Prevalence and characteristics of post COVID-19 condition five months after SARS-COV-2 infection in inpatients and outpatients.

We are well aware of the worldwide problems caused by the COVID-19 pandemic and thanks to health measures such as vaccination this situation has been positively controlled. However, in clinical practice we continue to observe patients suffering from persistent symptoms, called post COVID-19 condition (PCC) and as many studies have reported, not only in patients who have been hospitalized but also in patients who suffered a mild SARS-CoV-2 infection [1Fernandez de las Peñas C. Palacios-Ceña D. Gómez-Mayordomo V. et al.Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: a systematic review and meta-analysis.EJIM. 2021; 92 (Volume): P55-P70https://doi.org/10.1016/j.ejim.2021.06.009Abstract Full Text Full Text PDF Scopus (220) Google Scholar, 2Goërtz Y. Van Herck M. Delbressine J. et al.Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?.ERJ Open Res. 2020; 6: 00542-02020https://doi.org/10.1183/23120541.00542-2020Crossref PubMed Scopus (453) Google Scholar, 3Xiong Q. Xu M. Li J. et al.Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study.Clin Microbiol Infect. 2021; 27: 89-95https://doi.org/10.1016/j.cmi.2020.09.023Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar, 4Huang L. Yao Q. Gu X. et al.1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.Lancet. 2021; 398: 747-758https://doi.org/10.1016/S0140-6736(21)01755-4Abstract Full Text Full Text PDF PubMed Scopus (494) Google Scholar, 5Huang C. Huang L. Wang Y. et al.6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232https://doi.org/10.1016/S0140-6736(20)32656-8Abstract Full Text Full Text PDF PubMed Scopus (2489) Google Scholar, 6Menges D. Ballouz T. Anagnostopoulos A. et al.Burden of post-COVID-19 syndrome and implications for healthcare service planning: a population-based cohort study.PLOS One. 2021; 6e0254523https://doi.org/10.1371/journal.pone.0254523Crossref Scopus (128) Google Scholar]. The current situation regarding PCC is unclear, as many patients are already vaccinated. Furthermore, many different variants of the virus and waves of SARS-CoV-2 infection may play an important role. Our primary aim was to evaluate the prevalence of PCC in inpatients and outpatients five months after SARS-CoV-2 infection. The secondary aims were to determine the relationship of the severity of SARS-CoV-2 infection and treatments in the acute phase of infection with PCC. This was a prospective, bicentric cohort study in patients infected with SARS-CoV-2 virus confirmed by polymerase chain reaction (PCR) between February and April 2022 (98% Omicron variant: BA.2 and B.1.1.529 [[7]BAG Bundesamt für Gesundheit. Covid-19 Schweiz. https://www.covid19.admin.ch/de/epidemiologic/virus-variants. Accessed February 28, 2023.Google Scholar]). Inpatients were recruited from the Central Hospital in Lucerne (CHL), outpatients from the Ambulatory Permanence Bahnhof Luzern (PMC). Demographic data for all patients, as well as data to determine the degree of severity of disease of the inpatients and their respective therapy received in the hospital, were retrieved from the electronic medical records. Data to determine the presence or absence of PCC were taken from 5 questionnaires filled in by the patients. PCC was defined according to the October 2021 publication of the World Health Organization (WHO). The first questionnaire assessed the current health status five months after SARS-CoV-2 infection. In case the patients indicated that they are currently not feeling well and their symptoms could not be explained otherwise, we assessed dyspnea (mMRC: The British Medical Research Council Modified Dyspnea Scale), fatigue (FAS: Fatigue Assessment Scale), quality of life (EQ-5D-5L: The EuroQol Five Dimensions Five Levels Questionnaire) and cognitive dysfunction. Detailed descriptions of the questionnaires are provided in the online supplementary material. The disease severity of the acute phase of SARS-CoV-2 infection was determined using the seven-point scale (The seven-category ordinal scale) [[5]Huang C. Huang L. Wang Y. et al.6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232https://doi.org/10.1016/S0140-6736(20)32656-8Abstract Full Text Full Text PDF PubMed Scopus (2489) Google Scholar]. From February to April 2022, 996 individuals were diagnosed with SARS-CoV-2 in CHL and PMC (see flowchart in online supplementary material). 