key: cord-0911585-moj49hhx authors: Sollini, Martina; Gelardi, Fabrizia; Biroli, Matteo; Chiti, Arturo title: Patients’ findings after COVID-19 infection and vaccinations: what to expect from [18F]FDG PET/CT date: 2021-12-20 journal: Eur J Nucl Med Mol Imaging DOI: 10.1007/s00259-021-05652-1 sha: 3d5f0447a83c51fd9b68a99d8c0b12ca554c8d2b doc_id: 911585 cord_uid: moj49hhx nan correlated with the history of recent vaccination (Fig. 1) . However, patients evaluated for certain diseases, such as lymphoma, melanoma, and breast and head and neck cancer, can be confusing and hard to interpret. Medical history should be taken into account during vaccination, and accordingly, the vaccination injection should be performed in the arm contralateral to the disease or even elsewhere (e.g. thigh). This shrewdness may reduce false-positive or inconclusive examinations. In the last months, rare cases of autoimmune diseases that occurred or worsened after the Covid-19 vaccination were also claimed. Recently, von Tresckow et al. [6] reported the case of a patient imaged by PET/CT for an autoimmune disease possibly related to vaccination. After mRNA vaccination (Spikevax, Moderna, TX), the patient complained of cephalgia, cervicalgia, ostealgia, and pain in multiple large joints and muscles associated with increased inflammatory indices. The clinical picture was suspected for large vessel vasculitis. Images showed increased [18F]FDG uptake on vertebral and femoral arteries (associated with vessel wall thickening) and on thoracolumbar inter-spinous and pelvic bursae, findings highly suspicious for rheumatic polymyalgia [6] . Another interesting report has been recently published by Boursier et al. [7] . They presented digital-PET/CT images from two patients who experienced myocarditis a few days after the second shot of the mRNA vaccine (Spikevax and COMIRNATY, respectively). Images acquired up to 3 days from peak troponin showed increased myocardial uptake related to myocardial inflammatory cells in the infiltrate overexpressing somatostatin receptors [7] . Other reports on autoimmune disease possibly related to COVID-19 vaccination are summarized in Table 1 . We also observed some anecdotal cases of autoimmune diseases after the COVID-19 vaccination (Figs. 2 and 3) . However, we must be cautious not to confound coincidental events with cause-effect relationships. Since the diseases, which were then disproved, such as between the hepatitis B vaccine and multiple sclerosis. Only in a few cases, the relationship has been scientifically proven (i.e. swine influenza vaccine and Guillain-Barré syndrome), with much lower risk than the disease itself and its related complications [12] . Also, regarding anti-COVID-19 vaccines, there is no solid scientific evidence that they may directly trigger autoimmune disorders. The above examples are predominantly rare isolated case reports. These phenomena might be explained by a genetic predisposition to develop such diseases, which probably would be precipitated equally by different factors and mechanisms. In addition, the risk of developing a severe form of COVID-19 is much higher in patients affected by autoimmune diseases than in the healthy population. Accordingly, the benefits of the vaccine are far greater than the risk of worsening the autoimmune disease. Therefore, clinical guidelines strongly recommend its administration also in patients suffering from autoimmune diseases [13] . Moreover, COVID-19 vaccination may also trigger positive effects. Indeed, the hyper-activation of innate immunity supporting the strong COVID-19-induced immune-stimulation also has potential effects on the tumour microenvironment. Cases of spontaneous regression post-COVID-19 infection have been described in lymphoma, renal carcinoma, and colorectal carcinoma patients [14] [15] [16] [17] [18] , and the hyper-activation of innate immunity with anticancer effects generated by acute infection may be elicited similarly also by anti-COVID-19 vaccination. A case of disease spontaneous regression after BNT162b2 vaccination (COMIRNATY, BioNTech/Pfizer) has been recently described in lymphoma [19] . We recently observed a similar case in a multi-refractory diffuse large B-cell lymphoma (DLBCL) patient who experienced a spontaneous metabolic complete response after COVID-19 vaccination (Fig. 4) . After all, vaccine-induced immune system stimulation for anti-tumour purposes is currently used in daily clinical practice. Bacillus Calmette-Guérin (BCG) is an attenuated vaccine from Mycobacterium bovis developed as an antituberculosis vaccine. BCG is the standard of therapy as intravesical adjuvant treatment for non-invasive high-and medium-risk muscle bladder cancer. BCG induces a local immune response resulting in an anti-tumour effect called trained immunity [20, 21] . We can conclude that the COVID-19 vaccine and the acute COVID-19 disease cause a strong activation of the immune system that may result in several phenomena that can be observed at PET/CT images. These "incidental" BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting. 101056/NEJMoa2101765 Prevalence and significance of hypermetabolic lymph nodes detected by 2-[18F]FDG PET/CT after COVID-19 vaccination: a systematic review and a meta-analysis A sigh of relief: vaccine-associated hypermetabolic lymphadenopathy following the third COVID-19 vaccine dose is short in duration and uncommonly interferes with the interpretation of [18F]FDG PET-CT studies performed in oncologic patients Duration of 18F-FDG avidity in lymph nodes after pandemic H1N1v and seasonal influenza vaccination Vasculitis and bursitis on [18F]FDG-PET/CT following COVID-19 mRNA vaccine: post hoc ergo propter hoc? 68Ga-DOTATOC digital-PET imaging of inflammatory cell infiltrates in myocarditis following COVID-19 vaccination Thymic hyperplasia after mRNA based COVID-19 vaccination Radiation recall pneumonitis on FDG PET/CT triggered by COVID-19 vaccination Features of systemic immune response from COVID-19 vaccination on 18F-FDG PET/CT 18F-fluorodeoxyglucose PET/ CT findings in a systemic inflammatory response syndrome after COVID-19 vaccine Vaccination and autoimmune disease: what is the evidence? ACR COVID-19 Vaccine Clinical Guidance Task Force. COVID-19 vaccine clinical guidance summary for patients with rheumatic and musculoskeletal diseases Can the host immune response against SARS-CoV2 also cause an anticancer effect? Complete remission of follicular lymphoma after SARS-CoV-2 infection: from the "flare phenomenon" to the "abscopal effect SARS-CoV-2-induced remission of Hodgkin lymphoma Spontaneous regression of metastatic renal cell carcinoma after SARS-CoV-2 infection: a report of two cases Unexpected tumor reduction in metastatic colorectal cancer patients during SARS-Cov-2 infection. London: SAGE Publications Sage UK; 2021 Primary cutaneous anaplastic large-cell lymphoma with marked spontaneous regression of organ manifestation after SARS-CoV-2 vaccination Bacillus Calmette-Guérin immunotherapy for cancer Improvement of different vaccine delivery systems for cancer therapy Acknowledgements We thank the physicians who cured and managed