Anakinra
Anakinra is an interleukin-1 inhibitor that is approved in Europe for adults with COVID-19 pneumonia who require low- or high-flow supplemental oxygen and who are at risk of developing severe respiratory failure, as determined by blood soluble urokinase plasminogen activator receptor (suPAR) levels of at least 6 nanograms/mL. It is authorised under an emergency-use authorisation in the US for the same indication. Guidelines do not currently recommend anakinra for the treatment of COVID-19, as there is insufficient evidence to recommend either for or against its use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Systematic reviews and meta-analyses have found that anakinra may reduce mortality and the need for invasive mechanical ventilation in hospitalised patients, particularly those with C-reactive protein levels >100 mg/L, compared with standard care alone.[952]Kyriazopoulou E, Huet T, Cavalli G, et al. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol. 2021 Oct;3(10):e690-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352496
http://www.ncbi.nlm.nih.gov/pubmed/34396156?tool=bestpractice.com
[953]Barkas F, Ntekouan SF, Kosmidou M, et al. Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a systematic review and meta-analysis. Rheumatology (Oxford). 2021 Dec 1;60(12):5527-37.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194671
http://www.ncbi.nlm.nih.gov/pubmed/33999135?tool=bestpractice.com
[954]Somagutta MKR, Lourdes Pormento MK, Hamid P, et al. The safety and efficacy of anakinra, an interleukin-1 antagonist in severe cases of COVID-19: a systematic review and meta-analysis. Infect Chemother. 2021 Jun;53(2):221-37.
https://www.icjournal.org/DOIx.php?id=10.3947/ic.2021.0016
http://www.ncbi.nlm.nih.gov/pubmed/34216117?tool=bestpractice.com
However, a Cochrane review did not find evidence for an important beneficial clinical effect of interleukin-1 inhibitors , and the evidence is uncertain for several outcomes. Anakinra probably results in little or no improvement in symptoms at 28 days after treatment (moderate-certainty evidence). It is uncertain whether anakinra makes a difference to the number of deaths at 28 days after treatment (low-certainty evidence).[955]Davidson M, Menon S, Chaimani A, et al. Interleukin-1 blocking agents for treating COVID-19. Cochrane Database Syst Rev. 2022 Jan 26;(1):CD015308.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015308/full
http://www.ncbi.nlm.nih.gov/pubmed/35080773?tool=bestpractice.com
Colchicine
Colchicine is an anti-inflammatory agent that downregulates multiple pro-inflammatory pathways. Guidelines recommend against the use of colchicine for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
A Cochrane review found that the use of colchicine probably has little to no influence on mortality or clinical progression in hospitalised patients with moderate to severe disease, compared with placebo or standard care alone (moderate-certainty evidence). Evidence for effect on all-cause mortality for people with asymptomatic or mild disease is uncertain; however, use probably results in a slight reduction in hospital admissions or 28-day mortality.[956]Mikolajewska A, Fischer AL, Piechotta V, et al. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;(10):CD015045.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015045/full
http://www.ncbi.nlm.nih.gov/pubmed/34658014?tool=bestpractice.com
Granulocyte-macrophage colony-stimulating factor inhibitors
Investigational granulocyte-macrophage colony-stimulating factor (GM-CSF) inhibitors (e.g., lenzilumab, mavrilimumab, otilimab) may mitigate lung inflammation in severe and critical disease by minimising downstream production of numerous pro-inflammatory mediators. Guidelines do not currently recommend GM-CSF inhibitors for the treatment of COVID-19, as there is insufficient evidence to recommend either for or against their use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Randomised controlled trials have shown positive results for lenzilumab, but not mavrilimumab.[957]Temesgen Z, Burger CD, Baker J, et al. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Mar;10(3):237-46.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00494-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34863332?tool=bestpractice.com
[958]Cremer PC, Abbate A, Hudock K, et al. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol. 2021 Jun;3(6):e410-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969143
http://www.ncbi.nlm.nih.gov/pubmed/33754144?tool=bestpractice.com
A meta-analysis found that GM-CSF inhibitors may reduce the incidence of mechanical ventilation and decrease mortality, but evidence is limited and further studies are required.[959]Xi AR, Luo YJ, Guan JT, et al. Efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients: a meta-analysis. Inflammopharmacology. 2022 Nov 29 [Epub ahead of print].
