Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
MD, MPH, FCCP Imtiaz Ahmad, MD Mohammud Alam, MD, MPH Ryan Saadi, Saborny Mahmud, BS Emily Saadi
doi:10.1101/2020.05.18.20066902
Importance: Patients in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to advanced age and multiple comorbidities. Without effective treatments, outbreaks in such facilities will become commonplace and will result in severe morbidity and mortality. The effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high risk COVID-19 patients in longterm care facilities is not yet understood. Objective: The goal of this analysis is to describe outcomes after use of DOXY-HCQ combination in high-risk COVID-19 patients in LTCF. Design: Case-series analysis. Setting: Three (3) LTCFs in New York. Participants: From March 19 to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and diagnosed (confirmed or presumed) with COVID-19, were included in this analysis. Exposure: All patients who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination therapy along with standard of care. Main Outcomes and Measures: Patients characteristics, clinical recovery, radiological improvements, medication side-effects, hospital transfer, and death were assessed as outcome measures. Results: A series of fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as: resolution of .
So far, no study was published from the United States using HCQ alone or in combination with AZ or DOXY. As a matter of fact, this study is the first case series conducted globally using a combination of DOXY-HCQ in COVID-19 patients in nursing home settings. We treated our moderate to severe patients in out-of-hospital settings and prevented hospital transfer in the majority of patients. Naive Indirect Comparison showed a better outcome than the data reported in MMWR (reported on March 26, 2020) 17 from a long-term care facility in King County, Washington where 57% of patients were hospitalized and 22% patients died. This effect can possibly be explained by the anti-inflammatory mechanism of action of DOXY-HCQ. However, data from the LTCF from King County, Washington was found to be similar to our population. These data also showed a reduction of hospitalization by 44% among LTCF residents compared to previously reported data by similar populations in MMWR. A limitation of our case-series analysis is that there was no control population available.
Conclusion: DOXY and HCQ combination therapy is known to be anti-inflammatory, and immunomodulatory in both in-vitro and in-vivo studies. In addition, HCQ has anti-viral properties. Although this sample size is small (n=54), the results suggest that early intervention of DOXY-HCQ may improve the clinical outcome of high-risk COVID-19 patients suffering from moderate-severe symptoms in LTCF. These data is also associated with a..
References
Caprio, Lembo, Costanzo, Balato, Monfrecola, Anti-Inflammatory Properties of Low and High Doxycycline Doses: AnIn VitroStudy, Mediators of Inflammation,
doi:10.1155/2015/329418Castro, Vado-Solis, Perez-Osorio, Fredeking, Modulation of Cytokine and Cytokine Receptor/Antagonist by Treatment with Doxycycline and Tetracycline in Patients with Dengue Fever, Clinical and Developmental Immunology,
doi:10.1155/2011/370872Cazalis, Bodet, Gagnon, Grenier, Doxycycline reduces lipopolysaccharide-induced inflammatory mediator secretion in macrophage and ex vivo human whole blood models, J Periodontol,
doi:10.1902/jop.2008.080051Cerisano, Buonamici, Valenti, Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodeling: the TIPTOP trial, European Heart Journal,
doi:10.1093/eurheartj/eht420Chen Jun, Liu Danping, Liu Li, A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19), J Zhejiang Univ (Med Sci,
doi:10.3785/j.issn.1008-9292.2020.03.03Chen, Hu, Zhang, Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial, medRxiv,
doi:10.1101/2020.03.22.20040758Cheung, Sawicki, Wozniak, Wang, Radomski et al., Matrix Metalloproteinase-2 Contributes to Ischemia-Reperfusion Injury in the Heart, Circulation,
doi:10.1161/01.cir.101.15.1833Conti, Ronconi, Caraffa, Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105949Kalish, Koujak, Minocycline inhibits antigen processing for presentation to human T cells: additive inhibition with chloroquine at therapeutic concentrations, Clin Immunol,
doi:10.1016/j.clim.2004.07.012Mcmichael, Clark, Pogosjans, COVID-19 in a Long-Term Care Facility -King County, Washington, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6912e1Shi, Qin, Shen, Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China, JAMA Cardiol. Published online,
doi:10.1001/jamacardio.2020.0950Swarnakar, Mishra, Paul, Bhattacharya, Paul, An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition, Lung India,
doi:10.4103/0970-2113.83972Villarreal, Griffin, Omens, Dillmann, Nguyen et al., Early Short-Term Treatment With Doxycycline Modulates Postinfarction Left Ventricular Remodeling, Circulation,
doi:10.1161/01.cir.0000089090.05757.34{ 'institution': [{'name': 'medRxiv'}],
'indexed': {'date-parts': [[2024, 2, 8]], 'date-time': '2024-02-08T18:09:24Z', 'timestamp': 1707415764698},
'posted': {'date-parts': [[2020, 5, 22]]},
'group-title': 'Infectious Diseases (except HIV/AIDS)',
'reference-count': 20,
'publisher': 'Cold Spring Harbor Laboratory',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'accepted': {'date-parts': [[2020, 5, 22]]},
'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Importance</jats:title><jats:p>Patients '
'in long-term care facilities (LTCF) are at a high-risk of contracting COVID-19 due to '
'advanced age and multiple comorbidities. Without effective treatments, outbreaks in such '
'facilities will become commonplace and will result in severe morbidity and mortality. The '
'effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high '
'risk COVID-19 patients in longterm care facilities is not yet '
'understood.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>The goal '
'of this analysis is to describe outcomes after use of DOXY-HCQ combination in high-risk '
'COVID-19 patients in '
'LTCF.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Case-series '
'analysis.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>Three (3) '
'LTCFs in New '
'York.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>From March 19 '
