotional distress and anxiety are common during pandemics such as the COVID-19 outbreak. It is important to help patients acknowledge that stress exists and help normalise it. Basic strategies can teach them how to recognise signs of distress (such as worry, fear, insomnia, etc.) and discuss ways to reduce them (e.g., healthy diet, exercise, talking to loved ones, etc.). 

What studies would you like to see done in the future to be able to treat patients better?

With the increased use of telehealth during COVID-19, current tele-therapeutic practices can be used to improve services for patients. Preventative measures can be taken after the pandemic subsides to avoid mental health care burdens in the future. 

There will be greater demand for primary care when it is already overloaded. In the following stages of the pandemic, it will be essential to study how stress on the primary care system can be eased, especially due to the high demand caused by mental health problems. Studies can also investigate methods of preventing suicide and setting up 24/7 hotlines for crisis situations in the UAE. A comparison study between delivering psychotherapy online and psychotherapy sessions conducted in-person while wearing masks would be beneficial.

Autism spectrum disorder is one of the more common childhood disorders, with the World Health Organization estimating that, globally, 1 in 160 children has autism spectrum disorder. Early detection and intervention for children with autism spectrum disorder could help millions worldwide gain greater developmentally appropriate skills, enhance independence, and harness their unique abilities, says an expert at a top American hospital, Cleveland Clinic Children’s.

Dr Cynthia Johnson, Director of Cleveland Clinic Children’s Center for Autism explains: “While every parent views their child as a perfect gift, we want to tell them that identifying and treating autism spectrum disorder is not changing their child, but rather helping them to adapt and to capitalise on their unique abilities.”

Related: New study reveals girls are often diagnosed with Autism Spectrum Disorders (ASD) at a later age

Autism spectrum disorder has two key components: lack of or weakness in social and social communication abilities, and presence of restrictive or repetitive behaviors, with identification possible as early as in the first year of life. While there is no one known medical cause for autism, research suggests a mix of many genetic and environmental factors are risks, such as older parents, premature birth, and environmental pollutants. Diagnosis can come from interviews with parents and teachers, along with specialised developmental tests.

Treatment options

Professionals focus treatment on one-on-one behavior therapy, and training parents on enhancing their children’s social skills. According to Dr Johnson, parent training is a psychotherapeutic technique, backed by decades of research, in which parents are main drivers of change for their children.

Related: Paediatric reference standards for biomarkers of health and disease

“Behaviorally-based parent training for parents of children with autism spectrum disorder (ASD) focuses on teaching parents skills to work on core deficits of ASD – communication skills, both verbal and nonverbal, and early prerequisite skills – e.g., imitation skills,” she explains. “It includes teaching parents strategies and approaches to decrease challenging and/or disruptive behaviors – tantrums, aggression, self-injurious behaviors. Parents can learn how to teach their child self-help skills like feeding self, toileting, settling for sleep, and dressing self.”

Technology solutions are also seeing increasing uptake among patients, according to Dr Johnson. For example, children with autism spectrum disorder can use tablet devices with special speech software to better develop their multiple-word communication and vocabulary. Meanwhile, medications are often used to treat disruptive behaviors and attention weakness and hyperactivity.

The SARS-CoV-2 pandemic is a global challenge and threat to the healthcare system and economy of all countries. Early in the pandemic, the limited supply chain of PCR reagents and extraction kits was a global challenge. However, the Pathology department at the DHA has taken the lead to engage the private laboratories for increasing testing capacity, and boost access to COVID-19 testing to public as well and facilitate mass screening programmes. The competition between private and public laboratories had disappeared and the testing price became lower. It had allowed increased access to COVID-19 testing via mass screening.

The objective of the partnership with private laboratories is to provide the Dubai community with accurate COVID-19 testing with high capacity and timely reporting within 24-48 hours of the PCR test. Timely reporting was crucial in quick tracing and isolation of infected patients and consequently, reducing transmission of the virus and reducing mortality. In addition, providing rapid PCR within two hours at all Emergency departments of all hospitals had a great impact on early triage of patients. Both routine PCR and rapid PCR had reduced the transmission of the virus, hospitalisation rate and mortality rate. The pathology department at DHA also had a crucial role in improving quality of testing, regulating private laboratories with DHA rigorous testing guidelines, mandating 24 hours turnaround time, inspection visits and mandating monthly interlaboratory comparison programmes among all private laboratories. Integrating PCR machines with Lab Information System (LIS) and interfacing LIS with Dubai’s Public Health software was very robust in making tracing and isolation of infected people and their contacts an efficient platform to fight the pandemic.

