Subject(s)
Herpes Zoster , Lymphoma, B-Cell , Receptors, Chimeric Antigen , Antigens, CD19 , Cell- and Tissue-Based Therapy , Herpes Zoster/epidemiology , Herpes Zoster/etiology , Herpes Zoster/prevention & control , Humans , Immunotherapy, Adoptive/adverse effects , Incidence , Lymphoma, B-Cell/etiology , Lymphoma, B-Cell/therapyABSTRACT
Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two consecutively negative SARS-CoV-2 viral RNA test ( interval ≥ 24 hours), improved respiratory symptoms and obvious absorption of inflammation in pulmonary imaging are the discharge criteria for COVID-19 patients. The clearance profile of viral RNA in the upper respiratory tract specimens, including nasopharyngeal swab and/or oropharyngeal swabs, is related to innate immune cells such as Natural Killer cells. A total of 168 patients were included for the study. In this cohort, non-severe and severe groups showed significant differences in white blood cells, neutrophils, lymphocytes, basophils and platelets counts, as well as in infection related parameters such as CRP and serum cytokine IL-6. For lymphocyte subsets tests at admission, the severe group displayed significantly lower cell counts than the non-severe group. Higher counts of total T cells, CD4 + T cells, CD8 + T cells, and NK cells in peripheral blood showed a significant correlation with the shorter time taken to obtain the first negative viral RNA test and first positive IgM/ IgG antibody test. The number of B cells was only correlated with time to achieve the first positive IgM/IgG test. The count of NK cells was also correlated with a higher level of IgG antibody (p = 0.025). The lymphocytopenia group had a significantly worse survival rate (p = 0.022) and a longer duration (p = 0.023) of viral shedding than the normal lymphocyte count group. A lower NK cell count correlates the most with the worse survival rate (p<0.001) and a longer duration (p<0.001) of viral shedding. This study suggests the potential value of allo-Natural Killer cell therapy as an universal COVID-19 treatment strategy.
ABSTRACT
BACKGROUND: Repositivity of SARS-CoV-2 nucleic acid in discharged COVID-19 patients was reported recently. However, the characteristics of repositive results are still not well understood, leading to a lack of effective monitoring strategies. METHODS: In the present study, a total of 59 COVID-19 patients were enrolled, and the characteristics of the repositive samples were analyzed. RESULTS: The repositive rate in this cohort was 15.79%. The N gene was the main target gene that was positive in the repositive results as well as in the last positive results of all patients. The median duration from diagnosis to the last positive test was 20 days (IQR, 16-31 days), and the longest duration was 40 days. Repositivity was only observed in IgM single- or both IgM- and IgG-positive patients, instead of IgG single-positive patients. CONCLUSIONS: There was a significant proportion of repositives in the recovered COVID-19 patients, and increasing the required number of negatives for consecutive nucleic acid tests may reduce the incidence of repositives. The recommended monitoring strategy for repositivity is monitoring the N gene in IgM-positive patients. This can ensure high sensitivity while reducing the time and cost of nucleic acid detection.
Subject(s)
COVID-19/genetics , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , Aged , COVID-19/diagnosis , COVID-19/epidemiology , China/epidemiology , Cohort Studies , Female , Humans , Immunoglobulin G/genetics , Immunoglobulin M/genetics , Male , Middle Aged , Real-Time Polymerase Chain Reaction/standards , Retrospective StudiesABSTRACT
Condition:
Diffuse Large B Cell Lymphoma;Relapsed Diffuse Large B-Cell Lymphoma;Refractory Diffuse Large B-Cell LymphomaIntervention:
Drug: SintilimabPrimary outcome:
Complete response rateCriteria:
Inclusion Criteria:
