Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19—A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Clinical Data
2.3. Treatment Strategy in Kihoku Hospital
2.4. Statistical Analysis
3. Results
3.1. Characteristics of Treated Patients with COVID-19 during the Fourth Pandemic Period
3.2. Comparisons of Clinical Characteristics between the Treatment Requirement and the Observation Groups in Our Hospital
3.3. Clinical Outcome of Hospitalized Patients with COVID-19
3.4. Factors Associated with the Therapeutic Intervention of Remdesivir in Hospitalized Patients with Mild to Moderate COVID-19
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- World Health Organization. World Health Organization Coronavirus Disease Dashboard. Available online: https://covid19.who.int (accessed on 1 June 2021).
- Karako, K.; Song, P.; Chen, Y.; Tang, W.; Kokudo, N. Overview of the characteristics of and responses to the three waves of COVID-19 in Japan during 2020–2021. Biosci. Trends 2021, 15, 1–8. [Google Scholar] [CrossRef]
- Graham, M.S.; Sudre, C.H.; May, A.; Antonelli, M.; Murray, B.; Varsavsky, T.; Kläser, K.; Canas, L.S.; Molteni, E.; Modat, M.; et al. Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: An ecological study. Lancet Public Health 2021, 6, e335–e345. [Google Scholar] [CrossRef]
- Tokumoto, A.; Akaba, H.; Oshitani, H.; Jindai, K.; Wada, K.; Imamura, T.; Saito, T.; Shobugawa, Y. COVID-19 Health System Response Monitor: Japan; World Health Organization, Regional Office for South-East Asia: Tokyo, Japan, 2020. [Google Scholar]
- Beigel, J.H.; Tomashek, K.M.; Dodd, L.E.; Mehta, A.K.; Zingman, B.S.; Kalil, A.C.; Hohmann, E.; Chu, H.Y.; Luetkemeyer, A.; Kline, S.; et al. ACTT-1 Study Group Members. Remdesivir for the treatment of COVID-19—Final report. N. Engl. J. Med. 2020, 383, 1813–1826. [Google Scholar] [CrossRef]
- Rochwerg, B.; Agarwal, A.; Siemieniuk, R.A.; Agoritsas, T.; Lamontagne, F.; Askie, L.; Lytvyn, L.; Leo, Y.S.; Macdonald, H.; Zeng, L.; et al. A living WHO guideline on drugs for covid-19. BMJ 2020, 370, m3379. [Google Scholar]
- Kalil, A.C.; Patterson, T.F.; Mehta, A.K.; Tomashek, K.M.; Wolfe, C.R.; Ghazaryan, V.; Marconi, V.C.; Ruiz-Palacios, G.M.; Hsieh, L.; Kline, S.; et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N. Engl. J. Med. 2021, 384, 795–807. [Google Scholar] [CrossRef]
- Kanda, Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013, 48, 452–458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Y.; Zhang, D.; Du, G.; Du, R.; Zhao, J.; Jin, Y.; Fu, S.; Gao, L.; Cheng, Z.; Lu, Q.; et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020, 395, 1569–1578. [Google Scholar] [CrossRef]
- Garibaldi, B.T.; Wang, K.; Robinson, M.L.; Zeger, S.L.; Bandeen-Roche, K.; Wang, M.C.; Alexander, G.C.; Gupta, A.; Bollinger, R.; Xu, Y. Comparison of time to clinical improvement with vs without remdesivir treatment in hospitalized patients with COVID-19. JAMA Netw. Open 2021, 4, e213071. [Google Scholar] [CrossRef]