Related: Sustaining a COVID-free medical facility during the world’s worst pandemic

The strategy adopted by the Pathology department in increasing testing capacity by the engaging private sector, governance, timely reporting to public health had a drastic impact in reducing the infection rate, hospital admission rate, and mortality rate in the community.

Engaging private laboratories with public laboratories removed the barriers and competitive edge. It facilitated the collaboration, resource utilisation, and operational efficiency to boost DHA’s management in fighting the pandemic.

Related: Countering antiviral drug resistance must be a priority within COVID-19 management

It also helped DHA in increasing testing capacity with fast turnaround time (TAT) and improving the quality of testing of private laboratories.

In addition, it allowed mass screening and national screening programme, consequently; rate of infection, rate of transmission, admission rate and fatality rate were reduced drastically. Providing testing for patients and other people in mass screening or screening hot spots requires fast TAT to isolate infected people promptly away from clusters in labour camps and work groups. This is a very important tactic used among testing, tracing and isolation strategy in fighting pandemics. It allows the government to relax public health measures and take decisions in re-opening the economy.

Unnecessary hospital admissions create a burden to the healthcare system. COVID-19 testing in a timely manner at the Emergency Departments of four DHA hospitals helped greatly in triaging positive COVID-19 patients promptly and reduced admission cost.

Following international statistics of COVID-19 cases in UAE compared with other countries, high-capacity testing within 24 hours by engaging private laboratories had enabled DHA and the Dubai community to trace and isolate infected people promptly. This strategy had reduced infection rate, admission rate and mortality rate. Patients in Dubai felt safe to access hospitals for elective procedures earlier than other countries as many hospitals declared that they are COVID-19 free hospitals.

Patients with other diseases were not hesitant or fearful to access hospitals early for clinical care, and this reduced complications of avoiding healthcare services. Hospitals had resumed provision of ordinary healthcare services and had sustainable financial income from providing the services.

The pathology department at the DHA established PCR guidelines of SARS-CoV2 testing along with Health Regulation sector. Consequently, COVID-19 testing was standardised among private laboratories to have consistency and reduced variations. DHA laboratory monitors private laboratories for TAT, capacity and percentage of presumptive positive.

Engagement of private laboratories with DHA had optimised shared resources regarding skills to set up PCR laboratories, logistics, LIS integration, sample transport and shared big data of all COVID-19 test results in Dubai.

Declaration of COVID-19 free hospitals had encouraged patients to access COVID-19 free hospitals for other treatment and clinical care. This had resumed the hospital financial income from outpatient visits, operations, and in patient services. The continuous financial income to hospitals and medical centres-maintained cash flow and sustainability.

Also, jobs are secured for healthcare workers, healthcare providers, as well as insurance (people resumed purchasing insurance policies and access hospitals.

Key performance indicators:

• 94.6 per cent of clinicians at DHA are confident that reporting of SARS-CoV2 Test results by RT-PCR was in less than 24 hrs.
• 90.3 per cent of private laboratories in Dubai were satisfied about the governance of DHA on SARS-CoV2 testing by rigorous guidelines for SARS-CoV2 testing, continuous inspections and interlaboratory comparison programmes conducted by Pathology department in order to improve quality of SARS-CoV2 Testing
• 91.3 per cent of clinicians strongly supported the fact that the DHA role in COVID-19 testing had a big impact on the safe return and restarting of elective and routine procedures.

Dr Rana Nabulsi

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

Contemporary Islamic bioethics

The ethical challenges and questions triggered by the twentieth-century biomedical advancements, especially in the fields of genetics of genomics, were great in number and often unprecedented in nature. To prove their relevance to our modern time and their capacity to address such complex dilemmas, moral traditions, including a world religion like Islam, instigated responses to these questions and challenges.

Related: Hemophilia gene therapy: Where do we stand?

For Muslim religious scholars, the ethical challenges posed by such modern advancements represented an important field-test to show how the relevance of Sharia and the centuries-old Islamic scholarly tradition to address the vexing problems of today.

