Therapeutic Options For COVID-19 Research Articles

Identification and evaluation of candidate COVID-19 critical genes and medicinal drugs related to plasma cells

The ongoing COVID-19 pandemic, caused by the SARS-CoV-2 virus, represents one of the most significant global health crises in recent history. Despite extensive research into the immune mechanisms and therapeutic options for COVID-19, there remains a paucity of studies focusing on plasma cells. In this study, we utilized the DESeq2 package to identify differentially expressed genes (DEGs) between COVID-19 patients and controls using datasets GSE157103 and GSE152641. We employed the xCell algorithm to perform immune infiltration analyses, revealing notably elevated levels of plasma cells in COVID-19 patients compared to healthy individuals. Subsequently, we applied the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm to identify COVID-19 related plasma cell module genes. Further, positive cluster biomarker genes for plasma cells were extracted from single-cell RNA sequencing data (GSE171524), leading to the identification of 122 shared genes implicated in critical biological processes such as cell cycle regulation and viral infection pathways. We constructed a robust protein-protein interaction (PPI) network comprising 89 genes using Cytoscape, and identified 20 hub genes through cytoHubba. These genes were validated in external datasets (GSE152418 and GSE179627). Additionally, we identified three potential small molecules (GSK-1070916, BRD-K89997465, and idarubicin) that target key hub genes in the network, suggesting a novel therapeutic approach. These compounds were characterized by their ability to down-regulate AURKB, KIF11, and TOP2A effectively, as evidenced by their low free binding energies determined through computational analyses using cMAP and AutoDock. This study marks the first comprehensive exploration of plasma cells’ role in COVID-19, offering new insights and potential therapeutic targets. It underscores the importance of a systematic approach to understanding and treating COVID-19, expanding the current body of knowledge and providing a foundation for future research.

An umbrella review on treatments and therapeutic options for COVID-19

Introduction. As the COVID-19 pandemic continues to pose a significant challenge to global health, effective therapeutic options for preventing and treating the disease have become increasingly important. We aimed to provide an update on current treatments and therapeutic options for COVID-19 patients.Materials and methods. The purpose of this umbrella review is to explore the current treatments and therapeutic options for COVID-19 patients. Keywords and their combinations were searched across online databases in Embase, PubMed/MEDLINE, Web of Science, and Scopus spanning from July 1, 2020, through March 3, 2023. Publications were selected for data extraction in two steps based on the study inclusion/exclusion criteria. The study adheres to the PRISMA checklist as well as NIH bias risk and quality assessment tool.Results. In this review, 28 relevant articles were selected for the final qualitative synthesis. The majority of included studies had reported on the efficacy of Lopinavir/Ritonavir (n = 4), Ivermectin (n = 3), Baricitinib (n = 2), Tocilizumab (n = 2), Remdesivir (n = 2), ACEI/ARB (n = 2), Vitamin D (n = 2), Molnupiravir (n = 2), Traditional Chinese medicine (TCM) (n = 2), Convalescent plasma transfusion (CPT) (n = 2) and hydroxychloroquine (n = 2) in treating COVID-19. It appeared that Baricitinib, Remdesivir, ACEI/ARB, TCM, and CPT may have beneficial effects on reducing mortality, hospitalization duration, and disease severity in COVID-19 patients. Other interventions, such as Lopinavir/Ritonavir, Ivermectin, Vitamin D, and Hydroxychloroquine did not show clear benefits or had inconclusive results.Conclusion. This umbrella review provides a comprehensive overview of the current evidence on the effectiveness and safety of various pharmacological and non-pharmacological interventions for COVID-19. These results provide an updated overview of the current landscape for COVID-19 treatments, highlighting potential avenues for further research and clinical practice. It is crucial to continue monitoring emerging evidence and conducting rigorous studies to guide the development and optimization of therapeutic strategies against COVID-19.

