Evaluation of Antibacterial and Antiviral Drug Effectiveness in COVID-19 Therapy: A Data-Driven Retrospective Approach
Rika Yulia, Putri Ayu Irma Ikasanti, Fauna Herawati, Ruddy Hartono, Puri Safitri Hanum, Lestiono, Dewi Ramdani, Abdul Kadir Jaelani, Kevin Kantono, Heru Wijono
Pathophysiology, doi:10.3390/pathophysiology29010009
The clinical manifestations associated with COVID-19 disease is mainly due to a dysregulated host response related to the overexpression of inflammatory markers. Until recently, only remdesivir had gained FDA approval for COVID-19 hospitalized patients and there are currently no evidence-based therapeutic options or options for prevention of complications that have been established. Some medical treatments such as antivirals, antibacterials, antithrombotics, antipyretics, corticosteroids, interleukin inhibitors, monoclonal antibodies, convalescent plasma, immunostimulants, and vitamin supplements have been utilized. However, there are limited data to support their effectiveness. Hence, this study was attempted to identify and evaluate the effectiveness of antibacterials and antivirals used for COVID-19 using a retrospective cross-sectional approach based on the medical records of adult patients in four hospitals. The number of antibacterials was calculated in defined daily dose (DDD) per 100 bed-days unit. Both mixed-logit regression and analysis of covariance were used to determine the effectiveness of the aforementioned agents in relation to COVID-19 outcome and patients' length of stay. The model was weighed accordingly and covariates (e.g., age) were considered in the model. Heart disease was found to be the most common pre-existing condition of COVID-19 hospitalized patients in this study. Azithromycin, an antibacterial in the Watch category list, was used extensively (33-65 DDD per 100 bed-days). Oseltamivir, an antiviral approved by the FDA for influenza was the most prescribed antiviral. In addition, favipiravir was found to be a significant factor in improving patients' COVID-19 outcomes and decreasing their length of stay. This study strongly suggests that COVID-19 patients' received polypharmacy for their treatment. However, most of the drugs used did not reach statistical significance in improving the patients' condition or decreasing the length of stay. Further studies to support drug use are needed.
Conflicts of Interest: The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.
References
Abubakar, Sani, Godman, Kumar, Islam et al., Systematic review on the therapeutic options for COVID-19: Clinical evidence of drug efficacy and implications, Infect. Drug Resist,
doi:10.2147/IDR.S289037Adebisi, Alaran, Okereke, Oke, Amos et al., COVID-19 and antimicrobial resistance: A review, Infect. Dis. Res. Treat,
doi:10.1177/11786337211033870Aumpan, Vilaichone, Ratana-Amornpin, Teerakapibal, Toochinda et al., Antiviral treatment could not provide clinical benefit in management of mild COVID-19: A retrospective experience from field hospital, J. Infect. Public Health,
doi:10.1016/j.jiph.2021.07.019Baracco, Remdesivir use and hospital length of stay-The paradox of a clinical trial vs real-life use, JAMA
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the Treatment of Covid-19-Final Report, N. Engl. J. Med,
doi:10.1056/NEJMoa2007764Biswas, Rahaman, Biswas, Haque, Ibrahim, Association of sex, age, and comorbidities with mortality in COVID-19 patients: A systematic review and meta-analysis, Intervirology,