To access credible and updated scientific knowledge about these modern advancements, religious scholars collaborated with biomedical scientists who will explain what these advancements actually are, what they can(not) achieve, and which questions they raise. This collaboration intended to facilitate and renovate the practice of the centuries-old concept of ijtihad, which starts by understanding the scientific/technical issues to develop an ethical position rooted in the Islamic tradition. Because of its interdisciplinary character, this practice was called collective ijtihad.

Related: Stem cells and gene therapy come under the spotlight in sickle cell disease awareness month

In the 1980s, this mechanism was institutionalised, and three institutions took the lead in this area, namely the Islamic Organization for Medical Sciences (IOMS) in Kuwait, the Islamic Fiqh Academy (IFA) in Mecca, and the International Islamic Fiqh Academy (IIFA) in Jeddah, Saudi Arabia.

Ethical deliberations on genomics

When the widely acclaimed Human Genome Project (HGP) took off in 1990, global discussions ensued about the ethical implications of the forthcoming genomic revolution. Within the Islamic tradition, the above mentioned mechanism of collective ijtihad facilitated the collaboration between religious scholars and biomedical scientists to initiate interdisciplinary ethical discussions on genomics and its revolution. Additionally, some religious scholars published books, articles or fatwas, which usually benefited from the output of the collective ijtihad. For a systematic analysis of the diverse Islamic deliberations on genomics, a distinction will be made between two phases, namely (1) Phase I: 1993 -2013 and (2) Phase II: 2014-now.

(1) Phase I: 1993-2013

The international symposium “Ethical Implications of Modern Researches in Genetics”, held in February 1993 in Qatar, was possibly the first event to employ collective ijtihad in deliberating on the then new HGP, which was described as “the largest scientific project in the history of humanity”. Between 1993 and 2013, at least 15 of such interdisciplinary conferences and symposia examined the ethical implications of genomics from an Islamic perspective.

These almost three-decade discussions grappled with broad questions related to how the new field of genomics should be evaluated from an Islamic perspective and whether Muslims should be part of the prospective genomic revolution. The focus was on whether Muslim-majority countries should (a) proactively contribute to this incoming revolution, or (b) anticipate more time for evaluating the overall benefits and risks. By time, these intensive, and at certain points polarizing, discussions matured and eventually produced a clearly majority position, whose advocates strongly supported the above mentioned (a) option. They argued that contributing to the genomic revolution is not only permissible from an Islamic perspective but even represents a collective obligation (fard kifaya) for Muslim-majority countries, and all possible means should be employed to implement this obligation. This position was also put into practice by several countries in the Muslim world. Below, we provide a concise overview of the various arguments advanced by this group.

Why should Muslims be part of the genomic revolution?

From a theological perspective, genomics and related scientific ventures should not be seen through the lens of conventional dichotomies, e.g., Western vs. Islamic practices or believing vs. non-believing scientists. They should rather be viewed as part of the natural human instinct to seek more knowledge about our human nature and our Creator; an endeavour which is recurrently presented in the Quran as a divine command, e.g., “Say, ‘Travel throughout the earth and see how He has originated the creation’” (29:20) and “And in your own selves; do you then not behold?” (51:21).

From a juristic perspective, reference was made to the famous legal principle of “original permissibility”, which implies that everything is in principle morally neutral and thus permissible unless there is evidence to judge it differently. Further, they stressed the relevance of genomics and its (prospective) applications to significant moral values like preserving life and offspring, which make part of the Higher Objectives of Sharia. They explained that as long as genomics aims to help save people’s life, treat incurable and life-threatening diseases, and improve overall health condition for adults and (forthcoming) children, then it should be highly valued from an Islamic perspective.

Additionally, embracing the genomic revolution and urging Muslim countries to provide impactful contributions was also moved by socio-political considerations. On one hand, almost all contributors to these deliberations conceded the deplorable state of scientific research in the Muslim world. On the other hand, genomics was framed as the future of powerful science, without which countries will have no say in shaping people’s future world. Thus, many argued, genomics represents a great opportunity for the Muslim world to regain the golden age of science in the Islamic civilisation and to be part of the future powerful nations.