1. Willingness to provide written informed consent.
2. Age range from 18 to 80 years;
3. Pathologically confirmed CD20+ diffuse large B-cell lymphoma
4. According to Lugano 2014, at least one measurable nodular lesion with a length of
greater than 15 mm, or extranodal lesion greater than 10 mm, lesion on FDG-PET scan
demonstrates uptake);
5. Diffuse large B-cell lymphoma patients failed to first-line rituximab based
chemotherapy including anthracycline or anthracycline
6. Patients are allowed to receive palliative radiotherapy, but the last time
radiotherapy cannot be within 7 days before the first study drug administration;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
8. Adequate organ function
9. Expectation survival time over 3 months;
Exclusion Criteria:
1. History of other malignancy within the past 5 years (except for 1. basal cell
carcinoma of the skin and 2. carcinoma in situ of the cervix and 3. patients who had
received treatment for the purpose of cure and had not developed a malignant tumor
with a known active disease in the previous 5 years);
2. Patients who had received other antitumor therapy (including corticosteroid therapy,
immunotherapy) or participated in other clinical studies within 4 weeks before the
start of the enrollment (if patients received small-molecule targeted drug therapy,
they could be included in the study if the drug was discontinued for more than 5
half-lives), or had not recovered from the previous toxicity;
3. Previous treatment with anti-PD-1 antibody, anti-PD-L1 antibody or other medications
that stimulates or collaboratively inhibits T cell receptors
4. Patients previously received anti-CD20 antibody combined GemOx regimen;
5. Evidence of central nervous system invasion;
6. Patients received systemic treatment of traditional Chinese herb with anti-tumor
indications or immunomodulatory drugs (including thyroxin, interferon and
interleukinin, except for local use to control pleural effusions) within 2 weeks
before first administration;
7. Patients with autoimmune diseases requiring treatment or with a history of syndrome
requiring systemic use of steroid immunosuppressive agents, such as hypophysitis,
pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc;
8. Patients received systemic glucocorticoid therapy (excluding nasal spray, inhaled or
other topical glucocorticoids) or any other form of immunosuppressive therapy within 7
days prior to the first administration;
9. Clinically uncontrollable pleural effusion/peritoneal effusion (patients who do not
need drainage effusion or do not significantly increase the effusion after 3 days of
drainage can be enrolled);
10. Patients who have had previous organ transplants (except autologous hematopoietic stem
cell transplants);
11. Patients are allergic to sintilimab, CD20 monoclonal antibody and GemOx regimen
12. Patients has not fully recovered from toxicity and/or complications due to any
intervention prior to initiation of treatment (i.e., = grade 1 or baseline, excluding
fatigue or hair loss);
13. A confirmed history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2
antibody positive);
14. A confirmed history of Novel Coronavirus infection;
15. Patients with hepatitis B (HBV HBsAg positive and HBV-DNA=105), hepatitis C (HCV)
infection (HCV antibody positive and HCV-RNA detectable); And subjects with other
acquired or congenital immune deficiency diseases, including but not limited to
hiv-infected;
16. Patients who received the live vaccine within 4 weeks of the start of the enrollment;
17. Pregnant or lactating women;
18. Patients who have received grade II or above surgery within 3 weeks before enrollment;
19. Patients with significant coagulation abnormality;
20. Other serious, uncontrolled concomitant diseases that may affect protocol compliance
or interfere with results interpretation, including uncontrolled diabetes, or
pulmonary disease (a history of interstitial pneumonia, obstructive pulmonary disease,
and symptomatic bronchospasm);
21. Patients who received the live vaccine within 4 weeks of the start of the enrollment;
22. Severe or uncontrolled infections;
23. Patients with history of severe neurological or psychiatric illness, including
dementia or epilepsy;
24. Patients with drug abuse, medical, psychological or social conditions that may
interfere with the study results or the assessment of the study results;
25. Patients are unsuitable for the enrollment according to investigator's judgement.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease, which lacks well-established diagnostic laboratory parameters that could be used to evaluate disease severity, thromboembolism or cardiovascular events and to predict clinical prognosis. Coagulation cascade and platelet functions have not been well studied in the COVID-19 patients. METHODS: A total of 178 patients enrolled in Wuhan Huoshenshan Hospital were included for the study. Blood platelets and coagulation functions were analyzed in COVID-19 patients with non-severe and severe subgroups. Other biochemical laboratory parameters were also analyzed. RESULTS: Forty-nine (27.5%) out of 178 patients were diagnosed with severe disease in this study, and 129 patients with non-severe disease. Severe disease group had significant lower platelet count 186.00 (103.50-249.00) ×109/L than 251.00 (202.00-317.00) ×109/L of non-severe group, p = 0.000. Severe group also had significantly abnormal coagulation parameters than non-severe group: prothrombin time (PT) 14.55 (13.40-16.53) s vs. 12.70 (12.15-13.59) s, p = 0.000; international normalized ratio (INR) 1.21 (1.13-1.36) vs. 1.06 (1.01-1.13), p = 0.000; thrombin time (TT) 16.35 (15.69-17.47) s vs. 15.68 (14.79-16.69) s, p = 0.011; D-Dimer 1.05 (0.68-5.90) mg/L vs. 0.42 (0.28-0.79) mg/L, p = 0.000; While the liver function parameter alanine aminotransferase (ALT) and aspartate aminotransferase (AST) didn't show significance between two groups, ALT 30.80 (19.00-58.30) IU/L vs. 28.80 (15.75-50.15) IU/L, p = 0.487; AST 27.80 (19.30-40.55) IU/L vs. 22.6 (16.7-32.03) IU/L, p = 0.102. Disseminated intravascular coagulation (DIC) rate was 6.1% in severe group while 0% in non-severe group. Survival rate of severe disease group was worse than non-severe group, 85.7% vs. 100%, p = 0.000. Thrombocytopenia correlated with coagulation function, DIC rate and survival. Six out of 7 death case had thrombocytopenia during hospitalization, and platelet count decreased subsequently until death. Thrombocytopenia occurred within 1 week after admission in 6 recovered patients. And increased platelet levels followed by positive SARS-CoV-2 IgM/IgG and negative coronavirus nucleic acid tested in 8 recovered patients. CONCLUSIONS: Low platelet count is associated with abnormal coagulation function and increased risk of DIC, severe disease manifestation and increased mortality in patients with COVID-19.