483. Pharmacokinetics of Nirmatrelvir and Ritonavir in COVID-19 Patients with Hemodialysis

Abstract Background Nirmatrelvir/ritonavir (Paxlovid) is one of the few therapeutic options for COVID-19. It is not recommended to use in patients with end-stage renal disease (ESDR), and large-scale clinical trials are needed to support its application in this population. We investigated the pharmacokinetics of nirmatrelvir/ritonavir (150 mg/100 mg twice a day) in COVID-19 patients with hemodialysis (HD). Methods SARS-Cov-2 tested positive patients with HD were included and given treatment with nirmatrelvir/ritonavir (150 mg/100 mg twice a day) for 5 days. For most patients, a 4 h-HD started 2 h after the morning dose on day 2. Blood samples were collected 4 h and 12 h after the first dose on day 1 to obtain peak and trough concentrations, respectively. And the blood samples at the start and finish time points of HD were drawn to observe the effect of dialysis on drug clearance. A tandem mass spectrometry (LC-MS/MS) method was conducted to quantify the nirmatrelvir and ritonavir concentrations. Results A total of 14 COVID-19 patients undergoing dialysis were enrolled, with 4 females and 10 males. The age was 66.6 ± 8.0 years and the body mass index (BMI) was 22.3 ± 3.5. The peak concentration of nirmatrelvir after the first dose was 4960 ± 1889 ng/mL. And the trough concentration was 2940 ± 1305 ng/mL, which was approximately 10 times above the EC90 (292 ng/mL). Nirmatrelvir concentration fell by 42% from 10426 ± 3191 ng/mL to 6035 ± 2402 ng/mL during 4 h-HD. The peak and trough concentrations of ritonavir were 816 ± 445 ng/mL and 326±201 ng/mL after the first dose, respectively. And the concentration fell by 17% during 4 h-HD. Based on the assumption of a first-order elimination kinetic, nirmatrelvir/ritonavir 150 mg/100 mg, once a day dose regimen was simulated which showed that the plasma concentration of nirmatrelvir could also achieve the target EC90 value.Figure 1.Plasma concentration of nirmatrelvir (blue circles) and ritonavir (orange circles) in COVID-19 patients with hemodialysis during the course of 150 mg/100 mg twice a day treatment. 4 h- hemodialysis was performed at 26 - 30 h after the first dose. Data are presented as the mean ± standard deviation. The open circles indicate the individual concentration data.Figure 2.Simulated plasma concentration data in dialysis patients following a single dose of 150 mg/100 mg nirmatrelvir/ritonavir. Long dashed line represents patients not on dialysis. Short dashed line represents patients receiving a 4 h - dialysis. Conclusion 150 mg/100 mg twice a day dose regimen of nirmatrelvir/ritonavir produced sufficient concentrations to reach the effective target in COVID-19 patients with HD. Simulation data suggested that a modified dose with 150 mg/100 mg once a day could also reach effective concentration. Our data provide evidence for the application of nirmatrelvir/ritonavir in patients with ESRD and further validation in large-scale investigation was needed. Disclosures All Authors: No reported disclosures

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies.

COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.

Blood levels of d-amino acids reflect the clinical course of COVID-19

d-Amino acids, rare enantiomers of amino acids, have been identified as biomarkers and therapeutic options for COVID-19. Methods for monitoring recovery are necessary for managing COVID-19. On the other hand, the presence of SARS-CoV2 virus in the blood is associated with worse outcomes. We investigated the potential of d-amino acids for assessing recovery from severe COVID-19. In patients with severe COVID-19 requiring artificial ventilation, the blood levels of d-amino acids, including d-alanine, d-proline, d-serine, and d-asparagine, which were lower than the normal range before treatment, quickly and transiently increased and surpassed the upper limit of the normal range. This increase preceded the recovery of respiratory function, as indicated by ventilation weaning. The increase in blood d-amino acid levels was associated with the disappearance of the virus in the blood, but not with inflammatory manifestations or blood cytokine levels. d-Amino acids are sensitive biomarkers that reflect the recovery of the clinical course and blood viral load. Dynamic changes in blood d-amino acid levels are key indicators of clinical course.