'to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and '
'diagnosed (confirmed or presumed) with COVID-19, were included in this '
'analysis.</jats:p></jats:sec><jats:sec><jats:title>Exposure</jats:title><jats:p>All patients '
'who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination '
'therapy along with standard of care.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes '
'and Measures</jats:title><jats:p>Patients characteristics, clinical recovery, radiological '
'improvements, medication side-effects, hospital transfer, and death were assessed as outcome '
'measures.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A series of '
'fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and '
'shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with '
'a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as: '
'resolution of fever and SOB, or a return to baseline setting if patients are '
'ventilator-dependent. A total of 11% (n=6) patients were transferred to acute care hospitals '
'due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect '
'Comparison suggests these data were significantly better outcomes than the data reported in '
'MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington '
'where 57% patients were hospitalized, and 22% patients '
'died.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The clinical '
'experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is '
'associated with a reduction in clinical recovery, decreased transfer to hospital and '
'decreased mortality were observed after treatment with DOXY-HCQ.</jats:p></jats:sec>',
'DOI': '10.1101/2020.05.18.20066902',
'type': 'posted-content',
'created': {'date-parts': [[2020, 5, 22]], 'date-time': '2020-05-22T15:24:49Z', 'timestamp': 1590161089000},
'source': 'Crossref',
'is-referenced-by-count': 10,
'title': 'Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from '
'Case Series of 54 Patients in Long-Term Care Facilities',
'prefix': '10.1101',
'author': [ {'given': 'Imtiaz', 'family': 'Ahmad', 'sequence': 'first', 'affiliation': []},
{'given': 'Mohammud', 'family': 'Alam', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ryan', 'family': 'Saadi', 'sequence': 'additional', 'affiliation': []},
{'given': 'Saborny', 'family': 'Mahmud', 'sequence': 'additional', 'affiliation': []},
{'given': 'Emily', 'family': 'Saadi', 'sequence': 'additional', 'affiliation': []}],
'member': '246',
'reference': [ { 'key': '2021011111230211000_2020.05.18.20066902v1.1',
'unstructured': 'ArcGIS Dashboards. '
'https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. '
'Accessed 18 May. 2020.'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.2',
'unstructured': 'https://www.news10.com/wp-content/uploads/sites/64/2020/04/04.04.20-COVID19-Briefing.pdf. '
'Accessed 5 Apr. 2020'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.3',
'doi-asserted-by': 'publisher',
'DOI': '10.23812/CONTI-E'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.4',
'doi-asserted-by': 'publisher',
'DOI': '10.1001/jamacardio.2020.0950'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.5',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.ijantimicag.2020.105949'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.6',
'doi-asserted-by': 'crossref',
'unstructured': 'Chen Z , Hu J , Zhang Z et al. Efficacy of hydroxychloroquine in '
'patients with COVID-19: results of a randomized clinical trial. medRxiv '
'2020.03.22.20040758; doi: https://doi.org/10.1101/2020.03.22.20040758',
'DOI': '10.1101/2020.03.22.20040758'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.7',
'doi-asserted-by': 'publisher',
'DOI': '10.3785/j.issn.1008-9292.2020.03.03'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.8',
'unstructured': 'Azithromycin Prescribing Information. Source: FDA '
'http://labeling.pfizer.com/ShowLabeling.aspx?id=511, Accessed 5 Apr. '
'2020.'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.9',
'doi-asserted-by': 'publisher',
'DOI': '10.1902/jop.2008.080051'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.10',
'doi-asserted-by': 'publisher',
'DOI': '10.1155/2011/370872'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.11',
'doi-asserted-by': 'publisher',
'DOI': '10.4103/0970-2113.83972'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.12',
'doi-asserted-by': 'publisher',
'DOI': '10.1155/2015/105828'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.13',
'unstructured': 'Azithromycin Prescribing Information. Source: FDA. '
'https://www.accessdata.fda.gov/drugsatfdadocs/label/2008/050795s005lbl.pdf. '
'Accessed 5 Apr. 2020.'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.14',
'doi-asserted-by': 'publisher',
'DOI': '10.1161/01.CIR.101.15.1833'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.15',
'doi-asserted-by': 'publisher',
'DOI': '10.1161/01.CIR.0000089090.05757.34'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.16',
'doi-asserted-by': 'publisher',
'DOI': '10.1093/eurheartj/eht420'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.17',
'unstructured': 'Clinical and microbiological effect of a combination of '
'hydroxychloroquine and azithromycin in 80 COVID-19 patients with at '
'least a six-day follow up: an observational study. '
'https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf. '
'Accessed 5 Apr. 2020.'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.18',
'doi-asserted-by': 'publisher',
'DOI': '10.15585/mmwr.mm6912e1'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.19',
'doi-asserted-by': 'publisher',
'DOI': '10.18632/oncotarget.10810'},
{ 'key': '2021011111230211000_2020.05.18.20066902v1.20',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.clim.2004.07.012'}],
'container-title': [],
'original-title': [],
'link': [ { 'URL': 'https://syndication.highwire.org/content/doi/10.1101/2020.05.18.20066902',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 1, 14]],
'date-time': '2021-01-14T08:10:52Z',
'timestamp': 1610611852000},
'score': 1,
'resource': {'primary': {'URL': 'http://medrxiv.org/lookup/doi/10.1101/2020.05.18.20066902'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 5, 22]]},
'references-count': 20,
'URL': 'http://dx.doi.org/10.1101/2020.05.18.20066902',
'relation': {},
'subject': [],
'published': {'date-parts': [[2020, 5, 22]]},
'subtype': 'preprint'}