276 patients were excluded and 219 patients were included in the study, the participation proportion was 30%: 37 (17%) inpatients (median age 71 years [interquartile range, 62 – 78]; 57% men), and 182 (83%) outpatients (median age 47 years [interquartile range, 34 – 58]; 40% men). The 5-month follow-up visit took place from July to September 2022 and patients who reported not feeling well at 5 months were invited for a follow-up 8 months after infection, which was performed between October and December 2022. Of the total study population, 62 Patients (28%) reported that they did not feel healthy five months after SARS-CoV-2 infection. After analyzing the questionnaires of these patients and according to the WHO definition, it was observed that 50 (23%; 95% CI, 18% to 29%) had a prevalent PCC, 29 (58%) of these were women. Overall, the odds of prevalent PCC increased with higher disease severity (p = 0.047), but no statistical relationship was observed between administered therapies in the acute phase and prevalent PCC (p = 0.843). Among the 50 patients with PCC, the proportion of dyspnea, fatigue, cognitive dysfunction/brain fog and problems with mobility was higher in inpatients than in outpatients. The difference was not significant in the other dimensions like personal care, usual activity, pain discomfort and anxiety or depression. In patients with comorbidities, we observed a higher percentage with PCC of 40% (20/30 patients) than without PCC with 30% (50/119 patients). With respect to vaccination status, prevalent PCC was observed in 7 (12%) of 58 unvaccinated patients, 43 (27%) of 161 with one dose, 42 (27%) of 153 with two doses and 21 (24%) of 87 with 3 doses. (Table 1)Table 1Prevalence and characteristics of post COVID-19 condition five months after SARS-CoV-2 infection.Post COVID-19 conditionNoYesTotalp-valueMissings / No. (%)No. (%)169 (77.2)50 (22.8)219 (100.0)0 / 219 (0.0)Age, median (IQR), y50.0 (35.5; 62.0)52.0 (38.0; 61.5)51.0 (37.0; 62.0)>0.990 / 219 (0.0)Sex, No. (%)>0.990 / 219 (0.0)Men73 (43.2)21 (42.0)94 (42.9)Women96 (56.8)29 (58.0)125 (57.1)Participants, No. (%)0.830 / 219 (0.0)Outpatients141 (83.4)41 (82.0)182 (83.1)Inpatients28 (16.6)9 (18.0)37 (16.9)Body mass index (BMI), median (IQR)24.7 (22.1; 27.9)24.8 (22.4; 27.3)24.7 (22.2; 27.8)0.931 / 219 (0.5)The seven-category ordinal scale, No. (%)0.010 / 219 (0.0)1 No hospitalization with resumption of normal activities95 (56.2)17 (34.0)112 (51.1)1 No hospitalization, but unable to resume normal activities46 (27.2)24 (48.0)70 (32.0)1 Hospitalization, but no need for supplemental oxygen14 (8.3)4 (8.0)18 (8.2)1 Hospitalization, with need for supplemental oxygen13 (7.7)3 (6.0)16 (7.3)1 Hospitalization requiring HFNC or non-IMIV, or both1 (0.6)1 (2.0)2 (0.9)1 Hospital admission requiring ECMO or IMV, or both0 (0.0)1 (2.0)1 (0.5)Comorbidities, No. (%)0.170 / 219 (0.0)No119 (70.4)30 (60.0)149 (68.0)Yes50 (29.6)20 (40.0)70 (32.0)Comorbidities, No. (%)Hypertension25 (50.0)13 (65.0)38 (54.3)0.30Coronary heart disease14 (28.0)4 (20.0)18(25.7)0.56Diabetes7 (14.0)3 (15.0)10 (14.3)>0.99Asthma14 (28.0)4 (20.0)18(25.7)0.56Chronic obstructive lung disease2 (4.0)4 (20.0)6 (8.6)0.05Chronic kidney disease11 (22.0)1 (5.0)12 (17.1)0.16COVID-19 vaccination status, No. (%)Vaccination first dose0.030/219 (0.0)No51 (30.2)7 (14.0)58 (26.5)Yes118 (69.8)43 (86.0)161 (73.5)Vaccination second dose0.680/161 (0.0)No7 (5.9)1 (2.3)8 (5.0)Yes111 (94.1)42 (97.7)153 (95.0)Vaccination third dose0.510/153 (0.0)No45 (40.5)21(50.0)66 (41.2)Yes66 (59.5)21 (50.0)87 (56.9)Laboratory test, No. (%)Leucocytes,G/l0.2811 / 219 (5.0)< 419 (11.9)2 (4.1)21 (10.1)4 – 10131 (82.4)45 (91.8)176 (84.6)> 109 (5.7)2 (4.1)11 (5.3)Lymphocytes,% (G/l)0.0713 / 219 (5.9)< 25 (< 1.0)87 (55.4)18 (36.7)105 (51.0)25 – 40 (1.0 – 3.0)60 (38.2)27 (55.1)87 (42.2)> 40 (>3.0)10 (6.4)4 (8.2)14 (6.8)C reactive protein, mg/l0.5511 / 219 (5.0)< 552 (32.7)12 (24.5)64 (30.8)5 – 2062 (39.0)22 (44.9)84 (40.4)> 2045 (28.3)15 (30.6)60 (28.8)Medication, No. (%)0.400 / 219 (0.0)No64 (37.9)15 (30.0)79 (36.1)Yes105 (62.1)35 (70.0)140 (63.9)Paracetamol0.520 / 219 (0.0)No88 (52.1)23 (46.0)111 (50.7)Yes81 (47.9)27 (54.0)108 (49.3)Metamizol0.270 / 219 (0.0)No146 (86.4)40 (80.0)186 (84.9)Yes23 (13.6)10 (20.0)33 (15.1)NSAR0.840 / 219 (0.0)No135 (79.9)41 (82.0)176 (80.4)Yes34 (20.1)9 (18.0)43 (19.6)Corticosteroids0.550 / 219 (0.0)No157 (92.9)45 (90.0)202 (92.2)Yes12 (7.1)5 (10.0)17 (7.8)Monoclonal antibodiesaMonoclonal antibodies: Tocilizumab or Casirivimab/Imdevimab.0.66182 / 219 (83.1)No22 (78.6)6 (66.7)28 (75.7)Yes6 (21.4)3 (33.3)9 (24.3)AntiviralsbAntivirals: Remdesivir.