COVID-19 and Parkinson’s disease: a single-centered study and Mendelian randomization study

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Methods A single-center survey was performed among patients with PD through a questionnaire from December 7, 2022, to March 10, 2023. Logistic regression was performed to analyze the infection-related risk factors. Then, a bidirectional two-sample Mendelian randomization was utilized to investigate the association between COVID-19 and PD. Results In cross-sectional analysis, the COVID-19 infection rate of PD was 65.7%. Forty-eight (35.3%) patients with PD experienced worsening of motor symptoms. Long PD course (OR: 3.296, P = 0.047) and duration of the last dose of COVID-19 vaccine (OR: 4.967, P = 0.034) were the infection-related risk factors. The MR analysis results supported that PD causally increases the risk of COVID-19 susceptibility (β = 0.081, OR = 1.084, P = 0.006). However, MR analysis showed that PD did not increases the risk of COVID-19 severity and hospitalization. In addition, no causal linkage of COVID-19 on PD was observed. Conclusion Our findings suggest that COVID-19 infection leads to worsened PD motor symptoms. Long PD course is the infection-related risk factors, and PD causally increases the risk of COVID-19 susceptibility. However, we found no evidence that COVID-19 contributes to PD. Parkinson’s disease COVID-19 COVID-19 susceptibility motor symptoms Mendelian randomization Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began spreading in November 2019 and remains a global concern [ 1 ] . The government of many countries worked to reduce the spread of COVID-19 by implementing various policy interventions before the widespread spread of omicron variants. However, the rapid spread of omicron made it become the dominant variety in a short time [ 2 ] . One study showed that the omicron variant showed potent immune-escape properties even in recently infected individuals, and that the variant could cause super-spread events [ 2 ] . After nearly 3 years of implementing a dynamic zero-coronavirus policy, China announced “10 new measures” to adjust the COVID-19 prevention and control strategies on December 7, 2022. A study showed that over 70% infections were recorded 3 weeks after the release of COVID-19 restrictions in Macao [ 3 ] . Another study showed that the omicron epidemic began in Beijing in November 2022, reaching an infection rate of > 70% about a week earlier than in Macao [ 4 ] . Parkinson’s disease (PD) is a common neurodegenerative disease with rigidity, bradykinesia, rest tremor, and postural instability [ 5 ] . A survey report showed that the prevalence rate in China was 1.37%, with an estimated total of 3.6 million PD cases over 60 years [ 6 ] . The current COVID-19 pandemic caused widespread attention among neurologists and patients with PD. A previous study has observed worsened motor symptoms and disease progression during the COVID-19 pandemic [ 7 ] . Few cases of parkinsonism have been reported after COVID-19 infection [ 8 ] . In addition, studies have shown that the mortality rate of COVID-19 in patients with PD was higher than that in the general elderly population [ 9 ] . Hence, the relationship between COVID-19 and PD is complex, and little is known about the causal relationship of COVID-19 and PD. Comprehending the causal correlation between PD and COVID-19 is vital in order to devise efficacious interventions and enhance patient outcomes. People with PD are recommended to receive the COVID-19 vaccine, unless they have specific contraindications [ 10 ] . A study shown that the COVID-19 vaccination rate in patients with PD was low [ 11 ] . However, little is known about the COVID-19 vaccination status and protective effect on these patients. The present study aimed to determine the effect on patients with PD after the release of COVID-19 restrictions and analyze the infection-related risk factors of these patients and the protective effect of COVID-19 vaccine on PD via a single-centered study. Mendelian randomization (MR) is an effective genetic method to study the causal relationship of certain exposures to disease. Hence, we performed a bidirectional two-sample MR study to explore the causal correlation between COVID-19 and PD. 2. Methods 2.1 Cross-sectional study design Questionnaire copies were collected from patients diagnosed with PD, who visited the outpatient and inpatient departments at the Affiliated Hospital of Guizhou Medical University between December 7, 2022, and March 10, 2023. The inclusion criteria were as follows: (1) patients diagnosed with PD according to the MDS clinical diagnosis criteria and (2) patients who did not change their medication 1 week before the December 7, 2022. The exclusion criteria included intellectual disability and unwillingness to participate in the study. The questionnaire included general information (age and sex), COVID-19 vaccination history (duration and type of last vaccination), clinical data on PD (motor and non-motor symptoms), clinical features of COVID-19, and change in PD symptoms after COVID-19 infection. Questionnaires were completed by the patients with PD or with the help of their family members if they had difficulty in reading or writing. The COVID-19 infection in this study was defined as having a positive COVID-19 nucleic acid or antigen result from December 7, 2022, to January 7, 2023. However, COVID-19 infection did not include symptomatic patients with negative laboratory results in this study. 2.2 Two-sample MR study 2.2.1 Data sources We used available data on COVID-19 phenotypes from the COVID-19 Host Genetics Project (RELEASE 5) based on a European population [ 12 ] . The comprehensive dataset include COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 severity. The susceptibility phenotype compared COVID-19 patients with controls without COVID-19 (Ncase = 38,984, Ncontrol = 1,644,784). The hospitalization phenotype compared hospitalized COVID-19 patients with a control group that was not hospitalized for COVID-19 or infected with COVID-19 (Ncase = 9,986, Ncontrol = 1,877,672). The severity phenotype compared hospitalized COVID-19 patients who died or required respiratory support with a control group without severe COVID-19 or free of COVID-19 (Ncase = 5,101, Ncontrol = 1,383,241). The PD dataset analyzed in this study was derived from a large GWAS meta-analysis published by International Parkinson's Disease Genomics Consortium [ 13 ] . The study was also based on a European population of 482,730 participants, including 33,674 cases of PD and 449,056 healthy controls. 2.2.2 Selection of instrumental variables Instrumental variables (single nucleotide polymorphisms, SNPs) were selected such that they are strongly correlated with exposure (P < 5 × 10 − 8 ) and pruned by linkage disequilibrium (r 2 < 0.001 and within 10,000 kb from the index variant). The underlying outlier SNPs were removed by MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) [ 14 ] . We examined whether the obtained instrumental SNPs were associated with the outcomes and the potential confounders by PhenoScanner ( http://www.phenoscanner.medschl.cam.ac.uk/ ). The F-statistics of these SNPs were used to evaluates the strength of an instrumental variable. The R 2 value for each SNP was determined employing the formula: R 2 = 2 × EAF × (1-EAF) × β 2[ 15 ] . 2.2.3 MR analysis and sensitivity analysis The random-effects inverse-variance weighted (IVW) was used to evaluate the causality. MR-Egger, weighted median, simple mode, and weighted mode methods were also employed to complement the IVW. The Cochran’s Q test of the IVW approach and leave-one-out analysis were used to investigate the degree of heterogeneity. The MR-Egger intercept test and MR-PRESSO global test were used to evaluate the horizontal pleiotropy. 