Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Adverse effects of hydroxychloroquine and azithromycin on contractility and arrhythmogenicity revealed by human engineered cardiac tissues.

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/- AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.

Safety and efficacy of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus-2 pneumonia: A retrospective cohort study.

Background: Cytokine release storm (CRS) in severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is thought to be the cause for organ damage and death which is independent of the actual viral burden. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for the treatment of CRS. We describe the efficacy and safety of TCZ in SARS CoV-2 pneumonia. Methods: This retrospective study was conducted at a tertiary care hospital from April 20 2020 to May 21 2020. The primary endpoint was the cumulative incidence of a composite of either need for admission to the intensive care unit (ICU) with invasive mechanical ventilation or death. Safety outcomes included an increase in liver transaminases and/or evidence of infection. Results: A total of 20 patients received TCZ during the study period. The median age was 54 years (95% confidence interval [CI] 47-63). About 85% of the patients were male. Nearly 70% of the patients had at least one comorbidity. About 55% required ICU admission. The median duration of ICU stay was 11 days (95% CI: 3-13 days). The cumulative incidence of the requirement for mechanical ventilation, clinical improvement and mortality was 11% (95% CI: 0.03%-1%), 74% (95% CI 37%-89%) and 25% (95% CI: 11%-63%), respectively. There was no difference in outcomes according to age, gender or computed tomography severity score. Asymptomatic transaminitis was the most common drug reaction (55%), and one patient developed bacteraemia. Conclusions: TCZ is likely a safe and effective modality of treatment for improving clinical and laboratory parameters of SARS CoV-2 patients with a reduction in ICU stay and ventilatory care need.