Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery

Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative therapies to treat COVID-19 and other inflammatory diseases which remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and death to develop tailored immunotherapy strategies to halt disease progression. Here we assembled the Mount Sinai COVID-19 Biobank which was comprised of ~600 hospitalized patients followed longitudinally during the peak of the pandemic. Moderate disease and survival were associated with a stronger antigen (Ag) presentation and effector T cell signature, while severe disease and death were associated with an altered Ag presentation signature, increased numbers of circulating inflammatory, immature myeloid cells, and extrafollicular activated B cells associated with autoantibody formation. Strikingly, we found that in severe COVID-19 patients, lung tissue resident alveolar macrophages (AM) were not only severely depleted, but also had an altered Ag presentation signature, and were replaced by inflammatory monocytes and monocyte-derived macrophages (MoMϕ). Notably, the size of the AM pool correlated with recovery or death, while AM loss and functionality were restored in patients that recovered. These data therefore suggest that local and systemic myeloid cell dysregulation is a driver of COVID-19 severity and that modulation of AM numbers and functionality in the lung may be a viable therapeutic strategy for the treatment of critical lung inflammatory illnesses.

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Suppressive myeloid cells are a hallmark of severe COVID-19

10.1101/2020.06.03.20119818 ◽

2020 ◽

Cited By ~ 7

Author(s):

Jonas Schulte-Schrepping ◽

Nico Reusch ◽

Daniela Paclik ◽

Kevin Baßler ◽

Stephan Schlickeiser ◽

...

Keyword(s):

Single Cell ◽

Mononuclear Cells ◽

Immune Cell ◽

Severe Disease ◽

Myeloid Cell ◽

Gene Signature ◽

Peripheral Blood Mononuclear ◽

Sequencing Technologies ◽

Inflammatory Monocytes ◽

Hla Dr

Abstract‘Severe Acute Respiratory Syndrome - Coronavirus-2’ (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DRhiCD11chi inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DRto monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.

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Interactions between helicobacter-induced inflammation acute changes in the gut microbiota, and colorectal cancer in Smad3-/- mice

10.32469/10355/79465 ◽

2020 ◽

Author(s):

◽

Annie E. Wolfie

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Disease Severity ◽

Community Dynamics ◽

Inflammatory Diseases ◽

Disease Incidence ◽

Severe Disease ◽

Underlying Mechanism ◽

Post Inoculation ◽

Disease Development

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for 551,269 deaths in 2018 alone. One subset of CRC, colitis associated CRC (CAC), develops as a sequela to chronic inflammatory diseases of the bowel. The underlying mechanism of CAC is poorly understood, but prognosis is poor due to difficulty of detection. Surveillance strategies are invasive and expensive. Risk factors of CAC include inflammatory bowel disease (IBD), diet, smoking, environment, and obesity--all of which impact or are impacted by the gut microbiota (GM), making the GM a prime target for understanding the etiology of CAC in order to develop preventative measures. Using the Smad3-/- CAC model, which requires inoculation of pathobiont Helicobacter spp., we tested the ability of the Th17-enhancing commensal Candidatus Savagella, more commonly denoted as Segmented Filamentous Bacteria (SFB), to influence the incidence and severity of CAC. To document the composition of the gut microbiota during CRC development and identify taxa associated with disease, fecal samples were collected before and throughout disease development and characterized via 16S rRNA sequencing. While there were no significant SFB-dependent effects on disease incidence or severity, SFB were found to exert a sex-dependent protective effect in male mice. Furthermore, SFB stabilized the GM against Helicobacter-induced changes post inoculation, resulting in a shift in disease association from Helicobacter spp. to Escherichia coli. These data support sex-dependent SFB-mediated effects on CRC risk, and highlight the complex community dynamics within the GM during exposure to inflammatory pathobionts. In order to artificially modulate disease severity, we repeated the above experiments using Smad3-/- mice rederived onto different GM backgrounds, using a technique called complex microbiota targeted rederivation (CMTR). Smad3-/- mice harboring distinct GM profiles termed GM1, GM2, and GM4 were similarly inoculated with Helicobacter spp. and followed longitudinally through disease development or lack thereof. We hypothesized that GM1 and 2 would develop the most severe disease, due to lack of richness and diversity. There was no difference in disease penetrance between the GM profiles, and no pre-disposing GM profile was found at pre-inoculation or early timepoints. However, GM2 developed greater disease severity than GM1 and GM4. Looking at static and dynamic differences between CRC- and CRC+ groups of each GM revealed OTUs, genera, and families which differed in disease development. Network construction analysis using overlapping timepoints from early to late, revealed that overall CRC+ bacterial communities had fewer connections than their CRC- counterparts. This was most striking in GM2 CRC+, which could account for the increased disease severity in this GM profile.