https://link.springer.com/article/10.1007/s10787-022-01105-9
http://www.ncbi.nlm.nih.gov/pubmed/36445552?tool=bestpractice.com
Convalescent plasma
High-titre convalescent plasma is a blood product that contains high titres of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from patients who have recovered. Guidelines recommend against the use of convalescent plasma for the treatment of hospitalised patients with COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
Guideline recommendations in patients with non-severe disease are conflicting. Some guidelines recommend it in select patients (e.g., outpatients who are at high risk for progression to severe disease).[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[960]Estcourt LJ, Cohn CS, Pagano MB, et al. Clinical practice guidelines from the association for the advancement of blood and biotherapies (AABB): COVID-19 convalescent plasma. Ann Intern Med. 2022 Sep;175(9):1310-21.
https://www.acpjournals.org/doi/10.7326/M22-1079
http://www.ncbi.nlm.nih.gov/pubmed/35969859?tool=bestpractice.com
Other guidelines recommend against its use in these patients.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
There is insufficient evidence to recommend either for or against the use of convalescent plasma for the treatment of hospitalised or non-hospitalised immunocompromised patients.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Convalescent plasma collected prior to the emergence of the Omicron variant is not recommended.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
A Cochrane review found that convalescent plasma does not reduce mortality, and has little to no impact on measures of clinical improvement for the treatment of moderate to severe disease (high-certainty evidence).[961]Piechotta V, Iannizzi C, Chai KL, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013600.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/34013969?tool=bestpractice.com
A living systematic review and network meta-analysis found that convalescent plasma may not confer any meaningful benefit in patients with any disease severity, but whether high-titre convalescent plasma confers any benefit remains uncertain.[962]Siemieniuk RA, Bartoszko JJ, Díaz Martinez JP, et al. Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis. BMJ. 2021 Sep 23;374:n2231.
https://www.bmj.com/content/374/bmj.n2231
http://www.ncbi.nlm.nih.gov/pubmed/34556486?tool=bestpractice.com
Evidence from meta-analyses is conflicting. While some meta-analyses found that treatment with convalescent plasma was not significantly associated with a decrease in all-cause mortality (or any benefit for other outcomes) compared with placebo or standard of care, others have found a reduction in mortality, especially when trials with low-titre convalescent plasma were removed from the analyses.[963]Janiaud P, Axfors C, Schmitt AM, et al. Association of convalescent plasma treatment with clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. JAMA. 2021 Mar 23;325(12):1185-95.
https://jamanetwork.com/journals/jama/fullarticle/2777060
http://www.ncbi.nlm.nih.gov/pubmed/33635310?tool=bestpractice.com
[964]Gupta T, Kannan S, Kalra B, et al. Systematic review and meta-analysis of randomised controlled trials testing the safety and efficacy of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19): evidence-base for practise and implications for research. Transfus Med. 2021 Dec;31(6):409-20.
https://onlinelibrary.wiley.com/doi/10.1111/tme.12803
http://www.ncbi.nlm.nih.gov/pubmed/34189780?tool=bestpractice.com
[965]Klassen SA, Senefeld JW, Johnson PW, et al. The effect of convalescent plasma therapy on mortality among patients with COVID-19: systematic review and meta-analysis. Mayo Clin Proc. 2021 May;96(5):1262-75.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888247
http://www.ncbi.nlm.nih.gov/pubmed/33958057?tool=bestpractice.com
[966]Wardhani SO, Fajar JK, Wulandari L, et al. Association between convalescent plasma and the risk of mortality among patients with COVID-19: a meta-analysis. F1000Res. 2021 Feb 3;10:64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182694
http://www.ncbi.nlm.nih.gov/pubmed/34136130?tool=bestpractice.com
[967]Kloypan C, Saesong M, Sangsuemoon J, et al. Convalescent plasma for COVID-19: a meta-analysis of clinical trials and real-world evidence. Eur J Clin Invest. 2021 Aug 10:e13663.
https://onlinelibrary.wiley.com/doi/10.1111/eci.13663
http://www.ncbi.nlm.nih.gov/pubmed/34375445?tool=bestpractice.com
[968]Axfors C, Janiaud P, Schmitt AM, et al. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials. BMC Infect Dis. 2021 Nov 20;21(1):1170.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605464
http://www.ncbi.nlm.nih.gov/pubmed/34800996?tool=bestpractice.com
Intravenous immunoglobulin
Intravenous immunoglobulin (IVIG) is a blood product prepared from serum pooled from healthy donors. It has an immunomodulatory effect that suppresses a hyperactive immune response. Guidelines do not currently recommend SARS-CoV-2-specific IVIG for the treatment of COVID-19, as there is insufficient evidence to recommend either for or against its use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Guidelines recommend against the use of non-SARS-CoV-2 specific IVIG for the treatment of COVID-19, except in the context of a clinical trial, unless otherwise indicated.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
A living systematic review and network meta-analysis found that IVIG may not confer any meaningful benefit in patients with any disease severity.[962]Siemieniuk RA, Bartoszko JJ, Díaz Martinez JP, et al. Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis. BMJ. 2021 Sep 23;374:n2231.
