High CD4-to-CD8 ratio identifies an at-risk population susceptible to lethal COVID-19.

Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.

Increased Blood Monocytic Myeloid Derived Suppressor Cells but Low Regulatory T Lymphocytes in Patients with Mild COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may produce a systemic disease, the coronavirus disease-19 (COVID-19), with high morbidity and mortality. Even though we do not fully understand the interaction of innate and adaptive immunity in the control and complications of the viral infection, it is well recognized that SARS-CoV-2 induces an immunodepression that impairs the elimination of the virus and favors its rapid dissemination in the organism. Even less is known about the possible participation of inhibitory cells of the innate immune system, such as the myeloid-derived suppressor cells (MDSCs), or the adaptive immune system, such as the T regulatory cells (Tregs). That is why we aimed to study blood levels of MDSCs, as well as lymphocyte subpopulations, including Tregs, and activated (OX-40+) and inhibited (PD-1) T lymphocytes in patients with mild COVID-19 in comparison with data obtained from control donors. We have found that 20 hospitalized patients with COVID-19 and no health history of immunosuppression had a significant increase in the number of peripheral monocytic MDSCs (M-MDSC), but a decrease in Tregs, as well as an increase in the number of inhibited or exhausted T cells, whereas the number of activated T cells was significantly decreased compared with that from 20 healthy controls. Moreover, there was a significant negative correlation (r = 0.496) between the number of M-MDSC and the number of activated T cells. Therefore, M-MDSC rather than Tregs may contribute to the immunosuppression observed in patients with COVID-19.

Comparison of Clinical and Laboratory Features and Treatment Options of 237 Symptomatic and Asymptomatic Children Infected with SARS-CoV-2 in the Early Phase of the COVID-19 Pandemic in Turkey.

Little is known about the therapeutic use of hydroxychloroquine in pediatric patients with coronavirus disease 2019 (COVID-19). Here, we retrospectively retrieved data of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive pediatric patients from 20 hospitals in 8 Turkish cities. We obtained epidemiological, clinical, and laboratory features of the patients, as well as the drugs used for treating COVID-19. A total of 237 nasopharyngeal swab SARS-CoV-2 PCR-positive children were included in the study from March 26, 2020 to June 20, 2020. The mean age of asymptomatic children (118 ± 62 months) was higher than that of symptomatic children (89 ± 69 months). Symptomatic children had significantly lower mean lymphocyte counts and higher mean CRP, D-dimer, procalcitonin, and LDH levels than asymptomatic children in the univariate analysis. Among 156 children, 78 (50%), 15, 44, and 21 were treated with a hydroxychloroquine-containing regimen, hydroxychloroquine + azithromycin + oseltamivir, hydroxychloroquine + azithromycin, and hydroxychloroquine alone, respectively. Among 156 patients who received medical treatment, 90 (58%) underwent pre- and/or post-treatment electrocardiogram (ECG). However, none of them had ECG abnormalities or required hydroxychloroquine discontinuation due to adverse drug reactions.

Comparison of Blood Counts and Markers of Inflammation and Coagulation in Patients With and Without COVID-19 Presenting to the Emergency Department in Seattle, WA.

OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.

Duration of Viral Clearance in Children With SARS-CoV-2 Infection in Rajasthan, India.

OBJECTIVE: To study the clinical and laboratory profile and to assess period for viral clearance in COVID 19 children. METHODS: We reviewed hospital records of children (<18 years) admitted from 1 April to 31 May, 2020 at a tertiary-care public hospital and identified those positive for severe acute respiratory syndrome corona virus (SARS-CoV-2) by RT-PCR of respiratory secretions. RESULTS: 81.2% of the 85 children studied were asymptomatic and 3 (8.5%) died. Severe lymphopenia (43.8%), raised C-reactive protein (93.8%), raised erythrocyte sedimentation rate (75%) and high (>500ng/mL) levels of D-dimer (37.5%) were common. Median (IQR) duration of viral shedding was 7 (5-10) days, with range of 2 to 45 days; 96.3% had viral clearance within 14 days. CONCLUSIONS: Majority of children aged <18 years with SARS-CoV-2 infection had viral clearance within 14 days.