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P135 Disease-related worries and concerns in UK patients with ulcerative colitis: 2-year data from ICONIC

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.264 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S204-S205

Author(s):

N Bhala ◽

A Hart ◽

D Watts ◽

S Lewis ◽

S Ghosh ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Severity ◽

Severe Disease ◽

Energy Levels ◽

Unmet Need ◽

Analysis Data ◽

Routine Care ◽

Inflammatory Bowel ◽

Patient Concerns

Abstract Background ICONIC is the largest ongoing, prospective, multi-country observational study assessing cumulative disease-associated burden in adults with ulcerative colitis (UC) under routine care. This local subanalysis evaluated patient worries and concerns up to 2 years in UK patients using the Rating Form of inflammatory bowel disease (IBD) Patient Concerns (RFIPC) questionnaire. Methods Adults with early UC (diagnosed ≤36 months) were enrolled irrespective of treatment regimen or disease severity. Patients completed RFIPC, a 25-item questionnaire comprising frequently reported worries/concerns of IBD patients, at each visit (6-month intervals). Responses are scored on a 10-cm visual analogue scale for each individual question from 0 (no concerns) to 10 (a great deal). The mean of all 25 items represents the total score (lower scores indicate less worries/concerns). In this analysis, data are reported for UK patients as observed using descriptive statistics at baseline (BL, visit 1 [V1]), 1 year (V3), and 2 years (V5). Patients were stratified by physician-assessed disease severity (mild, moderate, severe, in remission) at baseline. Results Sixty-three UK patients were included (37 [59%] female; mean ± SD age 43.4 ± 15.7 years; median [interquartile range] time since UC diagnosis 126 (59 to 260) days; physician-assessed UC severity: mild 18 [29%], moderate 18 [29%], severe 11 [17%], in remission 16 [25%]). Mean ± SD total RFIPC scores for all patients were 2.9 ± 2.3 (n = 63) at V1, 2.7 ± 2.5 (n = 40) at V3, and 2.2 ± 2.0 (n = 35) at V5. At BL, mean ± SD RFIPC total scores by physician-assessed disease severity at BL were: mild 3.2 (1.9); moderate 2.6 (2.6); severe 4.8 (2.4); in remission 1.8 (1.7). The changes from BL to 2 years, stratified by physician-assessed disease severity at BL, were: mild −1.2 (1.4); moderate −0.7 (1.7); severe −2.2 (2.7); in remission −0.2 (1.0). The disease-related-specific concerns with the highest mean total RFIPC scores (i.e. scores >4.0) for all patients at BL were ‘energy level’, ‘having an ostomy bag’ and ‘effects of medication’. Mean total RFIPC scores for these specific concerns decreased between V1 and V5 for all patients. Of 5 UK sites, all had established multi-disciplinary teams (MDTs) and four had a psychologist in situ. Conclusion Despite all UK centres having MDTs and most having a psychologist in situ, this subanalysis from ICONIC demonstrated a high burden of worries and concerns in early UC patients with more severe disease. These concerns were most notable at BL, and appeared to decrease over time. The greatest concerns were with the treatment and complications of the disease; this included concerns about energy levels, highlighting that fatigue remains an unmet need for UC patients.

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Serum β2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

PLoS ONE ◽

10.1371/journal.pone.0247758 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247758

Author(s):

Walter Conca ◽

Mayyadah Alabdely ◽

Faisal Albaiz ◽

Michael Warren Foster ◽

Maha Alamri ◽

...

