As we are speaking here, India is battling one of the deadliest second wave of SARS-CoV2. Although it seemed we were victorious from covid-19, there was a surge of cases in the country in the last 2 months, there were many media reports and we also know, the incidents that happened in the last few months, that may be the consequence for the current situation either directly or indirectly. We, doctors, were working tirelessly, under the pressures of the pandemic, giving it everything to the public of this country. The situation has changed compared to the first wave, when we hardly knew the effects of covid-19 on the body, fortunately, the science of covid-19 infection has evolved since now we understand its major effects on the human body thanks to medical scientists and doctors who are working towards understanding this ever-evolving science.
The treatment strategies also changed drastically, for example- the Hydroxychloroquine which we were after in the first wave, was now out from our covid-19 treatment practices, thanks to those clinical trials which proved no evidence of benefit. Still, there is much dilemma about treatment among the public and also among professionals as well.
As in any pandemic, there is panic not only among the general public but also among the practitioners, this may be leading to treatment protocols that have some or any evidence against covid-19.
So, in this article, I will try to summarise the existing evidence for covid-19, and also undergoing trials and some myths which are nothing but nugatory.
- Hydroxychloroquine (HCQ)
There is a Cochrane review by Bhagteshwar Singh, et al. which concludes no clinical benefit for HCQ. (1) There are many other studies, which showed no clinical benefit. There is an editorial published on Cochrane detailing what has happened with HCQ’s. So from being a wonder drug, it was reduced to rubbles in the covid-19 treatment guidelines, this is one such example to say how science evolves rapidly.
2. Azithromycin/ doxycycline/ ivermectin.
Azithromycin – no evidence to date suggests benefit in covid-19. There was data from the PRINCIPLE trial (2), which adds to this.
Doxycycline– no role of its use in the absence of another indication.
Ivermectin– An randomised controlled trial was published in JAMA in 2021, results showed no benefit in the resolution of symptoms. (3)
Steroids are a double-edged weapon. when given at the right time at the right dose they are wonderful drugs, but they can also be very deleterious when used non judiciously.
The current evidence is for using them in patients with hypoxia (spo2 <94%) in hospital settings requiring oxygen or mechanical ventilation (4) There is no data on its benefit in outpatient settings, moreover this may lead to deleterious effects, as it can cause erratic sugars and can prolong the illness, and can lead to some deadly secondary infections like cytomegalovirus, mucormycosis etc, for which many patients died. No role in patients with our hypoxia.
4. Convalescent plasma.
Data from the largest covid-19 trial, the RECOVERY trial, did not show benefit with Convalescent plasma. (5)
The PLACID trial, done among Indian population neither showed benefit. (6)
5. Monoclonal antibodies.
Regeneron’s cocktail/ Roche cocktail – casirivimab-imdevimab– interim analysis showed reduced viral load in outpatients who are yet to mount their inflammatory response. May be used in patients with a high risk of progression to severe disease with comorbidities.
6. Inhaled steroids.
7. Zinc/ multivitamins/ vitamin D.
Among the studies, zinc deficiency was found in covid-19 patients in one study, where they found poor outcomes in deficient patients. there is no proper data to show the benefit of vitamin supplementation in covid-19 patients.
8. Symptomatic management.
Cough can be treated with dextromethorphan, in case of fever, patients are to be advised to stay well hydrated, and paracetamol can be taken to lower the body temperature.
Breathing exercises, incentive spirometry should be advised, to improve cough.
Awake proning can be advised to improve hypoxia.
Studies showed that Remdesivir has some benefit in reducing the hospital stay but has no mortality benefit, and again the patients should be appropriately selected, it has shown not much benefit in mechanically ventilated or in patients on ECMO. (8) The WHO solidarity trial consortium also showed no significant impact on clinical outcomes, other drugs that were evaluated are HCQ, lopinavir/ritonavir and interferon-ß. (9)
In an RCT, Baricitinib and Remdesivir combination was studied in hospitalised patients, it showed reduced recovery time, but no mortality benefit, in patients with oxygen or noninvasive ventilation. (10)
The studies did not show any significant benefit in covid-19 patients, although the manufacturer nitpicked some of the results in their favour, they have no statistical significance. (11) Many studies are undergoing to access the benefit in covid-19 patients.
The REMAP-CAP trial showed improved recovery and reduced mortality when given to hospitalised patients within 24hrs of admission requiring oxygen support. (12)
A living systematic review, published in Cochrane, also suggests mortality benefit with Tocilizumab, but no significant improved clinical outcomes. (13)
13. Methylene blue, progesterone etc.
There are no concrete evidence against any other agents that we have not discussed. multiple studies are undergoing, hopefully we will find respectable evidence, till then we can contribute to this evolving science by conducting clinical trials and accessing the benefits of these investigational drugs in covid-19.
Many trials are undergoing evaluating multiple treatment options, as I have said earlier, this is an evolving area, we may see some magic drugs coming that can effectively treat covid-19. One size that does not fit all is the reality, the clinician should take a decision based on the available evidence at their disposal.
For the public- one should always never forget “prevention is better than cure”, so please, follow social distancing, avoid gathering, wear a Double mask, and maintain good hand hygiene, and get yourself vaccinated.
1. Singh B, Ryan H, Kredo T, Chaplin M, Fletcher T. Chloroquine or hydroxychloroquine for prevention and treatment of COVID‐19. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD013587. DOI: 10.1002/14651858.CD013587.pub2. Accessed 17 May 2021.
2. PRINCIPLE Trial Collaborative Group. Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021 Mar 20;397(10279):1063-1074. doi: 10.1016/S0140-6736(21)00461-X. Epub 2021 Mar 4. PMID: 33676597; PMCID: PMC7972318.
3. López-Medina E, López P, Hurtado IC, et al. Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(14):1426–1435. doi:10.1001/jama.2021.3071
4. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020;324(13):1330–1341. doi:10.1001/jama.2020.17023
5. Group TRC, Horby PW, Estcourt L, Peto L, Emberson JR, Staplin N, et al. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. medRxiv. 2021 Mar 10;2021.03.09.21252736.
6. Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 Oct 22;371:m3939.
7. Ramakrishnan S, Nicolau DV, Langford B, Mahdi M, Jeffers H, Mwasuku C, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. The Lancet Respiratory Medicine [Internet]. 2021 Apr 9 [cited 2021 May 17];0(0). Available from: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/abstract
8. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 — Final Report. New England Journal of Medicine. 2020 Nov 5;383(19):1813–26.
9. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for Covid-19-Interim WHO solidarity trial results. N Engl J Med 2021;384:497-511.
10. Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. New England Journal of Medicine. Available from: https://www.nejm.org/doi/10.1056/NEJMoa2031994
11. Pulla P. Is Favipiravir Good for COVID-19? Clinical Trial Says No, Press Release Says Yes. The Wire Science. 2020. Available from: https://science.thewire.in/the-sciences/favipiravir-glenmark-open-label-trial-primary-endpoints-efficacy-cure-times-misleading-press-release/
12. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. New England Journal of Medicine. 2021 Apr 22;384(16):1491–502.
13. Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, et al. Interleukin‐6 blocking agents for treating COVID‐19: a living systematic review. Cochrane Database of Systematic Reviews. 2021 Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013881/full?highlightAbstract=tocilizumab