SARS-2-CoV and COVID-19 disease

Background

• Previous names: ‘Wuhan coronavirus’, ‘nCoV-2019’, ‘novel coronavirus 2019’.
• Causes the human disease ‘COVID-2019’.
• Classified as Hazard Group 3 organism, which determines laboratory handling of samples and patient isolation facilities.
• The virus and disease are distinct from those coronaviruses causing Middle East respiratory syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) coronaviruses [1].
• Note that there are other human coronaviruses regularly circulating in the human population worldwide (named 229E, HKU1, NL63, and OC43), and are not associated with severe illness. Some standard panels of respiratory virus tests have these included, so pay attention not to confuse such results as being for SARS-2 coronavirus.

The origins of the virus are not clear, but strongly suspected to have an animal origin; based on RNA sequencing studies of similar coronaviruses found in bats, snakes, and pangolins. The virus was first detected in humans during late December 2019 in the city of Wuhan, China, during investigations of accumulating cases of undiagnosed pneumonia. Since then, there is undoubtedly human-to-human transmission occurring, and at the time of writing is expected to become a pandemic.

The disease caused by SARS-2-CoV in humans is called ‘COVID-2019’. The majority of cases – approximately 80% – have been a mild respiratory infection, from which patients recover without apparent sequelae. However, 20% of recorded COVID-2019 cases have developed pneumonia requiring hospitalisation. Most of these recover and are discharged, but a small proportion of these pneumonia cases have resulted in death. At the time of writing, international surveillance shows that 56% of deaths are >80y, 32% are 70-79y, and 10% are 60-69y, with other risk factors such as diabetes and asthma being the predominant co-morbidities. Overall percentage case fatality rates are still unreliable, since countries that were at the epicentre of the outbreak were not able to identify all the cases of mild infection to compare with the numbers of deaths.

Infection and infectivity

The average incubation period from time of exposure to onset of symptoms is 4-6 days, with a large range from 1 day to 11 days. There is no consistent evidence that people infected with SARS-2-CoV are infectious before becoming symptomatic. However, once symptoms begin, they can be very infectious. The evidence is that the virus can be detected in the upper respiratory tract from the first days of infection, and at a relatively higher viral load. Although viral RNA can be detected in stool and blood samples (fleetingly), it is extremely difficult to cultivate virus from these samples. The implication is that it is non-infectious material, and therefore these routes of excretion may not be important in transmission events.

At a population level, transmissibility of an infection is measured using the basic reproduction number (R₀ – the average number of people further infected by a single case). Estimates of R₀ are beginning to emerge from several studies in different countries. Most current estimates of R₀ fall into the range 2 to 3, which means that good infection control precautions are likely to limit the spread of the virus.

Infection prevention and control

All healthcare facilities should have a policy describing the preparation necessary, and the steps that need to be taken to establish local control of infection. This should be based on risk assessments compatible with PHE guidance, newly updated here -> click

Note that the basic structure of coronaviruses includes an envelope, which is very susceptible to disruption by simple mild detergents and disinfectants such as soap (liquid or solid), alcohol, floor and other hard-surface cleaners. Therefore simple cleaning measures are likely to reduce the spread of infection in rooms and buildings.

The level of personal protective equipment (PPE) required for healthcare workers has changed (as of 06/03/2020), to allow the adoption of less rigorous outfits for suspected cases of SARS-2-infection whilst awaiting test results. Confirmed cases still require the full PPE recommended. If a healthcare worker comes into contact with a confirmed COVID-19 patient whilst not wearing PPE, they can remain and continue to work. However, bearing in mind the incubation period of 4-6 days:

• they must not come to work if they later develop symptoms while at home. Their line manager must be informed immediately
• if symptoms develop whilst at work, they should immediately inform their line manager, leave work and self-isolate at home
• refer to the ‘stay at home’ guidance
• whilst isolated, if the HCW has not improved and not already sought medical advice, they should call NHS 111, or 999 in an emergency.

Patient presentation to healthcare

Community. At the time of writing, people with signs of mild infection who suspect they are infected with SARS-2-CoV should not attend healthcare facilities. Instead, they should self-isolate at home for at least 7 days. See guidance for them here -> click. In line with the ‘no-test’ practice, all contact tracing on community cases has now stopped.

