Summary
Background
Chilblains (‘COVID toes’) are being seen with increasing frequency in children and young adults during the COVID‐19 pandemic. Detailed histopathological descriptions of COVID‐19 ...chilblains have not been reported, and causality of SARS‐CoV‐2 has not yet been established.
Objectives
To describe the histopathological features of COVID‐19 chilblains and to explore the presence of SARS‐CoV‐2 in the tissue.
Methods
We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID‐19 pandemic. Immunohistochemistry for SARS‐CoV‐2 was performed in all cases and electron microscopy in one.
Results
Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS‐CoV‐2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.
Conclusions
Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS‐CoV‐2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID‐19 chilblains and perhaps also in a group of patients severely affected by COVID‐19 presenting with features of microangiopathic damage.
What is already known about this topic?
Despite the high number of cases of chilblains seen during the COVID‐19 pandemic, a definite causative role for SARS‐CoV‐2 has not yet been proven.
Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors.
What does this study add?
The demonstration of SARS‐CoV‐2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID‐19.
Virus‐induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID‐19 chilblains.
Our findings support the hypothesis that widespread endothelial infection by SARS‐CoV‐2 could have a pathogenetic role in the severe forms of COVID‐19.
Linked Comment: Wetter. Br J Dermatol 2020; 183:611.
Linked Comment: Wetter. Br J Dermatol 2020; 183:611.
Plain language summary available online
Abstract
Background
In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.
Methods
Demographic and clinical data of all confirmed cases with COVID-19 on ...admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection.
Results
Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases.
Conclusions
The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
Dysregulation of immune response, especially T lymphocytes, might be highly involved in the pathological process of COVID-19. Surveillance of neutrophil-to-lymphocyte ratio and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure
, but little is known about its pathophysiology. Here we generated single-cell ...atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63
intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
Scientists are piecing together how SARS-CoV-2 operates, where it came from and what it might do next -- but pressing questions remain about the source of COVID-19.
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