Finally, it was conceded that the promised genomic revolution is not exclusively beneficial or purely good and that it may entail harms. However, it was stressed that geonomics is inherently or entirely evil because expected harms can be controlled and sometimes even mitigated. The main tool to ensure Sharia-compliant genomics is to develop well-defined criteria and standards (dawabit Shar’iyya), which were the main subject of the second phase of the Islamic deliberations on genomics, as outlined below.

(2) Phase II: 2014-Now

In November 2013, the above-sketched pro-genomics position was formally adopted by prominent institutions like the IIFA and IOMS. In December 2013, both Qatar and Saudi Arabia initiated their national genome projects, with huge budgets and wide national support, and other countries started their own initiatives later. Thus, the focus of the deliberations on genomics in this phase shifted from the yes/no question (should Muslims join the genomic revolution?) to the how question (how should genomics and its applications be Sharia-compliant?).

Because of this shift, increasing attention was given to developing measurable Sharia-compliant criteria and standards (dawabit Shar’iyya) that can help scientists and policymakers manage the scientific research in genomics and its applications. The long list of such practical issues included patenting, ownership of DNA samples stored in biobanks and/or data generated from these samples, incidental findings and human genome editing.

Due to the relatively young age of the discussions on these specific issues and their complex character, most of the time one can hardly identify the mainstream vs. the peripheral or the majority vs. minority positions. However, the increasing number of recent publications reveal that some positions are more likely to gain majority support. Examples include rejecting the return of incidental findings related to misattributed genetic paternity, the obligation of returning such findings when they will help in saving someone’s life, and accepting human genome editing at the level of somatic cells when there is no other possible option for treating an incurable disease, once the efficacy and safety of such intervention are in order.

References available on request

Mohammed Ghaly

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

Clinical laboratories are a critical component of healthcare globally, providing an essential service through the assessment of patient specimens for important biomarkers of health and disease in blood, urine, and other body fluids. Laboratory test results contribute evidence-based objective data to patient charts and are fundamental to inform clinical decision-making in the assessment, prognostication, and monitoring of patients in tertiary care and community settings. Clinical laboratories are thus responsible for establishing appropriate reference standards to ensure the accuracy of test results reported to patient charts and also the accompanying interpretative recommendations. Reference standards are health-associated benchmarks against which blood test results can be compared, allowing clinical laboratories to flag abnormal results to notify clinicians of the need for follow-up testing and/or the initiation of treatment. Given their importance, most would assume comprehensive reference standards are readily available and implemented at clinical institutions worldwide. Unfortunately, critical gaps continue to exist in accurate and up-to-date reference standards, particularly in paediatrics.

Children are not small adults!

Children and adolescents undergo immense physiological changes throughout growth and development, influencing blood test result values for various markers of health and disease. For example, alkaline phosphatase changes significantly from birth to adolescence due to several physiological processes, including placental production at birth and increased muscle mass in adolescence. Reports have demonstrated that the application of reference standards derived in adults for alkaline phosphatase interpretation in children inappropriately flags over 80 per cent of test results. This further emphasises the importance of using age- and sex- appropriate paediatric reference standards for clinical decision making and avoiding the potential risk of erroneous or missed diagnosis.

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While the historic gap in the availability of paediatric reference standards is concerning, it is not necessarily surprising. Reference standard establishment guidelines by recognised bodies require the recruitment of 120 healthy volunteers for appropriate derivation by nonparametric methods, considered the ‘gold standard’ approach. In paediatrics, this target sample size is incredibly challenging particularly given that biomarkers commonly need to be partitioned by age and sex, substantially increasing required sample size and subsequent resources. This is simply not feasible for most paediatric clinical laboratories. While recognised guidelines also allow the verification of previously derived reference standards from manufacturers or other research groups using smaller sample sizes, manufactures often do not include paediatric reference standards in their documentation. Thus, the majority of reference standards used in paediatric clinical laboratories worldwide were either determined in the adult population, derived using samples from hospitalised patients without appropriate statistically considerations, or determined decades ago on older/less accurate laboratory instruments or methodologies. In recent years, a number of international initiatives have begun to address these gaps, contributing to significant improvements in paediatric laboratory medicine.

