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1.
Respir Med ; 189: 106669, 2021.
Article in English | MEDLINE | ID: covidwho-1482946

ABSTRACT

INTRODUCTION: Cytokine storm is one of the consequences of the severe forms of COVID-19 due to excessive immune response. In this study, we investigated the therapeutic effect of plasmapheresis and its role on the inflammatory cytokines levels in patients suffering from severe COVID-19. METHODS: In plasmapheresis group, 22 severe cases of COVID-19 receiving three cycles of plasmapheresis with time interval of 24-36 h and 22 COVID-19 patients as the control group were enrolled. Clinical history and laboratory parameters as well as IL-1, IL-6, IFN-γ and IL-17 cytokines serum levels in the time points of before and after plasmapheresis were studied. RESULTS: In severe COVID-19 patients, plasmapheresis significantly improved clinical and laboratory parameters such as cough, weakness, fever, blood oxygen saturation and CRP levels. Serum levels of IL-1, IL-6, IFN-γ and IL-17 in the group of patients receiving plasmapheresis, had a significant decrease following plasmapheresis courses. Although only IL-6 level in the control group had a significant decrease between the days 1-14 of disease. Also, at both time points of before and after plasmapheresis, serum levels of IL-1, IL-6, IFN-γ and IL-17 were inversely correlated to blood oxygen saturation. CONCLUSION: Based on the obtained results, plasmapheresis therapy in severe forms of COVID-19 can effectively improve the clinical symptoms of the disease and reduce inflammatory markers. Therefore, it is suggested that plasmapheresis can be evaluated in standard treatment protocols for severe forms of COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , Cytokines/blood , Inflammation Mediators/blood , Plasmapheresis/methods , Adult , Aged , Biomarkers/blood , COVID-19/immunology , Female , Humans , Interferon-gamma/blood , Interleukin-1/blood , Interleukin-17/blood , Interleukin-6/blood , Male , Middle Aged , Patient Acuity , Treatment Outcome
3.
Neurologist ; 26(5): 196-224, 2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1398198

ABSTRACT

BACKGROUND: Central nervous system complications are reported in an increasing number of patients with Coronavirus Disease 2019 (COVID-19). COVID-19-related Guillain-Barré syndrome (GBS) is of particular importance given its association with higher mortality rates and prolonged respiratory failure. REVIEW SUMMARY: We conducted a systematic review of published cases for COVID-19-related GBS, and provide a summary of clinical management strategies for these cases. Sixty-three studies, including 86 patients, were included. Seventy-six cases with reported outcome data were eligible for the outcome analysis. Ninety-nine percent of patients were diagnosed with COVID-19 before diagnosis of GBS (median: 14 d prior, interquartile range: 7 to 20). Intravenous immunotherapy (intravenous immunoglobulin: 0.4 g/kg/d for 5 d) was the most frequently used treatment approach. The review indicated that the outcome was not favorable in 26% of cases (persistent neurological deficits). A mortality rate of 3.5% was observed in patients with COVID-19-related GBS. CONCLUSIONS: Although evidence to support specific treatments is lacking, clinicians should consider the benefits of immunotherapy and plasma exchange in addition to the standard antimicrobial and supportive therapies for patients who meet the diagnostic criteria for acute sensory and motor polyradiculoneuritis. Intravenous immunoglobulin treatment alone is not shown to result in improved outcomes or mortality. More extensive studies aimed at exploring the neurological manifestations and complications of COVID-19 and distinctive treatment options for COVID-19-related GBS are warranted.


Subject(s)
COVID-19/drug therapy , Guillain-Barre Syndrome/drug therapy , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/drug effects , Thyroid Neoplasms/drug therapy , Guillain-Barre Syndrome/diagnosis , Humans , Plasma Exchange/methods , Plasmapheresis/adverse effects , Plasmapheresis/methods
6.
Front Immunol ; 12: 711915, 2021.
Article in English | MEDLINE | ID: covidwho-1317228

ABSTRACT

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , Immunization, Passive/methods , Immunocompromised Host , Immunoglobulin G/therapeutic use , Plasmapheresis/methods , SARS-CoV-2/genetics , Antineoplastic Agents, Immunological/adverse effects , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunity/drug effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Middle Aged , RNA, Viral/genetics , Rituximab/adverse effects , Treatment Outcome
9.
BMJ Case Rep ; 14(3)2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1153655

ABSTRACT

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.


