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Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

ABSTRACT: Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline.Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here.The reviews of this paper are available via the supplemental material section.

SUBMITTER: Yates PA

PROVIDER: S-EPMC7476338 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

Yates Paul A PA Newman Steven A SA Oshry Lauren J LJ Glassman Robert H RH Leone Ashton M AM Reichel Elias E

Therapeutic advances in respiratory disease 20200101

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatm ...[more]

PMID: 32873175

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Project description:Rationale Due to the cluster and associated comorbidities in residents of long-term care facilities (LTCFs), COVID-19-associated morbidity and mortality are significantly increased. Multiple therapeutic options, including hydroxychloroquine (HCQ) and azithromycin (AZI), were tried initially to treat moderate to severe COVID-19 and high-risk patients in LTCFs, but they were abandoned due to unfavorable reports. As a less toxic option, we initiated treatment with doxycycline (DOXY) very early in the course of illness. DOXY has antiviral, cardioprotective, immunomodulatory, and anti-inflammatory properties, but the efficacy of early intervention with DOXY in high-risk COVID-19 patients in LTCFs is unknown. Objective The goal of this retrospective study is to describe the clinical outcomes of high-risk COVID-19 patients with moderate to severe symptoms in LTCFs after early intervention with DOXY. Design Case-series analysis Setting LTCFs in New York Participants This observational study examines 89 patients who were diagnosed with COVID-19 from March 18 to May 13, 2020. Exposure All patients who were diagnosed with COVID-19 received DOXY and regular standard of care within 12 hours of the onset of symptoms. Additionally, four patients received meropenem, three patients received Zosyn, two patients received linezolid, and two patients received Bactrim DS. Four patients were on chronic ventilator support. No patients received any steroids or any other antiviral or immunomodulatory agents. The majority of the patients received zinc and calcium supplements as well. Main outcomes and measures Assessed measures were patients' characteristics, fever, shortness of breath (SOB), cough, oxygen saturation/pulse oximetry (POX), radiologic improvements, laboratory tests, DOXY side effects, hospital transfers, and death. Results Eighty-nine (89) high-risk patients, who developed a sudden onset of fever, cough, SOB, and hypoxia and were diagnosed with COVID-19, were treated with DOXY (100 mg PO or intravenous (IV) for seven days) and regular standard of care. Eighty-five percent (85%) of patients (n=76) demonstrated clinical recovery that is defined as resolution of fever (average 3.7 days, Coeff = -0.96, p = 0.0001), resolution of SOB (average 4.2 days), and improvement of POX: average 84% before treatment and average 95% after treatment (84.7 ± 7% vs. 95 ± 2.6%, p = 0.0001). Higher pre- and post-treatment POX is associated with lower mortality (oxygen saturation (Spo2) vs. Death, Coeff = -0.01, p = 0.023; post-Spo2 vs. Death, Coeff = -0.05, p = 0.0002). Within 10 days of symptom onset, 3% of patients (n=3) were transferred to hospital due to clinical deterioration and 11% of patients (n=10) died. The result was followed for 30 days from the onset of symptoms in each patient. Conclusion Early treatment with DOXY for high-risk patients with moderate to severe COVID-19 infections in non-hospital settings, such as LTCFs, is associated with early clinical recovery, decreased hospitalization, and decreased mortality.

Project description:ObjectiveTo evaluate clinical effectiveness of regdanvimab, a monoclonal antibody agent for treating coronavirus 2019 (COVID-19).MethodsA retrospective cohort study was conducted at two general hospitals during the study period of December 2020 to May 2021. Mild COVID-19 patients with risk factors for disease progression admitted to the hospitals within seven days of symptom onset were enrolled and followed until discharge or referral. Multivariate analyses for disease progression were conducted in the total and propensity score (PS)-matched cohorts.ResultsA total of 778 mild COVID-19 patients were included and classified as the regdanvimab (n = 234) and supportive care (n = 544) groups. Significantly fewer patients required O2 supplementation via nasal prong in the regdanvimab group (8.1%) than in the supportive care group (18.4%, P < 0.001). The decreased risk for O2 support by regdanvimab treatment was noticed in the multivariate analysis of the total cohort (HR 0.570, 95% CI 0.343-0.946, P = 0.030), but it was not statistically significant in the PS-matched cohort (P = 0.057). Progression to severe disease was also significantly lower in the regdanvimab group (2.1%) than in the supportive care group (9.6%, P < 0.001). The significantly reduced risk for progression to severe disease by regdanvimab treatment was observed in the analysis of both the total cohort (HR 0.262, 95% CI 0.103-0.667, P = 0.005) and PS-matched cohort (HR 0.176, 95% CI 0.060-0.516, P = 0.002). Potential risk factors for progression were investigated in the supportive care group and SpO2 < 97% and CRP elevation >1.5 mg/dL were common risk factors for O2 support and progression to severe disease. Among the patients with any of these factors, regdanvimab treatment was associated with decreased risk for progression to severe disease with slightly lower HR (HR 0.202, 95% CI 0.062-0.657, P = 0.008) than that of the total cohort.ConclusionRegdanvimab treatment was associated with a decreased risk of progression to severe disease.

Project description:BackgroundDoxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes.MethodsWe did a national, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in older people (PRINCIPLE) across primary care centres in the UK. We included people aged 65 years or older, or 50 years or older with comorbidities (weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or neurological problem, and self-reported obesity or body-mass index of 35 kg/m2 or greater), who had been unwell (for ≤14 days) with suspected COVID-19 or a positive PCR test for SARS-CoV-2 infection in the community. Participants were randomly assigned using response adaptive randomisation to usual care only, usual care plus oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days), or usual care plus other interventions. The interventions reported in this manuscript are usual care plus doxycycline and usual care only; evaluations of other interventions in this platform trial are ongoing. The coprimary endpoints were time to first self-reported recovery, and hospitalisation or death related to COVID-19, both measured over 28 days from randomisation and analysed by intention to treat. This trial is ongoing and is registered with ISRCTN, 86534580.FindingsThe trial opened on April 2, 2020. Randomisation to doxycycline began on July 24, 2020, and was stopped on Dec 14, 2020, because the prespecified futility criterion was met; 2689 participants were enrolled and randomised between these dates. Of these, 2508 (93·3%) participants contributed follow-up data and were included in the primary analysis: 780 (31·1%) in the usual care plus doxycycline group, 948 in the usual care only group (37·8%), and 780 (31·1%) in the usual care plus other interventions group. Among the 1792 participants randomly assigned to the usual care plus doxycycline and usual care only groups, the mean age was 61·1 years (SD 7·9); 999 (55·7%) participants were female and 790 (44·1%) were male. In the primary analysis model, there was little evidence of difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian Credible Interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, hazard ratio 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI -0·99 to 2·04] and the probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalisation or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group and 43 (4·5%) in the usual care only group (estimated absolute percentage difference -0·5% [95% BCI -2·6 to 1·4]); there were five deaths (0·6%) in the usual care plus doxycycline group and two (0·2%) in the usual care only group.InterpretationIn patients with suspected COVID-19 in the community in the UK, who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths related to COVID-19, and should not be used as a routine treatment for COVID-19.FundingUK Research and Innovation, Department of Health and Social Care, National Institute for Health Research.

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Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

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Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

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