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.

Computationally engineered ACE2 decoy binds with nanomolar affinity with the SARS-CoV-2 spike protein

Even with the availability of vaccines, therapeutic options for COVID-19 still remain highly desirable, especially in hospitalized patients with moderate or severe disease. Soluble ACE2 (sACE2) is a promising therapeutic candidate that neutralizes SARS CoV-2 infection by acting as a decoy. By using computational mutagenesis, we designed a number of sACE2 derivatives carrying 3 to 4 mutations. The top predicted sACE2 decoy based upon the in silico mutagenesis scan was subjected to molecular dynamics and free energy calculations for further validation.

COVID-19 in Children

COVID-19 in children accounts for up to 8% of all the cases and is less severe than in adults. This could be an underestimation. A significant number of children are asymptomatic. Symptomatic infection is hard to distinguish from other respiratory tract viral infections based on symptoms and laboratory results. Anosmia is the only symptom in children that is highly suggestive of COVID-19. Infected children mostly have a positive household member. However, the role of children in SARS-CoV-2 transmission is still controversial. Data suggest that schoolchildren have a greater impact in SARS-CoV-2 transmission compared to younger children. Multisystem inflammatory syndrome in children is a new entity reported since April 2020 and is considered a rare complication of SARS-CoV-2 infection. It occurs in previously healthy older children and adolescents presenting with multisystem involvement and elevated inflammatory markers. Most children respond well to immune-modifying therapy. Treatment of COVID-19 in children is based solely on data received from adults and consists of supportive treatment and, in rare occasions, antiviral therapy (remdesivir), corticosteroids (dexamethasone) and monoclonal antibodies (tocilizumab). Further studies in children are needed in order to better understand this disease. This article discusses clinical presentation and therapeutic options for COVID-19 in children.

Computationally Designed ACE2 Decoy Receptor Binds SARS-CoV-2 Spike (S) Protein with Tight Nanomolar Affinity.

Even with the availability of vaccines, therapeutic options for COVID-19 still remain highly desirable, especially in hospitalized patients with moderate or severe disease. Soluble ACE2 (sACE2) is a promising therapeutic candidate that neutralizes SARS CoV-2 infection by acting as a decoy. Using computational mutagenesis, we designed a number of sACE2 derivatives carrying three to four mutations. The top-predicted sACE2 decoy based on the in silico mutagenesis scan was subjected to molecular dynamics and free-energy calculations for further validation. After illuminating the mechanism of increased binding for our designed sACE2 derivative, the design was verified experimentally by flow cytometry and BLI-binding experiments. The computationally designed sACE2 decoy (ACE2-FFWF) bound the receptor-binding domain of SARS-CoV-2 tightly with low nanomolar affinity and ninefold affinity enhancement over the wild type. Furthermore, cell surface expression was slightly greater than wild-type ACE2, suggesting that the design is well-folded and stable. Having an arsenal of high-affinity sACE2 derivatives will help to buffer against the emergence of SARS CoV-2 variants. Here, we show that computational methods have become sufficiently accurate for the design of therapeutics for current and future viral pandemics.

