The Importance of Diagnostic Testing in SARS-CoV-2 Adverse Outcomes
SARS-CoV-2 (COVID-19), a newly discovered and highly contagious disease, primarily manifests as an acute respiratory illness, however, for those with health complications, including: autoimmune diseases, asthma, heart disease and diabetes, the risk of developing serious illness and adverse outcomes is much greater. It is estimated that 1 in 6 will experience adverse outcomes that could be life-threatening 1. The spread and devastation of COVID-19 highlights the vital role laboratory diagnostics plays in the diagnosis and management of suspected and affected patients. As the COVID pandemic continues, it is imperative that fast and accurate diagnostic testing strategies are implemented for effective risk stratification and monitoring of treatment and recovery.
In this article, we will review how Randox Reagents can aid in diagnosing and managing SARS-CoV-2 adverse outcomes.
The immune system activates a pro-inflammatory response to enhance host immunity against viruses and decrease colonisation and infection, but only if the pro-inflammatory response is controlled. Uncontrolled pro-inflammatory responses can result in a cytokine storm 2. A cytokine storm is a serious complication associated with SARS-CoV-2, which can trigger life-threatening pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ failure 3, 4. Cytokine storms occur in 5% of severe COVID-19 cases, with several inflammatory cytokines observed at high levels. Due to the elevation of several pro-inflammatory and anti-inflammatory cytokines, a multiplex immunoassay approach can offer several advantages over the widely utilised single ELISA tests. The simultaneous detection of multiple cytokines from a single patient sample will provide clinicians with a comprehensive overview of cytokine markers and complete patient profile, facilitating a personalised treatment plan to be implemented 5, 6.
In COVID-19 patients, CRP testing has proved to perform well in discriminating disease severity and predicting adverse outcomes 7. Elevated CRP levels have been identified in 86% of patients admitted to hospital. CRP measurements are useful in diagnosis, prognosis and monitoring for clinical improvements or deterioration. Moreover, the acute phase reactant, ferritin, has been observed to increase in approximately 60% of COVID-19 patients. In the critically ill COVID-19 patients, extremely elevated ferritin concentrations were recorded, which could be attributed to a cytokine storm and secondary haemophagocytic lymphohistiocytosis (a hyper-inflammatory syndrome associated with multi-organ failure) 8.
Acute kidney injury (AKI) is a common complication in diabetic patients who test positive for COVID-19. Regardless, the National Institute for Health and Care Excellence (NICE) recommend AKI testing in all COVID-19 patients upon hospital admission and their condition monitored throughout their stay 9.
The most commonly utilised screening test for renal impairment is serum creatinine (SCr); however, it is important to consider the accuracy and reliability of the method. Two commercially available methods exist for SCr determination: Jaffe and enzymatic. Whilst the Jaffe method is less expensive, it is more susceptible to interferences which can lead to the misdiagnosis of patients, which isn’t ideal in the current pandemic 7. Moreover, the sensitivity of SCr, regardless of method, in the early detection of renal disease is poor, as SCr is insensitive to small changes in glomerular filtration rate (GFR). Up to 50% of renal function can potentially be lost before significant SCr levels become detectable 8, 9. In comparison, cystatin C (CysC) is a superior marker of renal function and is useful in the determination of the extent of renal damage, as well as distinguishing those with severe and mild COVID-19 10.
Abnormal liver function tests significantly increases a COVID-19 patients risk of developing severe disease and complications such as pneumonia 11. Bilirubin levels, 3 times the upper limit have been observed in COVID-19 patients 11, 12. Whilst the diazo method is commonly utilised in bilirubin testing, superior methods exist. The vanadate oxidation (VO) method offers several advantages particularly in haemolytic and lipemic samples. These advantages are particularly evident in neonatal and infant populations where haemolysis is extremely common. Moreover, the VO method offers a wider analytical measurement range for the comfortable detection of clinically important results 13.
Other liver function markers are known to be elevated in COVID-19 patients including both AST and ALT, with markers like albumin decreased.
The Importance of Lp(a) Testing
Lipoprotein(a) / Lp(a), a strong independent marker of cardiovascular disease risk has recently been identified as a key risk marker of cardiovascular complications in COVID-19 patients. Those with either baseline elevated or elevated levels of Lp(a) following COVID-19 infection may be at a significantly increased risk of developing thromboses. Consideration should be given to measurement of Lp(a) and prophylactic anticoagulation of infected patients to reduce the risk. Elevated Lp(a) levels may also cause acute destabilization of pre-existing but quiescent, atherosclerotic plaques, which could induce an acute myocardial infarction (AMI) or cerebrovascular accident (CVA) (stroke) 14.