2.3 Statistical analysis Statistical analyses were performed using SPSS statistical software for Windows version 24.0 (SPSS, Chicago, IL, USA) for cross-sectional study. Independent sample t-test was used for the analyses of general data and clinical basic information, which were continuous variables and had normal distributions. Chi-square test and Fisher exact test were used to compare categorical variables. Logistic regression was performed to analyze the infection-related risk factors. P < 0.05 indicated statistical significance. For MR analysis, we performed all the analyses in R (version 4.3.0) using the TwoSample MR [ 16 ] and MR-PRESSO [ 14 ] packages. P < 0.05 was considered as nominally significant and P < 0.05/6 (0.008) was considered as significant after correcting by Bonferroni measures. 3. Results 3.1 Cross-sectional study 3.1.1 Characteristics of patients with PD In the period of study, a total of 258 patients with PD were admitted to the study hospital. A total of 209 patients met the inclusion criteria, and they were asked to participate in the study. Two patients were excluded because of loss of important messages. Finally, 207 PD patients participated in this study. The baseline patients and clinical features of PD and COVID-19 are shown in Table 1 . Table 1 The basic characteristics of PD patients in the survey COVID-19 infected group (N = 136) Uninfected group (N = 71) P values Age (mean ± SD) 67.33 ± 9.71 68.58 ± 9.75 0.439 Gender 0.917 Male 70 (51.5) 36 (50.7) Female 66 (48.5) 35 (49.23) Course of PD M (P25, P75) (years ) 4.5 (2, 8) 4 (2, 6) 0.262 Motor symptoms 0.984 Rest tremor 107 (78.7) 56 (78.9) Bradykinesia 136 (100.0) 71 (100.0) Rigidity 122 (89.7) 68 (95.8) Posture instability 88 (64.7) 49 (69.0) Non-motor symptoms 0.979 Hyposmia 72 (52.9) 39 (54.9) Sleep disorders 48 (35.3) 24 (33.8) Depression and anxiety 35 (25.7) 17 (23.9) Constipation 51 (37.5) 26 (36.6) Cognitive disorder 33 (24.3) 14 (19.7) Vaccination 1.000 With vaccination 109 (80.1) 57 (80.3) Without vaccination 27 (19.9) 14 (19.7) A total of 106 men and 101 women participated in this study. Their mean age was 67.76 (SD ± 9.71, range: 39–88) years, and the mean PD duration was 5.24 years. A total of 136 patients with PD were infected with COVID-19, with an infection rate of 65.7%. The mean ages of the patients infected or uninfected with COVID-19 were 67.33 (SD ± 9.71, range: 39–84) and 68.58 (SD ± 9.75, range: 46–88) years, respectively (P = 0.439). The mean courses of the PD patients infected or uninfected with COVID-19 were 5.52 and 4.68 years, respectively ( P = 0.262). The results showed no significant differences between the COVID-19-infected and uninfected groups in terms of gender ( P = 0.917), vaccination status ( P = 1.000), motor symptoms ( P = 0.984), and non-motor symptoms ( P = 0.979). 3.1.2 Clinical features of COVID-19 in patients with PD In this study, 70 males and 66 females were infected with COVID-19. Their COVID-19 symptoms included cough ( N = 94), fever ( N = 84), fatigue ( N = 69), dry or sore throat ( N = 63), stuffy or runny nose ( N = 60), myodynia ( N = 48), dizziness and headache ( N = 44), digestive tract symptoms ( N = 44), hyposmia ( N = 20), difficulty breathing ( N = 17), chest pain ( N = 8), hypoxemia ( N = 3), and rash ( N = 2) (Fig. 1 ). Among them, 69 (50.74%), 40 (29.41%), and 27 (19.85%) had symptoms of COVID-19 for 1, 2, and over 2 weeks, respectively. Forty-eight patients experienced worsening of motor symptoms, with an exacerbation rate of 35.3%. These patients required adjustments to their PD medications. The worsened motor symptoms included rest tremor ( N = 14), bradykinesia ( N = 16), rigidity ( N = 12), posture instability ( N = 10), wearing-off ( N = 8), weakness ( N = 8), and dyskinesia ( N = 1) (Fig. 2 ). Sixteen (11.8%) patients with PD were hospitalized for COVID-19 infection, and one died due to respiratory failure. More than half of the hospitalized patients were hospitalized for a duration of 1 week. 3.1.3 Infection-related risk factors and protective effect of COVID-19 vaccine A total of 166 patients with PD were vaccinated against COVID-19, with a vaccination rate of 80.2%. Age, sex, course of PD, and duration and type of the last dose of vaccination were set as independent variables in the logistic regression to analyze the infection-related risk factors of these patients. The results showed that long PD course (OR = 3.296, 95% CI: 1.018–10.673) and duration of the last dose of COVID-19 vaccine (OR = 4.967, 95% CI: 1.125–21.938) were the risk factors (Table 2 ). Those patients who were vaccinated within 3 months had a lower infection rate than those vaccinated after more than 3 months (50% vs. 67.3%). This result indicated that COVID-19 vaccine has a short-term protective effect on patients with PD. Table 2 Multivariate logistic regression analysis for screening the COVID-19 infection predictors in PD patients Index OR 95% CI P value Age 0.979 0.936–1.024 0.358 Gender (Ref: Male) Female 1.601 0.775–3.310 0.204 Course of PD (Ref: 10 year 1.183 2.393 3.296 0.484–2.892 0.803–7.133 1.018–10.673 0.712 0.117 0.047* Duration of last COVID-19 vaccination (Ref: 12 month 0.538 2.122 4.967 0.128–2.256 0.560–8.041 1.125–21.938 0.397 0.269 0.034* Vaccination type (Ref: Vero) Cho Adenovirus Unkown 1.393 1.543 1.530 0.567–3.420 0.309–7.707 0.254–9.210 0.469 0.597 0.642 Ref: Reference; * indicate that the P Value is significant; Vero: inactivated COVID-19 vaccine; Cho: Recombinant COVID-19 vaccine; Adenovirus: Adenovirus vaccine for COVID-19. 3.2 MR analysis results To investigate the causality of COVID-19 on PD, three COVID-19 traits (hospitalization, severity, and susceptibility) were used as exposures, and PD from IEU database acted as outcome, with 4, 8 and 5 instrumental SNPs included for each trait, respectively. While, to investigate the causality of PD on COVID-19, 8, 21 and 12 instrumental SNPs of PD were selected for genetically predicting COVID-19 hospitalization, severity, and susceptibility after removing palindromes SNPs and potential pleiotropy or outliers. These SNPs were strongly correlated (P < 5E-8) (Supplemental Tables 1 and 2) and independent (R 2 < 0.001) (Supplemental Table 3) for exposure. All F-statistics were greater than 10 (Supplemental Table 3). We found no statistically significant effect of COVID-19 on the increased risk of PD (Hospitalization: OR = 0.979, 95% CI: 0.847–1.044, P = 0.249; Severity: OR = 0.967, 95% CI: 0.905–1.033, P = 0.322; Susceptibility: OR = 1.023, 95% CI: 0.821–1.274, P = 0.840) (Table 3 , Fig. 3 ) . Table 3 Mendelian randomization estimates for associations between COVID-19 and PD Exposure Outcome Beta 95% CI P- IVW P- heterogeneity P- intercept P- PRESSO COVID-19 hospitalization PD −0.062 0.847–1.044 0.249 0.711 0.443 0.738 COVID−19 severity −0.034 0.905–1.033 0.322 0.529 0.374 0.587 COVID−19 susceptibility 0.023 0.821–1.274 0.840 0.965 0.713 0.966 PD COVID-19 hospitalization −0.014 0.837–1.162 0.871 0.035 0.608 0.056 COVID−19 severity 0.058 0.935–1.201 0.362 0.008 0.229 0.008 COVID−19 susceptibility 0.081 1.023–1.149 0.006* 0.048 0.945 0.058 CI: confidence interval; IVW: inverse variance-weighted; P-heterogeneity: P-value for heterogeneity using Cochran’s Q test; P-intercept: P-value for MR-Egger intercept; P-PRESSO: P-value for MR-PRESSO global test. * indicate that the P Value is significant. We also found no statistically significant effect of PD on the increased risk of COVID-19 hospitalization and severity (Hospitalization: OR = 0.987, 95% CI: 0.837–1.162, P = 0.871; Severity: OR = 1.060, 95% CI: 0.935–1.201, P = 0.362). However, the results of the IVW method supported that PD causally increases the risk of COVID-19 susceptibility (OR = 1.084, 95% CI:1.023–1.149, P = 0.006) (Table 3 , Figs. 3 and 4 ). MR-Egger regression analysis was used to test the existence of gene pleiotropy, all of the intercept term was close to zero (P > 0.05). The MR-PRESSO method was also tested and consistent with the MR-Egger regression. Although the P-values of the MR-PRESSO analysis was less than 0.05 in COVID-19 severity, horizontal pleiotropy did not present in the result of MR-PRESSO destruction test (P > 0.05). The Cochran’s statistical test showed no statistically significant heterogeneity effect (Q-value > 0.05) (Table 3 ). Discussion The rapid spread of the COVID-19 pandemic poses particular challenges for the management of patients with PD. The omicron variant shows potent immune-escape properties and could cause super-spread events that patients with PD may need