Enhanced Thymopoiesis as an Alternative Therapeutic Option for COVID-19

The pandemic caused by SARS-CoV-2 infection (COVID-19 disease) has expanded worldwide. Currently, it is well known that advanced age is an independent predictor of mortality and severe clinical outcome, apart from other comorbidities [1]. Underlying molecular and cellular mechanisms that could explain the severe clinical outcome among elderly subjects are not well known [2], although it has been described that both immunosenescence and a low-level systemic inflammation (inflamm-aging) could also play a relevant role [3,4]. Now a days, apart from an effective vaccine development, research efforts are focused on therapeutic approaches that could minimize both the viral replication and the further inflammatory cascade driving to respiratory distress and multiorgan failure; however, up to now, no specific therapy for SARS-CoV-2 infection has been established [5]. Awaiting for definitive and conclusive results from prospective clinical trials, antiviral and immunomodulatory drugs currently employed in SARS-CoV-2-infected subjects are based on their biological plausibility according to the mechanism of action or in vitro efficacy, but not in a definitive scientific evidences. Taken altogether, alternative hypothesis about underlying mechanisms driving to an impaired clinical outcome in COVID-19 disease are required. In this sense, even the universally accepted role of the cytokine storm has been questioned [6]. Hence, the greater hypothesis is considered the greater and more beneficial therapeutic options could be tested. Recently, our group has suggested that thymic dysfunction could play a relevant role in the impaired clinical outcome observed in elderly SARS-CoV-2-infected subjects [7]. Thus, the main objective of the present opinion paper is to explore a new therapeutic option for COVID-19 disease, based on enhancing thymic function.

COVID-19: molecular pathophysiology, genetic evolution and prospective therapeutics\u2014a review

The Covid-19 pandemic is highly contagious and has spread rapidly across the globe. To date there have been no specific treatment options available for this life-threatening disease. During this medical emergency, target-based drug repositioning/repurposing with a continuous monitoring and recording of results is an effective method for the treatment and drug discovery. This review summarizes the recent findings on COVID-19, its genomic organization, molecular evolution through phylogenetic analysis and has recapitulated the drug targets by analyzing the viral molecular machinery as drug targets and repurposing of most frequently used drugs worldwide and their therapeutic applications in COVID-19. Data from solidarity trials have shown that the treatment with Chloroquine, hydroxychloroquine and lopinavir-ritonavir had no effect in reducing the mortality rate and also had adverse side effects. Remdesivir, Favipiravir and Ribavirin might be a safer therapeutic option for COVID-19. Recent clinical trial has revealed that dexamethasone and convalescent plasma treatment can reduce mortality in patients with severe forms of COVID-19.

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

BackgroundThe timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China.MethodsWe conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated.FindingsInterferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (−8.8 days, 95%CI −9.7, −7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (−2.35 days, 95%CI −3.65, −1.06) compared to interferon-beta-1b monotherapy.InterpretationOur findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients.FundingHong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.

Impact of the COVID-19 pandemic on clinical research in hospitals: observational study in the first epicenter of the epidemic during the general lockdown in France.

The COVID-19 epidemic has had a strong impact on the entire healthcare sector in France with priority being given to research for new therapeutic options for COVID-19. Nevertheless, continuity of care for patients suffering from other diseases represents a crucial challenge, and clinical research is no exception in this respect. This study aims to assess the impact of the strict Covid-19 lockdown on non-Covid-19 clinical research in the French University Hospital of Strasbourg. Clinical research activity (non-Covid-19) from the point of view of pharmacy department was estimated and compared to the pre-lockdown period. The impact of lockdown was assessed through five indicators: site initiation visits, the initiation of experimental therapies in non-Covid-19 patients, the delivery of non-Covid-19 investigational medical products, the number of drug shipments to patients' homes, and the number of monitoring or closure visits. During the study period, the number of site initiation visits decreased by 90%, total inclusions by 72%, and delivery of investigational medical products by 30%. During the lockdown period, 15 treatments were sent to patients' homes. Monitoring activity decreased by 98%. Although the COVID-19 outbreak has created an incredible momentum in the field of clinical research, research not focused on SaRS-CoV-2 has suffered greatly from this situation. The impact on patients is difficult to estimate but should be further investigated.

COVID-19: What Should the General Practitioner Know?

