COVID-19 Vaccine and Complications: Systematic Review with ☸️SAIMSARA.

• Generated: 2025-10-21 22:15:56 CEST
• Plan: Premium (expanded craft tokens; source: Europe PMC)
• Source: Europe PMC
• Scope: Titles/Abstracts (tiab)
• Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
• Total Abstracts/Papers: 4222
• Downloaded Abstracts/Papers: 4222
• Included original Abstracts/Papers: 499
• Total study participants (naïve ΣN): 779781

• Cardiovascular Complications: Myocarditis and pericarditis are rare post-vaccination events, primarily with mRNA vaccines in young males, often with a favorable prognosis [1, 3, 8, 24, 58, 129, 131, 189, 217, 243, 248, 251, 252, 266, 267, 268, 279, 280, 282, 289, 290, 291, 292, 294, 297, 302, 303, 304, 306, 313, 314, 317, 346, 353, 387, 394, 396, 411, 423, 455, 457]. Thrombotic events (VTE, ATE, VITT, CSVT, PE, DVT) are extremely rare post-vaccination, especially compared to the higher risk from COVID-19 infection [4, 8, 24, 90, 134, 137, 141, 164, 165, 170, 223, 243, 255, 258, 260, 298, 308, 309, 310, 318, 321, 323, 390, 397, 428, 491, 493, 497, 499]. Pre-infection vaccination provides significant protection against major acute cardiovascular events (MACE) and all-cause mortality in individuals with COVID-19 [18, 42].
• Neurological Complications: Rare neurological side effects, including Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM), stroke, Bell's palsy, and encephalopathy, have been reported after vaccination [5, 10, 25, 93, 117, 119, 120, 124, 126, 127, 130, 136, 139, 151, 152, 155, 161, 163, 169, 197, 222, 263, 271, 274, 281, 283, 284, 287, 296, 300, 304, 307, 312, 320, 334, 335, 361, 364, 391, 398, 399, 434, 439, 441, 445, 475, 476, 483, 490]. The incidence of vaccine-related GBS was significantly lower than that related to COVID-19 infection [10].
• Autoimmune and Inflammatory Conditions: Vaccination can be associated with autoimmune phenomena such as new-onset primary membranous nephropathy [21], glomerulonephritis [66], thyroid disease (Graves' disease, thyroiditis) [133, 301], autoimmune encephalopathy [130, 155, 307], autoimmune rheumatic diseases (ARDs) [286], and exacerbation of autoimmune bullous diseases (AIBDs) [447]. However, anti-COVID-19 vaccines were found to be safe long-term for patients with Systemic Lupus Erythematosus (SLE), with no observed excess flares [17].
• Pregnancy and Neonatal Outcomes: COVID-19 vaccination during pregnancy is generally considered safe and effective, reducing the risk of severe infection and hospitalization for the mother [7, 40, 91, 166, 191, 198, 220, 315, 325, 443]. While some studies reported associations with premature rupture of membrane and neonatal jaundice [144], or higher rates of overall preterm delivery [236], these were not consistently found to be independent risk factors. Concerns about vaccine safety for the fetus are a barrier to uptake [9, 95, 154, 234, 430].
• Impact on Vulnerable Populations: Vaccination is crucial for immunocompromised patients (e.g., cancer, organ transplant recipients, HIV, IMID, MS) to reduce severe COVID-19 outcomes and complications, despite potentially lower immunogenicity or specific risks [13, 14, 33, 38, 92, 113, 114, 142, 147, 150, 157, 177, 188, 192, 194, 201, 202, 207, 215, 218, 244, 270, 328, 333, 345, 348, 359, 370, 376, 377, 381, 389, 416, 417, 440, 448, 450, 461, 479, 480]. Unvaccinated status is an independent risk factor for acute kidney injury (AKI) [27, 102], fibromyalgia [23], and severe outcomes in chronic kidney disease (CKD) and diabetes patients [34, 37, 96, 109, 171, 216, 247, 343, 372, 431, 442].
• General Adverse Events and Vaccine Acceptance: Most vaccine adverse events are mild to moderate and transient (e.g., fatigue, headache, injection site pain) [76, 108, 112, 128, 146, 204, 246, 249, 269, 272, 273, 324, 336, 351, 356, 358, 420]. Vaccine hesitancy is influenced by fear of side effects, lack of risk perception, and mistrust in information sources [9, 53, 83, 97, 123, 154, 200, 209, 214, 216, 221, 232, 234, 242, 247, 254, 256, 277, 337, 339, 340, 347, 350, 352, 357, 381, 388, 393, 412, 430, 443].
• Benefits of Vaccination vs. Infection Risks: Overall, the benefits of COVID-19 vaccination in preventing severe illness, hospitalization, and mortality far outweigh the risks of vaccine-related complications [3, 5, 8, 18, 34, 36, 37, 42, 50, 54, 58, 64, 68, 69, 72, 87, 90, 91, 98, 101, 102, 103, 104, 109, 113, 114, 121, 149, 150, 156, 159, 167, 172, 177, 188, 194, 198, 201, 202, 207, 208, 218, 220, 239, 241, 248, 260, 278, 293, 325, 345, 348, 370, 395, 416, 423, 424, 440, 448, 461, 479, 492]. COVID-19 infection itself is associated with a wide array of severe and long-term complications across multiple organ systems, often more severe than vaccine-related events [1, 2, 4, 10, 16, 20, 28, 30, 32, 33, 37, 41, 44, 47, 49, 54, 55, 56, 59, 60, 62, 65, 66, 67, 73, 77, 78, 82, 84, 86, 89, 90, 91, 96, 98, 99, 100, 105, 106, 107, 110, 111, 145, 147, 150, 151, 153, 155, 156, 158, 160, 162, 163, 168, 169, 171, 173, 175, 179, 180, 181, 182, 184, 186, 190, 193, 199, 205, 211, 212, 213, 215, 220, 225, 226, 227, 228, 229, 230, 231, 235, 240, 248, 265, 275, 276, 318, 326, 327, 331, 334, 338, 341, 343, 344, 354, 355, 362, 364, 368, 372, 373, 375, 376, 377, 378, 379, 382, 384, 386, 389, 391, 399, 400, 401, 403, 404, 405, 406, 407, 410, 413, 414, 415, 417, 418, 421, 426, 429, 431, 432, 433, 434, 438, 439, 441, 442, 444, 449, 450, 452, 454, 456, 458, 459, 462, 463, 464, 466, 467, 468, 469, 471, 472, 473, 474, 475, 476, 477, 478, 480, 482, 483, 484, 485, 486, 487, 489, 490, 494, 495, 498, 499].

