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SARS-COV-2: Virology and Testing in COVID-19
Reading time: 10 minutes
Introduction
COVID -19 or coronavirus disease 2019 is caused by a virus designated SARS-COV-2 (Figure 1). It belongs to the family of betacoronavrirdae and the same subgenus as SARS (Severe Acute Respiratory Syndrome) virus. It utilises the same receptor ACE-2 (Angiotensin Converting Enzyme 2) to gain entry into cells as the SARS virus.
MERS (Middle Eastern Respiratory Syndrome) is a distant relative of SARS-COV-2 in the same family.
Some of the knowledge in management of SARS-COV-2 has been derived from the experience with SARS/ MERS.
Figure 1
Transmission of virus
Let me first start by saying that our understanding of the virus is still incomplete. I shall try to summarise what we know so far.
- Person to person spread occurs via respiratory droplets when an infected individual coughs or sneezes like all airborne viruses.
- Droplets do not tend to travel farther than 6 feet – hence the social distancing advice.
- In experimental conditions, the virus has been found to linger in aerosols for up to 3 hours. Hence the advice on using full PPE in aerosol generating procedures in hospital settings.
- Aerosol generating procedures include high flow nasal oxygen, nebulisers, intubation, bronchoscopy and cardio-respiratory resuscitation.
Viral testing
What tests do we have for SARS-COV-2?
The same as any other viral infection. We can either look for direct evidence of the invader: genetic material of the virus in biological samples like respiratory secretions from the nose, pharynx, sputum or bronchial samples. The genetic material of viruses is in the form of RNA. All we do is use a technique where we amplify the viral RNA found in the sample using an enzyme (transcriptase). With every amplification in a chain reaction, a fluorescent reporter molecule is released, from which the starting level of viral RNA can be determined. This is called reverse transcriptase polymerase chain reaction (rt-PCR).
The alternative is to look for signs of the host response to the invader. This is often in the form of antibodies produced against the virus. From simple biology we know that the initial antibody response is in the form of IgM. With time this is then replaced by IgG as the illness proceeds. So, it depends on what point you do the blood test. For the sake of simplicity, IgM points to current/ recent infection and IgG indicates previous infection.
What we do not know is whether SARS-COV-2 elicits lasting immunity.
The following are some facts about SARS-COV-2:
- The viral RNA can be detected in blood and stool. Although live virus has been found in stool, faeco-oral transmission has not been recognised (evolving area).
- Viral RNA is found in higher titres in the early stage of illness after symptom onset.
- Detecting viral RNA does not equate to infectivity!
- Tests that we have, detect viral RNA using reverse transcriptase – polymerase chain reaction (rt-PCR).
- Infective virus however, is found in oro-nasopharyngeal secretions and sputum for the 1st week of illness and peters out thereafter even though high titres of viral RNA are still detected.
- Mild illness tends to give more false negatives than severe illness on testing.
- Secondary rates of infection range from 1-5% for persons in close contact to the infected individual. Transmission can occur from asymptomatic individuals too but this is in the minority.
Test Accuracy
It is sobering to note that in a study of 205 patients with confirmed COVID-19, the extent of false negatives was quite high. For instance the diagnostic accuracy of finding the virus in bronchoscopic specimens using rt-PCR was 93%, sputum 72%, nasal swabs 63% and pharyngeal swabs 32% (1).
In another study using ELISA to detect antibodies to the virus, IgM positivity was around 85% to 93% and the positive detection rate rose to 98.6% when combined with rt-PCR. The median duration of IgM positivity from symptom onset was 5 days (2).
ELISA tests are under development with a recent test having been approved by the FDA in US.
Clinical Implications
If clinical suspicion remains high, especially in the setting of a CT scan suggestive of viral pneumonia (ground glass opacities ± consolidation) – re-test using rt-PCR while continuing to maintain adequate isolation/ PPE precautions.
Co-infection with SARS-COV-2 is known to occur and this can help in management decisions e.g. co-existent influenza can be treated with antivirals.
References
- Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA – Journal of the American Medical Association. American Medical Association; 2020.
- Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, et al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020 Mar 21;
Do you think that serological tests looking for antibodies should be made more widely available? What do you think are the
pros and cons of such an approach? Please write your answers in the comments section below and I will respond 🙂
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medbookprof
I'm a Consultant Pulmonologist having experienced medicine first-hand across two continents stretching from the South Indian peninsula to the British Isles, the emerald nation of Ireland, to the Mediterranean climes of Italy and to the happiest country on earth, Denmark. Along the way, I have served as an honorary Associate Clinical Teacher and Royal College Associate tutor at University Hospital of Wales, collected a Masters in Medical Education and a passion for teaching. My enthusiasm is matched only by my thirst for simplifying clinical knowledge for medical students and making it accessible on a global scale.