BackgroundSARS-CoV-2 infection is currently the most significant public health challenge. Its presentation ranges from mild to severe respiratory failure and septic shock. Rapid transmission of the virus is dangerous with a high possibility of life-threatening complications. Lack of treatment standards for SARS-CoV-2 is responsible for the current dilemma in clinical medicine.MethodsAn electronic literature search was done using PubMed to gather information on the pathogenesis, transmission of infection, clinical symptoms, diagnosis, and therapeutic options for COVID-19. Search items included “SARS-CoV-2”, “COVID-19” and “coronavirus infection”.ResultsIn light of the current global crisis caused by SARS-CoV-2, the exchange of information within the scientific community should be quick and extremely transparent. Thus, this review presents the available information necessary for a general practitioner. Such presentation of data should allow the reader quick access to basic and crucial information related to epidemiology, viral transmission, clinical symptoms, diagnostics, treatment, and complications that may occur in the course of COVID-19.ConclusionRapidly increasing amounts of information about the diagnosis and treatment of patients with SARS-CoV-2 allow a better understanding of the etiology and course of the infection. In the current epidemiological situation, readily accessible information helps minimize the time to acquire knowledge and focus on prevention methods, diagnostic and treatment options. Thus, this review highlights key issues related to SARS-CoV-2 infection and contains the most useful data for daily medical practice.

Primena kortikosteroida u terapiji COVID-19 infekcije (kortikosteroidi u COVID-19 infekciji)

At the end of December 2019, a certain number of patients with pneumonia of unknown etiology appeared in the Chinese city of Wuhan. The etiological agent of corona virus disease (COVID-19) was identified as a virus from the Coronaviridae family called Novel Coronavirus, or SARS-CoV-2 (Severe Acute Respiratory Coronavirus 2). COVID-19 took on the proportions of a pandemic. Therapeutic options for COVID-19 include antiviral, anticoagulant, corticosteroid, biological, antibiotic, multivitamin, symptomatic therapy, and oxygen support. Corticosteroid immunosuppressive and anti-inflammatory role is helpful for a disease with immune response dysregulation and excessive cytokine production. The effect of corticosteroids in the treatment of COVID-19 depends on disease severity, the time of initiation, and the appropriate dose. Individual risk/benefit assessment is required before initiating treatment. Corticosteroids have beneficial effects on patients on oxygen support, especially on those who are on mechanical ventilation. Their use in those with mild forms of the disease and comorbidities carries an increased risk of complications. The benefits of corticosteroids are shorter hospitalization, reduced admission in intensive care units, and reduced need for non-invasive and invasive mechanical ventilation. The results of previous research have facilitated the administration of corticosteroids in the treatment of patients with COVID-19 infection, but further research is needed to remove the existing doubts.

Systematic Review on the Therapeutic Options for COVID-19: Clinical Evidence of Drug Efficacy and Implications.

A novel coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China, and quickly spread globally. Several treatments have been proposed, many of which have proven ineffective. Consequently, there is a need to review the published evidence of drug clinical trials to guide future prescribing. A systematic review of published clinical trials and retrospective observational studies was carried out. The search was made using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Articles published between January 2020 and October 2020 and written in the English language were retrieved and included in the study. Researches that used traditional medicine, in-vitro and in-vivo animal studies, as well as reviews were excluded. Seventy-three relevant articles that fulfilled the inclusion criteria were finally selected and reviewed. Hydroxychloroquine, chloroquine, and azithromycin produced no clinical evidence of efficacy in randomized controlled clinical trials (RCT). However, retrospective observational studies reported the efficacy of remdesivir and lopinavir/ritonavir in reducing viral load, although there have been concerns with lopinavir/ritonavir and, more recently, remdesivir. Recently, tocilizumab, dexamethasone, and methylprednisolone significantly relieved lung inflammation and decreased mortality in patients with severe COVID-19. In addition, convalescent plasma was effective in boosting strong immunity among patients with mild COVID-19. There is currently no single worldwide approved therapeutic option for patients with COVID-19 despite the initial hype with medicines, including hydroxychloroquine. Nonetheless, dexamethasone has shown promise in symptomatic treatment and convalescent plasma in boosting immunity. New treatments are currently being researched, and the findings will be reported accordingly to provide evidence-based guidance for prescribers and policymakers.

