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1.
Int J Lab Hematol ; 43(6): 1309-1318, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1409690

ABSTRACT

INTRODUCTION: Developing prognostic markers can be useful for clinical decision-making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID-19). METHODS: Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID-19. Patients with COVID-19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN-3000 automated hematology analyzer and Sysmex DI-60 employing the convolutional neural network-based automatic image-recognition system. RESULTS: Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P < .001). Granular lymphocyte counts were normal or higher in mild cases and persistently decreased in fatal cases. Temporary increase in granular lymphocytes was associated with survival of patients with severe infection. Red cell distribution width was significantly higher in severe cases than in mild cases (P < .001). Neutrophil dysplasia was consistently observed in COVID-19 cases, but not in HCs. Levels of giant neutrophils and toxic granulation/Döhle bodies were increased in severe cases. CONCLUSION: Basic PB examination can be useful to predict the prognosis of COVID-19, by detecting SARS-CoV-2 infection-induced multi-lineage changes in blood cell counts and morphological anomalies. These changes were dynamically correlated with disease severity and may be associated with disruption of hematopoiesis and the immunological system due to bone marrow stress in severe infection.


Subject(s)
Blood Cell Count , COVID-19/blood , Leukocytosis/etiology , Lymphocytes/ultrastructure , Lymphopenia/etiology , Neutrophils/ultrastructure , SARS-CoV-2 , Aged , Anemia/blood , Anemia/etiology , Blood Cell Count/instrumentation , Blood Cell Count/methods , COVID-19/mortality , Cell Shape , Cytoplasmic Granules/ultrastructure , Erythrocyte Indices , Female , Humans , Image Processing, Computer-Assisted , Leukocytosis/blood , Lymphocyte Count , Lymphopenia/blood , Male , Middle Aged , Neural Networks, Computer , Prognosis , Severity of Illness Index
2.
Pharmacol Res ; 160: 105036, 2020 10.
Article in English | MEDLINE | ID: covidwho-1364401

ABSTRACT

OBJECTIVES: The current diagnosis and medicines approach in coronavirus disease 2019 (COVID-19) does not reflect the heterogeneous characteristics of this disease. This study aims to find a new antiviral combination regimen by investigating the frequency of clinically relevant and objectively identified comorbidities, and the clustering of these clinical syndromes and varying results of treatment with antiviral drugs in patients hospitalized with severe COVID-19. METHODS: This study recruited 151 severe COVID-19 infection cases diagnosed in our hospital examination and illustrated the clinical potential during a consecutive 25-day medication period. Potential differences in disease severity and clinical characteristics, hematological profile, and current pharmacologic treatments (single agent, double or triple combinations, and the combined antiviral drugs plus Lianhua Qingwen) among comorbidity clusters were explored. RESULTS: Although disease severity was comparable among three clusters, it was markedly different in terms of laboratory test status. Coagulable abnormality was mainly present in cluster 1 and cluster 2. Other indicators were normal, except for a significant increase of neutrophils presented in cluster 2. Patients showed the most complicated haematological results in cluster 3, including severe coagulation abnormalities, leukocytosis, neutrophilic granulocytosis, and lymphopenia. Our results for the first time suggest that a quadruple combination therapy (Ribavirin, Lopinavir/ritonavir, Umifenovir, and Lianhua Qingwen) can be considered as a preferred treatment approach to severe COVID-19 patients. After treatment, abnormal coagulation and leukocyte had markedly improved with a better prognosis. CONCLUSION: This study expands the understanding of the co-occurrence of combination therapy in patients with COVID-19, which provides the probability of developing novel combined therapy. Furthermore, explore clinical trials of variable antivirus treatments based on subgroup analyses or on using subgroups in the selection criteria would be the next step.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/blood , Coronavirus Infections/drug therapy , Pneumonia, Viral/blood , Pneumonia, Viral/drug therapy , Adult , Aged , Blood Cell Count , Blood Coagulation , COVID-19 , Comorbidity , Drug Therapy, Combination , Female , Granulocytes , Humans , Leukocyte Count , Leukocytosis/etiology , Lymphopenia/etiology , Male , Middle Aged , Pandemics , Treatment Outcome
4.
Int J Lab Hematol ; 43(6): 1302-1308, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1288297

ABSTRACT

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.