Subject(s)
Coinfection/therapy , Coinfection/virology , Hepatitis C, Chronic/therapy , Hepatitis, Autoimmune/therapy , Plasmapheresis/methods , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/therapy , Drug Therapy, Combination , Female , Hepatitis C, Chronic/complications , Hepatitis, Autoimmune/complications , Humans , Interferon alpha-2/therapeutic use , Middle Aged , Polyethylene Glycols/therapeutic use , Positive-Strand RNA Viruses/isolation & purification , Ribavirin/therapeutic use , SARS-CoV-2 , Treatment Outcome , Viral Load
10.
J Clin Apher ; 36(3): 499-504, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1033045

ABSTRACT

Management of aTTP in patients who refuse or are intolerant to plasma remains challenging, but new drugs can be implemented with success. A 39-year-old woman presented to the Emergency department for bruises at the upper and lower limbs together with worsening anemia and thrombocytopenia; PLASMIC score was seven, indicative of high risk to have a thrombotic microangiopathy due to severe ADAMTS-13 deficiency: indeed, it was 1.4%. We immediately started Plasma Exchange, but after the third procedure she developed severe anaphylaxis to Octaplas plasma, so PEXs were discontinued. We proceeded to a salvage strategy with rituximab and caplacizumab that was rapidly effective to resolve symptoms and hemolysis. It has been already reported a case in which a patient developed severe reactions to fresh-frozen plasma that required discontinuation of PEX. Differently from this case, our patient was already using the less immunogenic pooled plasma units Octaplas, therefore a strategy with caplacizumab was the only available option. Moreover, rituximab is associated with a shorter time to obtain a durable remission in aTTP and a faster time (15 days) to final ADAMTS13 activity recovery >10%. To our knowledge, this is the first case of early discontinuation of caplacizumab in a patient allergic to PEX by actively monitoring ADAMTS13 activity, allowing optimization of healthcare resources during COVID-19 pandemic.


Subject(s)
Plasmapheresis/methods , Purpura, Thrombotic Thrombocytopenic/therapy , Rituximab/therapeutic use , Single-Domain Antibodies/therapeutic use , ADAMTS13 Protein/metabolism , Adult , Emergency Service, Hospital , Female , Hemolysis , Humans , Plasma Exchange , Remission Induction , Risk
11.
PLoS One ; 15(12): e0243967, 2020.
Article in English | MEDLINE | ID: covidwho-992705

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic emerged in December 2019. Convalescent plasma represents a promising COVID-19 treatment. Here, we report on the manufacturing of a plasma-based product containing antibodies specific to SARS-CoV-2 obtained from recently recovered COVID-19 patients. Convalescent plasma donors were screened as follows: 1) previously confirmed SARS-CoV-2 infection (by real-time PCR (RT-PCR)); 2) a subsequent negative PCR test followed by a 2-week waiting period; 3) an additional negative PCR test prior to plasmapheresis; and 4) confirmation of the presence of SARS-CoV-2 specific antibodies. Convalescent plasma was stored fresh (2-6°C) for up to 5 days or frozen (-30°C) for long-term storage. Donor peripheral blood and final plasma product were assayed for binding antibodies targeting the SARS-CoV-2 S-protein receptor-binding domain (RBD) and their titers measured by an enzyme-linked immunosorbent assay (ELISA). We performed 72 plasmaphereses resulting in 248 final products. Convalescent plasma contained an RBD-specific antibody titer (IgG) ranging from 1:100 to 1:3200 (median 1:800). The titer was congruent to the titer of the blood (n = 34) before collection (1:100-1:6400, median 1:800). Levels of IL-8 and LBP of donors were slightly increased. Therapeutic products derived from a human origin must undergo rigorous testing to ensure uniform quality and patient safety. Whilst previous publications recommended RBD-specific binding antibody titers of ≥ 1:320, we selected a minimum titer of 1:800 in order to maximize antibody delivery. Production of highly standardized convalescent plasma was safe, feasible and was readily implemented in the treatment of severely ill COVID-19 patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , COVID-19/therapy , Adolescent , Adult , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Neutralization Tests , Pandemics , Plasma/immunology , Plasma/virology , Plasmapheresis/methods , SARS-CoV-2/immunology , Tissue Donors , Young Adult
12.
Medicine (Baltimore) ; 99(49): e23449, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-963627

