COVID-19, Can it be Cured?

An interesting editorial in The Lancet Infectious Diseases published September 10, 2020 reflects on this question and helps to provide answers.

As the COVID-19 pandemic moves into its tenth month, there is a greater patient survival which might suggest that the treatment of this severe disease has improved.

But how much of this improvement is due to better supportive care?  And how much is due to pharmaceutical addition?

The editorial suggests that a huge effort has been put into finding drugs to treat COVID-19 by the biomedical community with thousands of trials completed and ongoing.   They ask what is the evidence for what has worked and what has not?

They go on to discuss the politicisation of COVID-19 treatments, none more so than with chloroquine and hydroxychloroquine trumpeted by President Trump.

Early observational studies suggested a beneficial effect of treatment with these cheap drugs.  However, randomised control trials in hospitalised patients showed no effect of hydroxychloroquine in reducing mortality.  One trial hinted at an effect when used as post-exposure prophylaxis, but this was not found to be statistically significant.  Unless new, high quality evidence emerges, these drugs appear to have no future in the management of COVID-19 patients. 

Remdesivir – This was also an antiviral subject to immense White House fanfare.

The US government attempted to corner of the market for this costly drug but results of clinical trials have been ambiguous.  One review concluded that Remdesivir may reduce time to clinical improvement and decrease mortality but had no effect on the need for invasive ventilation or length of hospital stay.  A subsequent trial found no effect on mortality.  Although the drug is approved to treat COVID-19 in the USA and Europe, conclusive evidence to support its use is lacking. 

Other antivirals – There is no good evidence for efficacy of Favipiravir, although it has been approved in Russia.  The Lopinavir-Ritonavir combination showed no clinical benefit in the UK recovery trial.

Immunomodulators – These are being widely tested in clinical trials.  Amongst the front runners, evidence to support the use of Tocilizumab, a monoclonal antibody against Interleukin 6 receptors, comes largely from observational studies.  Roche, the manufacturer announced that the drug did not improve clinical status in phase 3 random control trials amongst patients with severe COVID-19 associated pneumonia.

Convalescent plasma – Good evidence for its use is still awaited. 

Large trials such as the RECOVERY trial, which includes Tocilizumab in convalescent plasma groups will and hopefully should provide answers. 

Dexamethasone – Dexamethasone was found in the RECOVERY trial to reduce deaths by 35% in ventilated patients and by 20% amongst those receiving oxygen as compared with those in the standard care group.  A randomised clinical trial in Brazil further supported the beneficial effects of dexamethasone.

The REMAP-CAP trial of hydrocortisone, another steroid, versus placebo in patients with severe COVID-19 show a 93% improvement in the intervention group in days when organ support was not needed. 

Based on these findings, the WHO recommended corticosteroids in patients with severe and critical COVID-19.

There has been a resurgence of COVID-19 cases to levels at least as high as when the pandemic first struck in the spring in areas such as the USA, France and Spain.  Yet this has not been followed by comparable increase in deaths nor of people requiring admission to hospital – could this be as a result of targeted treatment?

Possible explanations for the disparity in cases and deaths may include more widespread testing, meaning that the number of cases being detected is closer to the true level of infection, whereas the accuracy of counting deaths remains unchanged. 

– Lower viral load at the point of transmission and hence less severe disease as a result of non-pharmaceutical measures such as mask wearing and changes in the distribution of cases towards younger age groups.  Data from England shows that until recently, cases were fairly evenly distributed across all ages from 20 years upwards.  However, by the last two weeks of August cases in the 20 to 39-year-old were about 10 times the number in those aged 70 or more.  The risk of COVID-19 deaths in young people is tiny compared with the elderly infected.  It is worrying though that cases in the young might still spill over into the older patient and the long term consequences of non fatal disease are still unknown. 

Whatever the reasons for this apparent declining mortality, the impact of drug treatments on the COVID-19 pandemic is still limited.  The Lancet editorial concludes that the massive research effort needs to bear fruit with a broader range of effective therapies.  Here at The London General Practice we have kept abreast with all investigations and treatments for COVID-19 disease.  We also have access to the very top specialists who have been looking after patients with COVID-19 throughout the whole pandemic and are readily available to confirm the diagnosis of SARS-CoV-2 infection by PCR swab, and then refer as accordingly to the leading specialists in their fields.

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