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1.
Clin Chim Acta ; 525: 54-61, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1568543

ABSTRACT

INTRODUCTION: During the recent SARS-CoV-2 pandemic, circulating calprotectin (cCLP) gained interest as biomarker to predict the severity of COVID-19. We aimed to investigate the prognostic value of cCLP measured in serum, heparin, EDTA and citrate plasma. MATERIALS AND METHODS: COVID-19 patients were prospectively included, in parallel with two SARS-CoV-2 negative control populations. The prognostic value of cCLP was compared with IL-6, CRP, LDH, procalcitonin, and the 4C-mortality score by AUROC analysis. RESULTS: For the 136 COVID-19 patients, cCLP levels were higher compared to the respective control populations, with significantly higher cCLP levels in serum and heparin than in EDTA or citrate. Higher cCLP levels were obtained for COVID-19 patients with i) severe/critical illness (n = 70), ii) ICU admission (n = 66) and iii) need for mechanical ventilation/ECMO (n = 25), but iv) not in patients who deceased within 30 days (n = 41). The highest discriminatory power (AUC [95% CI]) for each defined outcome was i) CRP (0.835 [0.755-0.914]); ii) EDTA cCLP (0.780 [0.688-0.873]); iii) EDTA cCLP (0.842 [0.758-0.925]) and iv) the 4C-mortality score (0.713 [0.608-0.818]). CONCLUSION: Measuring cCLP in COVID-19 patients helps the clinician to predict the clinical course of COVID-19. The discriminatory power of EDTA and citrate plasma cCLP levels often outperforms heparin plasma cCLP levels.


Subject(s)
COVID-19 , Heparin , Citrates , Citric Acid , Edetic Acid , Humans , Leukocyte L1 Antigen Complex , Prognosis , SARS-CoV-2
2.
J Clin Lab Anal ; 35(11): e24004, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525447

ABSTRACT

BACKGROUND: To explore the association of thrombo-inflammatory biomarkers with severity in coronavirus disease (COVID-19), we measured antiphospholipid antibodies (aPL) and calprotectin in sera of COVID-19 patients. METHODS: Anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I antibodies were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex flow immunoassay (MFIA) in hospitalized COVID-19 patients (N = 105) and healthy controls (N = 38). Anti-phosphatidylserine/prothrombin antibodies, calprotectin, and C-reactive protein (CRP) levels were also measured. We assessed the potential correlation between calprotectin levels and various laboratory parameters that were measured during the hospitalization period. After stratifying COVID-19 patients into two groups by their oxygenation status or acute respiratory distress syndrome presentation, the discriminatory performance of each biomarker was evaluated. RESULTS: A high proportion of COVID-19 patients (29.5%, 31/105) had low aCL IgM titers that were detectable by ELISA but mostly below the detection limit of MFIA. Calprotectin levels in severe groups of COVID-19 were significantly higher than those in non-severe groups, while CRP levels revealed no significant differences. Serum calprotectin levels showed strong to moderate degree of correlation with other routinely used parameters including peak levels of CRP, ferritin, procalcitonin, BUN, and neutrophil-to-lymphocyte ratio, but a negative correlation with minimal lymphocyte count and CD4+ T cells. The discriminatory performance was highest for calprotectin in discriminating severe groups of COVID-19. CONCLUSIONS: Serum calprotectin levels were significantly elevated in severe COVID-19 cases. The prevalence of clinically significant aPL did not differ. The link between calprotectin and inflammatory pathway in COVID-19 may help improve the management and outcomes of COVID-19 patients.


Subject(s)
Antibodies, Antiphospholipid/blood , COVID-19/blood , Leukocyte L1 Antigen Complex/blood , SARS-CoV-2 , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/diagnosis , Female , Humans , Male , Middle Aged , Severity of Illness Index
3.
Sci Rep ; 11(1): 22001, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1510612

