THE HOME TREATMENT OF THE COVID-19 PATIENT
M. Caeran1 , M. Font2
1. Student of Hospital Pharmacy Speciality. Padova University.
2. Pharmacist. UOC Assistenza Farmaceutica Territoriale ULSS 9 Scaligera. Verona. Italy
Several guidelines have recently been published in Italy for the home care of patients with COVID-191-5. They are targeted at physicians working in the primary health care (USCA, on-call doctors, GPs/PLSs).
Five documents have been considered in this article:
- The first and most recent of these is the Ministry of Health document1.
- Two documents at regional level; the one published by the Veneto Region4 and almost simultaneously the one published by the Lombardy medical orders named “Vademecum” for the home treatment of patients with COVID-192.
- Two guideline documents correspond to the Scientific Societies: one from the Italian Society of General Medicine, SIMG, which is an update of a previous guideline published some time ago3. The second is the Consensus document produced by a group of doctors belonging to the FIMMG Study Centre in Verona5.
The simultaneity with which these documents were prepared and disseminated highlights the urgent need to activate home care for COVID-19 patients (positive, symptomatic and/or not serious) at a time when hospital care is showing signs of saturation in some situations. A consensus/guideline was therefore needed on how the doctor in the area can and should act in COVID-19 patients with mild to moderate disease to be treated at home with the available therapeutic tools.
However, there are heterogeneities among these documents as highlighted in table 1, mainly due to their methodological differences and in relation to symptomatic treatments. The differences become even more relevant when evaluating the specific recommended treatments (see table 2).
With regard to the treatments currently available, there is a clear need for a treatment that can slow down the initial stages of the disease and prevent it from progressing to a severe form. However, there is currently no treatment that can do this.6
The objectives of this article are:
1. To compare the recommendations in COVID-19 home care published by the various institutions in November-December 2020.
2. To report the evidence supporting the most controversial treatments proposed to date for patients with COVID-19: Hydroxychloroquine (ICQ), remdesivir.
1.Recommendations for COVID-19 care at home in 5 documents published by different italian Institutions in November-December 2020.
The five documents considered appear to be addressed to primary care physicians (GPs/PLSs, USCAs*, medical guards), but the Lombardy document does not clearly specify either the target of the “vademecum” or the definition of the type of patient or the level of severity that can be taken care of at home. However, it is the only guide that reported the quality of the evidence and the strength of the recommendations it contains.
With regard to symptomatic treatments, the majority expressed themselves in favour of paracetamol or NSAIDs use and only in 3 of these did they refer to the use of an antitussive.
With regard to specific treatments (table 2), none of the documents recommends the use of hydroxychloroquine (ICQS) or antivirals. The use of antibiotics is only recommended in cases of bacterial overinfection.
Heparin prophylaxis and the use of corticosteroids is recommended under certain risk conditions in all the guides except that of the Veneto Region. On the other hand, the use of oxygen in patients whose respiratory condition worsens has not been considered in either the Ministry of Health or the SIMG guidelines.
2.Evidences of two controversial treatments: hydroxychloroquine and remdesivir.
With regard to ICQ, despite the evidence showing its ineffectiveness in both prophylaxis and treatment, some voices still seem to want to claim a role for this drug in the early stages of the disease. As table 3 shows, the various randomised controlled trials published so far do not support this hypothesis, so AIFA (Italian Drug Agency) does not currently grant reimbursement.
After the approval of remdesivir by the EMA in July, the publication of the SOLIDARITY study, organized by the WHO, strongly questioned the role of this drug. Recent WHO guidelines exclude this drug in the treatment of COVID-19 patients regardless of severity, based on the results of a systematic review and meta-analysis that included 4 RCTs. The results of the main RCTs published so far support this position (see table 4).
However, the WHO recognizes that the evidence does not clearly show that remdesivir has any benefit, but also takes into account the resources this use implies for health systems given the high cost of the drug. It also recognizes the need for further research into this drug, particularly in certain patient groups. In light of this, the EMA has requested full data from the SOLIDARITY study and is currently reviewing data on remdesivir.