ABSTRACT

RATIONALE: Multiorgan/system injury was observed in severely infected coronavirus disease 2019 (COVID-19) patients, in addition to viral pneumonia. Recognizing and correcting the key and immediate dysfunctions may reduce mortality. PATIENT CONCERNS: A 66-year-old previously healthy male patient was referred to the isolation ward in Guanggu Branch of Hubei Province Maternity and Childcare Hospital with a high fever and nonproductive cough for twenty days. DIAGNOSES: Diagnosis of severe COVID-19 infectious pneumonia was established by travel history, clinical features, chest imaging, and a positive oropharyngeal swab specimen result for the severe acute respiratory syndrome coronavirus 2 RT-PCR assay. INTERVENTIONS: In addition to standard supportive care, combined inflammatory cytokine depletion therapy (double filtration plasma pheresis and tocilizumab) and convalescent plasma were administered. OUTCOMES: The patient's homeostatic parameters (blood pressure, heart rate, spontaneous respiration, SPO2, and blood gas) recovered, along with the recovery on chest imaging. All the intravenous catheters were removed. Supportive care continued for several days, and the patient was transferred to a non-ICU isolation ward. LESSONS: It is not safe to draw causal conclusions between cytokine depletion and clinical manifestation improvement with only 1 case, but this is a potential research direction in facing the COVID-19 crisis.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/therapy , Plasmapheresis/methods , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/complications , Combined Modality Therapy , Cytokines , Hemodynamics , Humans , Immunization, Passive , Male , Pandemics , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , SARS-CoV-2
13.
Transfusion ; 60(8): 1773-1777, 2020 08.
Article in English | MEDLINE | ID: covidwho-733193

ABSTRACT

BACKGROUND: A novel coronavirus has caused an international outbreak. Currently, there are no specific therapeutic agents for coronavirus infections. Convalescent plasma (CP) therapy is a potentially effective treatment option. METHODS: Patients who had recovered from COVID-19 and had been discharged from the hospital for more than 2 weeks were recruited. COVID-19 convalescent plasma (CCP)-specific donor screening and selection were performed based on the following criteria: 1) aged 18-55 years; 2) eligible for blood donation; 3) diagnosed with COVID-19; 4) had two consecutive negative COVID-19 nasopharyngeal swab tests based on PCR (at least 24 hr apart) prior to hospital discharge; 5) had been discharged from the hospital for more than 2 weeks; and 6) had no COVID-19 symptoms prior to convalescent plasma donation. In addition, preference was given to CCP donors who had a fever lasting more than 3 days or a body temperature exceeding 38.5°C (101.3°F), and who donated 4 weeks after the onset of symptoms. CCP collection was performed using routine plasma collection procedures via plasmapheresis. In addition to routine donor testing, the CCP donors' plasma was also tested for SARS-CoV-2 nucleic acid and S-RBD-specific IgG antibody. RESULTS: Of the 81 potential CCP donors, 64 (79%) plasma products were collected. There were 18 female donors and 46 male donors. There were 34 first-time blood donors and 30 repeat donors. The average time between CCP collection and initial symptom onset was 49.1 days, and the average time between CCP collection and hospital discharge was 38.7 days. The average volume of CCP collected was 327.7 mL. All Alanine transaminase (ALT) testing results met blood donation requirements. HIV Ag/Ab, anti-HCV, anti-syphilis, and HBsAg were all negative; NAT for HIV, HBV, and HCV were also negative. In addition, all of the CCP donors' plasma units were negative for SARS-CoV-2 RNA. Of the total 64 CCP donors tested, only one had an S-RBD-specific IgG titer of 1:160, all others had a titer of ≥1:320. CONCLUSION: Based on a feasibility study of a pilot CCP program in Wuhan, China, we demonstrated the success and feasibility of CCP collection. In addition, all of the CCP units collected had a titer of ≥1:160 for S-RBD-specific IgG antibody, which met the CCP quality control requirements based on the Chinese national guidelines for CCP.


