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1.
Transfus Clin Biol ; 28(3): 264-270, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1201297

ABSTRACT

OBJECTIVES: The patients with hematological malignancies are a vulnerable group to COVID-19, due to the immunodeficiency resulting from the underlying disease and oncological treatment that significantly impair cellular and humoral immunity. Here we report on a beneficial impact of a passive immunotherapy with convalescent plasma to treat a prolonged, active COVID-19 infection in a patient with a history of nasopharyngeal diffuse large B-cell lymphoma treated with the therapy inducing substantial impairment of particularly humoral arm of immune system. The specific aim was to quantify SARS-CoV2 neutralizing antibodies in a patient plasma during the course of therapy. MATERIALS AND METHODS: Besides the standard of care treatment and monitoring, neutralizing antibody titers in patient's serum samples, calibrated according to the First WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human), were quantified in a time-dependent manner. During the immunotherapy period peripheral blood flow cytometry immunophenotyping was conducted to characterize lymphocyte subpopulations. RESULTS: The waves of clinical improvements and worsening coincided with transfused neutralizing antibodies rises and drops in the patient's systemic circulation, proving their contribution in controlling the disease progress. Besides the patient's lack of own humoral immune system, immunophenotyping analysis revealed also the reduced level of helper T-lymphocytes and immune exhaustion of monocytes. CONCLUSION: Therapeutic approach based on convalescent plasma transfusion transformed a prolonged, active COVID-19 infection into a manageable chronic disease.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19/therapy , Immunocompromised Host , Lymphoma, Large B-Cell, Diffuse/complications , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/blood , Antibodies, Viral/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Chlorocebus aethiops , Combined Modality Therapy , Hematopoietic Stem Cell Transplantation , Humans , Immunization, Passive , Immunophenotyping , Lymphocyte Subsets/drug effects , Lymphocyte Subsets/immunology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphopenia/etiology , Lymphopenia/immunology , Male , Middle Aged , Monocytes/immunology , Nasopharynx/virology , RNA, Viral/analysis , RNA, Viral/blood , Radiotherapy, Adjuvant , Rituximab/administration & dosage , Rituximab/adverse effects , SARS-CoV-2/isolation & purification , Vero Cells , Virus Cultivation
2.
Transfus Apher Sci ; 60(3): 103071, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1051973

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), generated an unprecedented global health and social emergency. Despite many efforts from clinicians to develop effective anti-COVID-19 treatment protocols, no specific therapy is currently available. Among anti-viral agents, convalescent plasma (CP) from recovered patients is the object of intense research following the first positive reports in severe COVID-19 patients. Passive immunotherapy the rationale to provide higher benefits in COVID-19 patients with humoral immune deficiencies, such as those with solid and hematologic cancers, patients with primary and acquired immunodeficiencies, and recipients of solid organ and hematopoietic stem cell transplants. The aim of this narrative review will be to critically discuss the literature evidence on CP use in these categories of patients.


Subject(s)
Antibodies, Neutralizing/administration & dosage , COVID-19/therapy , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , COVID-19/immunology , COVID-19/virology , Humans
3.
Int J Infect Dis ; 103: 628-635, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1002639

ABSTRACT

OBJECTIVES: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified. METHODS: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. RESULTS: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts. CONCLUSIONS: The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.


Subject(s)
B-Lymphocytes/immunology , Bone Marrow/immunology , COVID-19/immunology , Lymphopenia/etiology , SARS-CoV-2 , Sepsis/immunology , Spleen/immunology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
4.
J Diabetes Metab Disord ; 19(2): 1293-1302, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-863202

ABSTRACT

PURPOSE: Diabetic's patients are supposed to experience higher rates of COVID-19 related poor outcomes. We aimed to determine factors predicting poor outcomes in hospitalized diabetic patients with COVID-19. METHODS: This retrospective cohort study included all adult diabetic patients with radiological or laboratory confirmed COVID-19 who hospitalized between 20 February 2020 and 27 April 2020 in Alborz province, Iran. Data on demographic, medical history, and laboratory test at presentation were obtained from electronic medical records. Diagnosis of diabetes mellitus was self-reported. Comorbidities including cancer, rheumatism, immunodeficiency, or chronic diseases of respiratory, liver, and blood were classified as "other comorbidities" due to low frequency. The assessed poor outcomes were in-hospital mortality, need to ICU care, and receiving invasive mechanical ventilation. Self-reported. Multivariate logistic regression models were fitted to quantify the predictors of in-hospital mortality from COVID-19 in patients with DM. RESULTS: Of 455 included patients, 98(21.5%) received ICU care, 65(14.3%) required invasive mechanical ventilation, and 79 (17.4%) dead. In the multivariate model, significant predictors of "death of COVID-19" were age 65 years or older (OR (95% CI): 2.0 (1.16-3.44), chronic kidney disease (CKD) (2.05 (1.16-3.62), presence of "other comorbidities" (2.20 (1.04-4.63)), neutrophil count ≥8.0 × 109/L)6.62 (3.73-11.7 ((, Hb level < 12.5 g/dl (2.05 (1.13-3.72) (, and creatinine level ≥ 1.36 mg/dl (3.10 (1.38-6.98)). (All p -values <0.05). Some of these factors were also associated with other assessed poor outcomes, e.g., need to ICU care or invasive mechanical ventilation. CONCLUSION: Diabetic patients with age 65 years or older, comorbidity CKD, "other comorbidities", as well as neutrophil count ≥8.0 × 109/L, Hb level < 12.5 g/dl, and creatinine level ≥ 1.36 mg/dl, were more likely to dead after COVID-19. Presence of hypertension and cardiovascular disease were associated with none of the poor outcomes.

