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Convalescent plasma therapy against the emerging SARS-CoV-2 variants: Delineation of the potentialities and risks.

ABSTRACT: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a catastrophic pandemic and severely impacted people's livelihoods worldwide. In addition, the emergence of SARS-CoV-2 variants has posed a severe threat to humankind. Due to the dearth of therapeutic options during the commencement of the pandemic, convalescent plasma therapy (CPT) played a significant part in the management of patients with severe form of COVID-19. Several recent studies have proposed various protective effects of CPT, such as antiviral, anti-inflammatory, anti-thrombotic, and immunomodulatory actions, curtailing the devastating consequences of the SARS-CoV-2 infection. On the contrary, several clinical studies have raised some serious concerns about the effectiveness and reliability of CPT in the management of patients with COVID-19. The protective effects of CPT in severely ill patients are yet to be proved. Moreover, the emergence of SARS-CoV-2 variants has raised concerns about the effectiveness of CPT against COVID-19. Therefore, to establish concrete evidence of the efficacy of CPT and adjudicate its inclusion in the management of COVID-19, an updated review of present literature is required, which could help in the development of an efficient therapeutic regimen to treat COVID-19 amid the emergence of new viral variants.

SUBMITTER: Dhawan M

PROVIDER: S-EPMC8717699 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), harboring spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) mutations, exhibit reduced in vitro susceptibility to convalescent-phase serum, commercial antibody cocktails, and vaccine neutralization and have been associated with reinfections. The accumulation of these mutations could be the consequence of intrahost viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on steroids and convalescent plasma therapy and identify the emergence of multiple NTD and RBD mutations. SARS-CoV-2 genomes from the first swab (day 0) and from three tracheal aspirates (days 7, 21, and 27) were compared at the sequence level. We identified a mixed viral population with five different S protein mutations (141 to 144 deletion, 243 to 244 deletion, E484K, Q493K, and Q493R) at the NTD or RBD region from the second tracheal aspirate sample (day 21) and a predominance of the S protein 141 to 144 LGVY deletion and E484K mutant on day 27. The neutralizing antibodies against various S protein lentiviral pseudovirus mutants, as well as the anti-SARS-CoV-2 total Ig and IgG, showed "U" shape dynamics, in support of the endogenous development of neutralizing antibodies. The patient's compromised immune status, the antirejection regiment, convalescent plasma treatment, and the development of neutralizing antibodies may have resulted in unique selective pressures on the intrahost genomic evolution, and this observation supports the hypotheses that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune escape mutants. IMPORTANCE Over a year of the COVID-19 pandemic, distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have arisen in multiple geographic areas around the world. SARS-CoV-2 variants of concern (VOCs), i.e., B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta), harboring mutations and/or deletions in spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) regions showed evidence of increased transmissibility and disease severity and possible reduced vaccine efficacy. In this study, we report the emergence of five different NTD and RBD mutations in an uncommon SARS-CoV-2 B.1.369 lineage from an immunosuppressed patient undergoing steroid and convalescent plasma therapy. The observation highlighted that VOCs can independently arise in immunocompromised populations undergoing anti-SARS-CoV-2 therapy, and enhanced measures will be required to reduce the transmission.

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Convalescent plasma therapy against the emerging SARS-CoV-2 variants: Delineation of the potentialities and risks.

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