to face with greater challenges. In addition, China announced “10 new measures” to adjust the COVID-19 prevention and control strategies on December 7, 2022, thus requiring further identification of the effect on patients with PD after the release of COVID-19 restrictions in China and providing intervention measures in the future. A study showed that the omicron variant epidemic reached an infection rate of 75% within 3 weeks after the release of COVID-19 restrictions in Macao, China [ 3 ] . Another study showed that the omicron epidemic reached an infection rate of > 70% about a week earlier than in Macao [ 4 ] . The present study also showed the rapid transmission of the omicron variant in patients with PD, with an infection rate of 65.7% within 1 month after the release of COVID-19 restrictions in China. One study showed that more than 60 percent of people infected with COVID-19 developed fever, dry or sore throats, stuffy and runny nose, fatigue, headaches or muscle aches [ 3 ] . Similarly, the most common COVID-19 symptoms of patients with PD in the present study included cough, fever, fatigue, dry or sore throat, stuffy or runny nose, myodynia, dizziness and headache, and digestive tract symptoms. More than half of patients with PD have symptoms of COVID-19 within 1 week. The effect of COVID-19 on patients with PD is complicated. Some studies have shown that COVID-19 infection could worsen the motor and non-motor symptoms of PD or lead to the appearance of some previously unseen symptoms [ 17 , 18 ] . In the present study, more than one-third of patients with PD showed worsened motor symptoms and required adjustment to their PD medications. The most worsened motor symptom was bradykinesia. Meanwhile, a case of probable PD after SARS-CoV-2 infection has been reported [ 8 ] . One study presented two patients with PD treated by subthalamic deep brain stimulation showing rapid worsening symptoms of PD after COVID-19 infection [ 19 ] . Studies showed that the mechanism of COVID-19 infection could worsen the symptoms of PD may be related to that the virus may enter the central nervous system via hematologic pathways or axonal transport with olfactory neuroepithelium and then causing inflammation, immunologically mediated mitochondrial injury, and neuronal oxidative stress [ 8 , 20 ] . Hence, to determine the causality of COVID-19 on PD, we performed two-sample MR analysis. However, we found no statistically significant effect of COVID-19 susceptibility, hospitalization and severity on the increased risk of PD at the genetic level. Vaccination is an effective measure for preventing severe COVID-19 illness and reducing the spread of infection. A study showed that the COVID-19 vaccination rate in patents with PD was 54.0% [ 11 ] . However, the COVID-19 vaccination rate in the present study was 80.2%, higher than that in the previous study [ 11 ] . The results also showed that the duration of the last dose of COVID-19 vaccine was one of the infection-related risk factors of patients with PD. In addition, the COVID-19 vaccine exhibited a short-term protective effect on patients with PD. Hence, these patients are recommended to be vaccinated against COVID-19, unless a specific contraindication exists. A study showed that the incidence of COVID-19 was similar between the PD group and the control group [ 5 ] , indicating that PD is not a risk factor of COVID-19. However, the findings of the present study showed that long PD course was another infection-related risk factor. Hence, we further determine the causality of COVID-19 on PD, and the MR study supported the association between PD and higher risk of COVID-19 susceptibility. However, we found no statistically significant effect of PD on the increased risk of COVID-19 hospitalization and severity at the genetic level. Due to the change in China’s current COVID-19 management policy, understanding the effect on patients with PD after the release of COVID-19 restrictions and taking timely preventive measures in the future, such as administrating booster vaccine and stockpiling antiviral drugs, could reduce the morbidity and mortality of these patients in the future epidemic wave. Conclusions More than one-third of patients with PD showed worsened motor symptoms and required adjustment to their PD medications, and the most worsened motor symptom was bradykinesia. The MR study supported the association between PD and higher risk of COVID-19 susceptibility. In addition, PD patients are encouraged to be receive booster vaccine because of the short-term protective effect of COVID-19 vaccine on them. Declarations Funding This work was supported by the Science and Technology Fund of Guizhou Health Commission (gzwkj2021-024), and the Cultivate Project 2021 of the National Natural Science Foundation of China, Affiliated Hospital of Guizhou Medical University (No. gyfynsfc-2021-14). Ethics approval The protocol for the research project has been approved by a suitably constituted Ethics Committee of the institution within which the work was undertaken and that it conforms to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013). Approval of the research protocol The study was conducted in accordance with the Declaration of Helsinki and was approved by the Affiliated Hospital of Guizhou Medical University. Informed consent All participants provided informed consent before enrollment. Data availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Competing interests The author declares no competing interests. References Atzrodt CL, Maknojia I, McCarthy R, Oldfield TM, Po J, Ta K, et al. A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2. FEBS Journal. 2020;287:3633-50. doi: 10.1111/febs.15375. Scott L, Hsiao NY, Moyo S, Singh L, Tegally H, Dor G, et al. Track Omicron's spread with molecular data. SCIENCE. 2021;374:1454-5. doi: 10.1126/science.abn4543. Liang J, Liu R, He W, Zeng Z, Wang Y, Wang B, et al. 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Additional Declarations No competing interests reported. Supplementary Files file.xlsx Cite Share Download PDF Status: Published Journal Publication published 17 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Apr, 2024 Reviews received at journal 22 Feb, 2024 Reviewers agreed at journal 22 Feb, 2024 Reviewers agreed at journal 20 Feb, 2024 Reviewers invited by journal 20 Feb, 2024 Editor assigned by journal 19 Feb, 2024 Editor invited by journal 04 Feb, 2024 Submission checks completed at journal 04 Feb, 2024 First submitted to journal 18 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3877315","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":271146136,"identity":"7d6bc5ac-d206-43d6-b8da-f2610c5bd86d","order_by":0,"name":"Jianhong Yin","email":"","orcid":"","institution":"Department of Neurology, Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jianhong","middleName":"","lastName":"Yin","suffix":""},{"id":271146137,"identity":"2ab03111-2b4e-4341-80bf-879801da8a1a","order_by":1,"name":"Qian Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYDACZuaDDxIYDoDZQNKGh5+9gYAWdrZkgw8ILWkykj0HCGjh5zGTnMEAV3XYxuCGA34d8s08ZtI8f+7ImfMv3njg547zPAw3GBg/fMzBrYWxma3YmofnmbHljGcFB3vP3OZhnN3ALDlzG24tzMzMG2/zSBxO3HDjjMEB3rbbPMwyB9iYefFoYWNmMJDmMThcD9Jy8G/bOR42iQT8WniYWYwkZyQcTjA432NwmLftAA8PIS0SzKBAPnDYcMMNtoLDsm3JPBI8B5vx+kW+/zAwKv8cljc4f3jzx7dtdvb2x5sPfviIRwuSfQkGUBZjAzHqgYD/gAFhRaNgFIyCUTAiAQAOvlff/50JEwAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Neurology, Affiliated Hospital of Guizhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Qian","middleName":"","lastName":"Zheng","suffix":""},{"id":271146138,"identity":"55e54bba-98b4-4d49-9754-e3897cbabd9c","order_by":2,"name":"Song Zhang","email":"","orcid":"","institution":"Department of neurosurgery, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Song","middleName":"","lastName":"Zhang","suffix":""},{"id":271146139,"identity":"5c5aa012-b11e-4cca-91a7-b671fe82745e","order_by":3,"name":"Zhanhui Feng","email":"","orcid":"","institution":"Department of Neurology, Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhanhui","middleName":"","lastName":"Feng","suffix":""}],"badges":[],"createdAt":"2024-01-19 01:59:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3877315/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3877315/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-66197-5","type":"published","date":"2024-07-17T16:04:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50752498,"identity":"df29afa6-f484-4807-a6a5-af8a1ab3e8f8","added_by":"auto","created_at":"2024-02-06 17:48:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66284,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical manifestations of PD patients after COVID-19 infection.