ABSTRACT
This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I2 = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I2 = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I2 = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , COVID-19/therapy , Humans , Immunization, Passive/methods , Randomized Controlled Trials as Topic , COVID-19 SerotherapyABSTRACT
Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases.