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Open Access 01-12-2024 | Research

Protective role of vaccination on the development of long COVID: data from a large, multicenter, prospective cohort study

Authors: Francesco Di Gennaro, Nicola Veronese, Francesco Vladimiro Segala, Luisa Frallonardo, Giacomo Guido, Mariangela Cormio, Greta Romita, Angela Parisi, Eliana Marrone, Maria Elena Ciuppa, Anna La Carrubba, Luca Carruba, Anna Licata, Giada Cavallaro, Vittorio Pagliuso, Teresa Maino, Silvia Lollo, Lorenzo Latino, Lidia Tina Solimeo, Antonia Ianniello, Domenico Montalbò, Davide Fiore Bavaro, Maria Luisa Fiorella, Mario Barbagallo, Annalisa Saracino

Published in: BMC Infectious Diseases | Issue 1/2024

Abstract

Background

Long COVID, a highly heterogeneous syndrome affecting millions of people worldwide, is emerging as an urgent public health threat, but data on the predictors of specific clinical manifestations over long follow-up periods are limited. The aim of this study is to investigate the role of viral variants and other predictors in long COVID incidence and clinical manifestations.

Methods

All COVID-19 patients aged > 18 years and hospitalized from March 1 2020 to April 2022 in two Italian University Hospitals were enrolled. Incidence and clinical presentation of long COVID were assessed through structured questionnaires delivered by phone calls. The association between possible risk factors collected during hospitalization and long COVID was reported using an adjusted logistic regression and reported as odds ratios (ORs) with their 95% confidence intervals (CIs).

Results

Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15–24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15–24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Overall, 54% reported long COVID symptomatology between 18 and 24 months. Multivariate analysis suggested that being vaccinated against SARS-CoV-2 was associated with reduced odds of reporting any long COVID symptomatology (OR: 0.34; 95% CI: 0.21–0.58), while infection with the Delta variant was a strong predictor (OR: 9.61, p < 0.0001) for the development of post-COVID conditions characterized by neuropsychiatric symptoms.

Conclusions

In this study long COVID symptoms were still highly prevalent after 18–24 months of follow-up and, when compared to wild-type virus, infection with the Delta variant was associated with a higher risk of developing a neurological post-COVID condition.

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Davis HE, McCorkell L, Vogel JM, Topol EJ, Long COVID. Major findings, mechanisms and recommendations. Nat Rev Microbiol Published Online January. 2023;13. https://doi.org/10.1038/s41579-022-00846-2.

Di Gennaro F, Belati A, Tulone O, et al. Incidence of long COVID-19 in people with previous SARS-Cov2 infection: a systematic review and meta-analysis of 120,970 patients. Intern Emerg Med. Published Online November. 2022;30:1–9. https://doi.org/10.1007/s11739-022-03164-w.CrossRef

Floridia. et Al. Front. Public Health, 19 August 2022 Sec. Infectious Diseases: Epidemiology and Prevention Volume 10–2022 | https://doi.org/10.3389/fpubh.2022.975527

Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583–90. https://doi.org/10.1038/s41591-022-01689-3.CrossRefPubMedPubMedCentral

Rebeiro PF, Jenkins CA, Bian A, et al. Risk of Incident Diabetes Mellitus, Weight Gain, and their relationships with Integrase inhibitor–based initial antiretroviral therapy among persons with Human Immunodeficiency Virus in the United States and Canada. Clin Infect Dis. 2021;73(7):e2234–42. https://doi.org/10.1093/cid/ciaa1403.CrossRefPubMed

Larsen NW, Stiles LE, Shaik R et al. Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults. Front Neurol. 2022;13. Accessed January 26, 2023. https://www.frontiersin.org/articles/https://doi.org/10.3389/fneur.2022.1012668

Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022;399(10343):2263–4. https://doi.org/10.1016/S0140-6736(22)00941-2.CrossRefPubMedPubMedCentral

COVID-19 Map. Johns Hopkins Coronavirus Resource Center. Accessed January 14. 2023. https://coronavirus.jhu.edu/map.html

Daily new estimated infections of COVID-19. Our World in Data. Accessed January 26. 2023. https://ourworldindata.org/grapher/daily-new-estimated-infections-of-covid-19

10.

Wang H, Paulson KR, Pease SA, et al. Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21. Lancet. 2022;0(0). https://doi.org/10.1016/S0140-6736(21)02796-3.

11.

Cutler DM. The costs of long COVID. JAMA Health Forum. 2022;3(5):e221809–221809. https://doi.org/10.1001/jamahealthforum.2022.1809.CrossRefPubMed

12.

Arthur JM, Forrest JC, Boehme KW, et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLoS ONE. 2021;16(9):e0257016. https://doi.org/10.1371/journal.pone.0257016.CrossRefPubMedPubMedCentral

13.