Keyword(s):

Disease Severity ◽

Viral Infections ◽

Linear Trend ◽

Severe Disease ◽

Tertiary Care ◽

Care Hospital ◽

Mhc I ◽

Mild Disease ◽

Moderate Disease ◽

Single Center Study

β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8–2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

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IL-16 and BCA-1 Serum Levels Are Associated with Disease Severity of C. difficile Infection

Pathogens ◽

10.3390/pathogens10050631 ◽

2021 ◽

Vol 10 (5) ◽

pp. 631

Author(s):

Dor Gotshal ◽

Maya Azrad ◽

Zohar Hamo ◽

Orna Nitzan ◽

Avi Peretz

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Serum Levels ◽

Serum Samples ◽

Clostridioides Difficile ◽

Cytokines And Chemokines ◽

Laboratory Confirmation ◽

Moderate Disease ◽

Clostridioides Difficile Infection ◽

Healthcare Epidemiology

Clostridioides difficile infection (CDI) is associated with a high risk for complications and death, which requires identifying severe patients and treating them accordingly. We examined the serum level of six cytokines and chemokines (IL-16, IL-21, IL-23, IL-33, BCA-1, TRAIL) and investigated the association between them and patients’ disease severity. Concentrations of six cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, MA, USA) in serum samples attained from CDI patients within 24–48 h after laboratory confirmation of C. difficile presence. Demographic and clinical data were collected from medical records. The disease severity score was determined according to guidelines of the “Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America” (SHEA-IDSA). Out of 54 patients, 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. IL-16 (p = 0.005) and BCA-1 (p = 0.012) were associated with a more severe disease. In conclusion, IL-16 and BCA-1, along with other cytokines and chemokines, may serve as biomarkers for the early prediction of CDI severity in the future. An improved and more accessible assessment of CDI severity will contribute to the adjustment of the medical treatment, which will lead to a better patient outcome.

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Development and Internal Validation of a Prediction Model to Risk Stratify Children With Suspected Community-Acquired Pneumonia

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1690 ◽

2020 ◽

Author(s):

Todd A Florin ◽

Lilliam Ambroggio ◽

Douglas Lorenz ◽

Andrea Kachelmeyer ◽

Richard M Ruddy ◽

...

Keyword(s):

Prediction Model ◽

Disease Severity ◽

Clinical Judgment ◽

Severe Disease ◽

Pediatric Emergency ◽

Community Acquired Pneumonia ◽

Positive Pressure ◽

Internal Validation ◽

Final Model ◽

Moderate Disease

Abstract Background Although community-acquired pneumonia (CAP) is one of the most common infections in children, no tools exist to risk stratify children with suspected CAP. We developed and validated a prediction model to risk stratify and inform hospitalization decisions in children with suspected CAP. Methods We performed a prospective cohort study of children aged 3 months to 18 years with suspected CAP in a pediatric emergency department. Primary outcome was disease severity, defined as mild (discharge home or hospitalization for <24 hours with no oxygen or intravenous [IV] fluids), moderate (hospitalization <24 hours with oxygen or IV fluids, or hospitalization >24 hours), or severe (intensive care unit stay for >24 hours, septic shock, vasoactive agents, positive-pressure ventilation, chest drainage, extracorporeal membrane oxygenation, or death). Ordinal logistic regression and bootstrapped backwards selection were used to derive and internally validate our model. Results Of 1128 children, 371 (32.9%) developed moderate disease and 48 (4.3%) severe disease. Severity models demonstrated excellent discrimination (optimism-corrected c-indices of 0.81) and outstanding calibration. Severity predictors in the final model included respiratory rate, systolic blood pressure, oxygenation, retractions, capillary refill, atelectasis or pneumonia on chest radiograph, and pleural effusion. Conclusions We derived and internally validated a score that accurately predicts disease severity in children with suspected CAP. Once externally validated, this score has potential to facilitate management decisions by providing individualized risk estimates that can be used in conjunction with clinical judgment to improve the care of children with suspected CAP.

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P110 ASSOCIATION OF FECAL CALPROTECTIN WITH ENDOSCOPIC AND HISTOLOGY ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.038 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S16-S16

Author(s):