doi:10.1159/000512592Burhan, Susanto, Nasution, Ginanjar, Pitoyo et al., Tim COVID-19 IDAI
Cai, Yang, Liu, Chen, Shu et al., Experimental treatment with favipiravir for COVID-19: An open-label control study, Engineering,
doi:10.1016/j.eng.2020.03.007Cao, Wang, Wen, Liu, Wang et al., A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N. Engl. J. Med,
doi:10.1056/NEJMoa2001282Chedid, Waked, Haddad, Chetata, Saliba et al., Antibiotics in treatment of COVID-19 complications: A review of frequency, indications, and efficacy, J. Infect. Public Health,
doi:10.1016/j.jiph.2021.02.001Dana, Bannay, Bourst, Ziegler, Losser et al., Obesity and mortality in critically ill COVID-19 patients with respiratory failure, Int. J. Obes,
doi:10.1038/s41366-021-00872-9Egyir, Obeng-Nkrumah, Kyei, COVID-19 pandemic and antimicrobial resistance: Another call to strengthen laboratory diagnostic capacity in Africa, Afr. J. Lab. Med,
doi:10.4102/ajlm.v9i1.1302Ge, Li, Wu, Candido, Wei, Association of pre-existing comorbidities with mortality and disease severity among 167,500 individuals with COVID-19 in Canada: A population-based cohort study, PLoS ONE,
doi:10.1371/journal.pone.0258154Getahun, Smith, Trivedi, Paulin, Balkhy, Tackling antimicrobial resistance in the COVID-19 pandemic, Bull. World Health Organ,
doi:10.2471/BLT.20.268573Ghosh, Bornman, Zafer, Antimicrobial resistance threats in the emerging COVID-19 pandemic: Where do we stand?, J. Infect. Public Health,
doi:10.1016/j.jiph.2021.02.011Giacomelli, Ridolfo, Oreni, Vimercati, Albrecht et al., Consumption of antibiotics at an Italian university hospital during the early months of the COVID-19 pandemic: Were all antibiotic prescriptions appropriate?, Pharmacol. Res,
doi:10.1016/j.phrs.2020.105403Grau, Echeverria-Esnal, Gómez-Zorrilla, Navarreterouco, Masclans et al., Evolution of antimicrobial consumption during the first wave of COVID-19 pandemic, Antibiotics,
doi:10.3390/antibiotics10020132Hartmann-Boyce, Rees, Otunla, Suklan, Schofield et al., Risks of and from SARS-CoV-2 (COVID-19) Infection in People with Asthma. Centre for Evidence-Based Medicine
Hasan, Haider, Stigler, Khan, Mccoy et al., The global Case-Fatality Rate of COVID-19 has been declining since May 2020, Am. J. Trop. Med. Hyg,
doi:10.4269/ajtmh.20-1496Holec, Mandal, Prathipati, Destache, Nucleotide Reverse Transcriptase Inhibitors: A thorough review, present status and future perspective as HIV therapeutics, Curr. HIV Res,
doi:10.2174/1570162X15666171120110145Jang, Seon, Yoon, Park, Lee et al., Comorbidities and factors determining medical expenses and length of stay for admitted COVID-19 patients in Korea, Risk Manag. Healthc. Policy,
doi:10.2147/RMHP.S292538Kassam, Aghan, Aziz, Mbithe, Hameed et al., Factors associated with mortality among hospitalized adults with COVID-19 pneumonia at a Private Tertiary Hospital in Tanzania: A retrospective cohort study, Int. J. Gen. Med,
doi:10.2147/IJGM.S330580Kim, An, Kim, Hwang, Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network metaanalysis, PLoS Med,
doi:10.1371/journal.pmed.1003501Kocayigit, Ozmen, Suner, Tomak, Demir et al., Observational study of the effects of favipiravir vs lopinavir/ritonavir on clinical outcomes in critically ill patients with COVID-19, J. Clin. Pharm. Ther,