https://www.bmj.com/content/374/bmj.n2231
http://www.ncbi.nlm.nih.gov/pubmed/34556486?tool=bestpractice.com
However, another meta-analysis found that IVIG reduced mortality in patients with critical disease, although there was no significant difference between the severe and non-severe subgroups.[969]Xiang HR, Cheng X, Li Y, et al. Efficacy of IVIG (intravenous immunoglobulin) for corona virus disease 2019 (COVID-19): A meta-analysis. Int Immunopharmacol. 2021 Jul;96:107732.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084608
http://www.ncbi.nlm.nih.gov/pubmed/34162133?tool=bestpractice.com
Stem cell therapy
Mesenchymal stem cells are an investigational product that have been studied for their immunomodulatory properties. Guidelines recommend against the use of mesenchymal stem cells for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Systematic reviews and meta-analyses have found that mesenchymal stem cells may reduce the incidence of adverse events and mortality in patients with severe or critical disease. However, evidence is limited.[970]Li Y, Wei Z, Ma X, et al. Efficacy and safety of mesenchymal stromal cells therapy for COVID-19 infection: a systematic review and meta-analysis. Curr Stem Cell Res Ther. 2021 Dec 6 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/34872483?tool=bestpractice.com
[971]Kirkham AM, Bailey AJM, Monaghan M, et al. Updated living systematic review and meta-analysis of controlled trials of mesenchymal stromal cells to treat COVID-19: a framework for accelerated synthesis of trial evidence for rapid approval - FASTER approval. Stem Cells Transl Med. 2022 Jul 20;11(7):675-87.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299509
http://www.ncbi.nlm.nih.gov/pubmed/35758400?tool=bestpractice.com
[972]Yao W, Dong H, Qi J, et al. Safety and efficacy of mesenchymal stem cells in severe/critical patients with COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2022 Sep;51:101545.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9270852
http://www.ncbi.nlm.nih.gov/pubmed/35844767?tool=bestpractice.com
Interferons
Interferons are a family of cytokines with antiviral properties. Guidelines recommend against the use of interferons (alfa, beta, or lambda) for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
The WHO Solidarity trial found that interferon beta appears to have little or no effect on hospitalised patients, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.[973]WHO Solidarity Trial Consortium; Pan H, Peto R, Henao-Restrepo AM, et al. Repurposed antiviral drugs for Covid-19: interim WHO Solidarity trial results. N Engl J Med. 2021 Feb 11;384(6):497-511.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727327
http://www.ncbi.nlm.nih.gov/pubmed/33264556?tool=bestpractice.com
A phase 2 trial found that peginterferon lambda reduced viral load and increased the number of participants with a negative nasopharyngeal swab at day 7 in outpatients with mild to moderate disease compared with placebo.[974]Feld JJ, Kandel C, Biondi MJ, et al. Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial. Lancet Respir Med. 2021 May;9(5):498-510.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906707
http://www.ncbi.nlm.nih.gov/pubmed/33556319?tool=bestpractice.com
Ivermectin
Ivermectin is a broad-spectrum antiparasitic agent that has shown to be effective against SARS-CoV-2 in vitro.[975]Caly L, Druce JD, Catton MG, et al. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787.
https://www.sciencedirect.com/science/article/pii/S0166354220302011
http://www.ncbi.nlm.nih.gov/pubmed/32251768?tool=bestpractice.com
Guidelines do not recommend ivermectin for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
There is insufficient evidence to be clear to what extent ivermectin is helpful or harmful. For most key outcomes, including mortality, mechanical ventilation, hospital admission, duration of hospitalisation, and viral clearance, the evidence is of very low certainty.[736]Agarwal A, Rochwerg B, Lamontagne F, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379.
https://www.bmj.com/content/370/bmj.m3379
http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com
[737]Agarwal A, Rochwerg B, Lamontagne F, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2022 Sep 15;378:o2224.