- Mehta, R.M.; Bansal, S.; Bysani, S.; Kalpakam, H. A shorter symptom onset to remdesivir treatment (SORT) interval is associated with a lower mortality in moderate-to-severe COVID-19: A real-world analysis. Int. J. Infect. Dis. 2021, 106, 71–77. [Google Scholar] [CrossRef] [PubMed]
- Spinner, C.D.; Gottlieb, R.L.; Criner, G.J.; López, J.R.A.; Cattelan, A.M.; Viladomiu, A.S.; Ogbuagu, O.; Malhotra, P.; Mullane, K.M.; Castagna, A.; et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: A randomized clinical trial. JAMA 2020, 324, 1048–1057. [Google Scholar] [CrossRef]
- Boehm, E.; Kronig, I.; Neher, R.A.; Eckerle, I.; Vetter, P.; Kaiser, L.; Geneva Centre for Emerging Viral Diseases. Novel SARS-CoV-2 variants: The pandemics within the pandemic. Clin. Microbiol. Infect. 2021, 27, 1109–1117. [Google Scholar] [CrossRef] [PubMed]
- Winger, A.; Caspari, T. The spike of concern-the novel variants of SARS-CoV-2. Viruses 2021, 13, 1002. [Google Scholar] [CrossRef]
- Terpos, E.; Ntanasis-Stathopoulos, I.; Elalamy, I.; Kastritis, E.; Sergentanis, T.N.; Politou, M.; Psaltopoulou, T.; Gerotziafas, G.; Dimopoulos, M.A. Hematological findings and complications of COVID-19. Am. J. Hematol. 2020, 95, 834–847. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chaudhary, R.; Garg, J.; Houghton, D.E.; Murad, M.H.; Kondur, A.; Chaudhary, R.; Wysokinski, W.E.; McBane, R.D., II. Thromboinflammatory biomarkers in COVID-19: Systematic review and meta-analysis of 17,052 patients. Mayo Clin. Proc. Innov. Qual. Outcomes 2021, 5, 388–402. [Google Scholar] [CrossRef]
- Arnold, D.T.; Attwood, M.; Barratt, S.; Morley, A.; Elvers, K.T.; McKernon, J.; Donald, C.; Oates, A.; Noel, A.; MacGowan, A.; et al. Predicting outcomes of COVID-19 from admission biomarkers: A prospective UK cohort study. Emerg. Med. J. 2021, 38, 543–548. [Google Scholar] [CrossRef]
- Garg, S.; Kim, L.; Whitaker, M.; O’Halloran, A.; Cummings, C.; Holstein, R.; Prill, M.; Chai, S.J.; Kirley, P.D.; Alden, N.B.; et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019—COVID-NET, 14 States, March 1–30, 2020. MMWR Morb. Mortal. Wkly. Rep. 2020, 69, 458–464. [Google Scholar] [CrossRef] [PubMed]
- Vakili, K.; Fathi, M.; Hajiesmaeili, M.; Salari, M.; Saluja, D.; Tafakhori, A.; Sayehmiri, F.; Rezaei-Tavirani, M. Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies. Eur. Neurol. 2021, 84, 307–324. [Google Scholar] [CrossRef] [PubMed]
- Trigo, J.; García-Azorín, D.; Planchuelo-Gómez, Á.; Martínez-Pías, E.; Talavera, B.; Hernández-Pérez, I.; Valle-Peñacoba, G.; Simón-Campo, P.; de Lera, M.; Chavarría-Miranda, A.; et al. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: A retrospective cohort study. J. Headache Pain 2020, 21, 94. [Google Scholar] [CrossRef]
- Caronna, E.; Ballvé, A.; Llauradó, A.; Gallardo, V.J.; Ariton, D.M.; Lallana, S.; López Maza, S.; Olivé Gadea, M.; Quibus, L.; Restrepo, J.L.; et al. Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution. Cephalalgia 2020, 40, 1410–1421. [Google Scholar] [CrossRef] [PubMed]
