Apropos of menstrual changes and abnormal uterine bleeding after COVID-19 vaccination.

It is news of 28 October 2022 that the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency has recommended to add heavy menstrual bleeding among the side effects of unknown frequency inside the package insert of nucleoside-modified messenger ribonucleic acid vaccines to prevent coronavirus disease 2019 (COVID-19). The decision has been made in the light of the numerous reports of unexpected menstrual changes or abnormal uterine bleeding following COVID-19 vaccination. Here we advance a possible involvement of the particular adenohypophyseal microcirculation in these strange and still unexplained events.

Vascular "Long COVID": A New Vessel Disease?

Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as "Long Covid (LC)" disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first "endotheliitis," is often followed by production of "Neutrophil Extracellular Trap," and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis. In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible "LC" disease.

Innate Immunity Stimulation during the COVID-19 Pandemic: Challenge by Parvulan.

Aim: We report an open spontaneous anecdotical retrospective survey of Corynebacterium parvum administration to 4000 fragile immune-depressed and multimorbid patients treated with a killed C. parvum strain to enhance innate immunity, integrating the adaptative immune response for long-standing antinfectious resistance. Methods: A total of 4000 patients (1900 men and 2100 women) with mild, moderate, or chronic disease, appealing to our Second Opinion Medical Consultation Network, signed an informed consent form and were injected subcutaneously with C. parvum. The treatment was followed up to 6 months, completing the short form of the medical outcome health survey questionnaire (SF-36) directly by the patients or their parents and monitoring their health status regularly via telemedicine (Skype, WhatsApp, mail, etc.) or outpatients visits. Results: The main efficacy endpoints, as assessed by the SF-36 questionnaire are: significant improvements in the mental and physical role functioning score (p < 0.02), better general health; social role performance (p < 0.02), vitality (p < 0.03), and a significant pain reduction (p < 0.03). A quick (48-72 hours) symptoms improvement and/or complete regression of the herpetic eruptions was observed in 1000 affected patients with disappearance or relieve of herpetic neuralgia (reduced in 80% of cases); also full recovery or frequency reduction (30%) of recurrent cystitis and prostatitis in 120 affected patients. Last but not least, a life quality improvement in 100 oncologic patients of overall 200 cases. A significant increase in the lymphocyte count (p < 0.01), mainly helper and killer lymphocytes, was noted 6 months after Parvulan injection vs. the baseline. The asymptomatic SARS-CoV-2 patients who were incidentally enrolled in our survey were tested at the sixth month for antibodies against SARS-CoV-2, and 14 patients had high levels of SARS-CoV-2 antibodies. The incubating COVID infections of the Parvulan-injected patients even if frail and multimorbid recovered in short term (48-96 hours) with a benign clinical course, without need of drugs administration except for the variants, such as Delta and Omicron, whose infections lasted on average one week and required some antipyretics and low-dose steroids for a few days. Conclusions: Our results confirm that C. parvum is quite safe and effective in supporting immune-compromised patients when epidemic or pandemic events increase the life risk and any kind of infection and complication rate. Further double-blind placebo evidence-based studies are urgently required, and our numerically substantial not sponsored spontaneous observation is exclusively intended to promote further evidence-based double-blind institutional studies.

Pituitary apoplexy following adenoviral vector-based COVID-19 vaccination

Pituitary apoplexy (PA) may complicate the course of coronavirus disease 2019 (COVID-19), posing a potential threat to life. Among vaccines designed to prevent COVID-19, there are those adenoviral vector-based, such as Vaxzevria® (formerly COVID-19 Vaccine AstraZeneca). The product insert states that it can cause very rare coagulation disorders, in particular thrombosis with thrombocytopenia syndrome in some cases accompanied by bleeding, cerebrovascular venous or sinus thrombosis, and thrombocytopenia, including immune thrombocytopenia, also associated with bleeding. Here, we report the onset of PA after Vaxzevria® in a 28-year-old healthy Caucasian female, who experienced long-lasting tension-type headache, hyperprolactinemia and menstrual changes, without thrombocytopenia or thrombosis.

A Three-Case Series of Thrombotic Deaths in Patients over 50 with Comorbidities Temporally after modRNA COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19) is the most dramatic pandemic of the new millennium; to counteract it, specific vaccines have been launched in record time under emergency use authorization or conditional marketing authorization by virtue of a favorable risk/benefit balance. Among the various technological platforms, there is that exploiting a nucleoside-modified messenger RNA (modRNA), such as Comirnaty®, and that which is adenoviral vector-based. In the ongoing pharmacovigilance, the product information of the latter has been updated about the risk of thrombotic thrombocytopenia, venous thromboembolism without thrombocytopenia and immune thrombocytopenia without thrombosis. However, from an in-depth literature review, the same adverse events can rarely occur with modRNA vaccines too. In support of this, we here report a three-case series of thrombotic deaths in patients over 50 with comorbidities temporally after Comirnaty®, investigated by means of post-mortem histopathology and immunohistochemistry. In two out of three cases, the cause of death is traced back to pulmonary microthromboses rich in activated platelets, quite similar morphologically to those described in patients who died from severe COVID-19. Even if remote in the face of millions of administered doses, clinicians should be aware of the possible thrombotic risk also after Comirnaty®, in order to avoid a misdiagnosis with potentially lethal consequences. Since COVID-19 vaccines are inoculated in subjects to be protected, maximum attention must be paid to their safety, and prophylactic measures to increase it are always welcome. In light of the evidence, the product information of modRNA COVID-19 vaccines should be updated about the thrombotic risk, as happened for adenoviral vector-based vaccines.

Type 3 hypersensitivity in COVID-19 vasculitis.

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.