Subject(s)
COVID-19/blood , Lymphocyte Count , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , COVID-19/mortality , China/epidemiology , Creatinine/blood , Female , Hospital Mortality , Hospitals, General/statistics & numerical data , Humans , Lymphopenia/blood , Lymphopenia/etiology , Male , Mass Screening , Middle Aged , Patient Admission , Prognosis , Retrospective Studies , Severity of Illness Index , Treatment Outcome
5.
Pharmacol Res ; 159: 104946, 2020 09.
Article in English | MEDLINE | ID: covidwho-1279674

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pandemics , Pneumonia, Viral/blood , Biomarkers/blood , COVID-19 , Coronavirus Infections/etiology , Coronavirus Infections/immunology , Cytokines/blood , Disease Progression , Humans , Interleukin-10/blood , Interleukin-6/blood , Lymphopenia/etiology , Lymphopenia/immunology , Pneumonia, Viral/etiology , Pneumonia, Viral/immunology , Procalcitonin/blood , SARS-CoV-2
6.
Sci Rep ; 11(1): 12775, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1275948

ABSTRACT

With increasing numbers of patients recovering from COVID-19, there is increasing evidence for persistent symptoms and the need for follow-up studies. This retrospective study included patients without comorbidities, who recovered from COVID-19 and attended an outpatient clinic at a university hospital for follow-up care and potential convalescent plasma donation. Network analysis was applied to visualize symptom combinations and persistent symptoms. Comprehensive lab-testing was ascertained at each follow-up to analyze differences regarding patients with vs without persistent symptoms. 116 patients were included, age range was 18-69 years (median: 41) with follow-ups ranging from 22 to 102 days. The three most frequent persistent symptoms were Fatigue (54%), Dyspnea (29%) and Anosmia (25%). Lymphopenia was present in 13 of 112 (12%) cases. Five of 35 cases (14%) had Lymphopenia in the later follow-up range of 80-102 days. Serum IgA concentration was the only lab parameter with significant difference between patients with vs without persistent symptoms with reduced serum IgA concentrations in the patient cohort of persistent symptoms (p = 0.0219). Moreover, subgroup analyses showed that patients with lymphopenia experienced more frequently persistent symptoms. In conclusion, lymphopenia persisted in a noticeable percentage of recovered patients. Patients with persistent symptoms had significantly lower serum IgA levels. Furthermore, our data provides evidence that lymphopenia is associated with persistence of COVID-19 symptoms.


Subject(s)
Anosmia/etiology , COVID-19/complications , Dyspnea/etiology , Fatigue/etiology , Immunoglobulin A/blood , Lymphopenia/etiology , SARS-CoV-2 , Adolescent , Adult , Aftercare , Aged , COVID-19/epidemiology , COVID-19/virology , Female , Follow-Up Studies , Germany/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
8.
PLoS One ; 16(5): e0251250, 2021.
Article in English | MEDLINE | ID: covidwho-1232461

ABSTRACT

OBJECTIVES: Clinical characterisation studies have been essential in helping inform research, diagnosis and clinical management efforts, particularly early in a pandemic. This systematic review summarises the early literature on clinical characteristics of patients admitted to hospital, and evaluates the quality of evidence produced during the initial stages of the pandemic. METHODS: MEDLINE, EMBASE and Global Health databases were searched for studies published from January 1st 2020 to April 28th 2020. Studies which reported on at least 100 hospitalised patients with Covid-19 of any age were included. Data on clinical characteristics were independently extracted by two review authors. Study design specific critical appraisal tools were used to evaluate included studies: the Newcastle Ottawa scale for cohort and cross sectional studies, Joanna Briggs Institute checklist for case series and the Cochrane collaboration tool for assessing risk of bias in randomised trials. RESULTS: The search yielded 78 studies presenting data on 77,443 people. Most studies (82%) were conducted in China. No studies included patients from low- and middle-income countries. The overall quality of included studies was low to moderate, and the majority of studies did not include a control group. Fever and cough were the most commonly reported symptoms early in the pandemic. Laboratory and imaging findings were diverse with lymphocytopenia and ground glass opacities the most common findings respectively. Clinical data in children and vulnerable populations were limited. CONCLUSIONS: The early Covid-19 literature had moderate to high risk of bias and presented several methodological issues. Early clinical characterisation studies should aim to include different at-risk populations, including patients in non-hospital settings. Pandemic preparedness requires collection tools to ensure observational studies are methodologically robust and will help produce high-quality data early on in the pandemic to guide clinical practice and public health policy. REVIEW REGISTRATION: Available at https://osf.io/mpafn.


Subject(s)
COVID-19/pathology , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Cough/epidemiology , Cough/etiology , Databases, Factual , Fever/epidemiology , Fever/etiology , Headache/epidemiology , Headache/etiology , Humans , Lymphopenia/etiology , Pandemics , SARS-CoV-2/isolation & purification
9.
Front Immunol ; 12: 661052, 2021.
Article in English | MEDLINE | ID: covidwho-1229177

ABSTRACT

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1ß, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.


Subject(s)
COVID-19/immunology , Lymph Nodes/immunology , Lymphopenia/immunology , SARS-CoV-2/immunology , Spleen/immunology , Angiotensin-Converting Enzyme 2/immunology , COVID-19/complications , COVID-19/pathology , Coronavirus Nucleocapsid Proteins/immunology , Cytokines/immunology , Female , Humans , Inflammation/immunology , Inflammation/pathology , Lymph Nodes/ultrastructure , Lymphopenia/etiology , Lymphopenia/pathology , Middle Aged , Phosphoproteins/immunology , RNA, Messenger/immunology , Retrospective Studies , SARS-CoV-2/pathogenicity , SARS-CoV-2/ultrastructure , Spleen/ultrastructure
10.
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
11.
Emerg Microbes Infect ; 10(1): 905-912, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1191602

ABSTRACT

Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections , COVID-19 Serological Testing , COVID-19/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , Pandemics , SARS-CoV-2/immunology , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , B-Lymphocytes , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , China/epidemiology , Convalescence , Cytokines/blood , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay , Follow-Up Studies , Food Handling , Genome, Viral , Humans , Immunity, Herd , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Lymphocyte Count , Lymphopenia/etiology , Phylogeny , RNA, Viral/blood , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , Seroepidemiologic Studies , Sputum/virology
13.
Int J Lab Hematol ; 43(5): 1237-1242, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1175057

ABSTRACT

INTRODUCTION: Outbreak of corona virus disease in 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Our aim is to document hematological parameters of patients with COVID-19 during initial stage of diagnosis and to identify early hematological indicators of severe infection. MATERIALS AND METHODS: This retrospective study was conducted at Shifa International Hospital, Pakistan from April to November 2020. Patients hospitalized with COVID-19, diagnosed on RT-PCR and had a complete blood count (CBC) done within 48 hours of diagnosis were included. Data was analyzed using IBM® SPSS Statistics. RESULTS: A total of 425 patients were included in this study out of whom 272(64%) were males. The mean age was 55.61 ± 17.84 years. 95 patients (22.4%) had normal blood counts within 48 hours of COVID-19 diagnosis. Cytopenias were seen in 193(45.4%) patients. There were 75(17.6%) mortalities during the study period. Chi-square test showed that thrombocytopenia, lymphopenia and neutrophilic leucocytosis were significantly associated with mortality (P = .037, P < .001, P < .001 respectively) and need for ventilator (P = .009, P < .001, P < .001, respectively). Neutrophilia was also associated with development of Acute Respiratory Distress Syndrome (P < .001). On ROC analysis, Neutrophil-to-Lymphocyte Ratio yielded an area under the curve (AUC) of 0.693 and 0.660 for the outcomes mortality and need for ventilator, respectively. For a subset of 288 patients who had D-dimer levels checked within 48 hours of COVID-19 diagnosis, the AUC for mortality and ventilator need was 0.708 and 0.671, respectively. CONCLUSION: Hematological indices are vital indicators in the prognosis and risk stratification of COVID-19 during initial stages of disease.