- Chachkhiani, D.; Soliman, M.Y.; Barua, D.; Isakadze, M.; Villemarette-Pittman, N.R.; Devier, D.J.; Lovera, J.F. Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization. Clin. Neurol. Neurosurg. 2020, 197, 106173. [Google Scholar] [CrossRef]
- Hentsch, L.; Cocetta, S.; Allali, G.; Santana, I.; Eason, R.; Adam, E.; Janssens, J.P. Breathlessness and COVID-19: A Call for Research. Respiration 2021, 100, 1016–1026. [Google Scholar] [CrossRef] [PubMed]
All N = 185 | Treatment N = 63 | Observation N = 122 | |
Male, n (%) | 94 (50.8%) | 36 (57.1%) | 58 (47.5%) |
Age (years), mean (SD) | 49.3 (19.8) | 59.6 (14.7) | 44.1 (20.1) |
Comorbidity, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Hyperlipidemia, n (%) Chronic obstructive pulmonary disease, n (%) Heart disease, n (%) Chronic kidney disease, n (%) Cancer, n (%) | 81 (43.8%) 46 (24.9%) 17 (9.2%) 11 (5.9%) 5 (2.7%) 8 (4.3%) 3 (1.6%) 4 (2.2%) | 35 (55.6%) 30 (47.6%) 14 (22.2%) 7 (11.1%) 5 (7.9%) 2 (3.2%) 3 (4.8%) 4 (6.3%) | 25 (16.4%) 16 (13.1%) 3 (2.5%) 4 (3.3%) 0 (0%) 6 (4.9%) 0 (0%) 0 (0%) |
Smoking, n (%) | 50 (27.0%) | 23 (36.5%) | 27 (22.1%) |
Body mass index (kg/m2), median (IQR) | 23.1 (20.3–25.9) | 23.9 (22.2–26.5) | 21.6 (20–25.5) |
COVID-19 B.1.1.7 variant, n (%) | 125 (67.6%) | 49 (77.8%) | 76 (62.3%) |
Asymptomatic at admission (excluding fever) Symptomatic at admission (excluding fever) Upper respiratory symptoms (nasal discharge, throat pain), n (%) Lower respiratory symptoms (cough, sputum), n (%) General fatigue, n (%) Headache, n (%) Arthralgia, n (%) Olfactory and taste disturbances, n (%) Gastrointestinal symptoms Shortness of breath, n (%) | 64 (34.6%) 120 (65.4%) 54 (29.2%) 63 (34.1%) 32 (17.3%) 29 (15.7%) 11 (5.9%) 17 (9.2%) 14 (7.6%) 4 (2.2%) | 12 (19.0%) 51 (81.0%) 31 (49.2%) 39 (61.9%) 23 (36.5%) 19 (30.2%) 11 (17.5%) 3 (4.8%) 8 (12.7%) 4 (6.3%) | 53 (43.4%) 69 (56.6%) 23 (18.9%) 24 (19.7%) 9 (7.4%) 10 (8.2%) 0 (0%) 14 (11.5%) 6 (4.9%) 0 (0%) |
Fever (°C) at admission, mean (SD) | 37.2 (0.89) | 38.0 (0.84) | 36.8 (0.60) |
SpO2 (%) at admission, median (IQR) | 97 (95–98) | 95 (94–95) | 98 (97–98) |
Pulse (/min) at admission, mean (SD) | 83 (12) | 87 (13) | 81 (11) |
Laboratory data at treatment initiation White blood cell count (/μL), median (IQR) Platelet count (×104/μL), median (IQR) Alanine Aminotransferase (U/L), median (IQR) Aspartate Aminotransferase (U/L), median (IQR) Creatinine (mg/dL), median (IQR) Lactate Dehydrogenase (U/L), median (IQR) C-reactive Protein (mg/dL), median (IQR) | - | 4640 (3230–5630) 14.8 (12.6–19.7) 26 (23–42) 31 (16–40) 0.88 (0.69–1.03) 234 (209–320) 2.52 (0.82–5.39) | - |
Additional treatment information Oral baricitinib, n (%) Subcutaneous injection of heparin calcium, n (%) | - | 12 (19.0%) 57 (90.5%) | - |
* Age upon admission, mean (SD) | 50.7 (19.8) | 59.6 (14.7) | 45.3 (20.6) |
* Duration from onset to admission, median (IQR) | 2 (1–4) | 2 (2–4) | 2 (1–4) |
* Duration from onset to treatment initiation, median (IQR) | - | 6 (4–7) | - |