ABSTRACT

Intestinal epithelial cell damage caused by SARS-CoV-2 infection was thought to be associated with gastrointestinal symptoms and decreased fecal consistency. The association of the gastrointestinal symptoms with the COVID-19-mediated inflammatory response triggered by the gastrointestinal immune system was investigated in this paper. Intestinal inflammation marker fecal calprotectin along with serum calprotectin and other inflammatory markers were measured in COVID-19 cases with and without GI manifestations as well as healthy individuals. Analyses were performed to compare COVID-19 patient subgroups and healthy controls and examine the relationship between fecal and serum calprotectin levels with gastrointestinal symptoms and disease severity. COVID-19 patients (n = 70) were found to have markedly elevated median levels of fecal (124.3 vs. 25.0 µg/g; P < 0/0001) and serum calprotectin (3500 vs. 1060 ng/mL; P < 0/0001) compared with uninfected controls. Fecal and serum calprotectin levels were not significantly different between COVID-19 patients who displayed GI symptoms and those who did not. Compared with other acute phase markers, both fecal and serum calprotectin were superior in identifying COVID-19 patients who progressed to severe illness. Although the progression of COVID-19 disease is marked by an elevation of fecal and serum calprotectin, gastrointestinal symptoms or diarrhea were not correlated with calprotectin increase level.


Subject(s)
Leukocyte L1 Antigen Complex , Adult , Gastrointestinal Diseases , Humans , Male , Middle Aged
4.
Front Cell Infect Microbiol ; 11: 751232, 2021.
Article in English | MEDLINE | ID: covidwho-1506821

ABSTRACT

Understanding of the basis for severity and fatal outcome of SARS-CoV-2 infection is of paramount importance for developing therapeutic options and identification of prognostic markers. So far, accumulation of neutrophils and increased levels of pro-inflammatory cytokines are associated with disease severity in COVID-19 patients. In this study, we aimed to compare circulatory levels of neutrophil secretory proteins, alpha-defensins (DEFA1), calprotectin (S100A8/A9), and myeloperoxidase (MPO) in COVID-19 patients with different clinical presentations. We studied 19 healthy subjects, 63 COVID-19 patients with mild (n=32) and severe (n=31) disease, 23 asymptomatic individuals identified through contact tracing programme and 23 recovering patients (1-4 months post-disease). At the time of disease presentation, serum levels of DEFA1 were significantly higher in patients with mild (mean230 ± 17, p<0.0001) and severe (mean452 ± 46, p<0.0001) disease respectively in comparison to healthy subjects (mean113 ± 11). S100A8/A9 proteins were significantly higher in COVID-19 patients (p<0.0001) irrespective of disease severity. The levels of DEFA1, S100A8/A9 and MPO reduced to normal in recovering patients and comparable to healthy subjects. Surprisingly, DEFA1 levels were higher in severe than mild patients in first week of onset of disease (p=0.004). Odds-ratio analysis showed that DEFA1 could act as potential biomarker in predicting disease severity (OR=11.34). In addition, levels of DEFA1 and S100A8/A9 were significantly higher in patients with fatal outcome (p=0.004 and p=0.03) respectively. The rise in DEFA1 levels was independent of secondary infections. In conclusion, our data suggest that induction of elevated levels of alpha-defensins and S100A8/A9 is associated with poor disease outcome in COVID-19 patients.


Subject(s)
COVID-19 , alpha-Defensins , Humans , Leukocyte L1 Antigen Complex , Neutrophils , Peroxidase , SARS-CoV-2 , Severity of Illness Index
7.
World J Gastroenterol ; 27(22): 3130-3137, 2021 Jun 14.
Article in English | MEDLINE | ID: covidwho-1268366

ABSTRACT

BACKGROUND: One third of coronavirus disease 2019 (COVID-19) patients have gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has been detected in stool samples of approximately 50% of COVID-19 individuals. Fecal calprotectin is a marker of gastrointestinal inflammation in the general population. AIM: To investigate if fecal calprotectin correlates with SARS-CoV-2 intestinal shedding in COVID-19 patients with pneumonia. METHODS: Patients with SARS-CoV-2 pneumonia admitted to the Infectious Disease Unit (University Hospital of Trieste, Italy) from September to November 2020 were consecutively enrolled in the study. Fecal samples were collected and analyzed for quantification of fecal calprotectin (normal value < 50 mg/kg) and SARS-CoV-2 RNA presence by polymerase chain reaction (PCR). Inter-group differences were determined between patients with and without diarrhea and patients with and without detection of fecal SARS-CoV-2. RESULTS: We enrolled 51 adults (40 males) with SARS-CoV-2 pneumonia. Ten patients (20%) presented with diarrhea. Real-time-PCR of SARS-CoV-2 in stools was positive in 39 patients (76%), in all patients with diarrhea (100%) and in more than two thirds (29/41, 71%) of patients without diarrhea. Obesity was one of the most common comorbidities (13 patients, 25%); all obese patients (100%) (P = 0.021) tested positive for fecal SARS-CoV-2. Median fecal calprotectin levels were 60 mg/kg [interquartile range (IQR) 21; 108]; higher fecal calprotectin levels were found in the group with SARS-CoV-2 in stools (74 mg/kg, IQR 29; 132.5) compared to the group without SARS-CoV-2 (39 mg/kg, IQR 14; 71) (P < 0.001). CONCLUSION: High fecal calprotectin levels among COVID-19 patients correlate with SARS-CoV-2 detection in stools supporting the hypothesis that this virus can lead to bowel inflammation and potentially to the 'leaky gut' syndrome.