Canadian laboratory initiative on paediatric reference intervals – our experience

The Canadian Laboratory Initiative on Paediatric Reference Intervals (CALIPER) programme is a nationwide health initiative to improve the diagnosis and monitoring of children and adolescents with medical concerns. Our main objective is to establish a comprehensive database of paediatric reference standards for various blood tests, in order to fill existing gaps that prevent the accurate test result interpretation with the ultimate goal of improving the care of children and adolescents around the world. Children from birth to 18 years of age are eligible to take part in CALIPER. Through a community-based approach, children and adolescents are recruited from schools, community centres, and summer camps. Participation involves informed consent, completion of a health questionnaire, anthropometric measurements, and blood collection. Since 2009, more than 12,000 healthy children and adolescents have participated, resulting in a robust biobank of paediatric blood specimens for reference standard establishment. Blood specimens are then analysed for various biomarkers of health disease on several analytical platforms to ensure utility in paediatric clinical institutions globally. Initial reports focused on routine biochemical parameters on the Abbott ARCHITECT platform. This was subsequently expanded through transference and de novo efforts to other common analytical platforms for test measurement (e.g. Beckman, Ortho, Roche, Siemens, and DiaSorin assays). New studies have also expanded to other laboratory areas, including critical care assays on point-of-care devices and hematology parameters.

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To date, comprehensive age- and sex-specific reference standards for over 200 laboratory biomarkers of health and disease on analytical instruments have been established and published in over 70 peer-reviewed papers in high-impact journals. Adhering to CLSI statistical guidelines, our direct approach utilises the robust or nonparametric methods for the derivation of upper and lower reference limits. Based on these peer-reviewed data, an online database and mobile application was developed (www.caliperdatabase.org). The CALIPER database is easily and freely accessible and has been adopted by thousands of healthcare institutions worldwide, highlighting the quality and richness of these data and global reach of this programme.

CALIPER is not alone in its work to improve paediatric test result interpretation. Several international initiatives have contributed to the availability of paediatric reference standards, including the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), the Scandinavian Initiative for the Establishment of Paediatric Reference Intervals (NORICHILD), the Children’s Health Improvement through Laboratory Diagnostics (CHILDx) in the U.S., Harmonising Age Pathology Parameters in Kids (HAPPI Kids) in Australia, and the Australasian Harmonised Reference Intervals for Paediatrics (AHRIP). Most initiatives use similar approaches by recruiting from healthy children and adolescents in community or outpatient settings, but often focus on select biomarkers of interest. Interestingly, new studies have harnessed high level statistical techniques to derive reference standards using patient data from Laboratory Information Systems. Key groups in Germany led by Zierk et al. have contributed immensely to establishing this indirect approach, which may serve as a useful option for paediatric clinical institutions worldwide moving forward, avoiding need to recruit hundreds of healthy children by using their own patient data. Together, the collective efforts of these groups have moved the field forward immensely, but the work still continues.

Current state and future directions

Key evidence gaps still remain in the field of paediatric reference standards. First, analytical platforms and assays are constantly being modified/newly developed. Changes to procedures in test measurement or calibration can significantly impact test results and thus reference standards. Leaders in the field should continue to monitor changes in analytical test measurement and conduct new studies when significant changes in assay technology occur.

With this in mind, the CALIPER programme recently derived age- and sex-specific paediatric reference standards for biochemical and immunochemical parameters on the new Alinity and Attellica assays from Abbott Diagnostics and Siemens Healthineers, respectively. Second, most paediatric reference standard studies have focused on routine blood tests that are commonly ordered as part of the standard of care. Critical gaps remain in specialised markers of health and disease, including markers of inflammatory disease (cytokines, calprotectin, autoimmune), nutritional deficiency (essential trace elements), and environmental toxicity (heavy metals). Our team has recently launched sub studies in these areas of specialised testing and will continue to expand the programme to other relevant diagnostic areas, particularly as new biomarkers emerge.

Finally, health-associated data for both routine and specialised parameters in neonates is lacking. It is very challenging to recruit and successfully collect an additional blood sample from neonates and children within the first year of life. Thus, most available data in the literature consists of residual specimens from outpatients. To address this significant gap, CALIPER has begun the new CALIPER Mother & Child Initiative, which is aimed at closing the gaps in both neonatal and maternal reference standards for important biomarkers of neonatal and maternal health (www.caliperproject.ca/mchi).

We have seen immense progress in the field of paediatric reference standards in the past decade as part of a global collective effort. However, we still have far to go to ensure every paediatric clinical institution has access to appropriate reference standards for their population and analytical instrumentation. We look forward to embarking on new studies to address remaining gaps and contributing to the field of paediatric reference standards alongside our colleagues globally.