Computational gene expression profiling in the exploration of biomarkers, non-coding functional RNAs and drug perturbagens for COVID-19

The coronavirus disease, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health crisis that is being endured with an increased alarm of transmission each day. Though the pandemic has activated innumerable research attention to decipher an antidote, fundamental understanding of the molecular mechanisms is necessary to halt the disease progression. The study focused on comparison of the COVID-19 infected lung tissue gene expression datasets -GSE155241 and GSE150316 with the GEO2R-limma package. The significant up- and downregulated genes were annotated. Further evaluation of the enriched pathways, transcription factors, kinases, noncoding RNAs and drug perturbations revealed the significant molecular mechanisms of the host response. The results revealed a surge in mitochondrial respiration, cytokines, neurodegenerative mechanisms and deprived oxygen, iron, copper, and glucose transport. Hijack of ubiquitination by SARS-CoV-2, hox gene differentiation, histone modification, and miRNA biogenesis were the notable molecular mechanisms inferred. Long non-coding RNAs such as C058791.1, TTTY15 and TPTEP1 were predicted to be efficient in regulating the disease mechanisms. Drugs-F-1566-0341, Digoxin, Proscillaridin and Linifanib that reverse the gene expression signatures were predicted from drug perturbations analysis. The binding efficiency and interaction of proscillaridin and digoxin as obtained from the molecular docking studies confirmed their therapeutic potential. Two overlapping upregulated genes MDH1, SGCE and one downregulated gene PFKFB3 were appraised as potential biomarkers candidates. The upregulation of PGM5, ISLR and ANK2 as measured from their expressions in normal lungs affirmed their possible prognostic biomarker competence. The study explored significant insights for better diagnosis, and therapeutic options for COVID-19. Communicated by Ramaswamy H. Sarma

Efficacy of COVID-19 Pathogen Inactivated Convalescent Plasma for Patients with Moderate to Severe Acute COVID-19: A Case Matched Control Study