Erin Crawford ◽

Catherine Gestrich ◽

Sindhoosha Malay ◽

Thomas Sferra ◽

Shahrazad Saab ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Severity ◽

Bowel Disease ◽

Severe Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Control Population ◽

Moderate Disease ◽

Endoscopic Remission ◽

Inflammatory Bowel

Abstract Background Inflammatory bowel disease (IBD) treatment strategies have evolved to target mucosal healing, which has been shown to be associated with clinical remission and reduced complications. Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation, and has been shown to correlate with disease activity in IBD patients, though values which correlate with mucosal healing vary across studies. We aim to examine the association of quantitative FC levels with endoscopic and histologic severity, and compare FC in IBD patients with endoscopic remission with a control population. Methods We conducted a retrospective chart review of patients who had a FC completed between 30 and 1 days before colonoscopy at UH Rainbow Babies and Children’s Hospital between 2014 and 2018. IBD patients had disease severity endoscopically graded using the SES-CD or Mayo UC score, and had disease severity histologically graded using the Geboes method. Severity was classed as no disease, mild, moderate or severe. FC values of IBD patients with mucosal healing and the control population (those without gastrointestinal pathology or diagnosis on evaluation) were compared. Results 331 cases were included in the study; 107 IBD cases and 224 controls. 63 patients (19%) had a diagnosis of Crohn’s disease (CD) and 44 patients (13%) had ulcerative colitis (UC). When assessing endoscopic scoring of IBD patients, the median FC was lowest in those with no disease (181 ug/g), followed by those with mild and moderate disease (499, 599 ug/g) and highest in those with severe disease (921 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.019, 0.003), and between mild and severe disease (p=0.012). When assessing histology, the median FC was lowest in IBD patients with no disease (328 ug/g), followed by those with mild and moderate disease (399 ug/g, 674 ug/g) and highest in those with severe disease (895 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.021, 0.018). In CD patients, there was significance in FC between no disease and moderate and severe disease (p=0.047, 0.0047) on endoscopic scoring. In UC patients, there was significance in FC between no disease and moderate disease (p=0.023) for histologic scoring. When comparing FC of endoscopically normal patients, the control group had a significantly lower median FC than the IBD population with endoscopic remission (43 ug/g vs 181 ug/g, p=0.018). Conclusion FC showed association with disease severity on gross endoscopy and histology and significance between severities in our IBD cohort. Additionally, normal cut-off values of FC may depend on the presence or absence of underlying disease. While larger studies are needed, this noninvasive test may help mitigate frequency of invasive procedures.

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Definition of fibromyalgia severity: findings from a cross-sectional survey of 2339 Italian patients

Rheumatology ◽

10.1093/rheumatology/keaa355 ◽

2020 ◽

Cited By ~ 1

Author(s):

Fausto Salaffi ◽

Marco Di Carlo ◽

Laura Bazzichi ◽

Fabiola Atzeni ◽

Marcello Govoni ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Fibromyalgia Impact Questionnaire ◽

Cross Sectional Survey ◽

External Criterion ◽

Cross Sectional ◽

Mild Disease ◽

Moderate Disease ◽

Definition Of ◽

Distress Scale

Abstract Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

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P058 Persistence of neutrophil abnormalities in COVID-19 convalescence

Rheumatology ◽

10.1093/rheumatology/keab247.055 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Thomas O Williams ◽

Verena Kästele ◽

Elizabeth R Mann ◽

Sean B Knight ◽

Madhvi Menon ◽

...

Keyword(s):