The size heterogeneity of apo(a) isoforms represents the biggest challenge faced by laboratories in accurately measuring Lp(a). The variable numbers of repeated KIV-2 units in act as multiple epitopes, and so standardisation across calibrators is vital. Unless the calibrants have the same range of isoforms as test samples, those with higher numbers of the KIV-2 repeat, will represent with an overestimation in Lp(a) concentrations and those with smaller numbers of the KIV-2 repeat, will represent with an underestimation. The smaller isoforms are strongly associated with higher Lp(a) concentrations 15.
Lp(a) assays that are standardised to the WHO/IFCC (World Health Organization/International Federation of Clinical Chemistry) reference material, transferring values from mg/dl to nmol/l are more uniform. The assay considered the most reliable commercially available Lp(a) assay is so because: 15
1. The isoform size variations are reduced as a range of calibrators from separate pools of serum used, which covered a range of Lp(a) concentrations.
2. The isoform size and concentrations are inversely correlated, better matching calibrants with test samples.
3. Methods are calibrated in nmol/l and traceable to WHO/IFCC reference material and give acceptable bias compared with the Northwest Lipid Metabolism and Diabetes Research Laboratory (NLMDRKL) gold standard method.
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Extended Coronavirus Array
Qnostics SARS-CoV-2 Control
 Complications coronavirus can cause. https://www.webmd.com/lung/coronavirus-complications#1 (accessed 22 July 2020).
 Sinha P, Matthey MA, Calfee CS. Is a “cytokine storm” relevant to COVID-19? JAMA 2020; (): 1-3. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767939#:~:text=Why%20has%20the%20%E2%80%9Ccytokine%20storm,and%20associated%20with%20adverse%20outcomes.&text=Several%20early%20case%20series%20in,elevated%20above%20the%20normal%20range. (accessed 22 July 2020).
 Del Valle DM, Kim-Schulze S, Huang HH, Beckmann M, Nirenberg S, et al. An inflammatory cytokine signature helps predict COVID-19 severity and death. The Preprint Server for Health Sciences https://www.medrxiv.org/content/10.1101/2020.05.28.20115758v1.full.pdf (accessed 24 July 2020).
 The Royal College of Pathologists. Guidance on the use and interpretation of clinical biochemistry tests in patients with COVID-19 infection. https://www.rcpath.org/uploads/assets/3f1048e5-22ea-4bda-953af20671771524/G217-RCPath-guidance-on-use-and-interpretation-of-clinical-biochemistry-tests-in-patients-with-COVID-19-infection.pdf (accessed 14 June 2020).
 Dhungana N, Morris C, Krasowski MD. Operational impact of using a vanadate oxidase method for direct bilirubin measurements at an academic medical center clinical laboratory. Practical Laboratory Medicine 2017; 8(2017): 77-85.
 Moriarty PM, Gorby LK, Stroes ES, Kastelein JP, Davidson M, et al. Lipoprotein(a) and its potential association with thrombosis and inflammation in COVID-19: a testable hypothesis. Current Atherosclerosis Reports 2020; 22(48): 1-8.
COVID-19 (2019-nCoV) was declared a global emergency of international concern. The WHO’s director-general’s greatest concern is the potential for COVID-19 to spread to countries with weaker health systems. The biggest catch with containing the epidemic of COVD-19 is the detection. It has been recognised that faulty kits have been shipped around America by the Centers for Disease Control and Prevention (CDC) and there simply aren’t enough kits in China 1. Randox can aid in overcoming these challenges.
What is COVID-19?
The COVID-19 is a new strain of coronavirus that has not been previously identified in humans. Consequently, research on this new strain is lacking. Symptoms are similar to that of the common cold or flu, including: fever, cough, difficultly breathing, muscle pain and fatigue. Like other respiratory infections, transmission occurs through respiratory droplets from coughing and sneezing, with an estimated incubation period of 2 to 14 days 2.
Globally, there are 46, 997 confirmed cases of COVID-19, with 46, 550 of these confirmed cases attributed to China. Only 447 of the total number of cases are outside of China, across 24 countries. The total number of deaths attributed to COVID-19 sits at 1, 369 of which all have been observed in China, except one. These statistics are laboratory-confirmed cases only 3. These statistics were reported by WHO on 13 February and is the situation of number, total and new cases, within the past 24hrs from being recorded. Whilst China is at a very high risk, the global risk level is high. These statistics indicate the necessity for COVID-19 diagnosis, especially as the above are only laboratory-confirmed cases combined with the faulty tests distributed in America and the lack of diagnostic tests in China.
The Randox Extended Coronavirus Array
Randox have developed a fast and accurate test for the detection of COVID-19, the new strain of coronavirus. The Randox Extended Coronavirus Array is the only test in the world that can identify the potentially lethal strain and differentiate between other respiratory pathogens with similar symptoms.
The new test utilises the Randox Biochip Technology, with results within 5 hours on the Randox Evidence Investigator, a semi-automated analyser capable of processing 54 patient samples simultaneously.