Subject(s)
COVID-19/blood , Adult , Aged , Blood Cell Count , COVID-19/complications , COVID-19/diagnosis , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitalization , Humans , Leukocyte Count , Lymphopenia/blood , Lymphopenia/diagnosis , Lymphopenia/etiology , Male , Middle Aged , Pakistan/epidemiology , Prognosis , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology
14.
Int Immunopharmacol ; 95: 107586, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1149235

ABSTRACT

The incidence of the novel coronavirus disease (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought daunting complications for people as well as physicians around the world. An ever-increasing number of studies investigating the characteristics of the disease, day by day, is shedding light on a new feature of the virus with the hope that eventually these efforts lead to the proper treatment. SARS-CoV-2 activates antiviral immune responses, but in addition may overproduce pro-inflammatory cytokines, causing uncontrolled inflammatory responses in patients with severe COVID-19. This condition may lead to lymphopenia and lymphocyte dysfunction, which in turn, predispose patients to further infections, septic shock, and severe multiple organ dysfunction. Therefore, accurate knowledge in this issue is important to guide clinical management of the disease and the development of new therapeutic strategies in patients with COVID-19. In this review, we provide a piece of valuable information about the alteration of each subtype of lymphocytes and important prognostic factors associated with these cells. Moreover, through discussing the lymphopenia pathophysiology and debating some of the most recent lymphocyte- or lymphopenia-related treatment strategies in COVID-19 patients, we tried to brightening the foreseeable future for COVID-19 patients, especially those with severe disease.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/virology , Lymphopenia/immunology , Lymphopenia/physiopathology , SARS-CoV-2/immunology , COVID-19/complications , Humans , Lymphopenia/etiology , Lymphopenia/virology , Prognosis
15.
J Psychiatry Neurosci ; 46(2): E232-E237, 2021 03 11.
Article in English | MEDLINE | ID: covidwho-1127808

ABSTRACT

Background: Monitoring of white cell counts during clozapine treatment leads to cessation of therapy if levels fall below predetermined values. Reductions in white cell counts, driven by lower levels of lymphocytes, have been observed with coronavirus disease 2019 (COVID-19). Neutropenia during COVID-19 has not been reported. We present data for 56 patients who were taking clozapine and had COVID-19. Methods: We included patients who were taking clozapine at the time they tested positive for COVID-19. We compared absolute neutrophil counts, lymphocyte counts and white cell counts between baseline and the first week of infection, and baseline and the second week of infection. Results: We observed reductions in absolute neutrophil counts (p = 0.005), lymphocyte counts (p = 0.003) and white cell counts (p < 0.001) between baseline and the first 7 days of COVID-19. All cell counts had returned to baseline levels by days 8 to 14. Six patients experienced neutropenia (absolute neutrophil counts < 2.0 × 109/L) and of those, 4 underwent mandatory cessation of clozapine. For 3 patients, clozapine treatment had been established for more than 6 months with no previous neutropenia, neutrophil levels returned to baseline within 2 weeks and no further neutropenia was observed on restarting treatment. Limitations: This was a retrospective chart review; larger cohorts are required. Clozapine plasma levels were largely not measured by clinicians. Conclusion: These data strongly suggest that mild neutropenia in the acute phase of COVID-19 in patients who are well established on clozapine is more likely to be a consequence of the virus than of clozapine treatment.


Subject(s)
Antipsychotic Agents/adverse effects , COVID-19/complications , Clozapine/adverse effects , Neutropenia/etiology , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Adult , Aged , Aged, 80 and over , Antipsychotic Agents/therapeutic use , COVID-19/blood , Clozapine/therapeutic use , Female , Humans , Leukocyte Count , Leukopenia/etiology , Lymphocyte Count , Lymphopenia/etiology , Male , Middle Aged , Neutropenia/chemically induced , Neutrophils , Retrospective Studies , SARS-CoV-2 , Young Adult
16.
Medicine (Baltimore) ; 100(5): e23991, 2021 Feb 05.
Article in English | MEDLINE | ID: covidwho-1087853