Background. COVID-19, caused by the SARS-CoV-2 virus, is a pandemic disease with high morbidity and mortality. Currently, available therapeutic options for COVID-19 are limited. Prior experience in epidemics with convalescent plasma (CP) containing antibodies to viruses has demonstrated variable indications of therapeutic efficacy for: Influenza, Argentine Hemorrhagic Fever, and SARS. Characterizing antibody titers to viruses has indicated correlation with therapeutic efficacy. Convalescent COVID-19 patients with potent SARS-CoV-2 antibody responses can serve as plasma donors for immune therapy. However, antibody responses are variable, many donors are first-time higher risk blood donors, and rapid assays to select optimal CP immune efficacy are limited. Pathogen inactivation (PI) of CP can reduce the risk of transfusion-transmitted infection by unrecognized pathogens. Objectives. This study characterized COVID-19 PI-CP activity; and evaluated efficacy and safety of PI CP transfusion in a case matched controlled cohort of acute COVID-19 patients. Methods. COVID-19 apheresis CP (650 - 1300 mL) was collected from nasopharyngeal PCR + outpatients following 2 PCR negative tests or 28 days after symptom resolution. Amotosalen-UVA PI of CP (INTERCEPT Blood System for Plasma) was performed, and antibody efficacy before and after PI was characterized by: VSV reporter pseudo-virus plaque neutralization (RVPN) NT-50 titer (Vitalant Research Institute, San Francisco), antibody to S and N virus proteins by agglutination-dependent antibody PCR (ADAP, Enable Biosciences, San Francisco), virus ACE-2 soluble receptor neutralization assay (Enable Biosciences), and SARS-CoV-2 antibody profile by coronavirus microarray (University of California, Irvine). Patient inclusion criteria were: confirmed SARS-CoV-2 infection, hospitalization, pulmonary infiltrates, availability of ABO compatible CP, and informed consent. CP patients were matched with control patients (CTRL) for disease severity at diagnosis by standardized clinical risk score (W. Liang et al JAMA Intern Med 2020) and concomitant Tocilizumab use. CP Patients received a total of 400 mL of PI CP from 2 donors over 48 hours and standard therapy. CTRL patients received standard COVID-19 therapy without CP. The primary outcome was in-hospital death to day 28. Secondary outcomes included: progression to intubation, admission to ICU, time to discharge, serious adverse events, NP viral clearance, plasma viral clearance, and humoral immune responses. Differences between CP and CTRL patients were assessed by the Mann-Whitney test for continuous variables, and by Fisher’s exact test for categorical variables. Progression to ICU and intubation were analyzed as odds ratios calculated by conditional logistic regression. Results. 15 CP and 30 CTRL patients were enrolled. One CP patient was admitted in cardiogenic shock. Only 2 of 15 CP cohort patients had detectable IgG antibody to SARS CoV-2 S1 antigen at study entry. 3 of 15 PI CP donors had negligible SARS CoV-2 IgG antibodies to all antigens, and demonstrated poor neutralization efficacy. 12/15 CP had effective RVPN titers (> 1:80), RVPN titers were correlated with ACE-2 neutralization antibody titers (r2 = 0.83), and had significant activity specific for S and RBD antigens by microarray profiling (Figure 1). SARS CoV-2 antibody levels were variable between CP donors, but not impacted by PI (Figure 1). Baseline characteristics of CP and matched CTRL patients were similar (Table 1). Sensitivity analysis was performed assessing mortality after exclusion of one CTRL patient admitted in cardiogenic shock and the 2 respective controls. In-hospital 28-day mortality was lower in the CP cohort (0/14) compared to 5/28 CTRL, p = 0.151, 2-sided Fisher’s exact test. Progression to intubation, ICU admission, and days in hospital were not significantly different (Table 1). There was a trend toward decreased inflammatory response (CRP normalization) in CP patients. Conclusions. In hospital mortality of COVID-19 patients was lower in the PI-CP cohort, but not statistically significant. 15% of CP had ineffective antibody by multiple assays. However, PI did not impact CP anti-SARS-CoV-2 activity. PI of plasma provides reduced risk of transfusion transmitted infection from COVID-19 CP donors. In this study, PI CP was safe, and may be effective for early treatment of hospitalized COVID-19 patients.Disclosuresvon Goetz:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Khan:Nanommune Inc.: Current equity holder in private company. Tsai:Enable Biosciences: Current Employment. Robinson:Enable Biosciences: Current Employment. Seftel:Enable Biosciences: Current Employment, Current equity holder in private company. Bagri:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.

Feline infectious peritonitis (FIP) and coronavirus disease 19 (COVID-19): Are they similar?

SARS‐CoV‐2 has radically changed our lives causing hundreds of thousands of victims worldwide and influencing our lifestyle and habits. Feline infectious peritonitis (FIP) is a disease of felids caused by the feline coronaviruses (FCoV). FIP has been considered irremediably deadly until the last few years. Being one of the numerous coronaviruses that are well known in veterinary medicine, information on FCoV could be of interest and might give suggestions on pathogenic aspects of SARS‐CoV‐2 that are still unclear. The authors of this paper describe the most important aspects of FIP and COVID‐19 and the similarities and differences between these important diseases. SARS‐CoV‐2 and FCoV are taxonomically distant viruses, and recombination events with other coronaviruses have been reported for FCoV and have been suggested for SARS‐CoV‐2. SARS‐CoV‐2 and FCoV differ in terms of some pathogenic, clinical and pathological features. However, some of the pathogenic and immunopathogenic events that are well known in cats FIP seem to be present also in people with COVID‐19. Moreover, preventive measures currently recommended to prevent SARS‐CoV‐2 spreading have been shown to allow eradication of FIP in feline households. Finally, one of the most promising therapeutic compounds against FIP, GS‐441524, is the active form of Remdesivir, which is being used as one therapeutic option for COVID‐19.

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