http://www.ncbi.nlm.nih.gov/pubmed/36109041?tool=bestpractice.com
Data from meta-analyses are conflicting. A meta-analysis of 24 randomised controlled trials found that ivermectin provided a significant survival benefit (moderate-certainty evidence), and a likely clinical benefit in terms of improvement and deterioration (low-certainty evidence). Overall, the evidence suggested that early use may reduce morbidity and mortality.[976]Bryant A, Lawrie TA, Dowswell T, et al. Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther. 2021 Jun 21;28(4):e434-60.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248252
http://www.ncbi.nlm.nih.gov/pubmed/34145166?tool=bestpractice.com
Other meta-analyses also support an improvement in clinical outcomes, although the quality of evidence was very low to low.[977]Kory P, Meduri GU, Varon J, et al. Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19. Am J Ther. 2021 Apr 22;28(3):e299-318.
https://journals.lww.com/americantherapeutics/Fulltext/2021/06000/Review_of_the_Emerging_Evidence_Demonstrating_the.4.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34375047?tool=bestpractice.com
[978]Zein AFMZ, Sulistiyana CS, Raffaelo WM, et al. Ivermectin and mortality in patients with COVID-19: a systematic review, meta-analysis, and meta-regression of randomized controlled trials. Diabetes Metab Syndr. 2021 Jun 27;15(4):102186.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236126
http://www.ncbi.nlm.nih.gov/pubmed/34237554?tool=bestpractice.com
[979]Kow CS, Merchant HA, Mustafa ZU, et al. The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis. Pharmacol Rep. 2021 Oct;73(5):1473-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005369
http://www.ncbi.nlm.nih.gov/pubmed/33779964?tool=bestpractice.com
[980]Padhy BM, Mohanty RR, Das S, et al. Therapeutic potential of ivermectin as add on treatment in COVID 19: a systematic review and meta-analysis. J Pharm Pharm Sci. 2020;23:462-9.
https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31457/21594
http://www.ncbi.nlm.nih.gov/pubmed/33227231?tool=bestpractice.com
[981]Bartoszko JJ, Siemieniuk RAC, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ. 2021 Apr 26;373:n949.
https://www.bmj.com/content/373/bmj.n949
http://www.ncbi.nlm.nih.gov/pubmed/33903131?tool=bestpractice.com
[982]Azeez TA, Lakoh S, Adeleke AA, et al. Chemoprophylaxis against COVID-19 among health-care workers using ivermectin in low- and middle-income countries: a systematic review and meta-analysis. Indian J Pharmacol. 2021 Nov-Dec;53(6):493-8.
https://www.ijp-online.com/article.asp?issn=0253-7613;year=2021;volume=53;issue=6;spage=493;epage=498;aulast=Azeez
http://www.ncbi.nlm.nih.gov/pubmed/34975139?tool=bestpractice.com
However, there are other meta-analyses that have found that ivermectin does not reduce all-cause mortality or result in improvement in other clinical outcomes.[981]Bartoszko JJ, Siemieniuk RAC, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ. 2021 Apr 26;373:n949.
https://www.bmj.com/content/373/bmj.n949
http://www.ncbi.nlm.nih.gov/pubmed/33903131?tool=bestpractice.com
[983]Roman YM, Burela PA, Pasupuleti V, et al. Ivermectin for the treatment of COVID-19: a systematic review and meta-analysis of randomized controlled trials. Clin Infect Dis. 2021 Jun 28 [Epub ahead of print].