ABSTRACT

ABSTRACT: Since the first infected case of Coronavirus Disease 2019 (COVID-19) was reported in Wuhan, China in December 2019, the virus has spread swiftly, inflicting upon millions of people around the globe. The objective of the study is to investigate and analyze the clinical characteristics and outcomes of patients infected with COVID-19 in Wuxi, China.Cross-sectional study.The Fifth People's Hospital of Wuxi, China.A total of 48 COVID-19 patients were enrolled in the study from 23 January 2020 to 8 March 2020, and the clinical data of these subjects were collected.Epidemiological, clinical, laboratory, and radiologic characteristics, as well as treatment and outcome data, were collected and analyzed.Of these 48 patients with confirmed COVID-19, 3 were mild cases (6.3%), 44 were moderate cases (91.7%), 1 was severe case (2.1%). The median age of the subjects was 45 years (interquartile range [IQR], 24-59; range, 5-75 years). Twenty-five of the patients (52.1%) were male and 23 (47.9%) were female. Twenty-eight cases (58.3%) returned to Wuxi, Jiangsu Province. Thirty-four (70.8%) cases were infected due to clustering epidemic and 29 cases (85.3%) were attributable to family-clustering epidemic. No obvious clinical symptoms were observed in the cohort of patients, except for 3 mild cases. The most common symptoms include fever (41 [85.4%]), cough (28 [58.3%]), asthenia (13 [27.1%]), expectoration (11 [22.9%]), diarrhea (10 [20.8%]), and dyspnea (5 [10.4%]). Seventeen (35.4%) patients had lower lymphocyte values than baseline, 31 patients (64.6%) had higher d-dimers to exceed the normal range. The distribution of high-resolution computed tomography (HRCT)-positive lesions were as follows: left lung in 5 cases (10.4%), right lung in 9 cases (18.8%), and bilateral lungs in 31 cases (64.6%). In terms of density of lesions: 28 cases (58.3%) showed ground glass shadows in the lung, 7 cases (14.6%) showed solid density shadows, and 10 cases (20.8%) showed mixed density shadows. Extrapulmonary manifestations found that mediastinal lymph nodes were enlarged in 2 cases (4.2%) and that pleural effusion was present in 1 case (2.1%). All patients underwent treatment in quarantine. Forty-five (93.8%) patients received antiviral treatments, 22 (45.8%) patients received antibacterial treatments, 6 (12.5%) patients received glucocorticoid treatments, 2 (4.2%) patients received high flow oxygen inhalation treatments, and 6 (12.5%) patients received noninvasive ventilation treatments. As of 8 March 2020, all 48 patients included in this study were cured. The average time of hospitalization of the 48 patients was 18 ±â€Š6 (mean ±â€ŠSD) days, the average time of the lesion resorption was 11 ±â€Š4 days, and the average time taken to achieve negativity in the result of nucleic acid examination was (10 ±â€Š4) days.The epidemiological characteristics of 48 COVID-19 patients in Wuxi were mainly imported cases and clustered cases. The clinical manifestations of these patients were mainly fever and cough. Laboratory results showed that the lymphocytopenia and increased d-dimer are positively correlated with disease severity. Pulmonary imaging showed unilateral or bilateral ground glass infiltration. Most of the patients entered clinical recovery stage within 15 days after hospitalization.


Subject(s)
COVID-19 , Cough , Fever , Hospitalization/statistics & numerical data , Patient Care , SARS-CoV-2/isolation & purification , Symptom Assessment/statistics & numerical data , COVID-19/blood , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , China/epidemiology , Cluster Analysis , Cough/diagnosis , Cough/etiology , Family Health/statistics & numerical data , Female , Fever/diagnosis , Fever/etiology , Fibrin Fibrinogen Degradation Products/analysis , Humans , Lymphopenia/diagnosis , Lymphopenia/etiology , Male , Middle Aged , Patient Care/methods , Patient Care/statistics & numerical data , Radiography, Thoracic/statistics & numerical data , Tomography, X-Ray Computed/methods
17.
Int J Hematol ; 113(1): 45-57, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1064611

ABSTRACT

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms. The most frequently reported coagulation/fibrinolytic abnormality in COVID-19 is the increase in D-dimer, and its relationship with prognosis has been discussed. However, limits exist to the utility of evaluation by D-dimer alone. In addition, since the coagulation/fibrinolytic condition sometimes fluctuates within a short period of time, regular examinations in recognition of the significance of the examination are desirable. The pathophysiology of disseminated intravascular coagulation (DIC) associated with COVID-19 is very different from that of septic DIC, and both thrombotic and hemorrhagic pathologies should be noted. COVID-19 thrombosis includes macro- and microthrombosis, with diagnosis of the latter depending on markers of coagulation and fibrinolysis. Treatment of COVID-19 is classified into antiviral treatment, cytokine storm treatment, and thrombosis treatment. Rather than providing uniform treatment, the treatment method most suitable for the severity and stage should be selected. Combination therapy with heparin and nafamostat is expected to develop in the future. Fibrinolytic therapy and adsorption therapy require further study.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anticoagulants/therapeutic use , Benzamidines , Blood Coagulation Disorders/physiopathology , Blood Coagulation Tests , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Guanidines/pharmacology , Guanidines/therapeutic use , Humans , Lymphopenia/etiology , Male , Middle Aged , Prognosis , Pulmonary Circulation , SARS-CoV-2/drug effects , Survivors , Thrombocytopenia/etiology , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombophilia/physiopathology
18.
Biomed Pharmacother ; 133: 110982, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060484

