ABSTRACT
COVID-19 convalescent plasma (CCP) use between October-December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations, and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance.
ABSTRACT
Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity. Here we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations (Vax) with or without recent Omicron COVID-19, as well as infection without vaccination (CCP) to determine level of BQ.1.* neutralizing antibodies and percent of plasma samples with neutralizing activity. More than 90â% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, and BF.7 with 100â% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50â% neutralizing titres (GM (GMT50) were 314, 78 and 204 for BQ.1.1, XBB.1 and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently (within 6 months) received at least a third vaccine dose had about half of the GM (GMT50) for all viral variants. Boosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, neutralizing antibody source against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/prevention & control , Vaccination , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
INTRODUCTION: When the COVID-19 pandemic struck no specific therapies were available and many turned to COVID-19 convalescent plasma (CCP), a form of antibody therapy. The literature provides mixed evidence for CCP efficacy. AREAS COVERED: PubMed was searched using the words COVID-19 and convalescent plasma and individual study designs were evaluated for adherence to the three principles of antibody therapy, i.e. that plasma 1) contain specific antibody; 2) have enough specific antibody to mediate a biological effect; and 3) be administered early in the course of disease. Using this approach, a diverse and seemingly contradictory collection of clinical findings was distilled into a consistent picture whereby CCP was effective when used according to the above principles of antibody therapy. In addition, CCP therapy in immunocompromised patients is useful at any time in the course of disease. EXPERT OPINION: CCP is safe and effective when used appropriately. Today, most of humanity has some immunity to SARS-CoV-2 from vaccines and infection, which has lessened the need for CCP in the general population. However, COVID-19 in immunocompromised patients is a major therapeutic challenge, and with the deauthorization of all SARS-CoV-2-spike protein-directed monoclonal antibodies, CCP is the only antibody therapy available for this population.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Pandemics , COVID-19 Serotherapy , Immunization, Passive , Antibodies, MonoclonalABSTRACT
Monoclonal antibodies (mAbs) targeting the spike protein of SARS-CoV-2 have been widely used in the ongoing COVID-19 pandemic. In this paper, we review the properties of mAbs and their effect as therapeutics in the pandemic, including structural classification, outcomes in clinical trials that led to the authorisation of mAbs, and baseline and treatment-emergent immune escape. We show how the omicron (B.1.1.529) variant of concern has reset treatment strategies so far, discuss future developments that could lead to improved outcomes, and report the intrinsic limitations of using mAbs as therapeutic agents.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus , Pandemics , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/therapeutic use , Antibodies, NeutralizingABSTRACT
Measurement of antibody content and function after a viral illness is important for diagnosis and selection of the best convalescent plasma (CP) units for passive immunization. Zhang et al. (mBio 14:e03523-22, 2013, https://doi.org/10.1128/mbio.03523-22) analyzed over 19,000 coronavirus disease 2019 (COVID-19) CP (CCP) samples from the early days of the COVID-19 pandemic and reported a moderately strong correlation between antibody amount and neutralizing titer. Strikingly, about one-third of the samples had little or no neutralizing activity. The results provide a detailed glimpse of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunologically naive humans and reveal major differences in the quality of CP units collected for passive therapy before antibody screening. Heterogeneity in CCP quality undoubtedly contributed to the variable therapeutic efficacy. Analysis of the COVID-19 serology data suggest that, for the next infectious disease emergency, the best approach after quick establishment of methods for robust antibody-level stratification would be to use CP units in the top quintile of antibody content and neutralizing capacity.
Subject(s)
COVID-19 , Humans , COVID-19/therapy , SARS-CoV-2 , Pandemics , Antibodies, Viral , COVID-19 Serotherapy , Antibodies, Neutralizing , Immunization, Passive/methodsSubject(s)
COVID-19 , Humans , COVID-19/therapy , COVID-19 Serotherapy , SARS-CoV-2 , Treatment OutcomeABSTRACT
When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , PandemicsABSTRACT
When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , PandemicsABSTRACT
When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.
Subject(s)
COVID-19 , Pandemics , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , Laboratories/standards , Research/standards , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Scientific Experimental Error , Viral Zoonoses/transmission , Viral Zoonoses/virology , Chiroptera/virology , Animals, Wild/virologyABSTRACT
COVID-19 in immunocompromised hosts has emerged as a difficult therapeutic management problem. Immunocompromised hosts mount weak responses to SARS-CoV-2 and manifest infection outcomes ranging from severe disease to persistent infection. Weakened immune systems mean greater viral loads and increased opportunities for viral evolution. Gupta, Konnova, et al. report the emergence of resistant SARS-CoV-2 variants in immunocompromised patients after monoclonal antibody (mAb) therapy. mAbs target only a single determinant in the viral Spike protein, which is a weakness of such therapy when treating a mutagenic and variable virus. Hence, the emergence of mAb resistance could have been anticipated, but its documentation is important because it has major public health implications, since such resistant variants have the potential to spread and escape vaccine immunity. For immunocompromised patients, these findings suggest the need for combination therapy with antiviral drugs and the use of polyclonal antibody preparations such as convalescent plasma.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Antibodies, Monoclonal/therapeutic use , Public Health , COVID-19 Serotherapy , Immunocompromised Host , Antibodies, Viral , Antibodies, NeutralizingABSTRACT
Invasive fungal diseases are rare in individuals with intact immunity. This, together with the fact that there are only a few species that account for most mycotic diseases, implies a remarkable natural resistance to pathogenic fungi. Mammalian immunity to fungi rests on two pillars, powerful immune mechanisms and elevated temperatures that create a thermal restriction zone for most fungal species. Conditions associated with increased susceptibility generally reflect major disturbances of immune function involving both the cellular and humoral innate and adaptive arms, which implies considerable redundancy in host defense mechanisms against fungi. In general, tissue fungal invasion is controlled through either neutrophil or granulomatous inflammation, depending on the fungal species. Neutrophils are critical against Candida spp. and Aspergillus spp. while macrophages are essential for controlling mycoses due to Cryptococcus spp., Histoplasma spp., and other fungi. The increasing number of immunocompromised patients together with climate change could significantly increase the prevalence of fungal diseases.
Subject(s)
Mycoses , Animals , Fungi , Humans , Immunity, Innate , Immunocompromised Host , Macrophages , MammalsABSTRACT
BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120â hours and negative SARS-CoV-2 test within 24â hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 RT-PCR positivity. Of the remaining 168 participants, 12/81 (14·8%) CCP and 13/87 (14·9%) control recipients developed SARS-CoV-2 infection; 6 (7·4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25·3 vs. 25·2 days; p = 0·49) and COVID-19 (26·3 vs. 25·9 days; p = 0·35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, while appearing safe, did not prevent SARS-CoV-2 infection.