doi:10.1111/jcpt.13305Limato, Nelwan, Mudia, De Brabander, Guterres et al., A multicentre point prevalence survey of patterns and quality of antibiotic prescribing in Indonesian hospitals, JAC Antimicrob. Resist,
doi:10.1093/jacamr/dlab047Maciorowski, Idrissi, Gupta, Medernach, Burns et al., A review of the preclinical and clinical efficacy of remdesivir, hydroxychloroquine, and lopinavir-ritonavir treatments against COVID-19, SLAS DISCOVERY,
doi:10.1177/2472555220958385Mahendra, Nuchin, Kumar, Shreedhar, Mahesh, Predictors of mortality in patients with severe COVID-19 pneumonia-A retrospective study, Adv. Respir. Med,
doi:10.5603/ARM.a2021.0036Manabe, Kambayashi, Akatsu, Kudo, Favipiravir for the treatment of patients with COVID-19: A systematic review and meta-analysis, BMC Infect. Dis,
doi:10.1186/s12879-021-06164-xMash, Presence-Vollenhoven, Adeniji, Christoffels, Doubell et al., Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa: Descriptive observational study, BMJ Open,
doi:10.1136/bmjopen-2020-047016Mustafa, Tolaj, Baftiu, Fejza, Use of antibiotics in COVID-19 ICU patients, J. Infect. Dev. Ctries
Nasrin, Mohaimenul, Chia, Chin, Wen-Shan et al., Obesity and mortality among patients diagnosed with COVID-19: A systematic review and meta-analysis, Front. Med,
doi:10.3389/fmed.2021.620044Olry, Meunier, Délire, Larrey, Horsmans et al., Drug-induced liver injury and COVID-19 infection: The rules remain the same, Drug Saf,
doi:10.1007/s40264-020-00954-zPaul, Pennell, Lemeshow, Standardizing the power of the Hosmer-Lemeshow goodness of fit test in large data sets, Stat. Med,
doi:10.1002/sim.5525Peña, Rascón-Pacheco, Ascencio-Montiel, González-Figueroa, Fernández-Gárate et al., Hypertension, diabetes and obesity, major risk factors for death in patients with COVID-19 in Mexico, Arch. Med. Res,
doi:10.1016/j.arcmed.2020.12.002Popp, Stegemann, Riemer, Metzendorf, Romero et al., Antibiotics for the treatment of COVID-19, Cochrane Database Syst. Rev,
doi:10.1002/14651858.CD015025Pourhoseingholi, Vahedi, Rahimzadeh, Sample size calculation in medical studies, Gastroenterol. Hepatol. Bed. Bench
Rahmani, Davoudi-Monfared, Nourian, Nabiee, Sadeghi et al., Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir, Daru,
doi:10.1007/s40199-020-00369-2Rawson, Moore, Zhu, Ranganathan, Skolimowska et al., Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing, Clin. Infect. Dis,
doi:10.1093/cid/ciaa530Rees, Nightingale, Jafari, Waterlow, Clifford et al., COVID-19 length of hospital stay: A systematic review and data synthesis, BMC Med,
doi:10.1186/s12916-020-01726-3Rodriguez-Guerra, Jadhav, Vittorio, Current treatment in COVID-19 disease: A rapid review, Drugs Context,
doi:10.7573/dic.2020-10-3Rodríguez-Baño, Rossolini, Schultsz, Tacconelli, Murthy et al., Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance, Trans. R. Soc. Trop. Med. Hyg,
doi:10.1093/trstmh/trab048Rosenberg, Dufort, Udo, Wilberschied, Kumar et al., Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State, JAMA,
doi:10.1001/jama.2020.8630Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review, JAMA,
doi:10.1001/jama.2020.6019Schultze, Walker, Mackenna, Morton, Bhaskaran et al., Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: An observational cohort study using the OpenSAFELY platform, Lancet Respir. Med,
doi:10.1016/S2213-2600(20)30415-XSetiati, Azwar, COVID-19 and Indonesia, Acta Med. Indones
