Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

In high-risk outpatients with COVID-19, neither colchicine nor aspirin reduced disease progression or death at 45 d.

SOURCE CITATION: Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022;10:1160-8. 36228639.

Colchicine and risk of hospitalization due to COVID-19: A population-based study.

Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76-1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91-1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67-1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19.

The effects of colchicine on hospitalized COVID-19 patients: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate the effects of colchicine in the improvement of clinical outcomes of hospitalized COVID-19 patients. This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on adult patients (>18 years) with severe COVID-19. The included patients were randomly (1:1) assigned to the colchicine (2 mg loading dose followed by 0.5 mg twice daily for 7 days) or placebo group. Both groups received remdesivir and interferon beta-1b. The primary outcome of the study was to receive clinical response as ordinal scale of 1 or 2. Secondary outcomes were hospital complications and 28-day mortality. Between February and May 2021, 110 patients were included and 106 of them were analyzed. Baseline clinical characteristics and demographics were not significantly different. According to the ordinal scale, 30 patients in the control group (58.8%) responded to treatment within 7 days, while 35 patients (63.6%) in the colchicine group showed the same response (p = 0.61, odds ratio (OR) = 1.23, 95% CI [0.560-2.68]). On the 14th day, 87.3% of the colchicine group (n = 48) and 82.4% of the control group (n = 42) responded (p = 0.48, OR = 1.47, 95% CI [0.50.3-4.29]. In addition, 28-day mortality, intensive care unit admission, and hospital duration were not different between the groups (p = 0.99, 0.59, 0.06). Diarrhea and nausea were the major side effects dominant in the colchicine group. Colchicine showed no beneficial effects on clinical improvement and hospital complications in patients with COVID-19. Moreover, in case of prescription, the safety concerns of colchicine, specially gastrointestinal side effects, should be taken into account.

Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause severe life-threatening diseases called acute respiratory distress syndrome (ARDS) owing to cytokine storms. The mortality rate of COVID-19-related ARDS is as high as 40% to 50%. However, effective treatment for the extensive release of acute inflammatory mediators induced by hyperactive and inappropriate immune responses is very limited. Many anti-inflammatory drugs with variable efficacies have been investigated. Colchicine inhibits interleukin 1 beta (IL-1ß) and its subsequent inflammatory cascade by primarily blocking pyrin and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) activation. Therefore, this cheap, widely available, oral drug might provide an added benefit in combating the cytokine storm in COVID-19. Here, we sought to determine whether adding colchicine to other standards of care could be beneficial for moderate COVID-19 pneumonia in terms of the requirement for advanced respiratory support and mortality. METHODS AND FINDINGS: This blinded placebo-controlled drug trial was conducted at the Dhaka Medical College Hospital, Dhaka, Bangladesh. A total of 300 patients with moderate COVID-19 based on a positive RT-PCR result were enrolled based on strict selection criteria from June 2020 to November 2020. Patients were randomly assigned to either treatment group in a 1:1 ratio. Patients were administered 1.2 mg of colchicine on day 1 followed by daily treatment with 0.6 mg of colchicine for 13 days or placebo along with the standard of care. The primary outcome was the time to clinical deterioration from randomization to two or more points on a seven-category ordinal scale within the 14 days post-randomization. Clinical outcomes were also recorded on day 28. The primary endpoint was met by 9 (6.2%) patients in the placebo group and 4 (2.7%) patients in the colchicine group (P = 0.171), which corresponds to a hazard ratio (95% CI) of 0.44 (0.13-1.43). Additional analysis of the outcomes on day 28 revealed significantly lower clinical deterioration (defined as a decrease by two or more points) in the colchicine group, with a hazard ratio [95%CI] of 0.29 [0.098-0.917], (P = 0.035). Despite a 56% reduction in the need for mechanical ventilation and death with colchicine treatment on day 14, the reduction was not statistically significant. On day 28, colchicine significantly reduced clinical deterioration measured as the need for mechanical ventilation and all-cause mortality. CONCLUSION: Colchicine was not found to have a significant beneficial effect on reducing mortality and the need for mechanical ventilation. However, a delayed beneficial effect was observed. Therefore, further studies should be conducted to evaluate the late benefits of colchicine. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: ClinicalTrials.gov Identifier: NCT04527562 https://www.google.com/search?client=firefox-b-d&q=NCT04527562.