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/05f96fc852f9993bd0376325.png"},{"id":50752832,"identity":"71d5183f-ef2d-4cd6-aa89-0f4833f26e8f","added_by":"auto","created_at":"2024-02-06 17:56:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46702,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eManifestations of worsened PD motor symptoms after COVID-19 infection.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/decde053f583e5f4070e9b29.png"},{"id":50752499,"identity":"c6aed2a4-e98a-4226-9445-3724ad2e37b2","added_by":"auto","created_at":"2024-02-06 17:48:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":565809,"visible":true,"origin":"","legend":"\u003cp\u003eMendelian randomization (MR) estimates for the causality of the association between COVID-19 and PD. Panels(\u003cstrong\u003eA-C\u003c/strong\u003e) respectively indicate the causal estimates of COVID-19 hospitalization, severity, and susceptibility on PD. Panels (D-F) respectively indicate the causal estimates of PD on COVID-19 hospitalization, \u0026nbsp;severity, and susceptibility.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/c2e93a5beb57aecc9481b679.png"},{"id":50752495,"identity":"785b5173-5540-4bd7-8227-b5ff3014876b","added_by":"auto","created_at":"2024-02-06 17:48:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":77466,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of the MR estimate for the effect of PD on the risk of COVID-19 susceptibility.\u003c/p\u003e","description":"","filename":"Figure4PD.png","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/59537b57c1272a460c04652c.png"},{"id":61594071,"identity":"1776d47f-644a-4099-8020-e9fab6990c80","added_by":"auto","created_at":"2024-08-01 16:30:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1382942,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/ca92ad41-1c96-4e12-b042-269e55e7cbd6.pdf"},{"id":50752497,"identity":"a8298599-66ac-4197-a056-2f971a4c9821","added_by":"auto","created_at":"2024-02-06 17:48:47","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18784,"visible":true,"origin":"","legend":"","description":"","filename":"file.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-3877315/v1/e12ee3661207e6888a9ea8d8.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"COVID-19 and Parkinson’s disease: a single-centered study and Mendelian randomization study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCoronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began spreading in November 2019 and remains a global concern\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The government of many countries worked to reduce the spread of COVID-19 by implementing various policy interventions before the widespread spread of omicron variants. However, the rapid spread of omicron made it become the dominant variety in a short time\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. One study showed that the omicron variant showed potent immune-escape properties even in recently infected individuals, and that the variant could cause super-spread events\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. After nearly 3 years of implementing a dynamic zero-coronavirus policy, China announced \u0026ldquo;10 new measures\u0026rdquo; to adjust the COVID-19 prevention and control strategies on December 7, 2022. A study showed that over 70% infections were recorded 3 weeks after the release of COVID-19 restrictions in Macao\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Another study showed that the omicron epidemic began in Beijing in November 2022, reaching an infection rate of \u0026gt;\u0026thinsp;70% about a week earlier than in Macao\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eParkinson\u0026rsquo;s disease (PD) is a common neurodegenerative disease with rigidity, bradykinesia, rest tremor, and postural instability\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. A survey report showed that the prevalence rate in China was 1.37%, with an estimated total of 3.6\u0026nbsp;million PD cases over 60 years\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The current COVID-19 pandemic caused widespread attention among neurologists and patients with PD. A previous study has observed worsened motor symptoms and disease progression during the COVID-19 pandemic\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Few cases of parkinsonism have been reported after COVID-19 infection\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. In addition, studies have shown that the mortality rate of COVID-19 in patients with PD was higher than that in the general elderly population\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Hence, the relationship between COVID-19 and PD is complex, and little is known about the causal relationship of COVID-19 and PD. Comprehending the causal correlation between PD and COVID-19 is vital in order to devise efficacious interventions and enhance patient outcomes.\u003c/p\u003e \u003cp\u003ePeople with PD are recommended to receive the COVID-19 vaccine, unless they have specific contraindications\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. A study shown that the COVID-19 vaccination rate in patients with PD was low\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, little is known about the COVID-19 vaccination status and protective effect on these patients.\u003c/p\u003e \u003cp\u003eThe present study aimed to determine the effect on patients with PD after the release of COVID-19 restrictions and analyze the infection-related risk factors of these patients and the protective effect of COVID-19 vaccine on PD via a single-centered study. Mendelian randomization (MR) is an effective genetic method to study the causal relationship of certain exposures to disease. Hence, we performed a bidirectional two-sample MR study to explore the causal correlation between COVID-19 and PD.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Cross-sectional study design\u003c/h2\u003e \u003cp\u003eQuestionnaire copies were collected from patients diagnosed with PD, who visited the outpatient and inpatient departments at the Affiliated Hospital of Guizhou Medical University between December 7, 2022, and March 10, 2023. The inclusion criteria were as follows: (1) patients diagnosed with PD according to the MDS clinical diagnosis criteria and (2) patients who did not change their medication 1 week before the December 7, 2022. The exclusion criteria included intellectual disability and unwillingness to participate in the study.\u003c/p\u003e \u003cp\u003eThe questionnaire included general information (age and sex), COVID-19 vaccination history (duration and type of last vaccination), clinical data on PD (motor and non-motor symptoms), clinical features of COVID-19, and change in PD symptoms after COVID-19 infection. Questionnaires were completed by the patients with PD or with the help of their family members if they had difficulty in reading or writing. The COVID-19 infection in this study was defined as having a positive COVID-19 nucleic acid or antigen result from December 7, 2022, to January 7, 2023. However, COVID-19 infection did not include symptomatic patients with negative laboratory results in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Two-sample MR study\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Data sources\u003c/h2\u003e \u003cp\u003eWe used available data on COVID-19 phenotypes from the COVID-19 Host Genetics Project (RELEASE 5) based on a European population\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The comprehensive dataset include COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 severity. The susceptibility phenotype compared COVID-19 patients with controls without COVID-19 (Ncase\u0026thinsp;=\u0026thinsp;38,984, Ncontrol\u0026thinsp;=\u0026thinsp;1,644,784). The hospitalization phenotype compared hospitalized COVID-19 patients with a control group that was not hospitalized for COVID-19 or infected with COVID-19 (Ncase\u0026thinsp;=\u0026thinsp;9,986, Ncontrol\u0026thinsp;=\u0026thinsp;1,877,672). The severity phenotype compared hospitalized COVID-19 patients who died or required respiratory support with a control group without severe COVID-19 or free of COVID-19 (Ncase\u0026thinsp;=\u0026thinsp;5,101, Ncontrol\u0026thinsp;=\u0026thinsp;1,383,241).