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab591/6310839
http://www.ncbi.nlm.nih.gov/pubmed/34181716?tool=bestpractice.com
[984]Deng J, Zhou F, Ali S, et al. Efficacy and safety of ivermectin for the treatment of COVID-19: a systematic review and meta-analysis. QJM. 2021 Dec 20;114(10):721-32.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500108
http://www.ncbi.nlm.nih.gov/pubmed/34570241?tool=bestpractice.com
[985]Bitterman A, Martins CP, Cices A, et al. Comparison of trials using ivermectin for COVID-19 between regions with high and low prevalence of strongyloidiasis: a meta-analysis. JAMA Netw Open. 2022 Mar 1;5(3):e223079.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790173
http://www.ncbi.nlm.nih.gov/pubmed/35311963?tool=bestpractice.com
[986]Marcolino MS, Meira KC, Guimarães NS, et al. Systematic review and meta-analysis of ivermectin for treatment of COVID-19: evidence beyond the hype. BMC Infect Dis. 2022 Jul 23;22(1):639.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308124
http://www.ncbi.nlm.nih.gov/pubmed/35870876?tool=bestpractice.com
A Cochrane review found no evidence to support the use of ivermectin for treating or preventing infection, but the evidence base was limited (as of 26 May 2021). The safety and efficacy of ivermectin was uncertain based on very low- to low-certainty evidence. Overall, the reliable evidence available does not support the use of ivermectin for treatment or prevention outside of well‐designed randomised trials.[987]Popp M, Stegemann M, Metzendorf MI, et al. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst Rev. 2021 Jul 28;(7):CD015017.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015017.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/34318930?tool=bestpractice.com
Nitazoxanide
Nitazoxanide is a broad-spectrum antiparasitic agent with in vitro activity against SARS-CoV-2. Guidelines recommend against the use of nitazoxanide for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
A systematic review and meta-analysis found that nitazoxanide did not decrease viral load, frequency of polymerase chain reaction test positivity, or the risk for disease progression or death compared with placebo in patients with mild to moderate disease.[988]Martins-Filho PR, do Nascimento-Júnior EM, Barreto-Alves JA, et al. Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials. Eur J Clin Pharmacol. 2022 Nov;78(11):1813-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9446612
http://www.ncbi.nlm.nih.gov/pubmed/36066651?tool=bestpractice.com
Fluvoxamine
Fluvoxamine is a selective serotonin-reuptake inhibitor that has anti-inflammatory and possible antiviral effects. Guidelines recommend against the use of fluvoxamine for the treatment of COVID-19, as there is insufficient evidence to recommend either for or against its use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication].
https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.5
A meta-analysis of randomised controlled trials, including the TOGETHER trial, found that patients receiving fluvoxamine were less likely to experience clinical deterioration or hospitalisation compared with placebo, although analysis of hospitalisation-only data was not statistically significant.[989]Guo CM, Harari O, Chernecki C, et al. Fluvoxamine for the early treatment of COVID-19: a meta-analysis of randomized clinical trials. Am J Trop Med Hyg. 2022 Mar 9;106(5):1315-20.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128689
http://www.ncbi.nlm.nih.gov/pubmed/35263710?tool=bestpractice.com
Metformin
Metformin is an antidiabetic agent that has been identified as a potential therapeutic due to its possible antiviral, anti-inflammatory, and antithrombotic properties. Guidelines recommend against the use of metformin for the treatment of COVID-19, except in the context of a clinical trial.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
Randomised controlled trials have not demonstrated benefit in reducing the risk of hospitalisation or death.[990]Reis G, Dos Santos Moreira Silva EA, Medeiros Silva DC, et al. Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: the TOGETHER randomized platform clinical trial. Lancet Reg Health Am. 2022 Feb;6:100142.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668402
http://www.ncbi.nlm.nih.gov/pubmed/34927127?tool=bestpractice.com
[991]Bramante CT, Huling JD, Tignanelli CJ, et al. Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19. N Engl J Med. 2022 Aug 18;387(7):599-610.
https://www.nejm.org/doi/10.1056/NEJMoa2201662
http://www.ncbi.nlm.nih.gov/pubmed/36070710?tool=bestpractice.com
Sabizabulin
Sabizabulin is an investigational drug that binds to the microtubules in cells (similar to colchicine), thereby interfering with the lifecycle of the SARS-CoV-2 virus, and has antiviral and anti-inflammatory effects. The European Medicines Agency has started a review of the available data on the use of sabizabulin for the treatment of COVID-19.[992]European Medicines Agency. EMA reviewing data on sabizabulin for COVID-19. 2022 [internet publication].
https://www.ema.europa.eu/en/news/ema-reviewing-data-sabizabulin-covid-19
The US Food and Drug Administration voted against an emergency-use authorisation for use in hospitalised patients with moderate to severe infection. Interim results from a small phase 3 trial (204 patients) found that sabizabulin was associated with a reduction in mortality compared with placebo (45% versus 20%).[993]Barnette KG, Gordon MS, Rodriguez D, et al. Oral sabizabulin for high-risk, hospitalized adults with Covid-19: interim analysis. NEJM Evid. 2022 Jul 6 [Epub ahead of print].
https://evidence.nejm.org/doi/10.1056/EVIDoa2200145
Vilobelimab
Vilobelimab is an investigational, first-in-class anti-C5a monoclonal antibody in development for the treatment of COVID-19 pneumonia. C5a plays a role in severe lung injury. A phase 3, double-blind, randomised placebo-controlled trial found that vilobelimab, in addition to standard of care, reduced mortality at 20 and 60 days in critically ill patients on invasive mechanical ventilation (absolute risk reduction of 11%) compared with placebo.[994]Vlaar APJ, Witzenrath M, van Paassen P, et al. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Dec;10(12):1137-46.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00297-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36087611?tool=bestpractice.com
The manufacturer has requested emergency-use authorisation from the US Food and Drug Administration for the treatment of critically ill patients.
