Background Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet. Objective To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection. Methods Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy. Results Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3. Conclusions Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.

Background: In Italy, the response to coronavirus disease 2019 (COVID-19) pandemic upgraded from social distancing on February 23, 2020, to national lockdown on March 11, 2020. We described how the pandemic affected a tertiary care children hospital with a dedicated COVID-19 regional center. Methods: We analyzed the characteristics of emergency department (ED) visits, urgent hospitalizations and severe acute respiratory syndrome (SARS)-COV-2 reverse transcription-polymerase chain reaction testing, and COVID-19 patients across 3 response phases: before the first Italian case, before national lockdown and during lockdown. Results: ED visits decreased from a daily mean of 239.1 before the first COVID-19 Italian case, to 79.6 during lockdown; urgent hospitalizations decreased from 30.6 to 21.2. As of April 20, 2020, 1970 persons were tested for SARS-CoV-2 reverse transcription-polymerase chain reaction and 2.6% were positive. Positive rates were 1.2% in the ED, 21.1% in the COVID center and 0.5% in other wards. The median age of COVID-19 patients (N = 33) was 6.7 years, 27% had coexisting conditions and 79% were related to family clusters. Conclusions: The pandemic strongly impacted on the use of hospital services, with a 67% reduction in ED visits and a 31% reduction in urgent hospitalizations. Separating the flows of suspected patients from all other patients, and centralization of suspected and confirmed cases in the COVID center enabled to control the risk of nosocomial SARS-CoV-2 transmission. Delay in hospital use for urgent care must be avoided, and clear communication on infection prevention and control must be provided to families. Further studies are needed to assess how the reduction in hospital use affected children healthcare needs during the pandemic.

Background: SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focussed on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. We have studied the individual response to SARS-CoV-2 of asympromatic, mild and severe COVID-19 patients in order to investigate the role of innnate and adaptive immunity in determining the clinical course after first infection. Methods: To understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: (28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; 8 patients with mild COVID-19 disease and 8 cases of severe COVID-19 disease). Results: Our data show that high frequency of NK cells and early and transient increase of specific IgA and, to a lower extent, IgG are associated to asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and rapidly declining antibodies are detected in mild COVID-19. Conclusions: The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.