\u003c/p\u003e \u003cp\u003eThe PD dataset analyzed in this study was derived from a large GWAS meta-analysis published by International Parkinson's Disease Genomics Consortium\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The study was also based on a European population of 482,730 participants, including 33,674 cases of PD and 449,056 healthy controls.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Selection of instrumental variables\u003c/h2\u003e \u003cp\u003eInstrumental variables (single nucleotide polymorphisms, SNPs) were selected such that they are strongly correlated with exposure (P\u0026thinsp;\u0026lt;\u0026thinsp;5 \u0026times; 10\u003csup\u003e\u0026minus;\u0026thinsp;8\u003c/sup\u003e) and pruned by linkage disequilibrium (r\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and within 10,000 kb from the index variant). The underlying outlier SNPs were removed by MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO)\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. We examined whether the obtained instrumental SNPs were associated with the outcomes and the potential confounders by PhenoScanner (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.phenoscanner.medschl.cam.ac.uk/\u003c/span\u003e\u003cspan address=\"http://www.phenoscanner.medschl.cam.ac.uk/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The F-statistics of these SNPs were used to evaluates the strength of an instrumental variable. The R\u003csup\u003e2\u003c/sup\u003e value for each SNP was determined employing the formula: R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;2 \u0026times; EAF \u0026times; (1-EAF) \u0026times; β\u003csup\u003e2[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 MR analysis and sensitivity analysis\u003c/h2\u003e \u003cp\u003eThe random-effects inverse-variance weighted (IVW) was used to evaluate the causality. MR-Egger, weighted median, simple mode, and weighted mode methods were also employed to complement the IVW. The Cochran\u0026rsquo;s Q test of the IVW approach and leave-one-out analysis were used to investigate the degree of heterogeneity. The MR-Egger intercept test and MR-PRESSO global test were used to evaluate the horizontal pleiotropy.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS statistical software for Windows version 24.0 (SPSS, Chicago, IL, USA) for cross-sectional study. Independent sample t-test was used for the analyses of general data and clinical basic information, which were continuous variables and had normal distributions. Chi-square test and Fisher exact test were used to compare categorical variables. Logistic regression was performed to analyze the infection-related risk factors. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e \u003cp\u003eFor MR analysis, we performed all the analyses in R (version 4.3.0) using the TwoSample MR\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e and MR-PRESSO\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e packages. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as nominally significant and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05/6 (0.008) was considered as significant after correcting by Bonferroni measures.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Cross-sectional study\u003c/h2\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e3.1.1 Characteristics of patients with PD\u003c/h2\u003e \u003cp\u003eIn the period of study, a total of 258 patients with PD were admitted to the study hospital. A total of 209 patients met the inclusion criteria, and they were asked to participate in the study. Two patients were excluded because of loss of important messages. Finally, 207 PD patients participated in this study. The baseline patients and clinical features of PD and COVID-19 are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe basic characteristics of PD patients in the survey\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOVID-19 infected group\u003c/p\u003e \u003cp\u003e(N = 136)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUninfected group\u003c/p\u003e \u003cp\u003e(N = 71)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP values\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (mean ± SD)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.33 ± 9.71\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.58 ± 9.75\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.439\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.917\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (51.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (50.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (48.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (49.23)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCourse of PD\u003c/p\u003e \u003cp\u003eM (P25, P75) (years\u0026nbsp;)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.5 (2, 8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2, 6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMotor symptoms\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRest tremor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107 (78.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (78.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradykinesia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136 (100.0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (100.0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRigidity\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (89.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (95.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePosture instability\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88 (64.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (69.0)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-motor symptoms\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyposmia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (52.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (54.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSleep disorders\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (35.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (33.8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression and anxiety\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (25.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (23.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (37.5)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (36.6)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive disorder\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (24.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (19.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccination\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWith vaccination\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109 (80.1)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (80.3)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout vaccination\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (19.9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (19.7)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eA total of 106 men and 101 women participated in this study. Their mean age was 67.76 (SD ± 9.71, range: 39–88) years, and the mean PD duration was 5.24 years. A total of 136 patients with PD were infected with COVID-19, with an infection rate of 65.7%. The mean ages of the patients infected or uninfected with COVID-19 were 67.33 (SD ± 9.71, range: 39–84) and 68.58 (SD ± 9.75, range: 46–88) years, respectively (P = 0.439). The mean courses of the PD patients infected or uninfected with COVID-19 were 5.52 and 4.68 years, respectively (\u003cem\u003eP\u003c/em\u003e = 0.262). The results showed no significant differences between the COVID-19-infected and uninfected groups in terms of gender (\u003cem\u003eP\u003c/em\u003e = 0.917), vaccination status (\u003cem\u003eP\u003c/em\u003e = 1.000), motor symptoms (\u003cem\u003eP\u003c/em\u003e = 0.984), and non-motor symptoms (\u003cem\u003eP\u003c/em\u003e = 0.979).