Extended Shedding and Enhanced Fitness of the SARS-CoV-2 Variant of Concern B.1.1.7 in Human Organoid Systems (preprint)

A new phase of the COVID-19 pandemic has started as SARS-CoV-2 variants are emerging globally, raising concerns for increased transmissibility. Early 2021 the B.1.1.7 (or Alpha) variant, became the dominant variant globally and epidemiological data suggests this variant spreads faster than its ancestors. However, this does not prove that a variant is intrinsically phenotypically different, let alone more transmissible or fit. Therefore, rapid phenotyping of SARS-CoV-2 variants of concern is urgently needed. We found that airway, intestinal and alveolar organoids infected with the B.1.1.7 variant produced higher levels of infectious virus late in infection compared to its 614G-containing ancestor. The B.1.1.7 variant also had a clear fitness advantage in human airway organoids. In alveolar organoids, the B.1.1.7 variant induced lower levels of innate immunity. These findings suggest that the B.1.1.7 variant is phenotypically different from its ancestor and may explain why this clade has spread rapidly across the globe.Funding Information: This work was supported by Netherlands Organization for Health Research and Development (10150062010008; B.L.H.), PPP allowance (LSHM19136; B.L.H.). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 874735. Declaration of Interests: H.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers. All other authors have nothing to declare. Ethics Approval Statement: The Medical Ethical Committee of the Erasmus MC Rotterdam granted permission for this study (METC 2012-512). The study was approved by the UMC Utrecht (Utrecht, The Netherlands) ethical committee and was in accordance with the Declaration of Helsinki and according to Dutch law. This study is compliant with all relevant ethical regulations regarding research involving human participants.

Interferon-α Auto-Antibodies in Convalescent Plasma Therapy for COVID-19 (preprint)

Purpose:  To study the effect of Interferon-α auto-antibodies (IFN-α Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α Abs transfer during convalescent plasma treatment. Methods: : Sera from cases of COVID-19 and other respiratory illness were tested for IFN-αAbs by ELISA and bioassay. IFN-α Abslevels were compared between critically, severely and moderately ill groups in both acute and convalescent stages. Longitudinal analyses were performed to determine whether IFN-α Abs levels change after convalescent plasma transfusion. Results: : Critically ill COVID-19 caseshad significantly higher IFN-α Abs detection rate and levels compared tonon-COVID-19 controls.Neutralizing IFN-α Abs levels were found in 1 out of 118plasma donors.Plasma from 2 positive donors was administered to 5 patients, with no subsequent elevation of IFN-α Abs levels in the recipients. Neutralizing levels of IFN-α Abswere associated with delayed viral clearance from the respiratory tract. Conclusions: : IFN-α Abs can be detected by ELISA in critical, severe, moderate and mild COVID-19 cases in both the acute and convalescent stages of disease. The presence of neutralizing IFN-α Abs in critically ill COVID-19 is associated with delayed viral clearance. Levels of IFN-α Abs inCOVID-19 convalescent plasma donorsare likely too low to be clinically relevant to the recipients.