Clinical features and risk factors for severe-critically ill COVID-19 adult patients in Jiangsu, China: A multiple-centered, retrospective study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) becomes a global pandemic in 2020. Early identification of severe ill patients is a top priority for clinicians. We aimed to describe clinical features and risk factors of severe-critically ill patients with COVID-19 in Jiangsu Province.This multi-centered retrospective study collected the information of 631 laboratory-confirmed COVID-19 patients hospitalized at 28 authorized hospitals in Jiangsu province from January 23, 2019 to March 13, 2020.A total of 583 adult patients with laboratory-confirmed COVID-19 were enrolled for final analysis, including 84 severe-critically ill patients and 499 mild-moderate patients. Median age of the severe-critically ill patients was 57.0 years old (interquartile range, 49.0-65.8), and 50 (59.5%) were males. Multisystemic laboratory abnormalities were observed on admission for severe-critically ill patients. These patients showed more noticeable radiologic abnormalities and more coexisting health issues as compared to the mild-moderate patients. Most of the severe-critically ill COVID-19 patients became deteriorated in 2 weeks after diagnosis. Age, D-dimer, and lymphocytes were independently associated with the progression of severe-critically illness.Older age, higher D-dimer levels and less lymphocyte counts on admission are potential risk factors for COVID-19 patients to develop into severe and critically illness.

Association between peripheral lymphocyte count and the mortality risk of COVID-19 inpatients.

BACKGROUND: To explore the relationship between peripheral lymphocyte counts (PLCs) and the mortality risk of coronavirus disease 2019 (COVID-19), as well as the potential of PLC for predicting COVID-19 hospitalized patients death. METHODS: Baseline characteristics, laboratory tests, imaging examinations, and outcomes of 134 consecutive COVID-19 hospitalized patients were collected from a tertiary hospital in Wuhan city from January 25 to February 24, 2020. Multiple regression analysis was used to analyze the relationship between the PLC at admission and mortality risk in COVID-19 patients and to establish a model for predicting death in COVID-19 hospitalized patients based on PLC. RESULTS: After adjusting for potential confounding factors, we found a non-linear relationship and threshold saturation effect between PLC and mortality risk in COVID-19 patients (infection point of PLC: 0.95 × 109/L). Multiple regression analysis showed that when PLCs of COVID-19 patients were lower than 0.95 × 109/L, the patients had a significantly higher mortality risk as compared to COVID-19 patient with PLCs > 0.95 × 109/L (OR 7.27; 95% CI 1.10-48.25). The predictive power of PLC for death in COVID-19 patients (presented as area under the curve) was 0.78. The decision curve analysis showed that PLC had clinical utility for the prediction of death in COVID-19 inpatients. CONCLUSIONS: PLC had a non-linear relationship with mortality risk in COVID-19 inpatients. Reduced PLCs (< 0.95 × 109/L) were associated with an increased mortality risk in COVID-19 inpatients. PLCs also had a potential predictive value for the death of COVID-19 inpatients.

COVID-19 in Older Adults: A Series of 76 Patients Aged 85 Years and Older with COVID-19.

BACKGROUND: Clinical presentation and risk factors of death in COVID-19 in oldest adults have not been well characterized. OBJECTIVES: To describe clinical features and outcome of COVID-19 in patients older than 85 years and study risk factors for mortality. DESIGN: Prospective cohort. PARTICIPANTS AND SETTING: Patients aged 85 years and older, admitted in noncritical care units at the University Hospital Lariboisière Fernand-Widal (Paris, France) for confirmed severe acute respiratory syndrome coronavirus 2 infection were included and followed up for 21 days. MEASUREMENTS: Clinical and laboratory findings were collected. Cox survival analysis was performed to explore factors associated with death. RESULTS: From March 14 to April 11, 2020, 76 patients (median age = 90 (86-92) years; women = 55.3%) were admitted for confirmed COVID-19. Of the patients, 64.5% presented with three or more comorbidities. Most common symptoms were asthenia (76.3%), fever (75.0%) and confusion and delirium (71.1%). An initial fall was reported in 25.0% of cases, and digestive symptoms were reported in 22.4% of cases. COVID-19 was severe in 51.3% of cases, moderate in 32.9%, and mild in 15.8%. Complications included acute respiratory syndrome (28.9%), cardiac decompensation (14.5%), and hypotensive shock (9.0%). Fatality at 21 days was 28.9%, after a median course of disease of 13 (8-17) days. Males were overrepresented in nonsurvivors (68.2%). In survivors, median length of stay was 12 (9-19.5) days. Independent predictive factors of death were C-reactive protein level at admission and lymphocyte count at nadir. CONCLUSION: Specific clinical features, multiorgan injury, and high case fatality rate are observed in older adults with COVID-19. However, rapid diagnosis, appropriate care, and monitoring seem to improve prognosis.