* Length of hospitalization, median (IQR) | 10 (8–12) | 10 (9–12) | 9 (8-10) |
Transferred to another hospital, n | 1 | 1 | 0 |
Treatment | (N = 63) | Observation | (N = 122) | p-Value | ||
---|---|---|---|---|---|---|
Sex | 0.277 | |||||
Male | 36 | (57.1%) | 58 | (47.5%) | ||
Female | 27 | (42.9%) | 64 | (52.5%) | ||
Age (years) | <0.001 | |||||
<60 | 32 | (50.8%) | 94 | (77.0%) | ||
≥60 | 31 | (49.2%) | 28 | (23.0%) | ||
Presence of comorbidity | ||||||
Hypertension | <0.001 | |||||
No | 40 | (63.5%) | 105 | (86.1%) | ||
Yes | 23 | (36.5%) | 17 | (13.9%) | ||
Diabetes mellitus | <0.001 | |||||
No | 49 | (77.8%) | 119 | (97.5%) | ||
Yes | 14 | (22.2%) | 3 | (4.1%) | ||
Hyperlipidemia | 0.11 | |||||
No | 56 | (88.9%) | 117 | (95.9%) | ||
Yes | 7 | (11.1%) | 5 | (4.1%) | ||
Chronic obstructive pulmonary disease | 0.013 | |||||
No | 59 | (93.7%) | 122 | (100%) | ||
Yes | 4 | (6.3%) | 0 | (0%) | ||
Heart disease | 1 | |||||
No | 61 | (96.8%) | 121 | (99.2%) | ||
Yes | 2 | (3.2%) | 1 | (0%) | ||
Chronic kidney disease | 0.115 | |||||
No | 60 | (95.2%) | 121 | (99.2%) | ||
Yes | 3 | (4.8%) | 1 | (0%) | ||
Cancer | 0.038 | |||||
No | 60 | (95.2%) | 122 | (100%) | ||
Yes | 3 | (4.8%) | 0 | (0%) | ||
Smoking history | 0.054 | |||||
No | 40 | (63.5%) | 95 | (77.9%) | ||
Yes | 23 | (36.5%) | 27 | (22.1%) | ||
Body mass index (kg/m2) | 0.871 | |||||
<30 | 60 | (95.2%) | 114 | (93%) | ||
≥30 | 3 | (4.8%) | 8 | (7%) | ||
COVID-19 genotype | 0.031 | |||||
Previous | 9 | (14.3%) | 39 | (32.0%) | ||
B.1.1.7 | 49 | (77.8%) | 76 | (62.3%) | ||
Unknown | 5 | (7.9%) | 7 | (5.7%) | ||
Symptoms at admission | ||||||
Upper respiratory symptoms | 1 | |||||
No | 46 | (73.0%) | 89 | (73.0%) | ||
Yes | 17 | (27.0%) | 33 | (27.0%) | ||
Lower respiratory symptoms | <0.001 | |||||
No | 31 | (49.2%) | 92 | (75.4%) | ||
Yes | 32 | (50.8%) | 30 | (24.6%) | ||
General fatigue | <0.001 | |||||
No | 40 | (63.5%) | 111 | (91.0%) | ||
Yes | 23 | (36.5%) | 11 | (9.0%) | ||
Headache | <0.001 | |||||
No | 43 | (68.3%) | 111 | (91.0%) | ||
Yes | 20 | (31.7%) | 11 | (9.0%) | ||
Arthralgia | <0.001 | |||||
No | 53 | (84.1%) | 122 | (100%) | ||
Yes | 10 | (15.9%) | 0 | (0%) | ||
Olfactory and taste disturbances | 0.058 | |||||
No | 61 | (96.8%) | 107 | (87.7%) | ||
Yes | 2 | (3.2%) | 15 | (12.3%) | ||
Gastrointestinal symptoms | <0.001 | |||||
No | 51 | (81.0%) | 116 | (95.1%) | ||
Yes | 12 | (19.0%) | 6 | (4.9%) | ||
Shortness of breath | 0.013 | |||||
No | 59 | (93.7%) | 122 | (100%) | ||
Yes | 4 | (3.2%) | 0 | (0%) | ||
Fever at admission | <0.001 | |||||
<37.5 °C | 30 | (47.6%) | 108 | (88.5%) | ||
≥37.5 °C | 33 | (52.4%) | 14 | (11.5%) | ||
SpO2 at admission | 0.003 | |||||
≥97% | 18 | (28.6%) | 64 | (52.5%) | ||
<97% | 45 | (71.4%) | 58 | (47.5%) | ||
Pulse at admission | <0.001 | |||||
<90/min | 34 | (54.0%) | 97 | (79.5%) | ||
≥90/min | 29 | (46.0%) | 25 | (20.5%) |
Odds Ratio (95% CI) | Univariate | |
---|---|---|
Female | 0.68 (0.37–1.25) | p = 0.22 |
≥60 years of age | 3.25 (1.70–6.23) | p < 0.001 |