Shinkai, Tsushima, Tanaka, Hagiwara, Tarumoto et al., Efficacy and safety of favipiravir in moderate COVID-19 pneumonia patients without oxygen therapy: A randomized, phase III clinical trial, Infect. Dis. Ther,
doi:10.1007/s40121-021-00517-4Silva, Estrela, Gomes, Piñeiro-Lamas, Figueiras et al., The impact of the COVID-19 pandemic on antibiotic prescribing trends in outpatient care: A nationwide, quasi-experimental approach, Antibiotics,
doi:10.3390/antibiotics10091040Sulis, Batomen, Kotwani, Pai, Gandra, Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis, PLoS Med,
doi:10.1371/journal.pmed.1003682Surendra, Elyazar, Djaafara, Ekawati, Saraswati et al., Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: A hospital-based retrospective cohort study, Lancet Reg. Health West Pac,
doi:10.1016/j.lanwpc.2021.100108Tavares, Mahadeshwar, Wan, Huston, Pyle, The global and local distribution of RNA structure throughout the SARS-CoV-2 genome, J. Virol,
doi:10.1128/JVI.02190-20Wang, Yang, Chen, Guo, Liu et al., The proportion and effect of corticosteroid therapy in patients with COVID-19 infection: A systematic review and meta-analysis, PLoS ONE,
doi:10.1371/journal.pone.0249481Yang, Liu, Zhou, Zhao, Zhao et al., The effect of corticosteroid treatment on patients with coronavirus infection: A systematic review and meta-analysis, J. Infect,
doi:10.1016/j.jinf.2020.03.062Yates, Razieh, Zaccardi, Rowlands, Seidu et al., Obesity, walking pace and risk of severe COVID-19 and mortality: Analysis of UK Biobank, Int. J. Obes,
doi:10.1038/s41366-021-00771-zZanella, Zizioli, Castelli, Quiros-Roldan, Tenofovir, another inexpensive, well-known and widely available old drug repurposed for SARS-CoV-2 infection, Pharmaceuticals,
doi:10.3390/ph14050454Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet
DOI record:
{
"DOI": "10.3390/pathophysiology29010009",
"ISSN": [
"1873-149X"
],
"URL": "http://dx.doi.org/10.3390/pathophysiology29010009",
"abstract": "<jats:p>The clinical manifestations associated with COVID-19 disease is mainly due to a dysregulated host response related to the overexpression of inflammatory markers. Until recently, only remdesivir had gained FDA approval for COVID-19 hospitalized patients and there are currently no evidence-based therapeutic options or options for prevention of complications that have been established. Some medical treatments such as antivirals, antibacterials, antithrombotics, antipyretics, corticosteroids, interleukin inhibitors, monoclonal antibodies, convalescent plasma, immunostimulants, and vitamin supplements have been utilized. However, there are limited data to support their effectiveness. Hence, this study was attempted to identify and evaluate the effectiveness of antibacterials and antivirals used for COVID-19 using a retrospective cross-sectional approach based on the medical records of adult patients in four hospitals. The number of antibacterials was calculated in defined daily dose (DDD) per 100 bed-days unit. Both mixed-logit regression and analysis of covariance were used to determine the effectiveness of the aforementioned agents in relation to COVID-19 outcome and patients’ length of stay. The model was weighed accordingly and covariates (e.g., age) were considered in the model. Heart disease was found to be the most common pre-existing condition of COVID-19 hospitalized patients in this study. Azithromycin, an antibacterial in the Watch category list, was