Inhaled corticosteroids
Inhaled corticosteroids are thought to modulate the inflammatory pathways in the upper respiratory tract and circulation following infection. Guidelines do not recommend inhaled corticosteroids for the treatment of COVID-19 except in the context of a clinical trial, as there is insufficient evidence to recommend either for or against their use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication].
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
A Cochrane review found that inhaled corticosteroids (budesonide and ciclesonide) probably reduced the combined end point of admission to hospital or death and increased the resolution of initial symptoms at day 14 in people with mild symptoms (moderate‐certainty evidence). However, inhaled corticosteroids make little to no difference in all‐cause 30-day mortality but may decrease duration to symptom resolution (low‐certainty evidence).[995]Griesel M, Wagner C, Mikolajewska A, et al. Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Mar 9;(3):CD015125.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015125/full
http://www.ncbi.nlm.nih.gov/pubmed/35262185?tool=bestpractice.com
Aspirin
Aspirin (and other antiplatelet drugs) are not currently recommended by guidelines, and the evidence for their use is conflicting. The RECOVERY trial found that aspirin was not associated with a reduction in 28-day mortality or a reduced risk of progression to ventilation or death, and was associated with an increased risk of major bleeding events.[996]RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022 Jan 8;399(10320):143-51.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01825-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34800427?tool=bestpractice.com
Other randomised controlled trials also demonstrate no benefit with aspirin (alone or in combination with rivaroxaban).[997]Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022 Dec;10(12):1160-8.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00299-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36228639?tool=bestpractice.com
[998]Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022 Dec;10(12):1169-77.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00298-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36228641?tool=bestpractice.com
However, meta-analyses have found that aspirin may reduce mortality.[999]Su W, Miao H, Guo Z, et al. Associations between the use of aspirin or other antiplatelet drugs and all-cause mortality among patients with COVID-19: a meta-analysis. Front Pharmacol. 2022 Oct 5;13:989903.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581252
http://www.ncbi.nlm.nih.gov/pubmed/36278186?tool=bestpractice.com
[1000]Wijaya I, Andhika R, Huang I, et al. The effects of aspirin on the outcome of COVID-19: a systematic review and meta-analysis. Clin Epidemiol Glob Health. 2021 Oct-Dec;12:100883.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556685
http://www.ncbi.nlm.nih.gov/pubmed/34754983?tool=bestpractice.com
Further randomised controlled trials are required.
Antibiotics
Azithromycin and tetracycline have been investigated for the treatment of COVID-19. Guidelines recommend against the use of these antibiotics for the treatment of COVID-19 in the absence of another indication for their use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
A Cochrane review found that azithromycin did not reduce 28-day all-cause mortality in hospitalised patients compared with standard care alone (high-certainty evidence). Hospitalised patients with moderate to severe disease did not benefit from azithromycin in terms of clinical worsening or improvement (moderate-certainty evidence). Azithromycin had no beneficial effect in the outpatient setting (low-certainty evidence).[1001]Popp M, Stegemann M, Riemer M, et al. Antibiotics for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 22;(10):CD015025.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015025/full
http://www.ncbi.nlm.nih.gov/pubmed/34679203?tool=bestpractice.com
The UK PRINCIPLE trial found that doxycycline use was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths in patients with suspected disease in the community who were at high risk of adverse outcomes.[1002]Butler CC, Yu LM, Dorward J, et al. Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet Respir Med. 2021 Sep;9(9):1010-20.
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00310-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34329624?tool=bestpractice.com
Vitamins and minerals
Vitamin C, vitamin D, and zinc have shown promise in the treatment of viral respiratory tract infections.[1003]Jolliffe DA, Camargo CA Jr, Sluyter JD, et al. Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials. Lancet Diabetes Endocrinol. 2021 May;9(5):276-92.