>0.99182 / 219 (83.1)No27 (96.4)9 (100)36 (97.3)Yes1 (3.6)0 (0.0)1 (2.7)Abbreviations: IQR, interquartile range; HFNC, high-flow nasal cannula; non-IMV, non-invasive mechanical ventilation; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; NSAR, non-steroidal anti-inflammatory drugs.a Monoclonal antibodies: Tocilizumab or Casirivimab/Imdevimab.b Antivirals: Remdesivir. Open table in a new tab Abbreviations: IQR, interquartile range; HFNC, high-flow nasal cannula; non-IMV, non-invasive mechanical ventilation; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; NSAR, non-steroidal anti-inflammatory drugs. Eight months after SARS-CoV-2 infection, patients who indicated that they did not feel healthy at the first visit were invited to a second survey. Of these, 23 (46%) patients responded and all of them reported not having recovered. This indicates that at least 11% (23 of 219) of the total study population still suffers from PCC (see online supplement). Similar results were observed in a prospective cohort study performed in Zurich in inpatients and outpatients, where the prevalence of PCC after 6 months SARS-CoV-2 infection was 26% [[6]Menges D. Ballouz T. Anagnostopoulos A. et al.Burden of post-COVID-19 syndrome and implications for healthcare service planning: a population-based cohort study.PLOS One. 2021; 6e0254523https://doi.org/10.1371/journal.pone.0254523Crossref Scopus (128) Google Scholar]. Furthermore, in an umbrella review published in November 2022, PCC was observed in 12% (CI 4.5% to 41%) of outpatients, 20% in mixed studies (hospitalized and not) with an estimated prevalence between 7- 38% in inpatients [[8]V. Nittas and M. Puhan Long COVID: evolving definitions, burden of disease and socio-economic consequences - umbrella review. SSPH+ Swiss School of Public Health. 2021. 20210607_Literaturrecherchen_Long_Covid_EN.pdf. Accessed February 28, 2023.Google Scholar]. Although there are many other studies where the prevalence of PCC was higher than in ours, the differences might be because the follow-up was performed 3–4 months after infection or due to the restriction to only hospitalized patients with higher severity of SARS-CoV-2 infection or because they were performed during the first wave of the pandemic with a higher rate of hospitalization and without vaccine [1Fernandez de las Peñas C. Palacios-Ceña D. Gómez-Mayordomo V. et al.Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: a systematic review and meta-analysis.EJIM. 2021; 92 (Volume): P55-P70https://doi.org/10.1016/j.ejim.2021.06.009Abstract Full Text Full Text PDF Scopus (220) Google Scholar, 2Goërtz Y. Van Herck M. Delbressine J. et al.Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?.ERJ Open Res. 2020; 6: 00542-02020https://doi.org/10.1183/23120541.00542-2020Crossref PubMed Scopus (453) Google Scholar, 3Xiong Q. Xu M. Li J. et al.Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study.Clin Microbiol Infect. 2021; 27: 89-95https://doi.org/10.1016/j.cmi.2020.09.023Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar, 4Huang L. Yao Q. Gu X. et al.1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.Lancet. 2021; 398: 747-758https://doi.org/10.1016/S0140-6736(21)01755-4Abstract Full Text Full Text PDF PubMed Scopus (494) Google Scholar, 5Huang C. Huang L. Wang Y. et al.6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232https://doi.org/10.1016/S0140-6736(20)32656-8Abstract Full Text Full Text PDF PubMed Scopus (2489) Google Scholar]. This is consistent with our results, since we observed that the prevalence of PCC increases with the higher degree of severity of infection in the acute phase, as was observed in another meta-analysis by Tsampasian et al. (2023) [[9]Tsampasian V. Elghazaly H. Chattopadhyay R. et al.Risk Factors associated With post−COVID-19 condition: a systematic review and meta-analysis.JAMA Inter Med. 2023; https://doi.org/10.1001/jamainternmed.2023.0750Crossref PubMed Scopus (41) Google Scholar]. There was a greater risk of presenting with PCC in women than in men. This is in agreement with similar results observed in previous studies [[3]Xiong Q. Xu M. Li J. et al.Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study.Clin Microbiol Infect. 2021; 27: 89-95https://doi.org/10.1016/j.cmi.2020.09.023Abstract Full Text Full Text PDF PubMed Scopus (372) Google Scholar,[5]Huang C. Huang L. Wang Y. et al.6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232https://doi.org/10.1016/S0140-6736(20)32656-8Abstract Full Text Full Text PDF PubMed Scopus (2489) Google Scholar,[6]Menges D. Ballouz T. Anagnostopoulos A. et al.Burden of post-COVID-19 syndrome and implications for healthcare service planning: a population-based cohort study.PLOS One. 2021; 6e0254523https://doi.org/10.1371/journal.pone.0254523Crossref Scopus (128) Google Scholar,[9]Tsampasian V. Elghazaly H. Chattopadhyay R. et al.Risk Factors associated With post−COVID-19 condition: a systematic review and meta-analysis.JAMA Inter Med. 2023; https://doi.org/10.1001/jamainternmed.2023.0750Crossref PubMed Scopus (41) Google Scholar]. The presence of comorbidities was associated with a higher prevalence of PCC as indicated by other studies [[9]Tsampasian V. Elghazaly H. Chattopadhyay R. et al.Risk Factors associated With post−COVID-19 condition: a systematic review and meta-analysis.JAMA Inter Med. 2023; https://doi.org/10.1001/jamainternmed.2023.0750Crossref PubMed Scopus (41) Google Scholar]. No protective effect of the first and second doses of vaccination was observed, although less PCC was observed with three doses and even lower prevalence in unvaccinated patients. Studies indicate that the number of vaccinations is associated with low prevalence of PCC [[9]Tsampasian V. Elghazaly H. Chattopadhyay R. et al.Risk Factors associated With post−COVID-19 condition: a systematic review and meta-analysis.JAMA Inter Med. 2023; https://doi.org/10.1001/jamainternmed.2023.0750Crossref PubMed Scopus (41) Google Scholar,[10]Azzolini E. Levi R. Sarti R. et al.Association between BNT162b2 vaccination and long COVID after infections not requiring hospitalization in health care workers.JAMA. 2022; 328: 676-678https://doi.org/10.1001/jama.2022.11691Crossref PubMed Scopus (81) Google Scholar]. In our study, the vaccination status may be biased due to retrospective data collection. This study has several limitations. First, our investigation did not include a control group, which precludes comparison of PCC prevalence with similar patients who did not experience COVID-19 (e.g., as part of a case-negative study). Second, most of the study patients were outpatients. Therefore, our findings may not represent the full spectrum of PCC experienced by individuals with a higher degree of severity of illness requiring hospitalization. Third, the prevalence of PCC was possibly overestimated in this cohort because patients with this problem may have been more motivated to participate in the study. Fourth, the sample of inpatients was smaller than initially anticipated in our sample size calculations this leads to a reduction of the precision of the respective PCC estimate. Fifth, this study was performed in central Switzerland. Thus, its results may not be generalizable to other regions or countries with different populations and health care systems. In conclusion, the prevalence of PCC five months after a SARS-CoV-2 infection (Omicron variant) is presented in a quarter of the population, it was higher in women, increased with the severity of infection, and was unrelated to the treatment patients received during the acute phase. Our research indicates that health consequences of COVID-19 extend well beyond the acute infection, even among patients experiencing mild illness, with persistent symptoms such as fatigue, dyspnea, impaired quality of life, and impaired cognition. Long-term research will be necessary to fully understand the long-term impact of this evolving viral pathogen. The study was approved by the responsible ethics committee in Switzerland (Ethik-Kommission Nordwest- und Zentralschweiz; BASEC Nr. 2022–00,922). Written informed consent was obtained from all participants. No funding received.