Zubchenko S, Kril I, Nadizhko O, Matsyura O, Chopyak V. Herpesvirus infections and post-COVID-19 manifestations: a pilot observational study. Rheumatol Int. 2022;42(9):1523–30. https://doi.org/10.1007/s00296-022-05146-9.CrossRefPubMedPubMedCentral

14.

Nunes JM, Kruger A, Proal A, Kell DB, Pretorius E. The occurrence of Hyperactivated platelets and fibrinaloid microclots in myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Pharmaceuticals. 2022;15(8):931. https://doi.org/10.3390/ph15080931.CrossRefPubMedPubMedCentral

15.

Recommendations |. COVID-19 rapid guideline: managing the long-term effects of COVID-19 | Guidance | NICE. Published December 18, 2020. Accessed January 27, 2023. https://www.nice.org.uk/guidance/ng188/chapter/Recommendations

16.

Veronese N, Bonica R, Cotugno S, et al. Interventions for improving long COVID-19 symptomatology: a systematic review. Viruses. 2022;14(9):1863. https://doi.org/10.3390/v14091863.CrossRefPubMedPubMedCentral

17.

A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021. Accessed January 26. 2023. https://www.who.int/publications-detail-redirect/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1

18.

Al-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med Published Online May 25, 2022:1–7. https://doi.org/10.1038/s41591-022-01840-0

19.

Bull-Otterson L, Baca S, Saydah S, et al. Post–COVID conditions among adult COVID-19 survivors aged 18–64 and ≥ 65 years — United States, March 2020–November 2021. MMWR Morb Mortal Wkly Rep. 2022;71(21):713–7. https://doi.org/10.15585/mmwr.mm7121e1.CrossRefPubMedCentral

20.

Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of Post-coronavirus Disease 2019 (COVID-19) Condition or Long COVID: a Meta-analysis and systematic review. J Infect Dis. 2022;226(9):1593–607. https://doi.org/10.1093/infdis/jiac136.CrossRefPubMed

21.

Han Q, Zheng B, Daines L, Sheikh A. Long-term sequelae of COVID-19: a systematic review and Meta-analysis of one-year Follow-Up studies on Post-COVID symptoms. Pathog Basel Switz. 2022;11(2):269. https://doi.org/10.3390/pathogens11020269.CrossRef

22.

Self-reported long COVID after infection with the Omicron variant in the UK - Office for National Statistics. Accessed January 27. 2023. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/selfreportedlongcovidafterinfectionwiththeomicronvariant/6may2022

23.

Group TC. COMEPA (COVID-19 Medicina Policlinico Palermo): a study in hospitalized patients. Geriatr Care. 2021;7(3). https://doi.org/10.4081/gc.2021.9895.

24.

EpiCentro. Monitoraggio delle varianti del virus SARS-CoV-2 di interesse in sanità pubblica in Italia. Accessed January 28. 2023. https://www.epicentro.iss.it/coronavirus/sars-cov-2-monitoraggio-varianti-rapporti-periodici

25.

Methods for the detection and characterisation of SARS-CoV-2 variants - second update. European Centre for Disease Prevention and Control. Published August 2. 2022. Accessed January 28, 2023. https://www.ecdc.europa.eu/en/publications-data/methods-detection-and-characterisation-sars-cov-2-variants-second-update

26.

Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Prevalence and determinants of fatigue after COVID-19 in non-hospitalized subjects: a Population-based study. Int J Environ Res Public Health. 2021;18(4):2030. https://doi.org/10.3390/ijerph18042030.CrossRefPubMedPubMedCentral

27.

Natarajan A, Shetty A, Delanerolle G et al. A systematic review and meta-analysis of long COVID symptoms. Published online March 9, 2022:2022.03.08.22272091. https://doi.org/10.1101/2022.03.08.22272091

28.

Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The post-traumatic stress disorder checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J Trauma Stress. 2015;28(6):489–98. https://doi.org/10.1002/jts.22059.CrossRefPubMed

29.

Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the hospital anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52(2):69–77. https://doi.org/10.1016/s0022-3999(01)00296-3.CrossRefPubMed

30.

Ceban F, Ling S, Lui LMW, et al. Fatigue and cognitive impairment in Post-COVID-19 syndrome: a systematic review and meta-analysis. Brain Behav Immun. 2022;101:93–135. https://doi.org/10.1016/j.bbi.2021.12.020.CrossRefPubMed

31.

Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021;27(4):626–31. https://doi.org/10.1038/s41591-021-01292-y.CrossRefPubMedPubMedCentral

32.

Fernández-de-Las-Peñas C, Martín-Guerrero JD, Pellicer-Valero ÓJ, et al. Female sex is a risk factor Associated with Long-Term Post-COVID related-symptoms but not with COVID-19 symptoms: the LONG-COVID-EXP-CM Multicenter Study. J Clin Med. 2022;11(2):413. https://doi.org/10.3390/jcm11020413.CrossRefPubMedPubMedCentral

33.

