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Background: Interruption of GM-CSF signaling leads to Pulmonary Alveolar Proteinosis (PAP), occasionally to lung infections and relates to the impaired ability of lung macrophages to catabolize phagocytized surfactant and handle microbes. COVID-19 is associated with worse prognosis in lung disorders. We hypothesized that PAP patients would be at increased risk for COVID-19 and poor outcome. Aim and objectives: This multi-center, retrospective, European study aimed to investigate prevalence and clinical consequences of COVID-19 in PAP and the impact of iGM-CSF treatment on hospitalization or death. Method(s): All patients with PAP and COVID-19 diagnosed and followed-up in 11 referral European centers from January 24th 2020 to August 31st 2021 were included. Prevalence, clinical course and outcome were investigated. Result(s): COVID-19 developed in 34/255 (13.3%) of patients, mostly adults (91.2%), all with autoimmune (a)PAP;all patients were infected before the preventive option of vaccination was available;11 (35.5%) were hospitalized, of whom almost half were in the ICU;3 (27%) of hospitalized patients either died or underwent lung-transplant;these three patients had worse DLCO% predicted (p=0.019) and had more often arterial hypertension (AH) (p=0.012), and a smoking history (p=0.002). All patients with mild disease treated at home survived. Among children, 3 developed COVID-19 with good outcome. Conclusion(s): PAP patients experienced similar rates of COVID-19 with the general population but increased rates of hospitalizations and deaths, underscoring the vulnerability of this population and the necessity of preventive measures to avoid infection. If infected, secondary prophylaxis with monoclonal antibodies and the impact of iGM-CSF must be considered.
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The present article provides an overview of the key messages of the plenary lectures on severe acute respira‑ tory syndrome coronavirus type 2 (SARS‑CoV‑2) infection in children, which were presented at the ‘6th Workshop on Paediatric Virology' organised by the Institute of Paediatric Virology on October 24, 2020. SARS‑CoV‑2 is a novel © 2021 Polish Otolaryngology Society. All rights reserved.
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Background and aims: Cerebral venous sinus thrombosis (CVST) has been acknowledged as a rare adverse event related to thrombosisthrombocytopenia syndrome (TTS) following COVID-19 vaccination. Methods: A systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases was performed, with the aim to calculate the odds ratio of TTS-CVST versus non-TTS-CVST (1) after vector-based vaccines and (2) after non-vector-based vaccines;(3) the inhospital mortality ratio of TTS-CVST compared to non-TTS-CVST;and (4) the dependency or death at discharge among TTS-CVST compared to non-TTS-CVST cases. Results: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS-CVST (OR: 52.34, 95%CI: 9.58-285.98). TTS-CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29;95%CI: 3.96-44.60) and death or dependency at discharge compared to non-TTS-CVST (OR: 6.70;95%CI: 3.15-14.26). TTS-CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):- 6.54 days;95%CI:-12.64 - -0.45], affecting younger patients (MD:-9.00 years;95%CI: -14.02 - -3.99) without risk factors for thromboses (OR:2.34;95%CI: 1.26-4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60;95%CI: 1.31-9.87) and concomitant thromboses in other sites (OR:11.85;95%CI: 3.51-39.98) compared to non-TTS-CVST cases. Conclusions: TTS-CVT following COVID-19 has distinct clinical phenotype and prognosis compared to non-TTS-CVT. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS-CVT cases following COVID-19 vaccination.
ABSTRACT
OBJECTIVES: To describe the placental pathology, fetal autopsy findings and clinical characteristics of pregnancies that resulted in stillbirth owing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, and to identify potential risk factors. METHODS: This was a prospective multicenter study of non-vaccinated pregnant women affected by coronavirus disease 2019 (COVID-19) in Greece from April 2020 to August 2021. A total of 165 placentas were examined histologically and six cases of stillbirth associated with SARS-CoV-2 placentitis were retrieved. Complete fetal autopsy was performed in three of these cases. Gross, histopathological, immunohistochemical, molecular and electron microscopy examinations were carried out in the stillbirth placentas and fetal organs. The histological findings of cases with SARS-CoV-2 placentitis were compared with those in 159 cases with maternal COVID-19 which resulted in a live birth. Regression analysis was used to identify predisposing risk factors for SARS-CoV-2 placentitis. RESULTS: The placentas of all six stillborn cases showed severe and extensive histological changes typical of SARS-CoV-2 placentitis, characterized by a combination of marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage, associated with intensely positive immunostaining for SARS-CoV-2 spike protein, the presence of virions on electron microscopy and positive reverse-transcription polymerase chain reaction test of placental tissues. The histological lesions obliterated over 75% of the maternal intervillous space, accounting for intrauterine fetal death. Similar histological lesions affecting less than 25% of the placenta were observed in seven liveborn neonates, while the remaining 152 placentas of COVID-19-affected pregnancies with a live birth did not show these findings. Complete fetal autopsy showed evidence of an asphyctic mode of death without evidence of viral transmission to the fetus. The mothers had mild clinical symptoms or were asymptomatic, and the interval between maternal COVID-19 diagnosis and fetal death ranged from 3 to 15 days. Statistically significant predisposing factors for SARS-CoV-2 placentitis included thrombophilia and prenatally diagnosed fetal growth restriction (FGR). Multiple sclerosis was seen in one case. CONCLUSIONS: SARS-CoV-2 placentitis occurred uncommonly in COVID-19-affected pregnancies of non-vaccinated mothers and, when extensive, caused fetal demise, with no evidence of transplacental fetal infection. Thrombophilia and prenatally detected FGR emerged as independent predisposing factors for the potentially lethal SARS-CoV-2 placentitis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.