Scientists identify common symptom patterns in post-COVID-19 vaccination syndrome

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Mar 16 2026

A large Japanese registry study identifies common symptom patterns and recovery timelines in patients with persistent post-COVID-19 vaccination symptoms, offering new insight into how these rare but complex conditions may be monitored and managed.

Study: Characterizing persistent Post-COVID-19 vaccination symptoms using MedDRA system organ class and preferred term classifications. Image Credit: moskha.com / Shutterstock

A recent study published in the journal Scientific Reports characterized the clinical features of post-coronavirus disease 2019 (COVID-19) vaccination syndrome (PCVS).

The emergence of COVID-19 sparked an unprecedented race to develop and deploy vaccines. Post-authorization surveillance has shown that continuous pharmacovigilance is indispensable. Novel vaccine platforms, especially messenger ribonucleic acid (mRNA) vaccines, may lead to adverse events (AEs) that evade detection in pre-approval trials. These findings underscore the need for robust long-term surveillance to monitor safety outcomes while large-scale studies continue to indicate that the overall risk of serious vaccine-related adverse events is low.

Researchers explore a poorly defined condition called PCVS

PCVS refers to persistent, multisystemic symptoms, such as cognitive impairment, fatigue, and exercise intolerance, developing after COVID-19 vaccination. It may lead to occupational disability and restricted access to healthcare. However, definitions of PCVS and estimates of its frequency remain inconsistent across studies, and clinical guidelines and compensation schemes remain underdeveloped. Expanded pharmacovigilance efforts and further research are therefore needed to support affected individuals and inform vaccination policy.

Registry study analyzes suspected vaccine-related adverse events

In the present study, researchers analyzed a registry of patients with suspected vaccine-related adverse events to characterize the clinical features of PCVS. Individuals who received care for AEs at 14 medical institutions in Japan were included. Symptoms were assessed and classified as clinically “probable” or “definitive” in relation to COVID-19 vaccination, based on the investigator's assessment of clinical and epidemiological evidence rather than definitive proof of causation. Data on clinical and demographic characteristics, as well as COVID-19 infection and vaccination history, were collected.

Information on the onset, severity, and causal links with vaccination, as well as treatment details and laboratory results, was also obtained. Causality assessment was based on epidemiological and clinical evidence derived from case data within the registry framework. The clinically definitive category was applied to individuals who were stable or asymptomatic before vaccination but experienced subsequent health deterioration requiring medical care.

The eligibility criteria for the clinically definitive designation included symptom persistence after vaccination and exclusion of alternative etiologies. Symptoms may occur within 1 month, 1 to 6 months, or more than 6 months after vaccination. Individuals with preexisting medical conditions that were stable for at least one month before vaccination but worsened afterward were categorized as clinically probable.

Adverse event severity was assessed using the National Cancer Institute Common Terminology Criteria for adverse events. Grade 1 denoted mild symptoms, while grade 2 indicated moderate symptoms manageable with non-invasive treatment. Grade 3 encompassed severe conditions requiring prolonged work absence or hospitalization. Grade 4 denoted life-threatening conditions, and grade 5 represented death attributable to adverse events.

The primary outcome was the clinical profile and registry-based frequency of adverse events deemed clinically definitive. Secondary outcomes included severe adverse events, vaccination-related adverse events, and the latency window between vaccination and symptom onset. Adverse events were also classified by preferred terms (PTs) and system organ classes (SOCs) using the Japanese version of the Medical Dictionary for Regulatory Activities (MedDRA). Because the registry did not capture the total number of vaccinated individuals served by participating sites, the reported values represent proportions within the registry rather than population-level incidence estimates.

Neurological, musculoskeletal, and general symptoms are the most common

The study enrolled 279 cases, including 179 patients whose symptoms were determined to be clinically definitive in association with COVID-19 vaccination. About 42.4% of participants received 3 vaccine doses, 20.7% received 2 doses, and 9.5% received 1 dose. Forty-seven patients had a history of COVID-19, while 131 had no confirmed history. Only one participant had experienced two infections. In total, 493 adverse events were recorded.

Most adverse events (70%) occurred within 90 days of vaccination. In contrast, 12.4% occurred more than 360 days after vaccination, with cognitive disorder and gait disturbance being the most frequent preferred terms. Because the study was observational and registry-based, delayed-onset events cannot be definitively attributed to vaccination.

Forty-seven adverse events were classified as grade 1 or 2, and 11 were at least grade 3. Three system organ classes: nervous system disorders, musculoskeletal and connective tissue disorders, and general disorders and administration site conditions, accounted for 61.7% of all adverse events.

The most common system organ class (29.2%) was general disorders and administration site conditions. Seven preferred terms within this category, fatigue, pyrexia, gait disturbance, chronic fatigue syndrome, chest pain, exhaustion, and pain, accounted for 87.5% of cases. Within nervous system disorders, floating dizziness, brain fog, dysgeusia, hypoesthesia, and headache constituted 76.4% of cases.

Within musculoskeletal and connective tissue disorders, back pain, arthralgia, fibromyalgia, muscle weakness, and polymyalgia rheumatica represented 74% of adverse events. Complete recovery was observed in 133 adverse events, and partial remission in 188, resulting in a 65.1% improvement rate, defined as either full recovery or partial symptom remission.

By contrast, 145 adverse events remained unresolved, five worsened, and six resulted in death. The recovery rate for 20 major preferred terms was below 50%, with median recovery times ranging from 150 to 300 days.

Registry findings highlight the need for continued vaccine safety monitoring

The study analyzed 179 PCVS cases and characterized their clinical features. The findings show that 61.7% of adverse events were concentrated within three system organ classes, 12% had delayed onset, and 63% of cases involving these systems showed no clinical improvement during the available follow-up period.

These results reinforce the growing vaccine safety profile: while the absolute risk of serious adverse events remains low, a subset of individuals may develop persistent multisystemic symptoms. The authors note that registry-based observational data cannot establish causal relationships between vaccination and individual adverse events but highlight the importance of continued pharmacovigilance and patient monitoring.