Administration of vaccine-boosted COVID-19 convalescent plasma to SARS-CoV-2 infected hamsters decreases virus replication in lungs and hastens resolution of the infection despite transiently enhancing disease and lung pathology

Abstract

The utility of COVID-19 convalescent plasma (CCP) for treatment of immunocompromised patients who are not able to mount a protective antibody response against SARS-CoV-2 and who have contraindications or adverse effects from currently available antivirals remains unclear. To better understand the mechanism of protection in CCP, we studied viral replication and disease progression in SARS-CoV-2 infected hamsters treated with CCP plasma obtained from recovered COVID patients that had also been vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. We found that Vaxplas dramatically reduced virus replication in the lungs and improved infection outcome in SARS-CoV-2 infected hamsters. However, we also found that Vaxplas transiently enhanced disease severity and lung pathology in treated animals likely due to the deposition of immune complexes, activation of complement and recruitment of increased numbers of macrophages with an M1 proinflammatory phenotype into the lung parenchyma.

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS‐CoV‐2 infection and vaccination

“…developed acute kidney injury and worsened pulmonary outcomes. 37 Despite these findings in animal models and clinical trials of CCP in patients with COVID-19, we found no association between exposure to plasma-containing blood products and adverse outcomes in SARS-CoV-2 negative patients during the COVID-19 pandemic. We hypothesized that patient outcomes other than mortality might be more sensitive to a potential antibody-mediated effect.…”

“…As noted, SARS‐CoV‐2 infection followed by vaccination of blood donors is known to result in dramatic boosting of binding and neutralizing antibodies in CCP 15 . Hamsters infected with SARS‐CoV‐2 who were infused with pooled vaccine‐boosted donor CCP (but not pooled normal titer CCP donor plasma or control plasma) developed acute kidney injury and worsened pulmonary outcomes 37 …”

Immunological sub-phenotypes and response to Convalescent Plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial.

“…Second, the panel of biomarkers that we used studies the innate immune and in ammatory response to viral infection, while CP is supposed to act via antibodies neutralizing SARS-CoV-2 [31] by reducing the quantity of viable virus in infected tissues, in this case the lung parenchyma. This action is located upstream of the in ammatory response.…”

The Keratinocyte in the Picture Cutaneous Melanoma Microenvironment

“…MC1R genetic variants are determinant also in the acquisition of skin aging-related features [ 45 , 46 ] including specific dermal variation during photoaging [ 47 , 48 ]. Since properties referred to functional aging of the skin have been associated with the potential pro-tumorigenic phenotype of fibroblast [ 49 , 50 ], impaired functionality of the (α-melanocyte stimulating hormone) α-MSH/MC1R axis might contribute to creating a favorable milieu for hyperproliferative diseases in photo-exposed bodies’ area. Notably, in the skin, the features of senescent fibroblast largely overlap with those of fibroblast associated with neoplastic cells [ 51 ].…”