key: cord-0954212-vtws865l authors: Tsuchida, Tomoya; Hirose, Masanori; Inoue, Yoko; Kunishima, Hiroyuki; Otsubo, Takehito; Matsuda, Takahide title: Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID date: 2022-03-08 journal: J Med Virol DOI: 10.1002/jmv.27689 sha: 53ec80d9ecae273c9c0c203f73b6d69277794d3d doc_id: 954212 cord_uid: vtws865l Coronavirus disease 2019 (COVID‐19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14–21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS‐CoV‐2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre‐ and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre‐ and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed. tion in patients with previous SARS-CoV-2 infection. 15 Annapaola recommended a single messenger RNA vaccine for achieving sufficient immunity in patients with previous SARS-CoV-2 infection. 16 In Japan, there has been a recent increase in the number of commercial and accommodation facilities that require full vaccination. Patients who cannot be completely vaccinated due to worsening sequelae symptoms may not access services of these facilities. In case the antibody titer after a single vaccination in patients with Long COVID is similar or higher than that in full vaccinated noninfected persons, patients with Long COVID may receive services from facilities using certificates confirming single vaccination and healing. However, the relationship between postvaccination antibody titers and symptom changes after a single vaccination in patients with Long COVID remains unclear. This study aimed to evaluate changes in symptoms and antibody titers after a single vaccination and assess the relationship in patients with Long COVID. Patients who visited the outpatient department specializing in Long COVID in our hospital were enrolled. The patients presented with several sequelae symptoms (fever, malaise, dyspnea, cough, taste abnormality, olfactory abnormality, hair loss, sore throat, joint pain, numbness of limbs, muscle pain, headache, chest pain, vomiting, diarrhea, decreased motivation, sleeplessness, anxiety, depressed mood, forgetfulness, and skin symptoms) after >2 months since the onset of the COVID-19 diagnosed using a polymerase chain reaction test or antigen test. For patients who requested vaccination and provided consent to participate in this study, antibody titers were measured before vaccination and approximately 2 weeks after the single vaccination. The patients were informed about the results and their interpretation. Quantitative anti-spike RBD IgG antibody responses were measured using the Abbott SARS-CoV-2 IgGII Quant assay (cut-off ≥ 50 AU/ml). Moreover, three self-assessments of postvaccination changes in the main sequelae symptoms were confirmed based on the patient's response as follows: unchanged, relief, and worsened. Forty-two patients were enrolled. Table 1 This study showed no postvaccination changes in the symptoms of Long COVID; moreover, the symptom relief rate was lower than that reported in a previous study. 8 Furthermore, the worsened group showed a significantly higher change ratio in the antibody titer than the nonworsened group. In most patients, prevaccination antibody titers are equal or less than those after a single vaccination in uninfected persons. 15 Lack of vaccination increases the risk of reinfection even in patients with previous SARS-CoV-2 infection. 11 Therefore, vaccination is necessary for preventing reinfection in patients with Long COVID. However, in our study, 29% of patients did not undergo the second vaccination. Patients refused to undergo the second vaccination because of worsening Long COVID symptoms, concerns about strong side effects, and satisfaction with the antibody titers after the first vaccination. Regarding antibody titers, studies have reported that sufficient antibody titers can be obtained by a single vaccination for patients with previous SARS-CoV-2 infection. 15, 16 Our findings showed that even in patients with Long COVID, a sufficient antibody titer can be obtained with a single vaccination. A small-scale study in real-world settings reported no significant difference in the occurrence of reinfection between infected individuals with only one vaccination and without vaccination. 11 Therefore, future studies are warranted. The third vaccination program has started; however, there is a need to address worries regarding additional vaccinations among patients with Long COVID. The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests that an excessive immune response to vaccination may be associated with worsening of sequelae. Numerous autoantibodies are produced after COVID-19 infection and cause various symptoms 17 ; moreover, immune disorders are associated with the pathophysiology of sequelae. 18 In case an immune overreaction to vaccination worsens the sequelae, the sequelae may result from an immune disorder. Gracia-Abellán et al. 19 reported a relationship between low antibody titers and sequelae. Antibodies are involved in the regulation of inflammatory responses through activation of Fc-γ receptors, Toll-like receptors, and complements, which induce the secretion or suppression of various proinflammatory and antiinflammatory mediators. Therefore, they suggested that low peak antibody titers worsened sequelae symptoms. The authors declare that there are no conflicts of interest. Conception and design of study: Tomoya Tsuchida. Acquisition of data: Matsuda. This study was approved by the ethics committee of St. Marianna University School of Medicine (Approval number: 5321). All the patients provided informed consent for each procedure and publication. The authors confirm that the data supporting the findings of this study are available within the article. Tomoya Tsuchida http://orcid.org/0000-0002-8517-3941 Ministry of Health, Labour and Welfare. Domestic outbreaks, etc About the novel coronavirus vaccines in Japan World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study Risk factors associated with development and persistence of Long COVID Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study The impact of COVID vaccination on symptoms of Long Covid. An international survey of 900 people with lived experience Symptoms after COVID-19 vaccination in patients with persistent symptoms after acute infection: a case series Choosing wisely for COVID-19: ten evidence-based recommendations for patients and physicians Reduced risk of reinfection with SARS-CoV-2 after COVID-19 vaccination-Kentucky Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study Covid-19 breakthrough infections in vaccinated health care workers The dynamics of quantitative SARS-CoV-2 antispike IgG response to BNT162b2 vaccination Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine Antibody response to SARS-CoV-2 vaccination is extremely vivacious in subjects with previous SARS-CoV-2 infection Diverse functional autoantibodies in patients with COVID-19 Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms Antibody response to SARS-CoV-2 is associated with long-term clinical outcome in patients with COVID-19: a longitudinal study Are vaccines safe in patients with Long COVID? A prospective observational study