Following on from the devastating spread of COVID-19, a major global priority has been the production, procurement, and distribution of effective vaccines to ensure that the global pandemic reaches an end. However, concerns were raised about worrying side effects, particularly the occurrence of thrombosis and thrombocytopenia after administration of the Oxford/AstraZeneca and Johnson & Johnson's Janssen COVID-19 vaccine, in a phenomenon being termed vaccine-induced thrombotic thrombocytopenia (VITT). Similar to heparin-induced thrombocytopenia (HIT), this condition has been associated with the development of anti-platelet factor 4 antibodies, purportedly leading to neutrophil-platelet aggregate formation. Although thrombosis has also been a common association with COVID-19, the precise molecular mechanisms governing its occurrence are yet to be established. Recently, increasing evidence highlights the NLRP3 (NOD-like, leucine-rich repeat domains, and pyrin domain-containing protein) inflammasome complex along with IL-1β and effete neutrophils producing neutrophil extracellular traps (NETs) through NETosis. Herein, we propose and discuss that perhaps the incidence of VITT may be due to inflammatory reactions mediated via IL-1β/NLRP3 inflammasome activation and consequent overproduction of NETs, where similar autoimmune mechanisms are observed in HIT. We also discuss avenues by which such modalities could be treated to prevent the occurrence of adverse events and ensure vaccine rollouts remain safe and on target to end the current pandemic. INTRODUCTIONEver since COVID-19, caused by SARS-CoV-2, was declared by the World Health Organization (WHO) as a global pandemic, the leading global strategy against this disease has been the effective development, procurement, and distribution of vaccines. Indeed, many vaccines have been authorized by global regulatory authorities since December 2020. 1,2 Coronaviruses are large single-stranded positive-sense RNA viruses with a helical nucleocapsid (N) and an envelope composed of matrix protein (M), an envelope protein (E), and spike protein (S). The spike protein is the receptor-binding site for angiotensin-converting enzyme 2 for viral entry into the cell.The developmental stage of the COVID-19 vaccine saw various approaches, all of which utilize S protein as the immunogen: recombinant vaccines using viral vectors; nucleic acid vaccines or mRNA vaccines; inactivated vaccines; nanoparticle or virus-like particle vaccines; protein subunit vaccines; and live attenuated vaccines. 3,4 However, as one would expect from vaccines developed at such an unprecedented pace, several side effects have been reported termed adverse events of special interests (AESI). Variable AESIs observed include acute myocardial infarction, hemorrhagic/nonhemorrhagic stroke, deep vein thrombosis, pulmonary embolism, Bell's palsy,

COVID-19 is an airway disease that has affected ~125 million people worldwide, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), spread through respiratory droplets, direct contact, and aerosol transmission. Although most patients presenting with absent or mild symptoms recover completely, the highest morbidity and mortality rates are seen in the elderly, and patients with comorbidities such as cardiovascular diseases, cancer, immunosuppressive diseases, diabetes, and pre-existing respiratory illnesses. Several therapeutic strategies have been examined, but a wide-ranging therapeutic option for particularly severe cases of COVID-19 remains to be elucidated. Considering the indications presented by COVID-19 patients who present similarly with inflammatory conditions, intravenous immunoglobulin (IVIG) administration has been examined as a possible route to reduce proinflammatory markers such as ESR, CRP and ferritin by reducing inflammation, based on its anti-inflammatory effects as indicated by utilisation of IVIG for numerous other inflammatory conditions. Herein, summarising the recent key clinical evaluations of IVIG administration, we present our hypothesis that administration of IVIG within a specific dosage would be extremely beneficial towards reducing mortality and perhaps even the length of hospitalisation of patients exhibiting severe COVID-19 symptoms.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection causes life-threatening respiratory illness, which has caused significant mortality and morbidity around the globe. Coronavirus disease 2019 (COVID-19) causes mild respiratory illness in most infected individuals; however, in some patients it may progress to sepsis, acute respiratory distress syndrome (ARDS), cytokine release syndrome (CRS), and multiorgan dysfunction (MODS), which results in intensive care unit (ICU) admissions and increased fatalities. Recent evidence shows that most of these comorbidities associated with COVID-19 infection are associated with dysregulation of the host immune response. Vitamins C and D have been shown to regulate immune response by decreasing the proinflammatory cytokine release from immune cells and inducing proliferation of other immune cells to robustly fight infection. This review critically evaluates the current literature on vitamins C and D in modulating an immune response in different diseases and their potential therapeutic effects in preventing complications in COVID-19 infection.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare disease with an unknown etiology which most commonly results in subacute diplopia and ataxia. Diagnosis is achieved through a triad of the following findings: lymphocytic pleocytosis with increased CD4+ T cells on cerebrospinal fluid (CSF) analysis; perivascular punctate and curvilinear hemorrhages in the pons, medulla, or cerebellum on magnetic resonance imaging (MRI) with contrast; and the cessation of symptoms after the initiation of corticosteroids. Here, we report the case of a 23-year-old male who presented with non-specific signs and symptoms, including diffuse weakness in all limbs, ataxia, and slurred speech. The diagnosis was achieved through a contrast MRI of the brain, suggestive of brainstem encephalitis, and a CSF analysis, which revealed elevated glucose and protein levels. Intravenous methylprednisolone was administered for five days and resulted in acute improvement of the patient's clinical status. Repeat CSF analysis and MRI of the brain with contrast two weeks later showed resolution of previous findings. CLIPPERS syndrome is a newly identified disease thought to cause a predominantly inflammatory reaction in the pons, medulla, cerebellum, and supratentorial region. MRI with contrast tends to reveal a "salt and pepper appearance" in a punctate and curvilinear fashion. The hallmark of treatment is corticosteroid therapy, and discontinuation of therapy should be done with caution as relapse of the syndrome with corticosteroid withdrawal has been documented.

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