5.
Front Oncol ; 10: 1272, 2020.
Article in English | MEDLINE | ID: covidwho-853981

ABSTRACT

Background: A recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which began in Wuhan, China, with a high level of human-to-human transmission has been reported. There are limited data available on Coronavirus Disease 2019 (COVID-19) patients with hematological malignancies with more than 60 days of follow-up. This study describes the clinical characteristics, including multiple recurrences of COVID-19, in a patient with chronic lymphocytic leukemia (CLL) during 69 days of follow-up. Case Presentation: A 72-year-old female was admitted to hospital isolation after being infected with COVID-19 as part of a family cluster on January 30, 2020. Apart from SARS-Cov-2 virus infection, laboratory results revealed lymphocytosis of uncertain etiology and abnormal distribution of T lymphocytes. On blood smears, small blue lymphocytes with scant cytoplasm were observed, and the presence of high levels of circulating clonal B cells was also demonstrated by flow cytometry. The patient was diagnosed with COVID-19 and CLL. Among her family members, she had the highest viral loads and the fastest progression on lung injury and developed severe pneumonia. Serological results showed she had both 2019-nCoV-specific IgM and IgG antibodies; however, only IgG antibodies were detected in her husband's plasma. Results: A combination regimen of antiviral therapy and high-dose intravenous immunoglobulin (IVIG) in the early stage seemed to be effective for treating CLL and SARS-Cov-2 infection. Because of the low humoral immune response, the CLL patient could not effectively clear the SARS-Cov-2 infection and suffered from recurrence twice during the 69-day follow-up. Conclusion: In CLL, a neoplastic antigen-specific B-cell clone proliferates, and the progeny cells accumulate and outgrow other B cells, leading to immune deficiency. Considering the low humoral immune response and ineffective clearance of SARS-Cov-2 in CLL patients, the follow-up and home quarantine period should be extended. We need further studies to clarify suspending or continuing CLL therapy during COVID infection. For those patients who are prone to progression to severe disease, administering humoral immunity therapies can help to prevent disease progression and quickly meet the cure criteria.

6.
Cancer Med ; 9(22): 8571-8578, 2020 11.
Article in English | MEDLINE | ID: covidwho-777421

ABSTRACT

BACKGROUND: Patients with malignancy are particularly vulnerable to infection with Severe Acute Respiratory Disease-Coronavirus-2 (SARS-CoV-2) given their immunodeficiency secondary to their underlying disease and cancer-directed therapy. We report a case series of patients with cancer who received convalescent plasma, an investigational therapy for severe Coronavirus Disease 2019 (COVID-19). METHODS: Patients with cancer were identified who received convalescent plasma. Enrolled patients had confirmed COVID-19 with severe or life-threatening disease and were transfused with convalescent plasma from donors with a SARS-CoV-2 anti-spike antibody titer of ≥ 1:320 dilution. Oxygen requirements and clinical outcomes of interests were captured as well as laboratory parameters at baseline and 3 days after treatment. RESULTS: We identified 24 patients with cancer, 14 of whom had a hematological malignancy, who were treated with convalescent plasma. Fifteen patients (62.5%) were on cancer-directed treatment at the time of COVID-19 infection. After a median of hospital duration of 9 days, 13 patients (54.2%) had been discharged home, 1 patient (4.2%) was still hospitalized, and 10 patients had died (41.7%). Non-intubated patients, particularly those on nasal cannula alone, had favorable outcomes. Three mild febrile non-hemolytic transfusion reactions were observed. C-reactive protein significantly decreased after 3 days of treatment, while other laboratory parameters including ferritin and D-dimer remained unchanged. CONCLUSIONS: Convalescent plasma may be a promising therapy in cancer patients with COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Hospitalization/statistics & numerical data , Neoplasms/therapy , Pneumonia, Viral/complications , Severity of Illness Index , Adult , Aged , Aged, 80 and over , COVID-19 , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Humans , Immunization, Passive , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/virology , Pandemics , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prognosis , Risk Factors , SARS-CoV-2 , Survival Rate , United States/epidemiology
7.
J Biol Regul Homeost Agents ; 34(3): 767-773, 2020.
Article in English | MEDLINE | ID: covidwho-457138

ABSTRACT

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.


Subject(s)
Coronavirus Infections/complications , Cytokines/physiology , Mucocutaneous Lymph Node Syndrome/virology , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Child , Cytokines/antagonists & inhibitors , Humans , Interleukin-1 , Interleukins , Pandemics , SARS-CoV-2
8.
Food Chem Toxicol ; 141: 111418, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-345861

ABSTRACT

Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)-B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics.


Subject(s)
Air Pollutants/toxicity , Betacoronavirus , Coronavirus Infections/epidemiology , Pesticides/toxicity , Pneumonia, Viral/epidemiology , Xenobiotics/toxicity , Animals , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Diet , Epidemics , Humans , Immune System/drug effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Prevalence , Receptors, Aryl Hydrocarbon/metabolism , Risk Factors , SARS-CoV-2 , Signal Transduction/drug effects , Time
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