Notarte KI, Catahay JA, Velasco JV, et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: a systematic review. eClinicalMedicine. 2022;53. https://doi.org/10.1016/j.eclinm.2022.101624.

34.

Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399(10328):924–44. https://doi.org/10.1016/S0140-6736(22)00152-0.CrossRefPubMedPubMedCentral

35.

WHO COVID-19. dashboard https://covid19.who.int/region/euro/country/fr

36.

Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet. 2021;397(10293):2461–2. https://doi.org/10.1016/S0140-6736(21)01358-1.CrossRefPubMedPubMedCentral

37.

Dinapoli L, Camardese G. A Lion sleeping next to me: preliminary considerations on the psychological consequences of surviving COVID-19 Journal of the Academy of Consultation-Liaison PsychiatryVolume 62, issue 3, May–June 2021, Pages 372–4 https://doi.org/10.1016/j.jaclp.2020.12.003

38.

Cecchetti G, Agosta F, Canu E, Basaia S, Barbieri A, Cardamone R, Bernasconi MP, Castelnovo V, Cividini C, Cursi M, Vabanesi M, Impellizzeri M, Lazzarin SM, Fanelli GF, Minicucci F, Giacalone G, Falini A, Falautano M, Rovere-Querini P, Roveri L, Filippi M. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study. J Neurol. 2022;269(7):3400–12. Epub 2022 Mar 6. PMID: 35249144; PMCID: PMC8898558.CrossRefPubMedPubMedCentral

39.

Savino R, Polito AN, Arcidiacono G, Poliseno M, Lo Caputo S. Neuropsychiatric disorders in Pediatric Long COVID-19: a Case Series. Brain Sci. 2022;12:514. https://doi.org/10.3390/brainsci12050514.CrossRefPubMedPubMedCentral

40.

Lianlian Bian Q, Gao F, Gao Q, Wang Q, He X, Wu Q, Mao M, Xu, Zhenglun Liang. Impact of the Delta variant on vaccine efficacy and response strategies. Expert Rev Vaccines. 2021;20(10):1201–9. https://doi.org/10.1080/14760584.2021.1976153.CrossRefPubMed

41.

Ottawa Hospital Research Institute. Accessed January 15. 2023. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

42.

SARS-CoV-2 variants in analyzed sequences. Our World in Data. Accessed August 8. 2022. https://ourworldindata.org/grapher/covid-variants-area

43.

Arjun MC, Singh AK, Roy P, et al. Long COVID following Omicron wave in Eastern India-A cspective cohort study. J Med Virol Published Online Oct. 2022;12. https://doi.org/10.1002/jmv.282.

44.

Mouliou DS, Dardiotis E. Current evidence in SARS-CoV-2 mRNA vaccines and post-vaccination adverse reports: knowns and unknowns. Diagnostics. 2022;12:1555. https://doi.org/10.3390/diagnostics12071555.CrossRefPubMedPubMedCentral

45.

Mouliou DS, Pantazopoulos I, Gourgoulianis KI, Medical/Surgical. Cloth and FFP/(K)N95 masks: unmasking preference, SARS-CoV-2 Transmissibility and Respiratory Side effects. J Pers Med. 2022;12:325. https://doi.org/10.3390/jpm12030325.CrossRefPubMedPubMedCentral

46.

Mouliou DS, Gourgoulianis KI. False-positive and false-negative COVID-19 cases: respiratory prevention and management strategies, vaccination, and further perspectives. Expert Rev Respir Med. 2021;15(8):993–1002. https://doi.org/10.1080/17476348.2021.1917389.CrossRefPubMed

47.

Mouliou DS, Kotsiou OS, Gourgoulianis KI. Estimates of COVID-19 risk factors among Social Strata and predictors for a vulnerability to the infection. Int J Environ Res Public Health. 2021;18:8701. https://doi.org/10.3390/ijerph18168701.CrossRefPubMedPubMedCentral

Title: Protective role of vaccination on the development of long COVID: data from a large, multicenter, prospective cohort study
Authors: Francesco Di Gennaro
Nicola Veronese
Francesco Vladimiro Segala
Luisa Frallonardo
Giacomo Guido
Mariangela Cormio
Greta Romita
Angela Parisi
Eliana Marrone
Maria Elena Ciuppa
Anna La Carrubba
Luca Carruba
Anna Licata
Giada Cavallaro
Vittorio Pagliuso
Teresa Maino
Silvia Lollo
Lorenzo Latino
Lidia Tina Solimeo
Antonia Ianniello
Domenico Montalbò
Davide Fiore Bavaro
Maria Luisa Fiorella
Mario Barbagallo
Annalisa Saracino
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2024
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-024-10226-1

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Abstract

Background

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Conclusions

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