ABSTRACT

The pathogenesis of Coronavirus disease 2019 is still obscure and the need for exploration of possible mechanisms to suggest drugs based on knowledge should never be delayed. In this manuscript, we present a novel theory to explain the pathogenesis of COVID-19; lymphocyte distraction theory upon which the author has used, in a preprinted protocol, non-steroidal anti-inflammatory drugs (NSAIDs); diclofenac potassium, ibuprofen and ketoprofen, successfully to treat COVID-19 patients. Furthermore, we agree with a recommendation that glucocorticoids should not be used routinely for COVID-19 patients and suggested to be beneficial only for patients with late acute respiratory distress syndrome. A clinical proof of ibuprofen safety in COVID-19 has been published by other researchers and we suggest that early administration of NSAIDs, including ibuprofen, in COVID-19 is not only safe but it might also prevent COVID-19 complications and this manuscript explains some of the suggested associated protective mechanisms.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/drug therapy , COVID-19/complications , COVID-19/pathology , Humans , Lymphopenia/etiology , Lymphopenia/prevention & control , Treatment Outcome
19.
J Gerontol A Biol Sci Med Sci ; 76(8): e97-e101, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1060193

ABSTRACT

Profound T-cell lymphopenia is the hallmark of severe coronavirus disease 2019 (COVID-19). T-cell proliferation is telomere length (TL) dependent and telomeres shorten with age. Older COVID-19 patients, we hypothesize, are, therefore, at a higher risk of having TL-dependent lymphopenia. We measured TL by the novel Telomere Shortest Length Assay (TeSLA), and by Southern blotting (SB) of the terminal restriction fragments in peripheral blood mononuclear cells of 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. TeSLA tallies and measures single telomeres, including short telomeres undetected by SB. Such telomeres are relevant to TL-mediated biological processes, including cell viability and senescence. TeSLA yields 2 key metrics: the proportions of telomeres with different lengths (expressed in %) and their mean (TeSLA mTL), (expressed in kb). Lymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (p < .001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kb (p = .005) and positively correlated with TeSLA mTL (p = .03). Lymphocyte count was not significantly correlated with SB mTL in either COVID-19 or non-COVID-19 patients. We propose that compromised TL-dependent T-cell proliferative response, driven by short telomere in the TL distribution, contributes to COVID-19 lymphopenia among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons. Clinical Trials Registration Number: NCT04325646.


Subject(s)
COVID-19/physiopathology , Hospitalization , Lymphocyte Count , Lymphopenia , Telomere Shortening/physiology , Aged, 80 and over , Cellular Senescence , Humans , Lymphopenia/etiology , Lymphopenia/pathology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology
20.
FASEB J ; 35(2): e21245, 2021 02.
Article in English | MEDLINE | ID: covidwho-1048438

ABSTRACT

Lymphopenia is commonly observed in SARS and COVID-19 patients although the lymphocyte count is not always below 0.8 × 109 /L in all the patients. It is suggested that lymphopenia serves as a useful predictor for prognosis in the patients. It is also hypothesized that lymphopenia is related to glucocorticoids and apoptosis. However, the ordering between lymphopenia and apoptosis appears different between SARS and COVID-19 patients, ie, lymphopenia is prior to apoptosis in SARS patients whereas apoptosis is prior to lymphopenia in COVID-19 patients. This paper attempts to figure out this contradiction through three players, lymphopenia, glucocorticoids, and apoptosis. Although the literature does not provide a solid explanation, the level of glucocorticoids could determine the ordering between lymphopenia and apoptosis because the administration of high doses of glucocorticoids could lead to lymphopenia whereas low doses of glucocorticoids could benefit patients. In the meantime, this paper raises several questions, which need to be answered in order to better understand the whole course of COVID-19.


Subject(s)
COVID-19 , Glucocorticoids , Lymphopenia , SARS Virus/metabolism , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome , Apoptosis/drug effects , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Lymphopenia/drug therapy , Lymphopenia/etiology , Lymphopenia/metabolism , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/metabolism
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