Diagnostic utility of C-reactive protein to albumin ratio as an early warning sign in hospitalized severe COVID-19 patients.

C-reactive protein-to-albumin ratio (CAR) has been used as an indicator of prognosis in various diseases. Here, we intended to assess the CAR's diagnostic power in early differentiation of hospitalized severe COVID-19 cases. In this retrospectively designed study, we evaluated 197 patients in total. They were divided into two groups based on their severity of COVID-19 as non-severe (n = 113) and severe (n = 84). The comparison of groups' demographic data, comorbidities, clinical symptoms, and laboratory test results were done. Laboratory data of the patients within the first 24 h after admission to the hospital were evaluated. The calculation of receiver operating characteristic (ROC) curve was used to determine the diagnostic power of CAR in differentiating severity of COVID-19. Independent risk factors predictive of COVID-19 severity were determined by using logistic regression analysis. Although lymphocyte count levels were lower, severe COVID-19 patients had higher mean age, higher levels of neutrophil count, CRP, aspartate aminotransferase (AST), ferritin, and prothrombin time (P < 0.05). Compared with non-severe patients (median, 0.23 [IQR = 0.07-1.56]), patients with severe COVID-19 had higher CAR levels (median, 1.66 [IQR = 0.50-3.35]; P < 0.001). Age (OR = 1.046, P = 0.003), CAR (OR = 1.264, P = 0.037), and AST (OR = 1.029, P = 0.037) were independent risk factors for severe COVID-19 based on the multivariate logistic regression analysis. ROC curve analysis assigned 0.9 as the cut-off value for CAR for differentiation of severe COVID-19 (area under the curve = 0.718, 69.1% sensitivity, 70.8% specificity, P < 0.001). CAR is a useful marker in early differentiation of severity in patients hospitalized due to COVID-19 that have longer hospital stay and higher mortality.

Differential white blood cell count in the COVID-19: A cross-sectional study of 148 patients.

BACKGROUND: SARS-CoV-2 infection alters various blood parameters, which may indicate disease severity and thus help in better clinical management. AIM: To study the association between various hematological parameters and disease severity of COVID-19. To analyze the effects of hypertension and diabetes on neutrophil-lymphocyte ratio and neutrophil-monocyte ratio in patients suffering from COVID-19. MATERIALS AND METHODS: The study was a cross-sectional study involving 148 laboratory-confirmed cases of SARS-CoV-2 infection. The patients were divided into three groups on the basis of disease severity. Various hematological parameters were analyzed. The effects of hypertension and diabetes on NLR and NMR in COVID-19 patients were evaluated. RESULTS: Of the 148 patients, 78.4%, 8.1% and 13.5% cases were in the mild, moderate and severe groups, respectively. Mean age was 42.63 ± 16.04 years (IQR: 29, 54.75; Range: 7-74). 58.8% patients were male while the rest (42.2%) were female. Mean TLC (cells/mm3), neutrophil (%), lymphocyte (%), monocyte (%), eosinophil (%), neutrophil-lymphocyte ratio (NLR) and neutrophil-monocyte ratio (NMR) among mild, moderate and severe COVID-19 was statistically significant (p < 0.05). Basophil (%) and lymphocyte-monocyte ratio (LMR) was statistically insignificant among the three groups. Lymphocyte (%), monocyte (%) and eosinophil (%) were negatively correlated to disease severity. Among diabetics, both NLR and NMR were statistically significant (p < 0.05). However, among hypertensive cases, only the NLR was statistically significant. CONCLUSION: Older age, higher TLC, neutrophilia, lymphopenia, eosinopenia, high NLR and high NMR are associated with severe COVID-19. High NLR and high NMR are indicative of severe disease among diabetic patients. High NLR also indicates severe disease among hypertensive patients.

Assessing the need for transfer to the intensive care unit for Coronavirus-19 disease: Epidemiology and risk factors.