• Clinicians should continue to strongly recommend COVID-19 vaccination, particularly for vulnerable populations such as the immunocompromised, elderly, and those with chronic conditions, as vaccination significantly reduces the risk of severe disease, hospitalization, and mortality from infection [3, 5, 8, 18, 34, 36, 37, 42, 50, 58, 64, 68, 69, 72, 87, 90, 91, 98, 101, 102, 103, 109, 113, 114, 121, 149, 150, 156, 159, 172, 177, 188, 194, 198, 201, 202, 207, 208, 239, 241, 248, 260, 278, 293, 325, 345, 348, 370, 395, 416, 423, 424, 440, 448, 461, 479, 492].
• For rare post-vaccination complications like myocarditis or thrombosis, early diagnosis and management are important, especially in young males for cardiac events [1, 3, 24, 58, 129, 131, 189, 217, 268, 290, 292, 302, 303, 304, 306, 313, 314, 317, 346, 353, 387, 394, 396, 411, 423, 455, 457] and for neurological symptoms like severe headaches post-adenovirus vector vaccines [5, 10, 25, 93, 117, 119, 120, 124, 126, 127, 130, 134, 136, 137, 139, 151, 152, 155, 161, 163, 169, 197, 222, 263, 271, 274, 281, 283, 284, 287, 296, 300, 304, 307, 312, 320, 334, 335, 361, 364, 391, 398, 399, 434, 439, 441, 445, 475, 476, 483, 490].
• Healthcare providers should address vaccine hesitancy by providing accurate, evidence-based information regarding vaccine safety and efficacy, especially concerning pregnant women and children [9, 53, 83, 95, 123, 154, 234, 254, 256, 339, 352, 357, 381, 412, 430, 443].
• Patients with pre-existing autoimmune diseases should be informed that vaccine-related exacerbations are generally not high enough to prevent vaccination, especially if their condition is controlled [17, 286, 348, 447].
• For patients requiring surgery, delaying procedures for at least 2 weeks (and potentially longer for long-term functional recovery) after COVID-19 infection is recommended to minimize postoperative complications [56, 82, 107, 173, 329, 331, 421].