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.

The UAE and Abu Dhabi’s response to the COVID-19 pandemic has been excellent. It is, therefore, no surprise that the UAE is ranked as one of the best and safest places to be in during the pandemic. The country’s authorities and emergency response team have taken swift action and coordinated the healthcare system’s response in collaboration with the UAE’s healthcare network led by SEHA.

SSMC, one of the UAE’s largest hospitals for serious and complex care and a joint-venture partnership between Abu Dhabi Health Services Company (SEHA) and Mayo Clinic, is an integral part of the Abu Dhabi healthcare network and has played a key role in the national efforts to mitigate the impact of COVID-19 and stop the spread of the virus. The deep resilience, collaboration and selfless hard work shown by our people and the sustained levels of care shown to our patients was astounding.

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During the first wave of the pandemic, SSMC operated as a COVID hospital and provided care to a large number of patients with COVID-19 as well as patients who did not have the disease. SSMC, therefore, had to significantly expand its emergency department, internal medicine and critical care services to look after the surge in COVID-19 patients.

However, in June 2020, a plan was put in place for SSMC to become a COVID-free hospital, and since then the hospital has been identified by the Department of Health – Abu Dhabi (DoH) as a prime COVID-free facility to meet the needs of other patients in the community.

What does it mean to be a COVID-free hospital?

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A COVID-free hospital provides care for patients who need hospitalisation and who tested negative for COVID-19. It ensures that maximum precautions are taken to reduce the risk of staff and patients acquiring and transmitting the novel coronavirus from the hospital environment. SSMC, therefore, admits and accepts patients who do not have COVID-19 unless a unique service needs to be provided for a patient who has the disease such as a patient who has a major burn and is admitted to the National Burns Unit. Implementing such measures facilitated access to high-quality medical and surgical care for all patients, whilst adhering to the globally recognised levels of safety standards across the hospital.

How did we do it?

We were able to draw from the legacy of SEHA in the UAE, the international best practice and expertise contributed by our Mayo Clinic partners. This, together with our highly committed SSMC team, uniquely positioned us to take queues and learnings from the international medical community and incorporate international best practice into our processes.

SSMC’s response to COVID-19 was coordinated by a multidisciplinary taskforce, which met daily, and at times more than once, and worked with internal and external stakeholders. Becoming COVID-free and maintaining our COVID-free status was reliant on a number of strategies, most importantly:

1. Working closely with other SEHA hospitals and designated healthcare facilities

SSMC could only become COVID-free because of the help of other SEHA hospitals such as Al Rahba and Sheikh Khalifa Medical City (SKMC) hospitals who were designated as COVID-19 hospitals. Patients who tested positive while in the Emergency Department would stay there until they were transferred to a COVID facility.

In addition, patients who were already admitted and subsequently found to be COVID-19 positive would also be transferred out. This was done efficiently on a daily basis with the help of our Bed Management Team working with the SEHA Operations Team to identify beds for the patients and transfer them out of SSMC. The laboratory at SSMC also introduced a rapid antigen and gene-based test (PCR) for COVID-19 in order to rapidly detect infection in a patient and speed up decision-making about his or her transfer.

2. Keeping staff safe

A number of interventions were used to reduce the risk of staff acquiring or transmitting COVID-19 in the hospital. For example, there were frequent reminders through screen savers, pop ups and email messages reminding staff about the importance of maintaining COVID-19 precautionary and preventive measures. Managers were also asked to ensure that all staff had their temperature checked before every shift. Any staff member with symptoms would be sent to the Occupational Health Clinic for assessment and testing.

The Infection Prevention and Control Team performed daily audits with feedback to staff and managers. Additionally, a COVID-19 preparedness checklist and audit tool was developed to help departments remain COVID-free.

Careful steps were also taken to minimise exposure and transmission risks amongst our staff, including universal masking, physical distancing measures, allocating remote working processes for staff who were able to work from home, switching to virtual meetings, managing ward rounds to minimise contact risk and initiating early vaccination when it became available to frontline workers.