Subject(s)
Coronavirus Infections/pathology , Donor Selection/standards , Plasmapheresis/methods , Pneumonia, Viral/pathology , Adolescent , Adult , Antibodies, Viral/blood , Betacoronavirus/immunology , Blood Donors , Blood Specimen Collection , COVID-19 , China , Convalescence , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Feasibility Studies , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Male , Middle Aged , Pandemics , Pilot Projects , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Young Adult
15.
Drug Des Devel Ther ; 14: 2607-2611, 2020.
Article in English | MEDLINE | ID: covidwho-683522

ABSTRACT

In March 2020, the WHO declared the COVID-19 disease as a pandemic disease. There have been studies on the COVID-19 to find a certain treatment, but yet, there is no certain cure. In this article, we present a possible way to treat severe cases of COVID-19. Based on the previous studies, there are similarities between the spike antigens of SARS-CoV and SARS-CoV-2 viruses. It is expected that these similarities (structural and affinity to the receptor of ACE2) can lead to the same pathophysiological activity of the virus by the use of ACE2 and FcγRII (the antibody-dependent enhancement mechanism). Therefore, we propose a way of washing out (by plasmapheresis) the possible antibodies against the spike protein of the virus out of patients' plasma to stop the antibody-dependent enhancement (ADE)-mediated infection of the immune system cells at the first phase of the treatment and simultaneous use of the anti-ACE2 with anti-FcγRII monoclonal antibodies at the second phase. We propose these procedures for the patients that have no significant response for typical anti-viral, ARDS and conservative therapies, and the disease persists or progresses despite sufficient therapies.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Coronavirus Infections/therapy , Plasmapheresis/methods , Pneumonia, Viral/therapy , Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Pandemics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Receptors, IgG/immunology , Severity of Illness Index
16.
Diagnosis (Berl) ; 7(4): 373-376, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-659924

ABSTRACT

Following the unprecedented global Coronavirus Disease 2019 (COVID-19) outbreak, multiple medical countermeasures ramped up to combat the virus and contain the spread of the pandemic. Despite continued uncertainty and a lack of clarity about the COVID-19, researchers have made tremendous strides in the development of prevention and treatment strategies. In this article, we focus on the use of convalescent plasma as therapeutic approach against COVID-19 infection.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Pandemics/prevention & control , Pneumonia, Viral/therapy , Survivors/statistics & numerical data , Adult , Aged , Blood Donors/supply & distribution , COVID-19 , Case-Control Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , Plasmapheresis/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Survival Rate
17.
Transfus Apher Sci ; 59(4): 102855, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-613576

ABSTRACT

The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Extracorporeal Circulation , Pandemics , Plasmapheresis , Pneumonia, Viral/therapy , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Humans , Plasma Exchange , Plasmapheresis/methods , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Respiratory Distress Syndrome/etiology , SARS-CoV-2
19.
Ther Apher Dial ; 25(2): 248-249, 2021 04.
Article in English | MEDLINE | ID: covidwho-574794
20.
Blood Purif ; 50(2): 141-149, 2021.
Article in English | MEDLINE | ID: covidwho-423313

ABSTRACT

The real issue with the COVID-19 pandemic is that a rapidly increasing number of patients with life-threatening complications are admitted in hospitals and are not well-administered. Although a limited number of patients use the intensive care unit (ICU), they consume medical resources, safety equipment, and enormous equipment with little possibility of rapid recovery and ICU discharge. This work reviews effective methods of using filtration devices in treatment to reduce the level of various inflammatory mediators and discharge patients from the ICU faster. Extracorporeal technologies have been reviewed as a medical approach to absorb cytokines. Although these devices do not kill or remove the virus, they are a promising solution for treating patients and their faster removal from the ICU, thus relieving the bottleneck.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/therapy , Cytokines/blood , Hemofiltration/methods , SARS-CoV-2 , Shock, Septic/therapy , Sorption Detoxification/methods , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Anti-Bacterial Agents/therapeutic use , COVID-19/blood , Coated Materials, Biocompatible , Combined Modality Therapy , Continuous Renal Replacement Therapy , Cross-Over Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Double-Blind Method , Equipment Design , Hemofiltration/instrumentation , Humans , Membranes, Artificial , Microspheres , Multiple Organ Failure/etiology , Multiple Organ Failure/therapy , Plasmapheresis/methods , Randomized Controlled Trials as Topic , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Shock, Septic/blood , Shock, Septic/etiology , Sorption Detoxification/instrumentation
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