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e3.1.2 Clinical features of COVID-19 in patients with PD\u003c/h2\u003e \u003cp\u003eIn this study, 70 males and 66 females were infected with COVID-19. Their COVID-19 symptoms included cough (\u003cem\u003eN\u003c/em\u003e = 94), fever (\u003cem\u003eN\u003c/em\u003e = 84), fatigue (\u003cem\u003eN =\u003c/em\u003e 69), dry or sore throat (\u003cem\u003eN\u003c/em\u003e = 63), stuffy or runny nose (\u003cem\u003eN\u003c/em\u003e = 60), myodynia (\u003cem\u003eN\u003c/em\u003e = 48), dizziness and headache (\u003cem\u003eN\u003c/em\u003e = 44), digestive tract symptoms (\u003cem\u003eN\u003c/em\u003e = 44), hyposmia (\u003cem\u003eN\u003c/em\u003e = 20), difficulty breathing (\u003cem\u003eN\u003c/em\u003e = 17), chest pain (\u003cem\u003eN\u003c/em\u003e = 8), hypoxemia (\u003cem\u003eN\u003c/em\u003e = 3), and rash (\u003cem\u003eN\u003c/em\u003e = 2) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among them, 69 (50.74%), 40 (29.41%), and 27 (19.85%) had symptoms of COVID-19 for 1, 2, and over 2 weeks, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eForty-eight patients experienced worsening of motor symptoms, with an exacerbation rate of 35.3%. These patients required adjustments to their PD medications. The worsened motor symptoms included rest tremor (\u003cem\u003eN\u003c/em\u003e = 14), bradykinesia (\u003cem\u003eN\u003c/em\u003e = 16), rigidity (\u003cem\u003eN\u003c/em\u003e = 12), posture instability (\u003cem\u003eN\u003c/em\u003e = 10), wearing-off (\u003cem\u003eN\u003c/em\u003e = 8), weakness (\u003cem\u003eN\u003c/em\u003e = 8), and dyskinesia (\u003cem\u003eN\u003c/em\u003e = 1) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Sixteen (11.8%) patients with PD were hospitalized for COVID-19 infection, and one died due to respiratory failure. More than half of the hospitalized patients were hospitalized for a duration of 1 week.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e3.1.3 Infection-related risk factors and protective effect of COVID-19 vaccine\u003c/h2\u003e \u003cp\u003eA total of 166 patients with PD were vaccinated against COVID-19, with a vaccination rate of 80.2%. Age, sex, course of PD, and duration and type of the last dose of vaccination were set as independent variables in the logistic regression to analyze the infection-related risk factors of these patients. The results showed that long PD course (OR = 3.296, 95% CI: 1.018–10.673) and duration of the last dose of COVID-19 vaccine (OR = 4.967, 95% CI: 1.125–21.938) were the risk factors (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Those patients who were vaccinated within 3 months had a lower infection rate than those vaccinated after more than 3 months (50% vs. 67.3%). This result indicated that COVID-19 vaccine has a short-term protective effect on patients with PD.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic regression analysis for screening the COVID-19 infection predictors in PD patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndex\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.936–1.024\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.358\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Ref: Male)\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.601\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.775–3.310\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.204\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCourse of PD (Ref: \u0026lt; 3 year)\u003c/p\u003e \u003cp\u003e3–5 year\u003c/p\u003e \u003cp\u003e5–10 year\u003c/p\u003e \u003cp\u003e\u0026gt; 10 year\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.183\u003c/p\u003e \u003cp\u003e2.393\u003c/p\u003e \u003cp\u003e3.296\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.484–2.892\u003c/p\u003e \u003cp\u003e0.803–7.133\u003c/p\u003e \u003cp\u003e1.018–10.673\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.712\u003c/p\u003e \u003cp\u003e0.117\u003c/p\u003e \u003cp\u003e0.047*\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of last COVID-19 vaccination (Ref: \u0026lt;3 month)\u003c/p\u003e \u003cp\u003e3–6 month\u003c/p\u003e \u003cp\u003e7–12 month\u003c/p\u003e \u003cp\u003e\u0026gt; 12 month\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.538\u003c/p\u003e \u003cp\u003e2.122\u003c/p\u003e \u003cp\u003e4.967\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.128–2.256\u003c/p\u003e \u003cp\u003e0.560–8.041\u003c/p\u003e \u003cp\u003e1.125–21.938\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003cp\u003e0.269\u003c/p\u003e \u003cp\u003e0.034*\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccination type (Ref: Vero)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCho\u003c/p\u003e \u003cp\u003eAdenovirus\u003c/p\u003e \u003cp\u003eUnkown\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.393\u003c/p\u003e \u003cp\u003e1.543\u003c/p\u003e \u003cp\u003e1.530\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.567–3.420\u003c/p\u003e \u003cp\u003e0.309–7.707\u003c/p\u003e \u003cp\u003e0.254–9.210\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.469\u003c/p\u003e \u003cp\u003e0.597\u003c/p\u003e \u003cp\u003e0.642\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eRef: Reference; \u003cb\u003e*\u003c/b\u003e indicate that the \u003cem\u003eP\u003c/em\u003e Value is significant; Vero: inactivated COVID-19 vaccine; Cho: Recombinant COVID-19 vaccine; Adenovirus: Adenovirus vaccine for COVID-19.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2 MR analysis results\u003c/h2\u003e \u003cp\u003eTo investigate the causality of COVID-19 on PD, three COVID-19 traits (hospitalization, severity, and susceptibility) were used as exposures, and PD from IEU database acted as outcome, with 4, 8 and 5 instrumental SNPs included for each trait, respectively. While, to investigate the causality of PD on COVID-19, 8, 21 and 12 instrumental SNPs of PD were selected for genetically predicting COVID-19 hospitalization, severity, and susceptibility after removing palindromes SNPs and potential pleiotropy or outliers. These SNPs were strongly correlated (P \u0026lt; 5E-8) (Supplemental Tables\u0026nbsp;1 and 2) and independent (R\u003csup\u003e2\u003c/sup\u003e \u0026lt; 0.001) (Supplemental Table\u0026nbsp;3) for exposure. All F-statistics were greater than 10 (Supplemental Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eWe found no statistically significant effect of COVID-19 on the increased risk of PD (Hospitalization: OR = 0.979, 95% CI: 0.847–1.044, P = 0.249; Severity: OR = 0.967, 95% CI: 0.905–1.033, P = 0.322; Susceptibility: OR = 1.023, 95% CI: 0.821–1.274, P = 0.840) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMendelian randomization estimates for associations between COVID-19 and PD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExposure\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/p\u003e \u003cp\u003eIVW\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/p\u003e \u003cp\u003eheterogeneity\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/p\u003e \u003cp\u003eintercept\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/p\u003e \u003cp\u003ePRESSO\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 hospitalization\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e−0.062\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.847–1.044\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.738\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID−19 severity\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e−0.034\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.905–1.033\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.587\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID−19 