Dexamethasone and COVID-19
SARS-CoV-2 causes no or mild symptoms in most people it infects, but a substantial minority develop symptoms that are serious, including difficulty breathing, cough and, in some cases, pneumonia. As the lungs become inflamed and injured, they become less efficient at extracting oxygen from the air and exchanging it for the waste product carbon dioxide. Thus, some people who are hospitalized with COVID-19 can require supplemental oxygen and, in some cases, invasive mechanical ventilation.
A team of researchers in the UK conducted a large study with people hospitalized with COVID-19. They randomly assigned participants to receive one of the following:
- a low daily dose of the steroid dexamethasone (6 mg) for up to 10 days + supportive care
- supportive care alone
Overall, 23% of participants who received dexamethasone and 26% who did not receive it died during the study. However, among people who were on some degree of what the researchers called respiratory support, results were different. Among participants who were on such support, such as invasive mechanical ventilation, 29% who had received dexamethasone died compared to 41% who did not receive the steroid who also died. This research has found that dexamethasone can save the lives of some people with COVID-19, but additional research is needed.
Study details
As the clinical trial was done during the first wave of COVID-19, limited information was collected from participants’ hospital charts.
The average profile of participants at the time they entered the study was as follows:
- age – 66 years
- 64% men, 36% women
- 56% of participants had at least one underlying condition such as the following:
- heart disease – 27%
- diabetes – 24%
- chronic lung disease – 21%
Respiratory assistance:
- 60% were receiving oxygen
- 16% needed invasive mechanical ventilation
- 24% were not receiving either of these interventions
Data were collected for an interim analysis, as researchers were interested in survival 28 days after participants entered the study.
A total of 6,425 participants were randomly assigned in a 2:1 ratio to receive one of the following interventions:
- dexamethasone + supportive care – 4,321 people
- supportive care alone – 2,104 people
Results
The overall effect of dexamethasone on survival may seem initially modest, with deaths distributed as follows:
- dexamethasone + supportive care – 23% died
- supportive care alone – 26% died
However, when researchers took into account the level of what they called “respiratory support” (invasive mechanical ventilation, oxygen) that people were on at the start of the study, there were larger differences in the deaths seen, as follows:
Invasive mechanical ventilation
- dexamethasone + supportive care – 29% died
- supportive care alone – 41% died
Among people who were on oxygen at the start of the study without invasive mechanical ventilation, the distribution of deaths was as follows:
- dexamethasone + supportive care – 23% died
- supportive care alone – 26% died
Readers should note the distribution of deaths among people who were not receiving respiratory support at the start of the study:
- dexamethasone + supportive care – 18% died
- supportive care alone – 14% died
Taking these and other findings into account, the researchers made the following statement:
“…there was no clear effect of dexamethasone among patients who were not receiving any respiratory support [at the start of the study].”
They also said that “patients who were receiving invasive mechanical ventilation [at the start of the study] were on average 10 years younger than those not receiving any respiratory support and had a history of symptoms before randomization for an average of seven days longer.”
Other findings
People who received dexamethasone spent one day less in the hospital than people who did not receive the drug.
Bear in mind
The British study uncovered a clear role for dexamethasone in some people with COVID-19 who were hospitalized. Specifically, the drug is useful in people who are receiving some degree of respiratory support—invasive mechanical ventilation or supplementary oxygen. However, dexamethasone was not beneficial among people who were not receiving respiratory support at the start of the study.
The researchers stated that the beneficial effect of steroids “on severe viral respiratory infections is dependent on a selection of the right dose, at the right time, in the right person.”
Several teams of researchers have suggested that SARS-CoV-2 seems to cause a high level of virus production early in the course of COVID-19. During this stage, steroids and other treatments that suppress inflammation could also hamper the immune system’s ability to contain the virus. They suggest that in later stages of COVID-19 the immune response may be excessive and cause harm, and that steroids and other drugs that dampen the immune system may be more useful at that point.
For the future
The present study, which examined survival 28 days after participants entered the study, is important. Although many participants have recovered and left the hospital, they are still being monitored and the research team will perform an analysis to assess the impact of dexamethasone on long-term survival.
Many potential volunteers were screened by research nurses for possible participation in the study—1,707 were excluded and it is not clear why. It is possible that for some people steroids may not have been safe due to certain pre-existing conditions, such as the following:
- uncontrolled diabetes
- a state of confusion, disorientation, memory loss and/or an inability to think clearly
- cancer
- immune suppression because of medicines for transplanted organs or autoimmune disorders such as arthritis
The present study did not assess the impact of steroids on SARS-CoV-2 replication. This would be an important point for future studies of steroids. Laboratory research suggests that dexamethasone can impair the ability of SARS-CoV-2 to enter cells. Does this drug have a significant antiviral effect in people with COVID-19?
—Sean R. Hosein
REFERENCES:
- RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine. 2021 Feb 25;384(8):693-704.
- Normand ST. The RECOVERY Platform. New England Journal of Medicine. 2021 Feb 25;384(8):757-758.
- Matthay MA, Thompson BT. Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties. Lancet Respiratory Medicine. 2020 Dec;8(12):1170-1172.
- Zhang Y, Hu S, Wang J, et al. Dexamethasone inhibits SARS-CoV-2 spike pseudotyped virus viropexis by binding to ACE2. Virology. 2021 Feb;554:83-88.
- Matsuyama S, Kawase M, Nao N, et al. The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting the viral replication-transcription complex in cultured cells. Journal of Virology. 2020 Dec 9;95(1):e01648-20.