used extensively (33–65 DDD per 100 bed-days). Oseltamivir, an antiviral approved by the FDA for influenza was the most prescribed antiviral. In addition, favipiravir was found to be a significant factor in improving patients’ COVID-19 outcomes and decreasing their length of stay. This study strongly suggests that COVID-19 patients’ received polypharmacy for their treatment. However, most of the drugs used did not reach statistical significance in improving the patients’ condition or decreasing the length of stay. Further studies to support drug use are needed.</jats:p>",
"alternative-id": [
"pathophysiology29010009"
],
"author": [
{
"affiliation": [],
"family": "Yulia",
"given": "Rika",
"sequence": "first"
},
{
"affiliation": [],
"family": "Ikasanti",
"given": "Putri Ayu Irma",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-8355-955X",
"affiliation": [],
"authenticated-orcid": false,
"family": "Herawati",
"given": "Fauna",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hartono",
"given": "Ruddy",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hanum",
"given": "Puri Safitri",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Lestiono",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ramdani",
"given": "Dewi",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Jaelani",
"given": "Abdul Kadir",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0001-6417-8455",
"affiliation": [],
"authenticated-orcid": false,
"family": "Kantono",
"given": "Kevin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wijono",
"given": "Heru",
"sequence": "additional"
}
],
"container-title": "Pathophysiology",
"container-title-short": "Pathophysiology",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2022,
3,
9
]
],
"date-time": "2022-03-09T06:53:54Z",
"timestamp": 1646808834000
},
"deposited": {
"date-parts": [
[
2022,
3,
9
]
],
"date-time": "2022-03-09T07:49:24Z",
"timestamp": 1646812164000
},
"funder": [
{
"DOI": "10.13039/501100012696",
"award": [
"Internal"
],
"doi-asserted-by": "publisher",
"name": "University of Surabaya"
}
],
"indexed": {
"date-parts": [
[
2022,
4,
1
]
],
"date-time": "2022-04-01T20:12:48Z",
"timestamp": 1648843968656
},
"is-referenced-by-count": 0,
"issue": "1",
"issued": {
"date-parts": [
[
2022,
3,
7
]
]
},
"journal-issue": {
"issue": "1",
"published-online": {
"date-parts": [
[
2022,
3
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2022,
3,
7
]
],
"date-time": "2022-03-07T00:00:00Z",
"timestamp": 1646611200000
}
}
],
"link": [
{
"URL": "https://www.mdpi.com/1873-149X/29/1/9/pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1968",
"original-title": [],
"page": "92-105",
"prefix": "10.3390",
"published": {
"date-parts": [
[
2022,
3,
7
]
]
},
"published-online": {
"date-parts": [
[
2022,
3,
7
]
]
},
"publisher": "MDPI AG",
"reference": [
{
"article-title": "COVID-19 and Indonesia",
"author": "Setiati",
"first-page": "84",
"journal-title": "Acta Med. Indones.",
"key": "ref1",
"volume": "52",
"year": "2020"
},
{
"DOI": "10.4269/ajtmh.20-1496",
"doi-asserted-by": "publisher",
"key": "ref2"
},
{
"DOI": "10.1016/j.lanwpc.2021.100108",
"doi-asserted-by": "publisher",
"key": "ref3"
},
{
"DOI": "10.7573/dic.2020-10-3",
"doi-asserted-by": "publisher",
"key": "ref4"
},
{
"DOI": "10.1001/jamanetworkopen.2021.16057",
"doi-asserted-by": "publisher",
"key": "ref5"
},
{
"DOI": "10.1056/NEJMoa2007764",
"doi-asserted-by": "publisher",