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00051-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33798465?tool=bestpractice.com
[1004]Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020 Apr 21:100190.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172861
http://www.ncbi.nlm.nih.gov/pubmed/32322486?tool=bestpractice.com
[1005]Abioye AI, Bromage S, Fawzi W. Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis. BMJ Glob Health. 2021 Jan;6(1):e003176.
https://gh.bmj.com/content/6/1/e003176.long
http://www.ncbi.nlm.nih.gov/pubmed/33472840?tool=bestpractice.com
Guidelines do not currently recommend vitamin C, vitamin D, or zinc for the treatment of COVID-19 except as part of a clinical trial, as there is insufficient evidence to recommend either for or against their use.[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication].
https://covid19treatmentguidelines.nih.gov
[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
Meta-analyses found that high-dose vitamin C reduced the risk of severe disease and mortality.[1006]Bhowmik KK, Barek MA, Aziz MA, et al. Impact of high-dose vitamin C on the mortality, severity, and duration of hospital stay in COVID-19 patients: a meta-analysis. Health Sci Rep. 2022 Sep;5(5):e762.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358542
http://www.ncbi.nlm.nih.gov/pubmed/35949675?tool=bestpractice.com
[1007]Olczak-Pruc M, Swieczkowski D, Ladny JR, et al. Vitamin C supplementation for the treatment of COVID-19: a systematic review and meta-analysis. Nutrients. 2022 Oct 10;14(19):4217.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570769
http://www.ncbi.nlm.nih.gov/pubmed/36235869?tool=bestpractice.com
However, these findings are inconsistent with other meta-analyses and need to be substantiated by further large-scale studies.[1008]Rawat D, Roy A, Maitra S, et al. Vitamin C and COVID-19 treatment: a systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2021 Oct 28;15(6):102324.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552785
http://www.ncbi.nlm.nih.gov/pubmed/34739908?tool=bestpractice.com
[1009]Kwak SG, Choo YJ, Chang MC. The effectiveness of high-dose intravenous vitamin C for patients with coronavirus disease 2019: a systematic review and meta-analysis. Complement Ther Med. 2021 Dec 22;64:102797.
https://www.sciencedirect.com/science/article/pii/S0965229921001382?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/34953366?tool=bestpractice.com
A Cochrane review found there is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation, and the evidence is very uncertain. There was substantial clinical and methodological heterogeneity of included studies, mainly due to different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes.[1010]Stroehlein JK, Wallqvist J, Iannizzi C, et al. Vitamin D supplementation for the treatment of COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 24;(5):CD015043.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015043/full
http://www.ncbi.nlm.nih.gov/pubmed/34029377?tool=bestpractice.com
Meta-analyses have found that vitamin D may be associated with improved clinical outcomes, including decreased risk of intensive care admission and mortality, and that there may be a potential role for vitamin D supplementation in reducing disease severity, but noted that additional evidence is required.[1011]Pal R, Banerjee M, Bhadada SK, et al. Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest. 2022 Jan;45(1):53-68.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223190
http://www.ncbi.nlm.nih.gov/pubmed/34165766?tool=bestpractice.com
[1012]Szarpak L, Filipiak KJ, Gasecka A, et al. Vitamin D supplementation to treat SARS-CoV-2 positive patients: evidence from meta-analysis. Cardiol J. 2021 Oct 13 [Epub ahead of print].
https://journals.viamedica.pl/cardiology_journal/article/view/85559
http://www.ncbi.nlm.nih.gov/pubmed/34642923?tool=bestpractice.com
[1013]Tentolouris N, Samakidou G, Eleftheriadou I, et al. The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients: a systematic review, meta-analysis and meta-regression. Diabetes Metab Res Rev. 2022 May;38(4):e3517.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015406
http://www.ncbi.nlm.nih.gov/pubmed/34965318?tool=bestpractice.com
[1014]Shah K, Varna VP, Sharma U, et al. Does vitamin D supplementation reduce COVID-19 severity? A systematic review. QJM. 2022 Oct 25;115(10):665-72.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383458
http://www.ncbi.nlm.nih.gov/pubmed/35166850?tool=bestpractice.com
[1015]Hosseini B, El Abd A, Ducharme FM. Effects of vitamin D supplementation on COVID-19 related outcomes: a systematic review and meta-analysis. Nutrients. 2022 May 20;14(10):2134.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147949
http://www.ncbi.nlm.nih.gov/pubmed/35631275?tool=bestpractice.com
[1016]D'Ecclesiis O, Gavioli C, Martinoli C, et al. Vitamin D and SARS-CoV2 infection, severity and mortality: a systematic review and meta-analysis. PLoS One. 2022 Jul 6;17(7):e0268396.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258852
http://www.ncbi.nlm.nih.gov/pubmed/35793346?tool=bestpractice.com
The UK National Institute for Health and Care Excellence recommends vitamin D supplementation in adults (including pregnant and breastfeeding women), young people, and children over 4 years of age between October and early March (and at other times of the year depending on age and risk of vitamin D deficiency) to maintain bone and muscle health, but does not recommend supplementation to solely prevent or treat COVID-19, except as part of a clinical trial.[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng191
[1017]National Institute for Health and Care Excellence. COVID-19 rapid guideline: vitamin D. 2022 [internet publication].
