Prognostic Factors for Predicting Post-COVID-19 Condition in Patients With COVID-19 in an Outpatient Setting
Myeong Geun Choi, Young Woong Joo, Min-Ho Kim, Sojung Park, Yune-Young Shin, MD Eun Mi Chun
Journal of Korean Medical Science, doi:10.3346/jkms.2024.39.e23
Background: Although data on post-coronavirus disease 2019 (COVID-19) conditions are extensive, the prognostic factors affecting symptom duration in non-hospitalized patients with COVID-19 are currently not well known. We aimed to investigate the various prognostic factors affecting symptom duration among outpatients with COVID-19. Methods: Data were analyzed from 257 patients who were diagnosed with mild COVID-19 and visited the 'post-COVID-19 outpatient clinic' between April and December 2022 after a mandatory isolation period. The symptom duration was measured from diagnosis to symptom resolution. Laboratory and pulmonary function test results from their first visit were collected. Results: The mean age of patients was 55.7 years, and the median symptom duration was 57 days. The development of post-COVID-19 conditions (> 12 weeks) were significantly correlated with not using antiviral drugs, leukocytosis (white blood cell > 10,000/µL), lower 25(OH)D 3 levels, forced vital capacity (FVC) < 90% predicted, and presence of dyspnea and anxiety/depression. Additionally, in multivariable Cox regression analysis, not using antiviral drugs, lower 25(OH)D 3 levels, and having dyspnea were poor prognostic factors for longer symptom duration. Particularly, vitamin D deficiency (< 20 ng/mL) and not using antivirals during the acute phase were independent poor prognostic factors for both post-COVID-19 condition and longer symptom duration.
Conclusion: The non-use of antivirals, lower 25(OH)D 3 levels, leukocytosis, FVC < 90% predicted, and the presence of dyspnea and anxiety/depression symptoms could be useful prognostic factors for predicting post-COVID-19 condition in outpatients with COVID-19. We suggest that the use of antiviral agents during the acute phase and vitamin D supplements might help reduce COVID-19 symptom duration.
SUPPLEMENTARY MATERIALS Supplementary Table 1 The incidence of clinical symptoms of patients with COVID- 4 Baseline characteristics of the study population at the time of their first visit to the outpatient department according to Vit D deficiency Click here to view Supplementary Table 5 Baseline characteristics of the study population at the time of their first visit to the outpatient department according to use of antiviral agent at acute phase of COVID-19
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References
Amin, Kakamad, Ahmed, Ahmed, Abdulla et al., Post COVID-19 pulmonary fibrosis; a meta-analysis study, Ann Med Surg (Lond),
doi:10.1016/j.amsu.2022.103590Aminian, Bena, Pantalone, Burguera, Association of obesity with postacute sequelae of COVID-19, Diabetes Obes Metab,
doi:10.1111/dom.14454Augustin, Schommers, Stecher, Dewald, Gieselmann et al., Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study, Lancet Reg Health Eur,
doi:10.1016/j.lanepe.2021.100122Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of COVID-19 -final report, N Engl J Med,
doi:10.1056/NEJMoa2007764Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms in endocrinology: vitamin D and COVID-19, Eur J Endocrinol,
doi:10.1530/EJE-20-0665Butt, Dargham, Coyle, Yassine, Al-Khal et al., COVID-19 disease severity in persons infected with Omicron BA.1 and BA.2 sublineages and association with vaccination status, JAMA Intern Med,
doi:10.1001/jamainternmed.2022.3351Carfì, Bernabei, Landi, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19, JAMA,
doi:10.1001/jama.2020.12603Chen, Haupert, Zimmermann, Shi, Fritsche et al., Global prevalence of postcoronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review, J Infect Dis,
doi:10.1093/infdis/jiac136Daines, Zheng, Elneima, Harrison, Lone et al., Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19, ERJ Open Res,
doi:10.1183/23120541.00274-2022Daneshkhah, Agrawal, Eshein, Subramanian, Roy et al., Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients, Aging Clin Exp Res,
doi:10.1007/s40520-020-01677-yDhawan, Gopalan, Howard, Vicente, Park et al., Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19, Lancet Respir Med,
doi:10.1016/S2213-2600(20)30407-0Dissanayake, Silva, Sumanatilleke, De Silva, Gamage et al., Prognostic and therapeutic role of vitamin D in COVID-19: systematic review and meta-analysis, J Clin Endocrinol Metab,
doi:10.1210/clinem/dgab892Dror, Morozov, Daoud, Namir, Yakir et al., Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness, PLoS One,
doi:10.1371/journal.pone.0263069Fernández-De-Las-Peñas, Palacios-Ceña, Gómez-Mayordomo, Florencio, Cuadrado et al., Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: a systematic review and meta-analysis, Eur J Intern Med,
