scholarly journals Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katie L. Kunze ◽  
Patrick W. Johnson ◽  
Noud van Helmond ◽  
Jonathon W. Senefeld ◽  
Molly M. Petersen ◽  
...  

AbstractSuccessful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

2021 ◽  
Author(s):  
Katie L. Kunze ◽  
Patrick W. Johnson ◽  
Noud van Helmond ◽  
Jonathon W. Senefeld ◽  
Molly M. Petersen ◽  
...  

AbstractSuccessful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma is likely to reflect the antigenic composition of local viral strains, we hypothesized that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to a national registry of hospitalized COVID-19 patients supported this hypothesis. These findings have implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.


2021 ◽  
Vol 8 ◽  
pp. 204993612110320
Author(s):  
Robert Rosolanka ◽  
Andres F. Henao-Martinez ◽  
Larissa Pisney ◽  
Carlos Franco-Paredes ◽  
Martin Krsak

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Teresa Aydillo ◽  
Alexander Rombauts ◽  
Daniel Stadlbauer ◽  
Sadaf Aslam ◽  
Gabriela Abelenda-Alonso ◽  
...  

AbstractIn addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans are also susceptible to six other coronaviruses, for which consecutive exposures to antigenically related and divergent seasonal coronaviruses are frequent. Despite the prevalence of COVID-19 pandemic and ongoing research, the nature of the antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here we longitudinally profile the early humoral immune response against SARS-CoV-2 in hospitalized coronavirus disease 2019 (COVID-19) patients and quantify levels of pre-existing immunity to OC43, HKU1 and 229E seasonal coronaviruses, and find a strong back-boosting effect to conserved but not variable regions of OC43 and HKU1 betacoronaviruses spike protein. However, such antibody memory boost to human coronaviruses negatively correlates with the induction of IgG and IgM against SARS-CoV-2 spike and nucleocapsid protein. Our findings thus provide evidence of immunological imprinting by previous seasonal coronavirus infections that can potentially modulate the antibody profile to SARS-CoV-2 infection.


Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.


Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 993
Author(s):  
Renuka Raman ◽  
Krishna J. Patel ◽  
Kishu Ranjan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.


2006 ◽  
Vol 193 (6) ◽  
pp. 792-795 ◽  
Author(s):  
Wei Liu ◽  
Arnaud Fontanet ◽  
Pan‐He Zhang ◽  
Lin Zhan ◽  
Zhong‐Tao Xin ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 898.1-898
Author(s):  
A. Gil-Vila ◽  
J. Perurena-Prieto ◽  
C. Nolla-Fontana ◽  
O. Orozco-Galvez ◽  
M. Miarons-Font ◽  
...  

Background:Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARS-CoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome.Objectives:Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2.Methods:Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation.Results:All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies.Conclusion:Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.References:[1]Xu Q. MDA5 should be detected in severe COVID-19 patients. Med Hypotheses. 2020; 143:109890.[2]Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020; 56:2001618.[3]Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020 Dec;79(12):1661-1663Disclosure of Interests:None declared


2021 ◽  
Author(s):  
Ruona Shi ◽  
Zhenhuan Feng ◽  
Xiaofei Zhang

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently a global pandemic. Extensive investigations have been performed to study the clinical and cellular effects of SARS-CoV-2 infection. Mass spectrometry-based proteomics studies have revealed the cellular changes due to the infection and identified a plethora of interactors for all SARS-CoV-2 components, except for the longest non-structural protein 3 (NSP3). Here, we expressed the full-length NSP3 proteins of SARS-CoV and SARS-CoV-2 to investigate their unique and shared functions using multi-omics methods. We conducted interactome, phosphoproteome, ubiquitylome, transcriptome, and proteome analyses of NSP3-expressing cells. We found that NSP3 plays essential roles in cellular functions such as RNA metabolism and immune response such as NF-kB signal transduction. Interestingly, we showed that SARS-CoV-2 NSP3 has both endoplasmic reticulum and mitochondrial localizations. In addition, SARS-CoV-2 NSP3 is more closely related to mitochondrial ribosomal proteins, whereas SARS-CoV NSP3 is related to the cytosolic ribosomal proteins. In summary, our multi-omics studies of NSP3 enhance our understanding of the functions of NSP3 and offer valuable insights for the development of anti-SARS strategies.


2021 ◽  
Vol 7 (3) ◽  
pp. 54
Author(s):  
Tobias Plowman ◽  
Dimitris Lagos

The highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, igniting an unprecedented pandemic. A mechanistic picture characterising the acute immunopathological disease in severe COVID-19 is developing. Non-coding RNAs (ncRNAs) constitute the transcribed but un-translated portion of the genome and, until recent decades, have been undiscovered or overlooked. A growing body of research continues to demonstrate their interconnected involvement in the immune response to SARS-CoV-2 and COVID-19 development by regulating several of its pathological hallmarks: cytokine storm syndrome, haemostatic alterations, immune cell recruitment, and vascular dysregulation. There is also keen interest in exploring the possibility of host–virus RNA–RNA and RNA–RBP interactions. Here, we discuss and evaluate evidence demonstrating the involvement of short and long ncRNAs in COVID-19 and use this information to propose hypotheses for future mechanistic and clinical studies.


2018 ◽  
Vol 1 (1) ◽  
pp. 19-24
Author(s):  
M. O. Katrichenko ◽  
I. I. Lisnyi

In the reviewed article, we consider epidemiological and laboratory data that confirm the protective effects of biologically active nutrients in our diet for various diseases. Along with various factors such as alcohol, smoking, nutrition plays a vital role in influencing the patient’s immune response by transforming cells or by preventing, or acceleration of malignancy. Many data suggest that immunoactive nutrients control inflammatory and precancerous reactions in immune cells. Immunoprophylaxis is usually associated with modulation of the immune response when inflamed, thereby improving clinical outcomes. Different nutrients, including glutamine, arginine, vitamins, minerals and long-chain fatty acids, are important components of immunological nutrition. Clinical studies associated with these substances show different results with minimal effect. However, some studies have shown that these nutrients may have immunomodulatory effects that can reduce the risk of developing cancer. Pre-clinical studies claim that most of these nutrients have a positive effect in the complex treatment of cancer patients. In this article, we will consider the effect of the above nutrients on the immune system in patients of oncologic profile. Recent evidences suggest that immunological nutrition plays an important role in the development of cancer and its progression. Data from animal studies have clearly shown that the use of immunomodulatory nutrients isolated from food, by launching a cascade of immunological reactions, can detect and eliminate the tumor. Although the technology has evolved to such an extent that we can study each individual cytokine or function of the immune cell, it is difficult to demonstrate the powerful role of the immune system in preventing or treating cancer due to the complexity of the tumor cell or heterogeneity in different patients' populations. However, the study sheds light on interactions in immune responses and cancer development, prevention and therapeutic strategies that involve modulation through biologically active agents.


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