Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic efficacy. Our earlier studies have shown the efficacy of the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) by reducing the induced Tregs pool and enhance immune stimulation as well as local tumor control. These findings have suggested its potential for enhancing the efficacy of immunotherapy, besides radiotherapy and chemotherapy. This review provides a brief account of the current status of Tregs as a component of the immune-biology of tumors and various preclinical and clinical strategies pursued to obviate the limitations imposed by them in achieving therapeutic efficacy.

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T-Regulatory Cells In Tumor Progression And Therapy.

Objective: 
To describe trends in the report of headache as an adverse event following vaccination according to the Vaccine Adverse Events Reporting System (VAERS).
 Background: 
The VAERS is a national vaccine safety surveillance program sponsored by the Centers for Disease Control and Prevention/U.S. Food and Drug Administration. Headache is a common symptom of multiple vaccines post-licensure, yet systematic investigations are lacking.
 Methods: 
We searched the VAERS database to identify reports of headache after receipt of any vaccine in the U.S. during the time period from January 1990 to August 2015. We evaluated epidemiological features, including event characteristics, demographics and vaccine type.
 Results: 
Headache was the 5th most commonly reported symptom after fever, injection site reactions, pain, and rash. We retrieved 28,286 reports of headache. The majority(94.60[percnt])were unspecified headache types; however, 29[percnt] also had nausea or vomiting. Only 1,344 cases of migraine were reported, representing 4.75[percnt] of all the headache cases. The onset was within one day of vaccination in 69[percnt] of cases. Headache resulted in 11,162 (39.5[percnt]) emergency room visits, 2,426 (8.5[percnt]) hospitalizations, and 833 (2.94[percnt]) cases of permanent disability by report. There were 3,159 cases (11.17[percnt]) considered serious. Females accounted for 19,187 reports (67.83[percnt]) and males accounted for 8,801 reports (31.11[percnt]). Patient age range spanned from infants to the elderly; 75[percnt] of cases reported were between 6-59 years of age. Reports of headache per year increased in number since 1990, with the majority of cases (10.93[percnt]) reported in 2009. Vaccine against Influenza virus and Hepatitis B virus were those most frequently associated with headache, accounting for over a third of cases.
 Conclusions: 
Headache is a commonly reported vaccine related adverse event; a small subset of reports were considered serious. The development of vaccine-related classification criteria may be useful to better evaluate headache as an adverse event. Disclosure: Dr. Cocores has nothing to disclose. Dr. Monteith has nothing to disclose.

Post-Vaccination Headache Reporting Trends According to the Vaccine Adverse Events Reporting System (VAERS) (P1.147)

This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID‐19) and as a post‐COVID‐19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).

Headache as a COVID‐19 onset symptom and post‐COVID‐19 symptom in hospitalized COVID‐19 survivors infected with the Wuhan, Alpha, or Delta SARS‐CoV‐2 variants

Coronavirus disease 2019 is an acute respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. As the virus spreads rapidly, it has become a major public health emergency, which has led to rapid vaccines development. However, vaccines can present harmful and unintended responses, which must be notified to the National Pharmacovigilance System. The aim of this study is to characterize the adverse drug reactions (ADRs) of these vaccines notified in the region covered by the Regional Pharmacovigilance Unit (RPU) of Beira Interior, in Portugal, between 1 and 31 December 2020. During this period, 4 vaccines were administered: Comirnaty®, Spikevax®, Vaxzevria® and Jcovden®. The RPU of Beira Interior received 2134 notifications corresponding to 5685 ADRs, of which 20.34% (n = 434) of the notifications were considered serious reactions. Of these, 9.52% (n = 42) resulted in hospitalization and 0.45% (n = 2) resulted in death. Among the ADRs notified, reactions at or around the injection site, myalgia, headaches and pyrexia were the most commonly notified. Most ADRs were resolved within a few hours or days without sequelae. These ADRs are in accordance with clinical trials, the summary of product characteristics (SmPC) of each vaccine and ADR notifications from other countries. However, further studies are needed to confirm these results.

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COVID-19 Vaccines Adverse Reactions Reported to the Pharmacovigilance Unit of Beira Interior in Portugal

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Results of a Web-Based Survey on 2105 Greek Migraine Patients—Second Part: Efficacy of Acute and Prophylactic Migraine Treatments and Corresponding Patients’ Reported Satisfaction

Abstract Background Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. Methods We searched PubMed and EMBASE covering the period between January 1 st 2020 and August 6 th , 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. “traditional” vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. Results Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18–27%) of subjects after the first dose of vaccine and in 29% (95% CI 23–35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10–12% of cases. No differences were detected across different vaccines or by mRNA-based vs. “traditional” ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. Conclusions Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40–60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid. 

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Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis

Daclizumab, a MS treatment targeting IL2-receptor, has been recently withdrawn following reports of immune-mediated encephalitis. We report the case of a 39-years-old woman treated with daclizumab that presented a progressive decrease in the strength at her lower limbs which further worsened after the drug was stopped. Post-treatment MRI showed more than 20 new enhancing lesions. No symptoms nor signs associated with immune-mediated encephalitis were present. Our case highlights the problem of disease course after daclizumab discontinuation and urge neurologists to strictly monitor patients discontinuing the drug in order to exclude both the occurrence of immune-mediated encephalitis and disease reactivation.

Micaela Robotti

Papers

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis

Severe disease activity in a patient with multiple sclerosis after daclizumab discontinuation