"key": "ref6"
},
{
"DOI": "10.2147/IDR.S289037",
"doi-asserted-by": "publisher",
"key": "ref7"
},
{
"DOI": "10.1177/2472555220958385",
"doi-asserted-by": "publisher",
"key": "ref8"
},
{
"DOI": "10.1371/journal.pmed.1003501",
"doi-asserted-by": "publisher",
"key": "ref9"
},
{
"DOI": "10.1001/jama.2020.8630",
"doi-asserted-by": "publisher",
"key": "ref10"
},
{
"DOI": "10.1001/jama.2020.6019",
"doi-asserted-by": "publisher",
"key": "ref11"
},
{
"DOI": "10.1007/s40495-020-00216-7",
"doi-asserted-by": "publisher",
"key": "ref12"
},
{
"DOI": "10.1016/j.jinf.2020.03.062",
"doi-asserted-by": "publisher",
"key": "ref13"
},
{
"DOI": "10.1371/journal.pone.0249481",
"doi-asserted-by": "publisher",
"key": "ref14"
},
{
"DOI": "10.1016/j.jiph.2021.02.011",
"doi-asserted-by": "publisher",
"key": "ref15"
},
{
"DOI": "10.1093/cid/ciaa530",
"doi-asserted-by": "publisher",
"key": "ref16"
},
{
"DOI": "10.1371/journal.pone.0263437",
"doi-asserted-by": "publisher",
"key": "ref17"
},
{
"key": "ref18",
"series-title": "Clinical Management of COVID-19 Interim Guidance—May 2020",
"year": "2020"
},
{
"DOI": "10.2471/BLT.20.268573",
"doi-asserted-by": "publisher",
"key": "ref19"
},
{
"DOI": "10.4102/ajlm.v9i1.1302",
"doi-asserted-by": "publisher",
"key": "ref20"
},
{
"DOI": "10.1002/sim.5525",
"doi-asserted-by": "publisher",
"key": "ref21"
},
{
"article-title": "Sample size calculation in medical studies",
"author": "Pourhoseingholi",
"first-page": "14",
"journal-title": "Gastroenterol. Hepatol. Bed. Bench.",
"key": "ref22",
"volume": "6",
"year": "2013"
},
{
"key": "ref23"
},
{
"DOI": "10.3390/antibiotics10020132",
"doi-asserted-by": "publisher",
"key": "ref24"
},
{
"key": "ref25",
"unstructured": "ATC/DDD Index 2021https://www.whocc.no/atc_ddd_index/"
},
{
"key": "ref26",
"unstructured": "WHO International Working Group for Drug Statistics Methodology; WHO Collaborating Centre for Drug Statistics Methodology; WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Serviceshttp://www.who.int/iris/handle/10665/42627"
},
{
"key": "ref27",
"unstructured": "Tim COVID-19 IDAI. Pedoman Tatalaksana COVID-19 Edisi 2 Agustus 2020. Perhimpunan Dokter Paru Indonesia (PDPI), Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI), Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia (PAPDI), Perhimpunan Dokter Anestesiologi dan Terapi Intensif Indonesia (PERDATIN), Ikatan Dokter Anak Indonesia (IDAI). Tahun 2020https://www.papdi.or.id/pdfs/938/Pedoman%20Tatalaksana%20COVID-19%20edisi%202.pdf"
},
{
"key": "ref28",
"unstructured": "The 2019 WHO AWaRe Classification of Antibiotics for Evaluation and Monitoring of Usehttps://apps.who.int/iris/handle/10665/327957"
},
{
"key": "ref29",
"unstructured": "The AWaRe Classification of Antibiotics Databasehttps://adoptaware.org/"
},
{
"DOI": "10.1093/trstmh/trab048",
"doi-asserted-by": "publisher",
"key": "ref30"
},
{
"DOI": "10.1371/journal.pmed.1003682",
"doi-asserted-by": "publisher",
"key": "ref31"
},
{
"DOI": "10.1016/j.phrs.2020.105403",
"doi-asserted-by": "publisher",
"key": "ref32"
},
{
"DOI": "10.1016/j.jiph.2021.02.001",
"doi-asserted-by": "publisher",
"key": "ref33"
},
{
"DOI": "10.3390/antibiotics10091040",
"doi-asserted-by": "publisher",
"key": "ref34"
},
{
"DOI": "10.1093/jacamr/dlab047",
"doi-asserted-by": "publisher",
"key": "ref35"
},
{
"DOI": "10.1177/11786337211033870",
"doi-asserted-by": "publisher",
"key": "ref36"
},
{
"DOI": "10.1128/JVI.02190-20",
