A Simple, Home-Therapy Algorithm to Prevent Hospitalization for COVID-19 Patients: A Retrospective Observational Matched-Cohort Study

Background Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. Methods This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. Findings All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the ‘recommended’ schedule cohort and 14 [7-30] days in the matched ‘control’ cohort (p=0·033). Other symptoms persisted in a lower percentage of patients in the ‘recommended’ than in the ‘control’ cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p=0·0107). Two patients in the ‘recommended’ cohort were hospitalised compared to 13 (14·4%) controls (Log-rank test, p=0·0038). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90% (from 481 to 44 days and from €296.000 to €28.000, respectively. 1.2 patients had to be treated to prevent one hospitalisation event. Interpretation Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID 19, but almost eliminated the risk of hospitalisation and related treatment costs. Evidence before this study We searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 19, 2021, using the search terms “2019-nCoV” or “SARS-CoV-2” or “COVID-19” and “early” or “outpatient” or “treatment” or “home”. Our search did not identify any randomised clinical trials or observational studies that assessed the effectiveness of treatment regimens targeting early, mild symptoms of COVID-19 in the outpatient setting. Added value of this study In this fully academic, observational matched-cohort study, we found that early home treatment of 90 consecutive patients with mild COVID-19 by their family physicians according to the proposed recommendation algorithm, designed based on a pathophysiologic and pharmacologic rationale, required few more days to achieve resolution of major symptoms including fever, dyspnea, musculoskeletal pain, headache and cough compared to 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens (primary outcome). Nonetheless, it is noteworthy that the home treatment of COVID-19 patients according to the proposed recommendation algorithm significantly reduced the risk of hospitalization compared to the other treatments in the ‘control’ cohort. Days of hospitalization and related treatment costs were reduced by over 90% in the ‘recommended’ cohort as compared to ‘control’ cohort. Just 1.2 patients needed to be treated according to the recommendation algorithm to prevent one hospitalization event. We also found that symptoms such as anosmia and ageusia/dysgeusia were less persistent and lasted a shorter time in the ‘recommendation’ than in the ‘control’ cohort. Implications of the available evidence The finding that the implementation of the proposed simple treatment algorithm during the initial, mild phase of COVID-19 has the potential to prevent disease progression, potentially limiting the need for hospital admission, may have major implications for patients and health care providers. Indeed, preventing hospitalisations due to the worsening of COVID-19 will not only save lives, but will also contribute to remarkably reduced treatment costs and to streamlining health care systems that are overburdened by the effects of the pandemic. However, time to hospitalization was a secondary outcome of the study and the possibility of a casual finding cannot be definitely excluded. Thus, the observed reduction in patients hospitalizations should be considered as an hypothesis generating finding that could provide a robust background for a prospective trial primarily aimed to test treatment effect on this outcome. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04794998 ### Funding Statement The study was partially supported by the generous donation of Fondazione Cav. Lav. Carlo Pesenti (Bergamo - Italy) to the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. The Fondazione Cav. Lav. Carlo Pesenti had not any role in study design, in the collection, analysis and interpretation of data; in writing the report; and in the decision to submit the paper for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The COVER study has been approved by the Centralised Ethical Committee for all COVID-19 trials in Italy based at the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Rome (Parere n 263, January 31, 2021) and registered at the ClinicalTrials.gov ([NCT04794998][1]). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Sharing of individual participant data with third parties was not specifically included in the informed consent of the study, and unrestricted diffusion of such data may pose a potential threat of revealing participants identities, as permanent data anonymization was not carried out (patient records were instead de-identified per protocol during the data retention process). To minimize this risk, individual participant data that underlie the results reported in this article will be available after three months and up to five years from article publication. Researchers shall submit a methodologically sound proposal to Dr. Annalisa Perna (annalisa.perna{at}marionegri.it), head of the Laboratory of Biostatistics of the Department of Renal Medicine of the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. To gain access, data requestors will need to sign a data access agreement and obtain the approval of the local ethics committee. 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