ABSTRACT
Background Passive immunotherapies to augment the humoral immunity against virus have been associated with prevention of severe illnesses and reduction of mortality of patients with coronavirus disease 2019 (COVID-19). However, less is known about the comparative effectiveness of different types of passive immunotherapies. The aim of this study is to compare efficacy and safety of passive immunotherapy in patients with COVID-19. Methods This is a two-part network meta-analysis which evaluate the efficacy of passive immunotherapy in outpatients and hospitalized patients separately. Electronic databases, including PubMed, EMBASE, and Cochrane CENTRAL were systematically searched for articles published before 26th April 2022. Randomized clinical trials that compared COVID-19 specific antiviral antibodies, convalescence plasma and hyperimmune anti-COVID-19 Intravenous Immunoglobulin with placebo, or control plasma, or standard of care in patients with COVID-19 were included. Two authors screened the studies independently. We extracted data and assessed the risk of bias of studies using the revised Cochrane risk of bias tool (RoB 2 tool) at study level. The primary outcome for outpatients is hospitalization within 30 days from randomization and are mortality, need of invasive mechanical ventilation, and severe advent events for hospitalized patients. Results In this systematic review and network meta-analysis, data were pooled from 41 eligible randomized control trials involving 42298 participants. In the first part of network meta-analysis which is consist of 9 eligible trials with 10093 participants, compared with control, specific antiviral antibodies (odds ratio [OR]: 0.22, 95% CI: 0.16, 0.28) rather than CP (OR: 0.75, 95%CI: 0.56, 1.01) reduced the risk of hospitalization; treatment with antibody reduced a greater risk of hospitalization (OR: 0.29, 95%CI: 0.19, 0.43) when compared with CP. For the analysis of secondary outcome in outpatients, antibody (OR: 0.10, 95%CI: 0.01, 0.37) rather than CP (OR: 0.81, 95%CI: 0.23, 2.78) reduced the risk of mortality. In the second party of meta-analysis, none of the passive immunotherapy was associated with the reduction of mortality, need of invasive mechanical ventilation and severe adverse events. Furthermore, none of passive immunotherapy was associated with improvement in 6 secondary outcomes. However, in subgroup analysis, the administration of antibody was associated with improvement of mortality, need of invasive mechanical ventilation, rate of discharge, duration of hospital stay, time to death and with less adverse events. Conclusions In this network meta-analysis of clinical trials of patients with COVID-19, we found that treatment with antiviral antibodies reduced the risk of hospitalization in outpatients. Among hospitalized adult patients, all three passive immunotherapies compared with control did not result in a statistically significant improvement of the primary outcomes, but use of neutralizing antibodies may lead to improvement of primary outcomes and key secondary outcomes in seronegative patients. Further development of broader-spectrum antibodies targeting to highly conserved domain of spike protein which avoids immune escape of new variants are needed.
Subject(s)
COVID-19ABSTRACT
As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.
Subject(s)
COVID-19ABSTRACT
Abstract Background In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. Methods In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation. Results Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. Conclusions Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.
Subject(s)
Multiple Organ Failure , Shock, Septic , Respiratory Distress Syndrome , Fever , Severe Acute Respiratory Syndrome , Critical Illness , Cough , Respiratory Insufficiency , COVID-19 , LymphopeniaABSTRACT
Background. Administration of convalescent plasma may be of clinical benefit for treatment of severe acute viral respiratory infections. However, no clear evidence exists to support or oppose convalescent plasma use in clinical practice. We conducted a systematic review and meta-analysis to assess the evidence of randomized controlled trials (RCTs) in the convalescent plasma for the treatment of severe influenza. Methods. Healthcare databases were searched in February 2020. All records were screened against the eligibility criteria. Data extraction and risk of bias assessments were undertaken. The primary outcome was case fatality rates by influenza. Results. We identified 5 RCTs of severe influenza. The pooled analyses showed no evidence for a reduction in mortality (Odds Ratio (OR) 1.06; p = 0.87; I2 = 35%). We also found non significant reductions in days in ICU and hospital, and days on mechanical ventilation. There seemed to have a biological benefit of increasing HAI titer levels and decreasing influenza B virus loads and cytokines after convalescent plasma treatment. No serious adverse events was reported between two groups. Studies were commonly of low risk of bias with high quality. Conclusions. Convalescent plasma appears safe but may not reduce mortality in severe influenza. This therapy should be studied within the context of a well designed clinical trial for treatment of SARS Cov 2 infection.