Patients who turn up at hospital with respiratory symptoms. Such patients should be moved to a side-room as soon as possible, pending initial assessment as per the criteria in the next section.

Existing in-patients where COVID-19 status changes. After admission, it may become apparent that patients develop symptoms which puts them in the category of a suspected case. Infection control measures should be immediately put in place, and if healthcare staff have been exposed to the case without PPE, then the procedure described under ‘Infection Prevention & Control’ should be followed.

If patient is already in a side-room, it may be better to leave them where they are. Certainly patients who are in ITU and too unstable to be moved, should remain or at the very most, transferred to a side-room on the unit. An appropriate sample should be taken, and a SARS-2-CoV test should be ordered at the first possible opportunity.

How to assess a patient for possible SARS-2-CoV infection

The guidance for risk assessing patients for SARS-2-CoV infection has recently changed, as of 13/03/2020.

Patients attending hospital with fever and/or cough who are not requiring admission after medical assessment must return home and self-isolate for at least 7 days. They should not be tested for SARS-2-CoV.

All patients requiring admission to hospital with:

• Acute respiratory distress syndrome (ARDS)
• clinical or radiological evidence of pneumonia
• a flu-like illness [2]

are suspected cases and should be tested for SARS-2-CoV, regardless of travel history.

Treatment and support

Suspected cases: Should be cared for in the side room by trained staff wearing appropriate PPE. A restricted set of laboratory tests – such as U&E, FBC, blood cultures – can be ordered for essential patient management. Hospitals should establish infection controlled pathways for suspected cases to get urgent procedures such as dialysis – these should not be delayed by waiting for the SARS-2-CoV laboratory diagnostic result. For emergency management, the use of near-patient testing such as blood-gas analysers should be restricted to a suitable type of machine, and must have had a prior risk assessment conducted on its use for suspected COVID-2019 patients.

Confirmed cases: If medically stable, such patients could be moved to a nearby High Consequence Infectious Disease Unit (HCID). If HCID beds become unavailable as more COVID-19 cases increase, the patient may be advised to self-isolate; or if admission is needed, transferred to a nearby designated ‘standard’ ID unit. There is no recommended antiviral treatment for patients with confirmed COVID-2019 disease. Management is entirely supportive, for which WHO has issued interim guidance (direct download here -> click)

How to test for SARS-2-CoV

Patients with pneumonia should have a lower respiratory tract sample taken, such as ETT secretions, because after several days the the virus may have become undetectable in the upper respiratory tract. However for a patient with only upper respiratory tract symptoms, a throat swab is best. To have a SARS-2-CoV test performed on a patient, it was a Government requirement to use a specific request form E28 (available here -> click). However as testing volumes increase, PHE laboratories are accepting standard request forms from local hospitals, as long as the COVID-19 test is clearly written on their form.

At the time of writing, testing for SARS-2-CoV is being performed at several PHE regional laboratories and some NHS Trusts (see here for a list of locations -> click). Testing is being further rolled out to other NHS Trusts to support the large volume of sample analysis.

Some PHE laboratories have declared a priority status, using a six-stage list to determine which samples are tested first. The top three of these are all related to hospital in-patients and their contacts. Community samples and other categories will be given a lower priority. Thus, with the 7-day ‘stay-at-home’ guidance applying to exposed healthcare workers as well as community patients, it is unlikely that individuals who are not in-patients will get a result before 7 days is up.

If the PHE laboratory screening test is weakly reactive or not easily interpreted, a second confirmation test will be performed to establish the true result. The screening result will be issued as ‘Presumptive positive’ and clinicians should still regard the patient as suspected of COVID-19 illness.

Due the large volume of testing taking place, only presumptive or clear positive results are likely to be telephoned to the requesting clinician. Where the test is being performed at a PHE lab, results will usually be transmitted electronically via the ‘e-labs’ system. NHS labs testing for SARS-2-CoV will have their own arrangements for communicating results.

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[1] SARS is considered to be extinct in the human population, but note that cases of MERS are still being detected in defined geographical areas. PHE and some other laboratories are able to test for MERS coronavirus according to the information here -> click.

[2] Defined as fever ≥37.8°C AND acute onset of at least ONE of the following: persistent cough, hoarseness, nasal discharge or congestion, shortness of breath, sore throat, wheezing, sneezing.