Presence of comorbidity | ||
Hypertension | 3.55 (1.72–7.33) | p < 0.001 |
Diabetes mellitus | 11.3 (3.12–41.2) | p < 0.001 |
Hyperlipidemia | 2.92 (0.89–9.62) | p = 0.08 |
Chronic obstructive pulmonary disease | - | p = 0.99 |
Heart disease | 0.77 (0.15–4.07) | p = 0.76 |
Chronic kidney disease | 6.05 (0.62–59.4) | p = 0.12 |
Cancer | - | p = 0.99 |
Presence of smoking history | 2.02 (1.04–3.94) | p = 0.039 |
Body mass index >30 kg/m2 | 0.71 (0.18–2.78) | p = 0.63 |
COVID-19 B.1.1.7 variant | 2.79 (1.24–6.27) | p = 0.013 |
Symptoms at admission | ||
Upper respiratory symptoms | 0.99 (0.50–1.98) | p = 0.92 |
Lower respiratory symptoms | 3.17 (1.66–6.02) | p < 0.001 |
General fatigue | 5.80 (2.60–13.0) | p < 0.001 |
Headache | 3.86 (1.77–8.45) | p < 0.001 |
Arthralgia | - | p = 0.99 |
Olfactory and taste disturbances | 0.23 (0.05–1.06) | p = 0.06 |
Gastrointestinal symptoms | 4.55 (1.62–12.8) | p = 0.004 |
Shortness of breath | - | p = 0.99 |
Fever > 37.5 °C at admission | 8.49 (4.03–17.9) | p < 0.001 |
SpO2 < 97% at admission | 2.76 (1.44–5.29) | p = 0.002 |
Pulse > 90/min at admission | 3.31 (1.71–6.42) | p < 0.001 |
Odds Ratio (95% CI) | Multivariate | |
---|---|---|
≥60 years of age | 6.90 (2.57–18.0) | p < 0.001 |
A previous history of diabetes mellitus | 20.9 (3.11–140) | p = 0.002 |
COVID-19 B.1.1.7 variant | 5.30 (1.65–17.0) | p = 0.005 |
Lower respiratory symptoms at admission | 3.13 (1.30–7.53) | p = 0.011 |
Headache at admission | 3.82 (1.37–10.6) | p = 0.011 |
Fever ≥ 37.5 °C at admission | 4.55 (1.83–11.3) | p = 0.001 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Tamura, S.; Kaki, T.; Niwa, M.; Yamano, Y.; Kawai, S.; Yamashita, Y.; Tanaka, H.; Saito, Y.; Kajimoto, Y.; Koizumi, Y.; et al. Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19—A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan. Medicina 2022, 58, 118. https://doi.org/10.3390/medicina58010118
Tamura S, Kaki T, Niwa M, Yamano Y, Kawai S, Yamashita Y, Tanaka H, Saito Y, Kajimoto Y, Koizumi Y, et al. Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19—A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan. Medicina. 2022; 58(1):118. https://doi.org/10.3390/medicina58010118
Chicago/Turabian StyleTamura, Shinobu, Takahiro Kaki, Mayako Niwa, Yukiko Yamano, Shintaro Kawai, Yusuke Yamashita, Harumi Tanaka, Yoshinobu Saito, Yoshinori Kajimoto, Yusuke Koizumi, and et al. 2022. "Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19—A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan" Medicina 58, no. 1: 118. https://doi.org/10.3390/medicina58010118
APA StyleTamura, S., Kaki, T., Niwa, M., Yamano, Y., Kawai, S., Yamashita, Y., Tanaka, H., Saito, Y., Kajimoto, Y., Koizumi, Y., Yamaue, H., Nakao, N., Nojiri, T., & Hironishi, M. (2022). Risk Factors for Therapeutic Intervention of Remdesivir in Mild to Moderate COVID-19—A Single-Center Retrospective Study of the COVID-19 Fourth Pandemic Period in Wakayama, Japan. Medicina, 58(1), 118. https://doi.org/10.3390/medicina58010118