https://www.nice.org.uk/guidance/ng187
A meta-analysis found that that zinc supplementation may be associated with a decreased risk of mortality.[1018]Tabatabaeizadeh SA. Zinc supplementation and COVID-19 mortality: a meta-analysis. Eur J Med Res. 2022 May 23;27(1):70.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125011
http://www.ncbi.nlm.nih.gov/pubmed/35599332?tool=bestpractice.com
Probiotics
Probiotics have been used in a variety of conditions, including respiratory infections. A systematic review and meta-analysis found that probiotics were associated with a 51% reduction in reported symptoms, with improvement noted in cough, headache, and diarrhoea.[1019]Neris Almeida Viana S, do Reis Santos Pereira T, de Carvalho Alves J, et al. Benefits of probiotic use on COVID-19: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2022 Sep 30:1-13.
http://www.ncbi.nlm.nih.gov/pubmed/36178362?tool=bestpractice.com
However, further research is required.
Melatonin
Melatonin has antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties. Small studies have suggested an improvement in symptoms and clinical outcomes.[1020]Lan SH, Lee HZ, Chao CM, et al. Efficacy of melatonin in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials. J Med Virol. 2022 May;94(5):2102-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9015545
http://www.ncbi.nlm.nih.gov/pubmed/35032042?tool=bestpractice.com
[1021]Faridzadeh A, Tabashiri A, Miri HH, et al. The role of melatonin as an adjuvant in the treatment of COVID-19: a systematic review. Heliyon. 2022 Oct;8(10):e10906.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540685
http://www.ncbi.nlm.nih.gov/pubmed/36254292?tool=bestpractice.com
[1022]Molina-Carballo A, Palacios-López R, Jerez-Calero A, et al. Protective effect of melatonin administration against SARS-CoV-2 infection: a systematic review. Curr Issues Mol Biol. 2021 Dec 22;44(1):31-45.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929125
http://www.ncbi.nlm.nih.gov/pubmed/35723382?tool=bestpractice.com
[1023]Wang XC, Wu GL, Cai YF, et al. The safety and efficacy of melatonin in the treatment of COVID-19: a systematic review and meta-analysis. Medicine (Baltimore). 2022 Sep 30;101(39):e30874.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524532
http://www.ncbi.nlm.nih.gov/pubmed/36181086?tool=bestpractice.com
However, further research is required.
Lung transplantation
Lung transplantation has been used as salvage therapy in patients with COVID-19–associated acute respiratory distress syndrome (ARDS) who do not recover despite maximum ventilatory support, extracorporeal membrane oxygenation, and optimal medical care. Between August 2020 and September 2021, 214 lung transplantations were performed in the US (7% of lung transplants nationally). The 3-month survival among these patients approached that among patients who underwent lung transplantation for reasons other than COVID-19.[1024]Roach A, Chikwe J, Catarino P, et al. Lung transplantation for Covid-19-related respiratory failure in the United States. N Engl J Med. 2022 Jan 26 [Epub ahead of print].
https://www.nejm.org/doi/full/10.1056/NEJMc2117024
http://www.ncbi.nlm.nih.gov/pubmed/35081299?tool=bestpractice.com
In a retrospective case series of 30 patients with COVID-19–associated ARDS who underwent lung transplantation, survival was 100% (median follow-up 351 days).[1025]Kurihara C, Manerikar A, Querrey M, et al. Clinical characteristics and outcomes of patients with COVID-19-associated acute respiratory distress syndrome who underwent lung transplant. JAMA. 2022 Feb 15;327(7):652-61.
https://jamanetwork.com/journals/jama/fullarticle/2788640
http://www.ncbi.nlm.nih.gov/pubmed/35085383?tool=bestpractice.com
Clinical trials
Various other treatments are in clinical trials around the world. International trials to identify treatments that may be beneficial, such as the World Health Organization’s Solidarity trial, and the UK’s randomised evaluation of COVID-19 therapy (RECOVERY) trial, are ongoing.
New drugs currently in clinical trials that show promise include narsoplimab (a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2), ensitrelvir (a protease inhibitor approved for the treatment of COVID-19 in Japan), asunercept (a fusion protein), and nangibotide (a TREM-1 inhibitor peptide).