susceptibility\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.821–1.274\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.840\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.965\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.713\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.966\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOVID-19 hospitalization\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e−0.014\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.837–1.162\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.608\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOVID−19 severity\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.935–1.201\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.362\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.229\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCOVID−19 susceptibility\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.023–1.149\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006*\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.945\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eCI: confidence interval; IVW: inverse variance-weighted; P-heterogeneity: P-value for heterogeneity using Cochran’s Q test; P-intercept: P-value for MR-Egger intercept; P-PRESSO: P-value for MR-PRESSO global test. \u003cb\u003e*\u003c/b\u003eindicate that the \u003cem\u003eP\u003c/em\u003e Value is significant.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWe also found no statistically significant effect of PD on the increased risk of COVID-19 hospitalization and severity (Hospitalization: OR = 0.987, 95% CI: 0.837–1.162, P = 0.871; Severity: OR = 1.060, 95% CI: 0.935–1.201, P = 0.362). However, the results of the IVW method supported that PD causally increases the risk of COVID-19 susceptibility (OR = 1.084, 95% CI:1.023–1.149, P = 0.006) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMR-Egger regression analysis was used to test the existence of gene pleiotropy, all of the intercept term was close to zero (P \u0026gt; 0.05). The MR-PRESSO method was also tested and consistent with the MR-Egger regression. Although the P-values of the MR-PRESSO analysis was less than 0.05 in COVID-19 severity, horizontal pleiotropy did not present in the result of MR-PRESSO destruction test (P \u0026gt; 0.05). The Cochran’s statistical test showed no statistically significant heterogeneity effect (Q-value \u0026gt; 0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe rapid spread of the COVID-19 pandemic poses particular challenges for the management of patients with PD. The omicron variant shows potent immune-escape properties and could cause super-spread events that patients with PD may need to face with greater challenges. In addition, China announced “10 new measures” to adjust the COVID-19 prevention and control strategies on December 7, 2022, thus requiring further identification of the effect on patients with PD after the release of COVID-19 restrictions in China and providing intervention measures in the future.\u003c/p\u003e\u003cp\u003eA study showed that the omicron variant epidemic reached an infection rate of 75% within 3 weeks after the release of COVID-19 restrictions in Macao, China\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Another study showed that the omicron epidemic reached an infection rate of \u0026gt; 70% about a week earlier than in Macao\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The present study also showed the rapid transmission of the omicron variant in patients with PD, with an infection rate of 65.7% within 1 month after the release of COVID-19 restrictions in China.\u003c/p\u003e\u003cp\u003eOne study showed that more than 60 percent of people infected with COVID-19 developed fever, dry or sore throats, stuffy and runny nose, fatigue, headaches or muscle aches\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Similarly, the most common COVID-19 symptoms of patients with PD in the present study included cough, fever, fatigue, dry or sore throat, stuffy or runny nose, myodynia, dizziness and headache, and digestive tract symptoms. More than half of patients with PD have symptoms of COVID-19 within 1 week.\u003c/p\u003e\u003cp\u003eThe effect of COVID-19 on patients with PD is complicated. Some studies have shown that COVID-19 infection could worsen the motor and non-motor symptoms of PD or lead to the appearance of some previously unseen symptoms\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. In the present study, more than one-third of patients with PD showed worsened motor symptoms and required adjustment to their PD medications. The most worsened motor symptom was bradykinesia. Meanwhile, a case of probable PD after SARS-CoV-2 infection has been reported\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. One study presented two patients with PD treated by subthalamic deep brain stimulation showing rapid worsening symptoms of PD after COVID-19 infection\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Studies showed that the mechanism of COVID-19 infection could worsen the symptoms of PD may be related to that the virus may enter the central nervous system via hematologic pathways or axonal transport with olfactory neuroepithelium and then causing inflammation, immunologically mediated mitochondrial injury, and neuronal oxidative stress \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Hence, to determine the causality of COVID-19 on PD, we performed two-sample MR analysis. However, we found no statistically significant effect of COVID-19 susceptibility, hospitalization and severity on the increased risk of PD at the genetic level.\u003c/p\u003e\u003cp\u003eVaccination is an effective measure for preventing severe COVID-19 illness and reducing the spread of infection. A study showed that the COVID-19 vaccination rate in patents with PD was 54.0%\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, the COVID-19 vaccination rate in the present study was 80.2%, higher than that in the previous study\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. The results also showed that the duration of the last dose of COVID-19 vaccine was one of the infection-related risk factors of patients with PD. In addition, the COVID-19 vaccine exhibited a short-term protective effect on patients with PD. Hence, these patients are recommended to be vaccinated against COVID-19, unless a specific contraindication exists.\u003c/p\u003e\u003cp\u003eA study showed that the incidence of COVID-19 was similar between the PD group and the control group\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, indicating that PD is not a risk factor of COVID-19. However, the findings of the present study showed that long PD course was another infection-related risk factor. Hence, we further determine the causality of COVID-19 on PD, and the MR study supported the association between PD and higher risk of COVID-19 susceptibility. However, we found no statistically significant effect of PD on the increased risk of COVID-19 hospitalization and severity at the genetic level.\u003c/p\u003e\u003cp\u003eDue to the change in China’s current COVID-19 management policy, understanding the effect on patients with PD after the release of COVID-19 restrictions and taking timely preventive measures in the future, such as administrating booster vaccine and stockpiling antiviral drugs, could reduce the morbidity and mortality of these patients in the future epidemic wave.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eMore than one-third of patients with PD showed worsened motor symptoms and required adjustment to their PD medications, and the most worsened motor symptom was bradykinesia. The MR study supported the association between PD and higher risk of COVID-19 susceptibility. In addition, PD patients are encouraged to be receive booster vaccine because of the short-term protective effect of COVID-19 vaccine on them.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Science and Technology Fund of Guizhou Health Commission (gzwkj2021-024), and the Cultivate Project 2021 of the National Natural Science Foundation of China, Affiliated Hospital of Guizhou Medical University (No. gyfynsfc-2021-14).