Other potential initial treatments for COVID-19:
Monoclonal antibodies in mild to moderate disease
Two antibodies are currently competing for marketing authorization, Regeneron’s REGN-COV2 and Eli Lilly’s LY-CoV555. Regeneron has issued a press release stating that it intends to apply to the FDA for EUA (Emergency Use Authorization), as was done for Remdesivir.
The other antibody, LY-CoV555, Bamlanivimab, has recently published the results of a phase 2 study in which three different doses were tested, one of which seems to accelerate the decline in viral load at day11,14
As the authors of a recent JAMA editorial pointed out, if the FDA issues an EUA for Regeneron’s product in the absence of published data, it would repeat the problem that occurred with remdesivir15 . Despite the urgent need for effective treatments for COVID-19, the use of regulatory reliefs requires transparency on clinical effectiveness data, equitable distribution, and cost control.
References
1. Gestione domiciliare dei pazienti con infezione da SARS-CoV-2. Ministero della Salute. In: http://www.salute.gov.it/portale/news/p3_2_1_1_1.jsp?lingua=italiano&menu=notizie&p=dalministero&id=5201
2. Federazione Regionale egli Ordini dei Medici chirurgi e odontoiatri della Lombardia. Vademecum della cura delle persone con infezione da SARS-CoV-2 non ospedalizzate. In: https://www.omceomi.it/docs/default-source/default-document-library/fromceo-vademecum-della-cura-delle-persone-con-infezione-da-sars-cov-2-non-ospedalizzate23accbd0b11066cb9190ff0000bb5bce.pdf?sfvrsn=0
3. Raccomandazioni per la gestione domiciliare del paziente on COVID-19. SIMG. Aggiornato al 25/11/2020. In: https://www.simg.it/raccomandazioni-per-la-gestione-domiciliare-del-paziente-con-covid-19/
4. Regione Veneto. Emergenza COVID-19. Gestione domiciliare dei pazienti con COVID-10. DGR n.1523 del 10 novembre 2020. BUR n.169 del 13/11/2020. In: file:///C:/Users/39320/Downloads/Dgr_1523_20_AllegatoA_433418.pdf
5. Suggerimenti operativi e terapeutici per pazienti affetti da COVID-19 trattati nel territorio. Gruppo di lavoro TERRITORIO/OSPEDALE/UNIVERSITA’ SUL COVID-19. Promosso dal Centro Studi di Medicina Generale FIMMG Verona e Keiron As.Me.G. Veneto, con il patrocinio dell’OMCeO di Verona. fimmgverona.org
6. Kim PS; Read SW & Fauci A: Therapy for early COVID-19. A critical need. JAMA published online 11.novembre 2020: JAMA
7. Boulware et al. N Engl J Med 2020;383:517-25. June 3, 2020
8. Skipper et al. Ann Intern Med. doi:10.7326/M20-4207. Pubblicato il 16.07.2020
9. Mitjà O et al. N Engl J Med. Published on November 24, 2020.
10. Cavalcanti et al. N Engl J Med 2020;383:2041-52. Pubblicato il 23.07.2020
11. Horby P RECOVERY Collab. group. N Engl J Med 2020;383:2030-40. Pubblicato il 8.10.2020
12. Hongchao Pan et al for SOLIDARITY trial. medRxiv preprint ;Published 15 October
13. Self WH t al. JAMA. Published online November 9, 2020.
14. Chen P et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med published 28 october .
15. Goldstein RH & Walensky RP. The challenge ahead with monoclonal antibodies. From authorisation to access. JAMA Published online 11 novembre
16. Wang et al. Lancet 2020; 395: 1569–78. Published Online April 29, 2020
17. Goldman et al. N Engl J Med 2020;383:1827-37. DOI: 10.1056/NEJMoa2015301. published on May 27, 2020,at NEJM.org.
18. Spinner et al. JAMA. 2020;324(11):1048-1057. doi:10.1001/jama.2020.16349 Published online August 21, 2020.
19. Beigel et al. N Engl J Med 2020;383:1813-26. DOI: 10.1056/NEJMoa2007764. published on October 8, 2020
20. Hongchao Pan et al for SOLIDARITY trial. medRxiv preprint doi: https://doi.org/10.1101/2020.10.15.20209817; Published 15 October 2020