Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell expression of ISGs and genes involved in IFN-α signaling, while upregulation of TNF-induced genes was observed in moderate disease. NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates prolonged IFN-α-induced NK cell response with poorer disease outcome.
Background: The German government has made it mandatory to wear respiratory masks covering mouth and nose (MNC) as an effective strategy to fight SARS-CoV-2 infections. In many countries, this directive has been extended on shopping malls or public transportation. The aim of this paper is to critically analyze the statutory regulation to wear protective masks during the COVID-19 crisis from a medical standpoint. Methods: We performed an extensive query of the most recent publications addressing the prevention of viral infections including the use of face masks in the community as a method to prevent the spread of the infection. We addressed the issues of practicability, professional use, and acceptability based on the community and the environment where the user resided. Results: Upon our critical review of the available literature, we found only weak evidence for wearing a face mask as an efficient hygienic tool to prevent the spread of a viral infection. However, the use of MNC seems to be linked to relevant protection during close contact scenarios by limiting pathogen-containing aerosol and liquid droplet dissemination. Importantly, we found evidence for significant respiratory compromise in patients with severe obstructive pulmonary disease, secondary to the development of hypercapnia. This could also happen in patients with lung infections, with or without SARS-CoV-2. Conclusion: Epidemiologists currently emphasize that wearing MNC will effectively interrupt airborne infections in the community. The government and the politicians have followed these recommendations and used them to both advise and, in some cases, mandate the general population to wear MNC in public locations. Overall, the results seem to suggest that there are some clinically relevant scenarios where the use of MNC necessitates more defined recommendations. Our critical evaluation of the literature both highlights the protective effects of certain types of face masks in defined risk groups, and emphasizes their potential risks.
Mebendazole and albendazole are the drugs of choice for the treatment of alveolar echinococcosis. In this open-labelled observational study we present and evaluate the outcome of long-term treatment with these drugs and present results of different treatment regimens. Thirty-five patients were started on either mebendazole or albendazole at the beginning of 1992 and followed for an average of 39 months (range 12-79 months). Treatment was classed as successful if the disease had not progressed for>1 year and if there were no side-effects necessitating a change of treatment. Lack of progression was evaluated mainly using ultrasound and computed tomography and was further substantiated by laboratory tests and clinical findings. The overall success rate was 97%. An initial regimen for cases of alveolar echinococcosis was recurrence-free in 71% of those treated with mebendazole and in 78% of those treated with albendazole. Four out of five cases with progressive disease stabilized after the therapeutic regimen was changed. Seven patients received a continuous regimen with albendazole. These patients were observed over an average of 28 months (range 13-50 months) without signs of progression or significant side-effects. This open-labelled prospective study demonstrates the high therapeutic efficacy of both mebendazole and albendazole with similar response rates in the treatment of alveolar echinococcosis. Albendazole reduced costs by >40% and is easier for patients to take, further arguing in favour of its preferred use. Albendazole in alveolar echinococcosis is only licensed for intermittent application. None the less, continuous treatment is safe and well tolerated and showed promising results when applied to patients in whom other treatment regimens had failed. It should thus be strongly considered in inoperable cases or progressive disease.
In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.
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