BACKGROUND: Although many patients with coronavirus disease 2019 (Covid-19) require direct admission to the intensive care unit (ICU), some are sent after admission. Clinicians require an understanding of this phenomenon and various risk stratification approaches for recognizing these subjects. METHODS: We examined all Covid-19 patients sent initially to a ward who subsequently required care in the ICU. We examined the timing transfer and attempted to develop a risk score based on baseline variables to predict progressive disease. We evaluated the utility of the CURB-65 score at identifying the need for ICU transfer. RESULTS: The cohort included 245 subjects (mean age 59.0 ± 14.2 years, 61.2% male) and 20% were eventually sent to the ICU. The median time to transfer was 2.5 days. Approximately 1/3rd of patients were not moved until day 4 or later and the main reason for transfer (79.2%) was worsening respiratory failure. A baseline absolute lymphocyte count (ALC) of ≤0.8 103/ml and a serum ferritin ≥1000 ng/ml were independently associated with ICU transfer. Co-morbid illnesses did not correlate with eventual ICU care. Neither a risk score based on a low ALC and/or high ferritin nor the CURB-65 score performed well at predicting need for transfer. CONCLUSION: Covid-19 patients admitted to general wards face a significant risk for deterioration necessitating ICU admission and respiratory failure can occur late in this disease. Neither baseline clinical factors nor the CURB-65 score perform well as screening tests to categorize these subjects as likely to progress to ICU care.

Laboratory Findings Associated With Severe Illness and Mortality Among Hospitalized Individuals With Coronavirus Disease 2019 in Eastern Massachusetts.

Importance: The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed. Objective: To quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals. Design, Setting, and Participants: Retrospective cohort study of all individuals admitted to the hospital who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction across these 6 hospitals through June 5, 2020, using hospital course, prior diagnoses, and laboratory values in emergency department and inpatient settings from 2 academic medical centers and 4 community hospitals. The data were extracted on June 11, 2020, and the analysis was conducted from June to July 2020. Exposures: SARS-CoV-2. Main Outcomes and Measures: Severe illness defined by admission to intensive care unit, mechanical ventilation, or death. Results: Of 2511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% White, and 27.0% Hispanic, with a mean [SD ]age of 62.6 [19.0] years), 215 (8.6%) were admitted to the intensive care unit, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded an area under the receiver operating characteristic curve of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212 of 292 deaths (72.6%) occurred in the highest-risk mortality quintile. Conclusions and Relevance: In this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19.

High Thrombus Burden in Patients With COVID-19 Presenting With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease. To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19. OBJECTIVES: The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients. METHODS: This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020. RESULTS: Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein. There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration. Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI. Higher doses of heparin to achieve therapeutic activated clotting times were also noted. Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission. CONCLUSIONS: In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes. This supports the need for establishing COVID-19 status in all STEMI cases. Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases.

Iron metabolism and lymphocyte characterisation during Covid-19 infection in ICU patients: an observational cohort study.

BACKGROUND: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. METHODS: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann-Whitney test. Trends over time were tested with the Kruskal-Wallis analysis. RESULTS: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 µg/L, IQR 69 µg/L at admission; median 73 µg/L, IQR 56 µg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 µg/L; IQR 1285 µg/L) to days 3 to 6 (median 6820 µg/L; IQR 6619 µg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. CONCLUSIONS: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

COVID-19 in rheumatic disease patients on immunosuppressive agents.

OBJECTIVE: To analyze clinical characteristics and outcome of COVID-19 patients with underlying rheumatic diseases (RD) on immunosuppressive agents. METHOD: A case series of COVID-19 patients with RD on disease modifying anti-rheumatic drugs (DMARDs) were studied by a retrospective chart review. A literature search identified 9 similar studies of single cases and case series, which were also included. RESULTS: There were 4 COVID-19 inpatients with RD from our hospital, and the mean age was 57 ± 21 years. Two patients had a mild infection, and 2 developed severe COVID-19 related respiratory complications, including 1 patient on secukinumab requiring mechanical ventilation and 1 patient on rituximab developing viral pneumonia requiring supplemental oxygenation. All 4 patients had elevated acute phase reactants, 2 patients had mild COVID-19 with lymphopenia, and 2 patients had severe COVID-19 with normal lymphocyte counts, and high levels of IL-6. None of the patients exhibited an exacerbation of their underlying RD. In the literature, there were 9 studies of COVID-19 involving 197 cases of various inflammatory RD. Most patients were on DMARDs or biologics, of which TNFα inhibitors were most frequently used. Two tocilizumab users had a mild infection. Two patients were on rituximab with 1 severe COVID-19 requiring mechanical ventilation. Six patients were on secukinumab with 1 hospitalization. Of the total 201 cases, 12 died, with an estimated mortality of 5.9% CONCLUSION: Patients with RD are susceptible to COVID-19. Various DMARDs or biologics may affect the viral disease course differently. Patients on hydroxychloroquine, TNFα antagonists or tocilizumab may have a mild viral illness. Rituximab or secukinumab could worsen the viral disease. Further study is warranted.

The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study.

Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.

Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis.

Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.