The Randox Coronavirus Array comprises five coronaviruses strains, including the COVID-19 (2019-nCoV) strain. The table below provides a breakdown of the viruses included in the Randox Extended Coronavirus Array:
Dr Peter FitzGerald, Managing Director of Randox Laboratories, commented;
“Current technologies for the diagnosis of coronavirus are designed simply to detect the presence or lack of COVID-19, and therefore neglect to differentiate between this strain and other respiratory infections. We have therefore developed an extended Viral Respiratory Infection Array that tests simultaneously for COVID-19 and nine other viruses. This will eliminate the need for multiple back-and-forth tests before the root cause of symptoms is found, and empower clinicians to make fast and informed decisions.”
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 Kamer F. Coronavirus (COVID-19) Test Kits are Broken in America, Scarce in China. https://futurism.com/neoscope/coronavirus-covid19-test-kits-broken-america-scarce-china (accessed 18 February 2020).
 World Health Organization (WHO). Coronavirus disease 2019 (COVID-19) Situation Report – 24. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200213-sitrep-24-covid-19.pdf?sfvrsn=9a7406a4_4 (accessed 18 February 2020).
There is still a lot unknown about the 2019 novel coronavirus (2019-nCoV), however, current knowledge is mostly based on the intel of existing coronaviruses including Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV) 1. Last week, the World Health Organization (WHO) declared the 2019-nCoV a global health emergency of international concern. The WHO’s director-general, Tedros Adhanom Ghebreyesus stated: “The main reason for this declaration is not because of what is happening in China but because of what is happening in other countries. Our greatest concern is the potential for this virus to spread to countries with weaker health systems, which are ill-prepared to deal with it” 2.
WHO recommend educating all and increasing knowledge of the 2019-nCoV. The aim of this article is to provide further information on the 2019-nCoV to aid in combatting the mass hysteria through education.
About the 2019-nCoV
The 2019-nCoV belongs to a large family of respiratory viruses with illnesses ranging from the common cold to more severe diseases such as MERS-CoV and SARS-CoV. 2019-nCoV is a new strain that has not been previously identified in humans 3. Coronaviruses are common in a variety of animal species including: bats, cats, cattle and camels 1. Coronaviruses are zoonotic which means the virus can be transmitted between animals and humans. SARS-CoV was transmitted from civet cats and MERS-CoV was transmitted from dromedary camels 3. Zoonotic viruses are commonplace with approximately 60% of current infectious diseases and 75% of all emerging infectious diseases in humans being zoonotic according to the UNEP Frontiers 2019 Report: Emerging Issues of Environmental Concern, with approximately one new infectious disease emerging in humans every four months 4.
2019-nCoV Transmission & Prevention
The exact origin of the 2019-nCoV is unknown and the analysis of the genetic trees of this virus is ongoing, however ‘it is important to note that person-to-person spread can happen on continuum’. Currently, it is unclear on how contagious the 2019-nCoV is 5. It is believed that the spread of the 2019-nCoV virus is similar to that of other respiratory pathogens (influenza). It is believed that the spread occurs via respiratory droplets produced when an infected person sneezes or coughs and lands in the mouth or noses or possibly inhaled into the lunch of people nearby (about 6 feet). It is unclear at this time if the 2019-nCoV can be caught via touching surfaces or objects that have the virus and then touching their nose, mouth and possibly eyes.
It is important to understand that the transmissibility and severity of viruses vary and there is still much to learn about the 2019-nCoV 6. Whilst there is no vaccine to prevent the transmissibility of the 2019-nCoV, daily steps can be taken to aid in the prevention of the spread, similar to that of respiratory infections in general 7:
1. Wash hands with soap and water for 20 seconds, especially after using the toilet, before eating, after blowing your nose, sneezing and coughing.
2. If soap and/or water is not readily available, alcohol-based (minimum 60% alcohol) hand sanitisers can be used.
3. Avoid toughing mouth, nose and eyes with unwashed hands.
4. Avoid close contact with those who are sick.
5. Stay at home when you are sick.
6. Always cover coughs and sneezing with a tissue and discard in a bin.
7. Clean and disinfect frequently touched objects and surfaces using a regular household cleaning wipe or spray.
It is vitally important to get tested if you believe you have the 2019-nCoV which can aid in preventing the further transmissibility of the virus.
Randox Coronavirus Arrays
Randox are developing a rapid test for the 2019-nCoV which will utilise the Randox Biochip Technology, with results available within 3 hours on the Vivalytic and with 5 hours on the Randox Evidence Investigator.
The Randox Novel Coronavirus Array detects the 2019-nCoV strain quickly and accurately, enabling effective and accurate medical protocols to be actioned.
The Randox Extended Coronavirus Array encompasses multiple strains of the coronaviruses including: 2019-nCoV, 229E, NL63, OC43 and HKUI. The wider panel provides a comprehensive coronavirus screening panel, enabling effective and accurate medical protocols to be actioned.
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Contact us or download our coronavirus flyer