Disease Severity ◽

Inflammatory Diseases ◽

Reactive Dye ◽

Ros Production ◽

Therapeutic Vaccines ◽

Moderate Disease ◽

Public Company ◽

Respiratory Inflammation ◽

Future Work ◽

Acute Patients

Abstract Background/Aims Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may develop acute respiratory inflammation, due to an exaggerated immune response and some develop chronic complications. Neutrophils play a major role in the pathology of inflammatory diseases and have been shown to contribute to lung and vascular damage in COVID-19. Our aim was to establish a relationship between neutrophil phenotype and disease severity and to determine whether neutrophil abnormalities persist in convalescent patients. Methods Peripheral blood samples were obtained from acute COVID-19 patients (n = 74), follow-up (FU) patients discharged following inpatient admission (n = 56), a median of 87 days after discharge, and healthy controls (HCs, n = 22). Patients were stratified by disease severity based on inspired oxygen (FiO2) and admission to intensive care (ICU). Neutrophils were isolated from whole blood by negative selection for phenotyping and functional analysis. PBMC Isolation Tubes were used to quantify and phenotype low density neutrophils (LDNs) within the PBMC fraction. For quantification of reactive oxygen species (ROS) production, isolated neutrophils were incubated with a ROS reactive dye, DHR-123 and stimulated with PMA. All samples were stained and fixed prior to analysis by flow cytometry. Results There was a marked increase in neutrophils expressing the activation and degranulation markers, CD64 (P < 0.0001) and CD63 (P < 0.0001) and a reduction in neutrophils expressing the maturity markers, CD10 (P < 0.0005) and CD101 (P < 0.0005) in patients with acute COVID-19 compared to HCs. Increased frequency of neutrophils expressing CD64 (P < 0.005), CD63 (P < 0.01) and expressing decreased CD101 (P < 0.0001) were also detected in FU patients compared to HCs. Notably, 42.3 ± 4.4% of neutrophils were CD101lo in FU patients, compared to 29.0 ± 3.7% in acute patients and 9.6 ± 4.1% in HCs. These changes were most apparent in FU patients recovering from severe COVID-19 compared to mild or moderate disease. The frequency of LDNs in PBMCs from acute patients was significantly higher than HCs (P < 0.0001), and correlated with disease severity. Similarly, the frequency of LDNs in FU patients was significantly higher than in HCs (P < 0.0005). We found a trend towards higher basal ROS production in acute and FU patients, but a blunted response to PMA stimulated ROS production in neutrophils from acute patients versus HCs (P < 0.0001). Impaired ROS production persisted in FU patients compared to HCs (P < 0.01). Conclusion Circulating neutrophils in acute COVID-19 have an altered phenotype and comprise immature and activated cells. This altered phenotype persisted in convalescence and may contribute to the persistence of symptoms and an increased susceptibility to subsequent infections. Future work will aim to investigate the functional implications of these findings. Disclosure T.O. Williams: None. V. Kästele: None. E.R. Mann: None. S.B. Knight: None. M. Menon: None. C. Jagger: None. S. Khan: None. J.E. Konkel: None. T.N. Shaw: None. M. Rattray: Consultancies; M.R. has a paid consultancy with AstraZeneca. L. Pearmain: None. A. Horsley: None. A. Ustianowski: None. I. Prise: None. N.D. Bakerly: None. P.M. Dark: None. G.M. Lord: Corporate appointments; G.M.L. is cofounder and scientific advisory board member of Gritstone Oncology Inc., which is a public company that develops therapeutic vaccines (primarily for the treatment of cancer). A. Simpson: None. T. Felton: None. L. Ho: None. M. Feldmann: None. I. Bruce: None. J.R. Grainger: None. T. Hussell: None.

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Lymphopenia as an early predictor of disease severity in COVID-19

Journal of Rehman Medical Institute ◽

10.52442/jrmi.v6i3.183 ◽

2020 ◽

Vol 6 (3) ◽

pp. 08-11

Author(s):

Shaheen Ali Khan ◽

Muhammad Naveed Anwar ◽

Laraib Saeed ◽

Wajeeha Qayyum ◽

Zuhayr Ahmad Mufti ◽

...

Keyword(s):

Disease Severity ◽

Statistical Significance ◽

Severe Disease ◽

Relevant Information ◽

Adverse Outcomes ◽

Medical Institute ◽

Laboratory Findings ◽

Cross Sectional ◽

Mild Disease ◽

Moderate Disease

Introduction: Research has implicated an exaggerated or self-directed immune response as a factor in determining patient outcome in COVID-19. Initial reports identify lymphopenia as having a predictive role in COVID-19 related disease severity.Objective: To document the occurrence of lymphopenia in COVID-19 patients and explore its association with demographic factors and disease course.Materials & Methods: This cross sectional, observational study was conducted at Rehman Medical Institute, Peshawar from May, 2020 to August, 2020. All patients admitted to the hospital with COVID-19 diagnosis were included. Relevant information including demographics, disease severity, laboratory findings & outcomes were noted in a predesigned Performa. The data were analyzed on SPSS 22 for descriptive and comparative statistics; p≤0.05 denoted significance.Results: A total of 216 patients were included, of whom 172 (79.6%) were males. The mean age was 54.61 ± 14.35 years. Classic lymphopenia was found in 67 (31.5%), 66 (31.0%) had borderline lymphopenia, and 80 (37.6%) had no lymphopenia. Of the classic lymphopenia group, 14 (20.9%) had mild disease, 21 (31.3%) had moderate disease, 18 (26.9%) had severe disease & 14 (20.9%) had critical disease. In patients with borderline lymphopenia 31 (47.0%) had mild disease, 17 (25.8%) moderate disease, 14 (21.2%) had severe disease and 04 (6.1%) had critical disease. In patients with no lymphopenia, 32 (40.0%) had mild, 32 (40.0%) had moderate, 14 (17.5%) had severe & 02 (2.5%) had critical disease. Mortality associated with classical lymphopenia was 37.3% (n=25) whereas 43.3% (n=29) patients recovered. Male gender, disease severity and outcome were statistically linked to lymphopenia; no statistical significance was observed with age.Conclusion: A statistically significant association of lymphopenia with severe/critical disease and adverse outcomes was noted.Keywords: Lymphopenia, COVID-19, Pandemic.

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