Subject(s)
COVID-19 , Leukocyte L1 Antigen Complex/analysis , Virus Shedding , Adult , COVID-19/diagnosis , Feces/chemistry , Female , Humans , Italy , Male , RNA, Viral , SARS-CoV-2
8.
J Intern Med ; 290(3): 677-692, 2021 09.
Article in English | MEDLINE | ID: covidwho-1255442

ABSTRACT

BACKGROUND: Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). RESULTS: COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. CONCLUSION: Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Leukocytes, Mononuclear/immunology , Transcriptome , Adaptive Immunity , Adult , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Female , HLA-DR Antigens/immunology , Humans , Immunity, Innate , Interleukin-2 Receptor alpha Subunit/immunology , Interleukin-7/immunology , Leukocyte L1 Antigen Complex/blood , Male , Middle Aged , Monocytes/immunology , Phenotype , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , Thromboplastin/immunology , Thromboplastin/metabolism
9.
BMJ Open Gastroenterol ; 8(1)2021 05.
Article in English | MEDLINE | ID: covidwho-1219408

ABSTRACT

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.


Subject(s)
COVID-19/epidemiology , Feces/chemistry , Inflammatory Bowel Diseases/therapy , Leukocyte L1 Antigen Complex/analysis , Pandemics , Point-of-Care Testing , Adolescent , Biomarkers/analysis , Child , Child, Preschool , Clinical Chemistry Tests/statistics & numerical data , Feedback , Female , Home Care Services , Humans , Male , Patient Portals , Patient Preference/statistics & numerical data , Prospective Studies , Reagent Kits, Diagnostic/statistics & numerical data , Reference Values , Surveys and Questionnaires
10.
Inflamm Res ; 70(6): 687-694, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1217416

ABSTRACT

OBJECTIVE AND DESIGN: Fecal calprotectin (CLP) is widely known for its detection in stools of patients with inflammatory bowel diseases (IBDs), to investigate the intestinal inflammatory status. Current research is promoting the circulating protein role as a systemic inflammatory marker. However, most studies report serum calprotectin analysis although plasma assay prevents its massive release by granulocytes. In this perspective, the ongoing SARS-CoV-2 pandemic deserves deployment of convenient and easy-to-dose markers that could reliably address the state of infection. METHODS: We analyzed serum circulating calprotectin (cCLP) levels in hospitalized COVID-19 patients and plasma cCLP levels from patients with suspected SARS-CoV-2 infection, then assessed negative or positive on molecular tests. RESULTS: Our results confirm a significant circulating calprotectin increase in infected subjects respect to controls, in serum and plasma. Moreover, plasma calprotectin has higher levels in suspected patients with positive SARS-CoV-2-RT-PCR, compared to suspected patients with negative SARS-CoV-2-RT-PCR. Furthermore, ROC curves results showed the circulating plasma calprotectin discriminatory ability to differentiate infected SARS-CoV-2 patients at a cutoff value greater than 131.3 ng/ml. CONCLUSIONS: Our data propose circulating calprotectin as a new, quantitative and predictive marker, which in addition to being an interesting generic inflammatory marker may provide important indications in SARS-CoV-2 infection.


Subject(s)
COVID-19/blood , Leukocyte L1 Antigen Complex/blood , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19 Testing , Female , Humans , Inflammation/blood , Inflammation/diagnosis , Male , Middle Aged , Real-Time Polymerase Chain Reaction
11.
Front Cell Infect Microbiol ; 11: 590874, 2021.
Article in English | MEDLINE | ID: covidwho-1158345

ABSTRACT

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.


