16 June 2020

 As of today, the cumulative number of confirmed COVID-19 cases in South Africa is

76 334

 Case Data

Reported COVID-19 Deaths and Recoveries:

Regrettably, we report a further 57 COVID-19 related deaths: 44 from Western Cape, 9 from the Eastern Cape, and 4 from KwaZulu Natal.

This brings the total national deaths to 1625 with a mortality rate of 2,1%.

We extend our condolences to the loved ones of the departed and thank the health care workers who treated the deceased.

The recoveries to date are 42 063– this translates to a recovery rate of 55,1%.

The provincial breakdown is as follows:

Breakthrough in COVID-19 therapeutics research

 We are extremely excited that there has been an important breakthrough in one of the ther- apeutic trials for COVID-19 management.

The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial has published results on the therapeutic merits of low dose dexamethasone which are extremely promising and are easily implementable in our country

Dexamethasone is a well known and widely used steroid which has potent anti-in- flammatory properties. It is used in allergic reactions, asthma and other conditions

where the inflammatory component of the disease needs to be controlled for better outcomes.

We are very pleased that the Ministerial Advisory Committee on COVID-19 has is- sued an advisory pertaining to the clinical applications of these breaking study re- sults. We attach the advisory to this statement

Ministerial Advisory Committee on COVID-19 Advisory

16 June 2020

Use of dexamethasone for the treatment of severe COVID-19 in South Africa

The use of corticosteroids for the treatment of COVID-19 in South Africa is currently defined in the National Department of Health’s Clinical Management of Suspected or Confirmed COVID-19 Disease (version 4, 18th May 2020) In summary, it states that ‘Given lack of ef- fectiveness and possible harm previously seen, routine corticosteroids should be avoided unless they are indicated for other reasons, such as an asthma or COPD exacerbation..

The COVID-19 sub-committee of the National Essential Medicines List Committee is current- ly updating their recommendations on the use of corticosteroids in COVID-19.

On Tuesday 16th June, a statement was issued from the chief investigators of the Random- ised Evaluation of COVid-19 thERapY (RECOVERY) trial, a UK-based adaptive trial of vari- ous potential treatments for COVID-19, one of which was a systemic corticosteroid (dexa- methasone, prednisolone or hydrocortisone).

The dexamethasone arm of the trial compared dexamethasone 6mg orally or intravenously once daily for 10 days (or prednisolone 40mg daily orally/hydrocortisone 80mg twice daily intravenously, in pregnant or breast-feeding women) against standard of care.

“A total of 2104 patients were randomised to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 pa- tients randomised to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%).

Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% con- fidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75; p=0.14).

Based on these results, 1 death would be prevented by treatment of around 8 ventilated pa- tients or around 25 patients requiring oxygen alone.”

As the Steering Committee of the RECOVERY considered that a meaningful benefit of dexamethasone had been demonstrated, further recruitment to the dexamethasone arm of the study has been stopped.

How should this Statement effect the management of COVID-19 in South Africa?

1. The full publication of this part of the RECOVERY trial is eagerly awaited. There are important aspects of the results that will be needed to make a full assessment of the data, none more so, than the number and type of adverse events in the dexa- methasone arm vs standard of care1. This is critical information needed to provide definitive guidance. Data on the absolute risk reduction and the numbers of events per patient group will also be needed to fully interpret the evidence
2. In the interim, we believe that intravenous dexamethasone 6mg daily or an equival- ent oral corticosteroid (such as prednisolone 40mg daily) for 10 days may be con- sidered in patients with a confirmed diagnosis of COVID-19 who are being mechan- ically ventilated. Although a lesser effect on mortality was shown in those patients requiring oxygen but not being mechanically ventilated, we also advise that dexa- methasone may be considered for patients admitted to hospital with COVID-19 who require oxygen support but are not mechanically ventilated, especially those requir- ing high flow nasal oxygen, CPAP, or non-invasive
3. Patients admitted to hospital with a confirmed or suspected diagnosis of COVID-19 who do not require oxygen support should not receive dexamethasone or other cor- ticosteroid, unless clinically indicated for a specific
4. Contraindications to dexamethasone and adverse effects are detailed in the EML and South African Medicines Formulary, and clinicians are encouraged to refer to these resources.
5. As oral dexamethasone is only accessible as a Section 21 medicine, an equivalent oral corticosteroid may be used. The RECOVERY trial included either oral predniso- lone (40mg daily) or intravenous hydrocortisone (80mg twice daily) in pregnant and breast-feeding women. Betamethasone is a further oral

     6.  It must be stressed that this advisory is based on a preliminary statement by the Chief Investigators of the RECOVERY Trial, and this advisory may be sub- ject to change following review of the full publication.

1 hJps://www.nature.com/arOcles/d41586-020-01824-5) has this quote from the Chief PI, Prof Peter Horby: “”The study found no outstanding adverse events from the treatment, invesOgators said. “This treatment can be given to preJy much anyone,” says Horby.” However, we await full publicaOon to make our assessment.