"doi-asserted-by": "publisher",
"key": "ref37"
},
{
"key": "ref38"
},
{
"DOI": "10.3390/ph14050454",
"doi-asserted-by": "publisher",
"key": "ref39"
},
{
"DOI": "10.2174/1570162X15666171120110145",
"doi-asserted-by": "publisher",
"key": "ref40"
},
{
"DOI": "10.1111/jcpt.13305",
"doi-asserted-by": "publisher",
"key": "ref41"
},
{
"DOI": "10.1016/j.jiph.2021.07.019",
"doi-asserted-by": "publisher",
"key": "ref42"
},
{
"DOI": "10.1056/NEJMoa2001282",
"doi-asserted-by": "publisher",
"key": "ref43"
},
{
"DOI": "10.1136/bmjopen-2020-047016",
"doi-asserted-by": "publisher",
"key": "ref44"
},
{
"DOI": "10.1016/j.coph.2014.07.008",
"doi-asserted-by": "publisher",
"key": "ref45"
},
{
"DOI": "10.1007/s40264-020-00954-z",
"doi-asserted-by": "publisher",
"key": "ref46"
},
{
"DOI": "10.1016/j.ijid.2020.10.069",
"doi-asserted-by": "publisher",
"key": "ref47"
},
{
"DOI": "10.1016/j.eng.2020.03.007",
"doi-asserted-by": "publisher",
"key": "ref48"
},
{
"DOI": "10.1007/s40121-021-00517-4",
"doi-asserted-by": "publisher",
"key": "ref49"
},
{
"DOI": "10.1186/s12879-021-06164-x",
"doi-asserted-by": "publisher",
"key": "ref50"
},
{
"DOI": "10.1002/14651858.CD015025",
"doi-asserted-by": "publisher",
"key": "ref51"
},
{
"DOI": "10.3855/jidc.14404",
"doi-asserted-by": "publisher",
"key": "ref52"
},
{
"DOI": "10.1159/000512592",
"doi-asserted-by": "publisher",
"key": "ref53"
},
{
"DOI": "10.18053/jctres.07.202103.010",
"doi-asserted-by": "publisher",
"key": "ref54"
},
{
"DOI": "10.2147/RMHP.S292538",
"doi-asserted-by": "publisher",
"key": "ref55"
},
{
"DOI": "10.5603/ARM.a2021.0036",
"doi-asserted-by": "publisher",
"key": "ref56"
},
{
"DOI": "10.2147/IJGM.S330580",
"doi-asserted-by": "publisher",
"key": "ref57"
},
{
"DOI": "10.1016/j.arcmed.2020.12.002",
"doi-asserted-by": "publisher",
"key": "ref58"
},
{
"DOI": "10.1371/journal.pone.0258154",
"doi-asserted-by": "publisher",
"key": "ref59"
},
{
"DOI": "10.3810/pgm.2009.11.2074",
"doi-asserted-by": "publisher",
"key": "ref60"
},
{
"DOI": "10.3389/fmed.2021.620044",
"doi-asserted-by": "publisher",
"key": "ref61"
},
{
"DOI": "10.1038/s41366-021-00771-z",
"doi-asserted-by": "publisher",
"key": "ref62"
},
{
"DOI": "10.1038/s41366-021-00872-9",
"doi-asserted-by": "publisher",
"key": "ref63"
},
{
"DOI": "10.1186/s12916-020-01726-3",
"doi-asserted-by": "publisher",
"key": "ref64"
},
{
"DOI": "10.1007/s40199-020-00369-2",
"doi-asserted-by": "publisher",
"key": "ref65"
},
{
"DOI": "10.1016/S0140-6736(20)30566-3",
"doi-asserted-by": "publisher",
"key": "ref66"
},
{
"DOI": "10.1186/s13223-020-00509-y",
"doi-asserted-by": "publisher",
"key": "ref67"
},
{
"key": "ref68",
"unstructured": "Risks of and from SARS-CoV-2 (COVID-19) Infection in People with Asthmahttps://www.cebm.net/covid-19/risks-of-and-from-sars-cov-2-covid-19-infection-in-people-with-asthma/"
},
{
"DOI": "10.1016/S2213-2600(20)30415-X",
"doi-asserted-by": "publisher",
"key": "ref69"
},
{
"DOI": "10.4103/lungindia.lungindia_965_20",
"doi-asserted-by": "publisher",
"key": "ref70"
}
],
"reference-count": 70,
"references-count": 70,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.mdpi.com/1873-149X/29/1/9"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"General Medicine"
],
"subtitle": [],
"title": "Evaluation of Antibacterial and Antiviral Drug Effectiveness in COVID-19 Therapy: A Data-Driven Retrospective Approach",
"type": "journal-article",
"volume": "29"
}