doi:10.1016/j.ejim.2021.06.009Fernández-De-Las-Peñas, Pellicer-Valero, Navarro-Pardo, Palacios-Ceña, Florencio et al., Symptoms experienced at the acute phase of SARS-CoV-2 infection as risk factor of long-term post-COVID symptoms: the LONG-COVID-EXP-CM multicenter study, Int J Infect Dis,
doi:10.1016/j.ijid.2022.01.007Gao, Piernas, Astbury, Hippisley-Cox, 'rahilly et al., Associations between bodymass index and COVID-19 severity in 6•9 million people in England: a prospective, community-based, cohort study, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(21)00089-9Gottlieb, Vaca, Paredes, Mera, Webb et al., Early remdesivir to prevent progression to severe COVID-19 in outpatients, N Engl J Med,
doi:10.1056/NEJMoa2116846Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Grein, Ohmagari, Shin, Diaz, Asperges et al., Compassionate use of remdesivir for patients with severe COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2007016Hammond, Leister-Tebbe, Gardner, Abreu, Wisemandle, Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2118542Huang, Kovalic, Graber, Prognostic value of leukocytosis and lymphopenia for coronavirus disease severity, Emerg Infect Dis,
doi:10.3201/eid2608.201160Jung, Ha, Choe, Lee, Jo et al., Persistent symptoms after acute COVID-19 infection in Omicron era, J Korean Med Sci,
doi:10.3346/jkms.2022.37.e213Kamal, Omirah, Hussein, Saeed, Assessment and characterisation of post-COVID-19 manifestations, Int J Clin Pract,
doi:10.1111/ijcp.13746Lopez-Leon, Wegman-Ostrosky, Perelman, Sepulveda, Rebolledo et al., More than 50 long-term effects of COVID-19: a systematic review and meta-analysis, Sci Rep,
doi:10.1038/s41598-021-95565-8Macintyre, Crapo, Viegi, Johnson, Van Der Grinten et al., Standardisation of the single-breath determination of carbon monoxide uptake in the lung, Eur Respir J,
doi:10.1183/09031936.05.00034905Magnúsdóttir, Lovik, Unnarsdóttir, Mccartney, Ask et al., Acute COVID-19 severity and mental health morbidity trajectories in patient populations of six nations: an observational study, Lancet Public Health,
doi:10.1016/S2468-2667(22)00042-1Michelen, Manoharan, Elkheir, Cheng, Dagens et al., Characterising long COVID: a living systematic review, BMJ Glob Health,
doi:10.1136/bmjgh-2021-005427Munker, Veit, Barton, Mertsch, Mümmler et al., Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity, Infection,
doi:10.1007/s15010-021-01669-8Oscanoa, Amado, Vidal, Laird, Ghashut et al., The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration -a metaanalysis, Adv Respir Med,
doi:10.5603/ARM.a2021.0037Pizzini, Aichner, Sahanic, Böhm, Egger et al., Impact of vitamin D deficiency on COVID-19-a prospective analysis from the CovILD registry, Nutrients,
doi:10.3390/nu12092775Renaud-Charest, Lui, Eskander, Ceban, Ho et al., Onset and frequency of depression in post-COVID-19 syndrome: a systematic review, J Psychiatr Res,
doi:10.1016/j.jpsychires.2021.09.054Song, Hui, Hull, Birring, Mcgarvey et al., Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses, Lancet Respir Med,
doi:10.1016/S2213-2600(21)00125-9Stavem, Ghanima, Olsen, Gilboe, Einvik, Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study, Thorax,
doi:10.1136/thoraxjnl-2020-216377Subramanian, Nirantharakumar, Hughes, Myles, Williams et al., Symptoms and risk factors for long COVID in non-hospitalized adults, Nat Med,
doi:10.1038/s41591-022-01909-wTenforde, Kim, Lindsell, Rose, Shapiro et al., Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network -United States, March-June 2020, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6930e1Townsend, Dyer, Mccluskey, 'brien, Dowds et al., Investigating the relationship between vitamin D and persistent symptoms following SARS-CoV-2 infection, Nutrients,
doi:10.3390/nu13072430Tsampasian, Elghazaly, Chattopadhyay, Debski, Naing et al., Risk factors associated with post-COVID-19 condition: a systematic review and meta-analysis, JAMA Intern Med,
doi:10.1001/jamainternmed.2023.0750Ulloa, Buchan, Daneman, Brown, Estimates of SARS-CoV-2 Omicron variant severity in Ontario, Canada, JAMA,
doi:10.1001/jama.2022.2274Wolter, Jassat, Walaza, Welch, Moultrie et al., Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study, Lancet,
doi:10.1016/S0140-6736(22)00017-4Yang, Luo, Gan, Chen, Li, Risk factors for predicting mortality of COVID-19 patients: a systematic review and meta-analysis, PLoS One,
doi:10.1371/journal.pone.0243124Ye, Pang, Li, Li, Liu et al., Both underweight and obesity are associated with an increased risk of coronavirus disease 2019 (COVID-19) severity, Front Nutr,
doi:10.3389/fnut.2021.649422Zhang, Bai, Yue, Qin, Zhang et al., Eight months follow-up study on pulmonary function, lung radiographic, and related physiological characteristics in COVID-19 survivors, Sci Rep,
doi:10.1038/s41598-021-93191-yZhu, Feng, Jiang, Mi, Yang et al., Correlation between white blood cell count at admission and mortality in COVID-19 patients: a retrospective study, BMC Infect Dis,
doi:10.1186/s12879-021-06277-3
