Occurrence of adverse drug reactions after Comirnaty® vaccine administration against SARS-CoV-2 in healthcare workers: a pilot study

Objective: A prospective observational study aimed at monitoring adverse drug reactions (ADR) in healthcare workers after a SARS-CoV-2 vaccination campaign was started in January 2021. We report preliminary results obtained from the pilot study. Methods: The first 300 Sars-CoV-2 vaccinated subjects (2 Comirnaty® (BioNTech, Pfizer) doses administrated 21 days apart) that signed informed consent were enrolled in the pilot study. For each patient, age, sex, body-mass-index (BMI), ADRs after vaccination and SARS-Cov-2-antibodies titer (quantitative evaluation of the neutralizing S1-RBD-IgG using Anti-SARS-CoV-2 QuantiVac ELISA (IgG)® Euroimmun diagnostic assay) were collected. The evaluation of SARS-Cov-2-antibodies was performed at the time of first dose administration (T0) and followed by four subsequent evaluations at different time-points. ADR developed within the first 8 days after the first and second dose were recorded. Exclusion criterion were cases with incomplete data. ADRs were divided into local (at injection site) and systemic, and their occurrence was correlated to sex, BMI and presence of SARS-Cov-2-IgG at T0. Fisher's exact test, Wilcoxon-Mann-Whitney test and multivariate logistic regression models were used for statistical analyses;p < 0.05 was considered significant. Results: In total 297 subjects (72.4% females;98.9% Caucasians, mean age 47 years) were included. Fifty (16.5%) subjects were positive for SARS-CoV-2-antibodies at T0. ADRs were reported in 67% and 74.1% of subjects after the first and second dose, respectively. Systemic ADRs were more common after the second dose (59.1% of subjects) compared to the first dose (31.4%). Systemic ADRs were reported in 44% of subjects positive for SARS-CoV-2 antibodies (22/50) and in only 28.9% of negative subjects (71/246) (p=0.044);this correlation was significant for fever (p=0.017) and lymphadenopathy (p=0.008). Systemic ADRs after the first dose occurred in 36.7% (79/215) of females and in 17.1% (14/82) of males (p=0.0012), while they occured in 63.7% (137/215) and 46.34% (38/82) after the second dose, respectively (p=0.0082). No correlation was found between ADR and BMI after both doses. Conclusion: These preliminary results demonstrate higher prevalence of systemic ADRs after a second dose and a positive correlation between female and ADRs after both the first and second doses. Moreover, there was a positive correlation between the presence of SARS-CoV-2-antibodies and systemic ADRs after the first dose. These data support the hypotheses that systemic reactions (fever, lymphadenopathy) could be a clinical expression of immune system reactivity to vaccination, which is greater in subjects with SARS-CoV-2-antibodies at the time of the first administration. These results will require confirmation from a greater sample size.

Iodoform medications may cause iodine toxicosis: Two case reports

Objective: Iodine is an essential oligoelement involved in the synthesis of thyroid hormones. Iodine is also used to promote antisepsis and iodoform medications release iodine and are commonly used for septic ulcers and surgery lesions. Few cases of iodine/iodoform toxicity due to systemic absorption from topical/ dermal application have been reported [1,2]. We report two cases of neurologic impairment and transient hypothyroidism induced by excess systemic absorption of iodoform after prolonged and extensive medications. Case series: Case 1. A 64-year-old male hospitalized for COVID-19 pneumonia, presented Klebsiella pneumoniae carbapenemase sepsis associated with decubitus ulcers, that were treated with iodoform gauze medication. After three medications, he developed diarrhoea, xerostomia and lethargy. Blood analysis showed renal impairment with creatinine 3.1 mg/dL and a total calcemia of 11mg/dL. Suspecting iodine poisoning, urine and serum concentrations were performed and were respectively 14,517 μg/L and 2,400 μg/L. Free thyroxine (FT4) was 13.80 ng/L (normal 9.30-17.00), thyroid stimulating hormone (TSH) 6.160 mIU/L (normal 0.270-4.200). A few days later, he died from multiorgan failure. Case 2. A 56-year-old male was admitted to hospital for severe traumatic perianal injury. After surgery, he was stable and treated with iodoform gauze medications, but presented with acute inhibition of thyroid hormone synthesis (Wolff-Chaikoff effect) with TSH 10.500 mIU/L and FT4 16.70 ng/L. Urinary and serum iodine concentrations were 53,500 and 1,087 μg/L, respectively. The patient gradually recovered normal thyroid function after discontinuation of iodoform treatment. Conclusion: Iodine/iodoform poisoning is an underestimated clinical event. Extensive surface and prolonged application are risk factors for developing toxicity. Thyroid function is efficiently regulated even with excessive iodine (Wolff-Chaikoff mechanism). However, in these patients, iodine/iodoform toxicity may be suspected when a new impairment occurs, including disturbance of consciousness, diarrhoea, liver dysfunction, renal failure, and metabolic acidosis. Iodoform (CHI3) is similar to chloroform (CHCl3) in molecular structure and has a similar anaesthetic effect [1]. Moreover, it is lipid soluble and may easily pass the bloodbrain barrier, causing headache, disorientation, delirium and coma. Urinary and serum iodine concentration can be useful in clinical practice to confirm and estimate the degree of toxicity;however, it seems that these values may be higher in iodine and lower in iodoform toxicity.

Foodborne botulism: A large outbreak in Sicily

Objective: In September-October 2020 our Poison Centre (PC) managed a cluster of 44 workmen who consumed food contaminated by botulinum neurotoxins (BoNT) at a workplace canteen in Sicily. Case series: Of the 100 workers using the canteen, 44 presented over a 7-day period to 6 Emergency Departments (ED) in Southern Italy complaining of neurological and gastrointestinal symptoms (Table 1). Our PC, consulted first by physicians in Cefalù, made the diagnostic suspicion of foodborne botulism. Heptavalent-botulism-antitoxin (HBAT) was mobilized from different National Stockpiles (Catania, Pavia, Rome, Trieste, Naples) after approval from the Ministry of Health (MoH). The early admitted patients (7/44, 17%, 2-days after meal) worsened rapidly and 5/7 required mechanical ventilation (MV) within 24 hours. Patients with minor symptoms were discharged and managed with telephone follow-up by PC toxicologists. Conclusion: Botulism diagnosis is based on clinical suspicion;laboratory testing has a crucial role in confirmation, but analyses do not always demonstrate BoNT (15/36 tested positive in our cluster). Therefore, the positivity of at least 1 patient of a cluster confirms the diagnosis. The antitoxin should be administered as soon as clinical suspicion is made. In our outbreak, HBAT was administered due to rapid worsening of neurological symptoms, in order to prevent MV. The rapid deterioration of the first 7 patients is attributable to the ingestion of higher titre of toxin. In Italy, HBAT in the National Stockpile can be mobilized only after MoH approval. The management of the outbreak was challenging because of difficulties in the capacity of the hospitals and the urgent need for antitoxin. An efficient collaboration between local physicians, clinical toxicologists, MoH and the National Stockpile system ensured optimal management with prompt HBAT mobilization in sufficient number. This was also possible because it occured before the second COVID-19 wave in which it would have been difficult to manage 44 patients potentially requiring ICU monitoring.