Subject(s)
COVID-19/pathology , Dysbiosis/microbiology , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/microbiology , Immunity, Innate/immunology , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Bacteria/metabolism , COVID-19/therapy , Cardiovascular Diseases/pathology , Diabetes Mellitus, Type 2/pathology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Gene Expression/genetics , Humans , Leukocyte L1 Antigen Complex/biosynthesis , Obesity/pathology , Probiotics/pharmacology , SARS-CoV-2/immunology , Severity of Illness Index
12.
Nat Rev Gastroenterol Hepatol ; 18(4): 269-283, 2021 04.
Article in English | MEDLINE | ID: covidwho-1085424

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 200 countries and regions globally. SARS-CoV-2 is thought to spread mainly through respiratory droplets and close contact. However, reports have shown that a notable proportion of patients with coronavirus disease 2019 (COVID-19) develop gastrointestinal symptoms and nearly half of patients confirmed to have COVID-19 have shown detectable SARS-CoV-2 RNA in their faecal samples. Moreover, SARS-CoV-2 infection reportedly alters intestinal microbiota, which correlated with the expression of inflammatory factors. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal infection by SARS-CoV-2. These lines of evidence highlight the nature of SARS-CoV-2 gastrointestinal infection and its potential faecal-oral transmission. Here, we summarize the current findings on the gastrointestinal manifestations of COVID-19 and its possible mechanisms. We also discuss how SARS-CoV-2 gastrointestinal infection might occur and the current evidence and future studies needed to establish the occurrence of faecal-oral transmission.


Subject(s)
COVID-19/physiopathology , Diarrhea/physiopathology , Dysbiosis/physiopathology , Gastroenteritis/physiopathology , Gastrointestinal Microbiome , Nausea/physiopathology , Vomiting/physiopathology , Abdominal Pain/physiopathology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Anorexia/physiopathology , COVID-19/transmission , Cell Line , Colon/metabolism , Cytokines/metabolism , Disease Models, Animal , Feces/chemistry , Gastroenteritis/virology , Humans , Intestinal Mucosa/metabolism , Intestine, Small/metabolism , Leukocyte L1 Antigen Complex/metabolism , Organoids , RNA, Viral , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Viral Load , Virus Shedding
13.
Sci Rep ; 11(1): 1580, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-1065929

ABSTRACT

Patients with coronavirus disease-19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. However, bleeding complications have also been observed in some patients. Understanding the balance between coagulation and fibrinolysis will help inform optimal approaches to thrombosis prophylaxis and potential utility of fibrinolytic-targeted therapies. 118 hospitalized COVID-19 patients and 30 healthy controls were included in the study. We measured plasma antigen levels of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and performed spontaneous clot-lysis assays. We found markedly elevated tPA and PAI-1 levels in patients hospitalized with COVID-19. Both factors demonstrated strong correlations with neutrophil counts and markers of neutrophil activation. High levels of tPA and PAI-1 were associated with worse respiratory status. High levels of tPA, in particular, were strongly correlated with mortality and a significant enhancement in spontaneous ex vivo clot-lysis. While both tPA and PAI-1 are elevated among COVID-19 patients, extremely high levels of tPA enhance spontaneous fibrinolysis and are significantly associated with mortality in some patients. These data indicate that fibrinolytic homeostasis in COVID-19 is complex with a subset of patients expressing a balance of factors that may favor fibrinolysis. Further study of tPA as a biomarker is warranted.


Subject(s)
COVID-19/diagnosis , Plasminogen Activator Inhibitor 1/blood , Tissue Plasminogen Activator/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Hospitalization , Humans , Leukocyte Count , Leukocyte L1 Antigen Complex/analysis , Male , Middle Aged , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index
14.
J Thromb Thrombolysis ; 51(2): 446-453, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-927286

ABSTRACT

Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. Elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have recently been described in patients with COVID-19. However, their potential role in COVID-19-associated thrombosis remains incompletely understood. In order to elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis, we conducted a case-control study of patients hospitalized with COVID-19 who developed thrombosis, as compared with gender- and age-matched COVID-19 patients without clinical thrombosis. We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19, as well as novel approaches for thrombosis prevention.


Subject(s)
COVID-19/blood , Extracellular Traps/metabolism , Neutrophils/metabolism , SARS-CoV-2/metabolism , Thrombosis/blood , Adult , Aged , Aged, 80 and over , COVID-19/complications , Case-Control Studies , Female , Histones/blood , Humans , Leukocyte L1 Antigen Complex/blood , Male , Middle Aged , Thrombosis/etiology
20.
Cell ; 182(6): 1401-1418.e18, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694669

ABSTRACT

Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Flow Cytometry , Humans , Leukocyte L1 Antigen Complex , Monocytes , Myeloid Cells , Prospective Studies , SARS-CoV-2
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