3. Encouraging COVID-19 vaccination and occupational health services

The Nursing and Occupational Health Team developed an effective vaccination campaign in January 2021 which led to rapid uptake of the Sinopharm COVID-19 vaccine. By March 2021, over 70 per cent of SSMC’s staff had been vaccinated and over 90 per cent of staff are currently fully vaccinated. Furthermore, a system was developed for staff to have weekly PCR tests including reminders directly being sent to them and their managers. The Infection Control Team and Occupational Health Team worked together to ensure that, on a daily basis, every staff member who tested positive was excluded from work and contact tracing was done to identify potential close contacts who required testing and quarantine

4. Maintaining infection prevention measures in outpatient clinics

Special measures were introduced to ensure that the outpatient clinics did not have patients with COVID-19. For example, a system was developed to automatically identify any patient who had tested positive for COVID-19 in the previous 14 days and had a clinic appointment at SSMC. Patients who were considered to be still infectious had their appointments rescheduled or changed to virtual visits or arrangements made to see them in the Emergency Department if they need acute care. Staff were also asked to consider all patients as potentially having COVID-19 and use N95 masks as well as eye protection for all close contacts with patients. Security staff and nursing staff screened all patients at the entrances of the outpatient building using temperature sensors. We also developed and used more telemedicine and home delivery of medication in order to reduce the number of hospital or clinic visits. Furthermore, we took away all unnecessary papers such as journals and newspapers in waiting rooms not only in the outpatient clinics, but also across all the hospital.

5. Implementing stringent precautionary safety measures in inpatient settings

All patients admitted to SSMC are screened for COVID-19 on admission and are put in isolation until screening test results come back negative and a physician decision is made to discontinue isolation. All specialities have also produced pathways to safely manage patients with suspected COVID-19 or when COVID-19 has not yet been excluded. In addition, patients waiting for procedures such as endoscopy or elective surgery are screened within five days of their procedure and asked to self-isolate. Extended use of N95 masks in Emergency Department and Critical care areas was introduced to further reduce the risk of transmission of COVID-19 to staff. SSMC implemented the DoH requirements to have all visitors tested for COVID-19 24 hours before visiting. We also reduced visit time and number of allowed visitors for patients.

Why was this important?

Like in most parts of the world, care for patients who do not have COVID-19 appeared to have suffered during the pandemic due to patients’ fear of contracting COVID-19 if they go to a clinic or hospital, therefore, delaying and waiting too long to seek care for any illness they may have. Patients were afraid to visit hospitals and many hospital services had to be suspended to divert resources towards looking after patients with COVID-19. SSMC has played a key role in maintaining the health and well-being of our communities during the pandemic by focusing on providing high-quality care for non-COVID patients, while other sister hospitals at SEHA like SKMC, Al Rahba concentrated their efforts for COVID 19.

What were some of our challenges, and how did we overcome them?

Inevitably, as a healthcare facility facing an unprecedented crisis, we did have our challenges. Firstly, we had to be flexible and modify our interventions in line with published evidence, surge in transmission of COVID-19 in the community as well as changing recommendations from regulatory authorities. This happened very shortly after we opened our new facility.

Secondly, keeping staff morale high despite long working hours and the constant pressure has been difficult. In addition to using different strategies to ensure they do continue to maintain preventive measures, we also had to ensure we pay particular attention to staff wellbeing and talk openly about the challenges and how to remedy them effectively. 

Lastly, we had to expand our services rapidly and run our hospital at high occupancy levels in order to cater for patients who can no longer be looked after by hospitals that have been converted into designated COVID-19 facilities. On that occasion, I have to send a word of appreciation to SEHA, Mayo Clinic and Zayed Military Hospital for all their assistance in providing additional health care providers and staff for an extended period of time.  We could not have expanded our facility without them. 

Responding to the COVID-19 pandemic and becoming a COVID-free hospital has helped us to think and work differently, develop a number of systems that have helped our overall operations meeting the needs of our patients. We have managed to maintain high-quality services for patients who do not have COVID-19 thanks to the unwavering support of our exceptional staff and government partners. We have also completely redesigned our services to ensure that we focus on looking after patients who do not have COVID-19 and maintain our COVID-free status. The lessons learnt will remain with us as we remain agile, enhance our readiness and ensure we’re able to continue to meet the needs of our communities – building our strength and resilience as an organisation. 

Dr Naser Ammash

This article appears in the latest issue of Omnia Health Magazine. Read the full issue online today.