Colchicine anti-inflammatory therapy for non-intensive care unit hospitalized COVID-19 patients: results from a pilot open-label, randomized controlled clinical trial.

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.

Multisystem Inflammatory Syndrome in an Adult Following COVID-19 mRNA Vaccination: Successful Treatment With Medium-Dose Steroids and Colchicine.

Multisystem inflammatory syndrome in children and adults (MIS-C/A) was rarely reported as a complication of coronavirus disease 2019 (COVID-19) and potential adverse events following COVID-19 vaccination. Recently, the case definition of MIS-C/A was developed by the Brighton Collaboration Network. However, only a limited number of adult patients with MIS-A following immunization have been reported, and there is still little evidence for adequate treatment. A 57-year-old man presented with fever, headache, vomiting, and hypotension 24 days after receiving the second COVID-19 vaccination with the Pfizer-BioNTech vaccine. According to the Brighton Collaboration Case Definition, the patient met a definitive case of MIS-A after vaccination (level 1 of diagnostic certainty). After administration of medium-dose prednisolone (20 mg/d) with colchicine (1.2 mg/d), all symptoms and signs improved rapidly. The dose of prednisolone was gradually tapered from the third week, and the patient confirmed a full recovery without medication after 8 weeks. This is the first report showing that low-dose steroids in combination with colchicine may be an effective treatment option for MIS-A after vaccination.

Comparative efficacy and safety of pharmacological interventions for severe COVID-19 patients: An updated network meta-analysis of 48 randomized controlled trials.

BACKGROUND: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19. METHODS: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). RESULTS: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients. CONCLUSION: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.

Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial.

BACKGROUND: The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. METHODS: The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. FINDINGS: Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions. INTERPRETATION: The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

The evidence from clinical trials on colchicine and corticosteroids' effect on COVID-19: a systematic review and meta-analysis.

OBJECTIVES: With no clear end for the outbreak, identifying the drugs that are effective in COVID-19's management is of utmost importance to reduce the impact on the general population and the healthcare systems. METHODS: This is a systematic review and a meta-analysis evaluating the evidence from clinical trials on the effect of colchicine and corticosteroids against COVID-19. In this review, we have systematically searched five databases [(PubMed, Embase, clinicaltrials.gov, ICTRP, CINAHL (EBSCO)]. Cochrane's data extraction sheet was used to collect the required information, and RevMan-5.4.1 was used to conduct the meta-analysis and to assess the risk of bias. The review was registered in Prospero (CRD42022299718). RESULTS: The total number of included studies was 17, with 18,956 participants; the majority were male 12,001. Out of which, 8772 participants were on colchicine, 569 took methylprednisolone, and 64 patients received prednisolone. The meta-analysis has shown that colchicine had no significant effect on reducing the mortality rate among COVID-19 patients [OR 0.98(95% CI 0.90-1.08), p = .70), I2:1%)], corticosteroids have significantly reduced the mortality rates [OR 0.55 (95% CI 0.33-0.91), p = .02, I2:40]. Colchicine did not reduce the incidence of ICU admissions [OR 0.74 (95% CI 0.39-1.40), p = .35, I2:0%], while steroidal drugs significantly reduced the ICU admissions [OR 0.42 (95% CI 0.23-0.78), p = .005, I2:0%]. Unlike steroidal drugs [OR 0.53 (95% CI 0.30-0.95), p = .03, I2:61%], colchicine failed to reduce the need for mechanical ventilation [OR 0.73 (95% CI 0.48-1.10), p = .13, I2:76%]. Steroidal drugs significantly reduced the duration of hospitalization among COVID-19 patients [OR -0.50 (95% CI -0.79-0.21), p = .0007, I2:36%]. CONCLUSIONS: The use of colchicine did not significantly reduce the mortality rate, ICU admissions, and mechanical ventilation among COVID-19 patients. Conversely, corticosteroids significantly reduced the mortality rate, ICU admissions, mechanical ventilation, and hospitalization duration among COVID-19 patients.

Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.

BACKGROUND: Colchicine has been proposed as a COVID-19 treatment. AIM: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. DESIGN AND SETTING: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). METHOD: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. RESULTS: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4). CONCLUSION: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.

A Review of the Rational and Current Evidence on Colchicine for COVID-19.

The current coronavirus disease (COVID-19) pandemic has affected millions of individuals worldwide. Despite extensive research efforts, few therapeutic options currently offer direct clinical benefits for COVID-19 patients. Despite the advances in our understanding of COVID-19, the mortality rates remain significantly high owing to the high viral transmission rates in several countries and the rise of various mutations in the SARS-CoV-2. One currently available and widely used drug that combines both anti-inflammatory and immunomodulatory actions is colchicine, which has been proposed as a possible treatment option for COVID-19. Colchicine still did not get much attention from the medical and scientific communities despite its antiinflammatory and immunomodulatory mechanisms of action and positive preliminary data from early trials. This literature review article provides the scientific rationale for repurposing colchicine as a potential therapy for COVID-19. Further, we summarize colchicine's mechanisms of action and possible roles in COVID-19 patients. Finally, we supplement this review with a summary of the doses, side effects, and early efficacy data from clinical trials to date. Despite the promising early findings from multiple observational and clinical trials about the potential of colchicine in COVID-19, the data from the RECOVERY trial, the largest COVID-19 randomized controlled trial (RCT) in the world, showed no evidence of clinical benefits in mortality, hospital stays, or disease progression (n = 11340 patients). However, multiple other smaller clinical trials showed significant clinical benefits. We conclude that while current evidence does not support the use of colchicine for treating COVID-19, the present body of evidence is heterogeneous and inconclusive. The drug cannot be used in clinical practice or abandoned from clinical research without additional large RCTs providing more robust evidence. At present, the drug should not be used except for investigational purposes.

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial.

Some patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or death (Funded by the Community of Madrid, EudraCT Number: 2020-001841-38; 26/04/2020).

A single-center COVID-19 vaccine experience with CoronaVac and BNT162b2 in familial Mediterranean fever patients.

AIM: To determine frequency of adverse events and attacks related to vaccination in recipients of CoronaVac and BNT162b2 in familial Mediterranean fever (FMF) patients, and to search whether history of prior COVID-19 or a booster dose increases occurrence of adverse events/attacks. METHODS: FMF patients were surveyed for administration of any COVID-19 vaccine and vaccine-related adverse events or FMF attacks. Demographic, clinical, vaccine-related data, history of COVID-19 infection before or after vaccination, adherence to FMF treatment during vaccination were collected. RESULTS: A total of 161 vaccinated FMF patients were included. Ninety-three patients out of 161 had reported suffering from an adverse event/attack after a vaccine dose. There were 54.7% of BNT162b2 recipients who reported any adverse event after any vaccine dose in comparison to 29.9% of CoronaVac recipients (P < .001). There were 22.2% of BNT162b2 recipients who reported suffering from a FMF attack within 1 month after vaccination in comparison to 19.4% of CoronaVac recipients (P = .653). When patients with or without adverse event/attack were compared, no significant differences were observed in means of demographics, comorbid diseases, disease duration, total vaccine doses, or treatments adhered to for FMF. Rates of adverse events/attacks were similar between patients with and without prior COVID-19. In booster recipients, adverse events/attacks were most frequent after the booster dose. CONCLUSIONS: A considerable number of FMF patients suffered from vaccine-related adverse events/attacks, particularly with BNT162b2. No serious events or mortalities due to vaccination were detected. Demographics, clinical characteristics and prior history of vaccination did not significantly affect these results. We observed an increased rate of adverse events/attacks with booster dose administration.