• Long-term Outcomes of Rare Complications — Prospective cohort studies are needed to track the long-term prognosis and quality of life for individuals experiencing rare but severe post-vaccination complications (e.g., myocarditis, GBS, VITT) [189, 394].
• Mechanisms of Autoimmune Reactions — Research into the immunological mechanisms underlying vaccine-associated autoimmune conditions (e.g., glomerulonephritis, thyroiditis, ADEM) is needed to identify biomarkers for risk stratification and targeted interventions [21, 66, 133, 135, 139, 152, 155, 271, 286, 300, 301, 307, 318, 322, 348, 447, 451, 499].
• Comparative Risk in Specific Populations — Further studies are required to precisely quantify the comparative risks of COVID-19 infection versus vaccination in highly specific vulnerable groups, such as very young children, individuals with rare genetic disorders, or those on complex immunomodulatory therapies [14, 33, 38, 92, 113, 114, 142, 147, 150, 156, 157, 177, 188, 192, 194, 201, 202, 207, 215, 218, 244, 270, 328, 333, 345, 348, 359, 370, 376, 377, 381, 389, 416, 417, 440, 448, 450, 461, 479, 480].
• Impact of Vaccine Type and Dosing Regimen — More granular research is needed to differentiate complication profiles across various vaccine platforms (mRNA, adenoviral vector, inactivated, protein subunit) and dosing schedules, especially concerning booster effects and specific age/sex groups [1, 3, 8, 22, 58, 72, 108, 112, 126, 129, 131, 141, 164, 165, 170, 243, 249, 253, 258, 263, 268, 272, 273, 285, 289, 290, 291, 292, 302, 308, 314, 315, 316, 321, 336, 346, 361, 390, 394, 396, 411, 423, 455, 457, 491, 493, 496, 497].
• Standardized Reporting of Adverse Events — Implementing standardized, global reporting systems for vaccine adverse events, including detailed clinical outcomes and follow-up, would improve data quality for robust risk-benefit analyses [356, 358].

• Heterogeneous Study Designs — The reliance on diverse study designs, including numerous case reports and retrospective analyses, limits the ability to establish definitive causality and precise incidence rates for many reported complications.
• Variable Follow-up Periods — Follow-up durations varied significantly, making it challenging to assess the true long-term incidence and persistence of both vaccine-related and infection-related complications.
• Inconsistent Data Reporting — Lack of standardized reporting metrics and detailed demographic/clinical information across studies sometimes hindered direct comparisons and robust quantitative synthesis.
• Potential for Reporting Bias — Rare and severe adverse events are more likely to be reported, potentially inflating perceived risks compared to actual population-level incidence, especially for vaccine-related complications.
• Confounding by Comorbidities — Many studies involved populations with pre-existing health conditions, making it difficult to disentangle whether observed complications were solely due to vaccination, underlying disease, or COVID-19 infection itself.

• Prospective Cohort Studies — Conduct large-scale prospective cohort studies with long-term follow-up to precisely quantify the incidence and natural history of rare vaccine-associated complications.
• Mechanistic Research — Investigate the immunological and genetic mechanisms underlying specific vaccine-related adverse events to identify predictive biomarkers and develop targeted prevention or treatment strategies.
• Comparative Effectiveness Research — Perform head-to-head comparative studies of different vaccine platforms and dosing regimens to refine risk-benefit profiles for diverse populations.
• Enhanced Surveillance Systems — Implement global, standardized active surveillance systems for adverse events following immunization (AEFI) with detailed clinical data capture and long-term follow-up.
• Risk Communication Strategies — Develop and test targeted educational interventions to address vaccine hesitancy, particularly in specific populations like pregnant women and parents, by clearly communicating comparative risks and benefits.