The outbreak of COVID-19 started in December 2019 in Wuhan, China and has since spread around the globe, infecting nearly 500,000 people and resulting in more than 22,000 deaths (at writing), and the numbers are continuously increasing. To date, there is no vaccine or approved treatment for COVID-19, and various trials are under study. However, considering the extent of the pandemic and challenges associated with its management, the compassionate use of various treatment therapies is a hot topic of discussion. Most treatment options are based on expert opinion or non-randomized trials. With all this evolving information, we can summarize the progress on currently proposed treatment options:
- Remdesivir: Displays potent in vitro activity against SARS-CoV-2, with a high genetic barrier to resistance in coronaviruses. Four clinical trials are currently enrolling patients in the United States. Its compassionate use is only considered for hospitalized patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 requiring mechanical ventilation. Emerging clinical evidence and available in vitro data suggest that remdesivir can be a promising agent for the treatment of COVID-19, but we need to wait for trial results and safety data before prescribing across the board.
- Chloroquine and hydroxychloroquine: They have anti-inflammatory and immunomodulatory activities, with potent in vitro activity of chloroquine against SARS-CoV-2. No efficacy data are available for hydroxychloroquine in COVID-19, with a currently ongoing trial. Cardiovascular toxicity concerns limit the use of chloroquine. The initial experience in China and France is encouraging for the potential role of chloroquine, or alternatively hydroxychloroquine, for the management of PCR-positive COVID-19. No data to support prophylactic use as of now.
- Lopinavir/Ritonavir: Limited data suggest no advantage over standard care for SARS-CoV-2/COVID-19, either as monotherapy or in combination.
- Tocilizumab: It is a humanized monoclonal antibody that inhibits both membrane-bound and soluble interleukin-6 (IL-6) receptors and is being considered as a treatment option for severe or critical cases of COVID-19, with elevated IL-6 having hyper-inflammatory states and cytokine storming. Two ongoing trials in China are evaluating that safety and efficacy of this therapy; to date, no concerning adverse events have been reported yet.
- Nitazoxanide: It has demonstrated potent in vitro activity against SARS-CoV-2. It interferes with host regulated pathways involved in viral replication, and is, hence, considered broad spectrum. More data are clearly needed to determine its role in the management of COVID-19.
- Corticosteroids: The risks and benefits of corticosteroids need to be carefully weighed on the individual patient level. Large-dose glucocorticoid suppresses the immune system and could delay clearance of SARS-CoV-2.
- Ribavirin +/- Interferon: Based on the poor in vitro activity, absence of animal or human data and significant toxicity profile of interferon, avoid use in patients with COVID-19 at this time. Despite the limited-to-poor data, Chinese have used ribavirin 500 mg IV 2-3 times daily in combination with Lopinavir/ritonavir or inhaled INF-α on expert opinion.
- Oseltamivir and Baloxavir: Coronaviruses do not utilize neuraminidase, and thus, there is no enzyme to be inhibited by oseltamivir. This would hold true for zanamivir, peramivir, or any other neuraminidase inhibitor agents. Baloxavir has not demonstrated in vitro activity against SARS CoV-2 or other coronaviruses.
- Convalescent Plasma: It has been used previously for SARS-CoV-1, Middle East respiratory syndrome, Ebola virus disease, and H1N1 influenza with reported success. The safety and efficacy of convalescent plasma transfusion in SARS-CoV-2-infected patients has not been established yet and is still under study.
While all these treatment options are surfacing, it is important to understand that the best techniques to slow the disease transmission remain social distancing, frequent hand washing, avoiding unnecessary travel, early screening, and isolation.
References
McCreary EK, J M Pogue JM, COVID-19 Treatment: A Review of Early and Emerging Options. Open Forum Infectious Diseases: http://doi.org/10.1093/ofid/ofaa105.
Stevens MP, Patel PK, Nori P. Involving Antimicrobial Stewardship Programs in COVID-19 Response Efforts: All Hands on Deck. Infection control and hospital epidemiology. 2020:1-6.
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research. 2020;30(3):269-271.
PWeekly
Drugs such as Methotrexate and 5-Fluorouracil act by decreasing nucleotide availability to cells as well as viruses. These drugs would make it more difficult for the virus to replicate. It would affect the host cell as well but the benefit should be greater than the risk. Has anyone thought of trying these agents against Covid 19?
I am no doctor or scientist but I have little background as i did btech chemical engineering
But that’s not to be considered at all. In was wondering what happens to corona virus after a person ia dead .. is it eating up dead cells or getting into incapable environment to survive ??? Probably pur solution may lie there …. Investigating the dead and the corona virus habitation inside dead people ..
As highlighted by WHO in their recent update:
Based on current evidence, the COVID-19 virus is transmitted between people through droplets, fomites and close contact, with possible spread through faeces. It is not airborne. As this is a new virus whose source and disease progression are not yet entirely clear, more precautions may be used until further information becomes available:
• Except in cases of hemorrhagic fevers (such as Ebola, Marburg) and cholera, dead bodies are
generally not infectious. Only the lungs of patients with pandemic influenza, if handled improperly
during an autopsy, can be infectious. Otherwise, cadavers do not transmit disease. It is a common
myth that persons who have died of a communicable disease should be cremated, but this is not true.
Cremation is a matter of cultural choice.
• To date, there is no evidence of persons having become infected from exposure to the bodies of persons who died from COVID-19.
I don’t understand how this publication (and pretty much all Western publications) can leave out Favipiravir in it’s discussion of treatment regimes. While the two trials that have been reported on (total patients c320) are by no means perfect they are easily the most robust studies released to date and show strong evidence of efficacy vs the controls tested against (Lopinavir/Ritonavir in one and Arbidol [umifenovir] in the other).
Importantly time to viral clearance was substantially better in both trials (important to reduce R0 (healthcare workers and housemates/family) and percentage requiring oxygen therapy was less than HALF in both trials (albeit just missed being statistically significant effect in Arbidol control trial).
The time to be looking at treatment regimes with ONLY the concerns of the patient in front of us is LONG since gone. A community wide risk trade off MUST be looked at. If a drug with a good safety profile (excluding pregnancy of course) can substantially reduce R0 AND substantially reduce the percentage of patients on ventilators we need to take the evidence seriously. Other patients lives WILL be impacted by how current patients are treated (or not treated as the case may be).
China is the ONLY country that appears to have licked this thing. Could we please take their evidence at face value for ONCE!
I understand in vitro data on Favipiravir doesn’t look fantastic (high EC50). Yet this is also the case against some other viruses that it appears to inhibit invivo (e.g. high EC50 in Ebola yet protects 100% in mice Ebola challenge models). There may be some immune modulating effect we don’t yet understand.
More relevantly TO DATE Favipiravir is clearly the drug with the best evidence for efficacy!