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol for the research project has been approved by a suitably constituted Ethics Committee of the institution within which the work was undertaken and that it conforms to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eApproval of the research protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and was approved by the\u0026nbsp;Affiliated Hospital of Guizhou Medical University.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided informed consent before enrollment.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAtzrodt CL, Maknojia I, McCarthy R, Oldfield TM, Po J, Ta K, et al. A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2. FEBS Journal. 2020;287:3633-50. doi: 10.1111/febs.15375.\u003c/li\u003e\n\u003cli\u003eScott L, Hsiao NY, Moyo S, Singh L, Tegally H, Dor G, et al. Track Omicron\u0026apos;s spread with molecular data. SCIENCE. 2021;374:1454-5. doi: 10.1126/science.abn4543.\u003c/li\u003e\n\u003cli\u003eLiang J, Liu R, He W, Zeng Z, Wang Y, Wang B, et al. Infection rates of 70% of the population observed within 3 weeks after release of COVID-19 restrictions in Macao, China. J Infect. 2023;86:402-4. doi: 10.1016/j.jinf.2023.01.029.\u003c/li\u003e\n\u003cli\u003eLeung K, Lau E, Wong C, Leung GM, Wu JT. Estimating the transmission dynamics of SARS-CoV-2 Omicron BF.7 in Beijing after adjustment of the zero-COVID policy in November-December 2022. NATURE MEDICINE. 2023;29:579-82. doi: 10.1038/s41591-023-02212-y.\u003c/li\u003e\n\u003cli\u003eCartella SM, Terranova C, Rizzo V, Quartarone A, Girlanda P. Covid-19 and Parkinson\u0026apos;s disease: an overview. JOURNAL OF NEUROLOGY. 2021;268:4415-21. doi: 10.1007/s00415-021-10721-4.\u003c/li\u003e\n\u003cli\u003eQi S, Yin P, Wang L, Qu M, Kan GL, Zhang H, et al. Prevalence of Parkinson\u0026apos;s Disease: A Community-Based Study in China. Mov Disord. 2021;36:2940-4. doi: 10.1002/mds.28762.\u003c/li\u003e\n\u003cli\u003eIneichen C, Baumann-Vogel H, Sitzler M, Waldvogel D, Baumann CR. Worsened Parkinson\u0026apos;s Disease Progression: Impact of the COVID-19 Pandemic. J Parkinsons Dis. 2021;11:1579-83. doi: 10.3233/JPD-212779.\u003c/li\u003e\n\u003cli\u003eCohen ME, Eichel R, Steiner-Birmanns B, Janah A, Ioshpa M, Bar-Shalom R, et al. A case of probable Parkinson\u0026apos;s disease after SARS-CoV-2 infection. LANCET NEUROLOGY. 2020;19:804-5. doi: 10.1016/S1474-4422(20)30305-7.\u003c/li\u003e\n\u003cli\u003eZhang Q, Schultz JL, Aldridge GM, Simmering JE, Narayanan NS. Coronavirus Disease 2019 Case Fatality and Parkinson\u0026apos;s Disease. Mov Disord. 2020;35:1914-5. doi: 10.1002/mds.28325.\u003c/li\u003e\n\u003cli\u003eBloem BR, Trenkwalder C, Sanchez-Ferro A, Kalia LV, Alcalay R, Chiang HL, et al. COVID-19 Vaccination for Persons with Parkinson\u0026apos;s Disease: Light at the End of the Tunnel? J Parkinsons Dis. 2021;11:3-8. doi: 10.3233/JPD-212573.\u003c/li\u003e\n\u003cli\u003eZhou Y, Lin Z, Wan X, Liu J, Ding J, Zhang C, et al. COVID-19 vaccine acceptance and hesitancy in patients with Parkinson\u0026apos;s disease. Front Public Health. 2022;10:977940. doi: 10.3389/fpubh.2022.977940.\u003c/li\u003e\n\u003cli\u003eThe COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. 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INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. 2013;42:1497-501. doi: 10.1093/ije/dyt179.\u003c/li\u003e\n\u003cli\u003eHemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. eLife. 2018;7. doi: 10.7554/eLife.34408.\u003c/li\u003e\n\u003cli\u003eArtusi CA, Romagnolo A, Imbalzano G, Marchet A, Zibetti M, Rizzone MG, et al. COVID-19 in Parkinson\u0026apos;s disease: Report on prevalence and outcome. Parkinsonism Relat Disord. 2020;80:7-9. doi: 10.1016/j.parkreldis.2020.09.008.\u003c/li\u003e\n\u003cli\u003eXu Y, Surface M, Chan AK, Halpern J, Vanegas-Arroyave N, Ford B, et al. COVID-19 manifestations in people with Parkinson\u0026apos;s disease: a USA cohort. JOURNAL OF NEUROLOGY. 2022;269:1107-13. doi: 10.1007/s00415-021-10784-3.\u003c/li\u003e\n\u003cli\u003eHainque E, Grabli D. Rapid worsening in Parkinson\u0026apos;s disease may hide COVID-19 infection. Parkinsonism Relat Disord. 2020;75:126-7. doi: 10.1016/j.parkreldis.2020.05.008.\u003c/li\u003e\n\u003cli\u003eVictorino DB, Guimaraes-Marques M, Nejm M, Scorza FA, Scorza CA. COVID-19 and Parkinson\u0026apos;s Disease: Are We Dealing with Short-term Impacts or Something Worse? J Parkinsons Dis. 2020;10:899-902. doi: 10.3233/JPD-202073.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Parkinson’s disease, COVID-19, COVID-19 susceptibility, motor symptoms, Mendelian randomization","lastPublishedDoi":"10.21203/rs.3.rs-3877315/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3877315/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo investigate the effects of the release of COVID-19 restrictions on patients with PD, and the association between COVID-19 and PD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA single-center survey was performed among patients with PD through a questionnaire from December 7, 2022, to March 10, 2023. Logistic regression was performed to analyze the infection-related risk factors. Then, a bidirectional two-sample Mendelian randomization was utilized to investigate the association between COVID-19 and PD.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn cross-sectional analysis, the COVID-19 infection rate of PD was 65.7%. Forty-eight (35.3%) patients with PD experienced worsening of motor symptoms. Long PD course (OR: 3.296, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047) and duration of the last dose of COVID-19 vaccine (OR: 4.967, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034) were the infection-related risk factors. The MR analysis results supported that PD causally increases the risk of COVID-19 susceptibility (β\u0026thinsp;=\u0026thinsp;0.081, OR\u0026thinsp;=\u0026thinsp;1.084, P\u0026thinsp;=\u0026thinsp;0.006). However, MR analysis showed that PD did not increases the risk of COVID-19 severity and hospitalization. In addition, no causal linkage of COVID-19 on PD was observed.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur findings suggest that COVID-19 infection leads to worsened PD motor symptoms. Long PD course is the infection-related risk factors, and PD causally increases the risk of COVID-19 susceptibility. However, we found no evidence that COVID-19 contributes to PD.\u003c/p\u003e","manuscriptTitle":"COVID-19 and Parkinson’s disease: a single-centered study and Mendelian randomization study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 17:48:42","doi":"10.21203/rs.3.rs-3877315/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-08T07:05:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-22T13:19:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"a5f8219c-d1ef-48b5-892e-f16dba993212","date":"2024-02-22T09:23:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2b26d533-5506-4564-af27-8629a9b9b135","date":"2024-02-20T17:45:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-20T17:17:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-19T14:31:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-02-04T16:43:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-04T16:42:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-01-19T01:57:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a3b6c279-0cb6-4a01-ab3b-262be0137c67","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T16:13:56+00:00","versionOfRecord":{"articleIdentity":"rs-3877315","link":"https://doi.org/10.1038/s41598-024-66197-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-07-17 16:04:50","publishedOnDateReadable":"July 17th, 2024"},"versionCreatedAt":"2024-02-06 17:48:42","video":"","vorDoi":"10.1038/s41598-024-66197-5","vorDoiUrl":"https://doi.org/10.1038/s41598-024-66197-5","workflowStages":[]},"version":"v1","identity":"rs-3877315","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3877315","identity":"rs-3877315","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}