Increased mortality in infants with abnormal T-cell receptor excision circles.

BACKGROUND: T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. METHODS: 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. RESULTS: Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. CONCLUSION: Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. IMPACT: This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

Systematic review and pooled analysis of the impact of treatment-induced lymphopenia on survival of glioblastoma patients.

PURPOSE/OBJECTIVE(S): Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT). MATERIALS/METHODS: Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS. RESULTS: Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies. CONCLUSION: These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.

Influence of lymphopenia on long-term mortality in septic shock, a retrospective observational study.

BACKGROUND AND OBJECTIVE: The diagnosis of infection, to diagnose septic shock, has been qualified by leukocyte counts and protein biomarkers. Septic shock mortality is persistently high (20%-50%), and rising in the long term. The definition of sepsis does not include leukocyte count, and lymphopenia has been associated with its mortality in the short term. Immunosuppression and increased mortality in the long term due to sepsis have not been demonstrated. The aim is to relate the occurrence of lymphopenia and its lack of recovery during septic shock with mortality at 2 years. PATIENTS AND METHODS: Cohort of 332 elderly patients diagnosed with septic shock. Mortality at 28 days and 2 years was analysed according to leukocyte, neutrophil, and lymphocyte counts, and the ability to recover from lymphopenia (LRec). RESULTS: A total of 74.1% of patients showed lymphopenia, and 73.5% did not improve during ICU stay. Mortality was 31.0% and 50.3% at 28 days and 2 years, respectively. Lymphopenia was a predictor of early mortality (OR 2.96) and LRec of late mortality (OR 3.98). Long-term mortality was associated with LRec (HR 1.69). CONCLUSIONS: In elderly patients with septic shock, 28-day mortality is associated with lymphopenia and neutrophilia, and LRec with 2-year mortality; this may represent 2 distinct phenotypes of behaviour after septic shock.

Characteristics and Clinical Prognosis of Septic Patients With Persistent Lymphopenia.

Background: Septic patients with persistent lymphopenia may be in an immunosuppressed state. Therefore, we evaluated and compared the clinical characteristics and outcomes of septic patients with persistent lymphopenia (≥2d) and those with nonpersistent lymphopenia. Methods: A retrospective cohort study was designed. A total of 1306 patients with sepsis who were attended to the First Affiliated Hospital of Dalian Medical University from March 2016 to August 2022 were included. The primary clinical outcome was 90d mortality. The secondary clinical outcomes were the length of stay, hospital mortality, 28d mortality, the incidence of secondary infection, and differences in clinical characteristics. Results: Among 1306 patients with sepsis, 913 (69.9%) patients developed persistent lymphopenia. Compared with patients with nonpersistent lymphopenia, patients with persistent lymphocytopenia were admitted to intensive care unit (75.7% vs 52.7%, P < .05), treated with mechanical ventilation (67.6% vs 39.2%, P < .05), positive rate of microbial culture pathogens (86.7% vs 71.2%, P < .05), SOFA [8.0 (6.0-10.0) vs 6.0 (4.0-8.0), P < .05], length of stay [17.0d (12.0-27.0) vs 13.0d (10.0-21.0), P < .05], hospital mortality (37.7% vs 24.2%, P < .05), 28d mortality (38.0% vs 22.9%, P < .05), and 90d mortality (51.2% vs 31.3%, P < .05) were higher. As the duration of lymphocytopenia increased, so did the mortality rate in hospital. In addition, the onset time of persistent lymphopenia was not associated with SOFA. But we found that the frequency of persistent lymphopenia during hospitalization was positively associated with SOFA. Conclusion: Septic patients with persistent lymphopenia have higher mortality, worse conditions, increased risk of secondary infection, and poor prognosis regardless of shock.

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

Complement C5a and Clinical Markers as Predictors of COVID-19 Disease Severity and Mortality in a Multi-Ethnic Population.

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.

Lymphopenia in hospitalized patients and its relationship with severity of illness and mortality.

BACKGROUND: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). METHOD AND FINDINGS: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001. CONCLUSIONS: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.

Immune correlates of therapy outcomes in women with cervical cancer treated with chemoradiotherapy: A systematic review.

BACKGROUND: Immune markers have been correlated with prognosis in a variety of solid tumors, including cervical cancer. OBJECTIVE: To review the literature on hematologic and immune markers and their association with recurrence and survival among patients with cervical cancer treated with chemoradiation. EVIDENCE REVIEW: This systematic review was conducted in accordance with PRISMA guidelines via searches of Ovid MEDLINE, Ovid Embase, and the Cochrane Library using keywords regarding cervical cancer, immune markers, and HIV. Studies involving patients treated with cisplatin-based chemoradiotherapy were selected and reviewed by at least two independent reviewers, with disagreements resolved by a third reviewer. FINDINGS: A total of 737 studies were identified, of which 314 assessed immune biomarkers in immunocompetent patients (30 included in the final analysis) and 327 studies in immunosuppressed patients (5 included in the final analysis). The strongest prognostic indicators were lymphopenia and elevated neutrophil-to-lymphocyte ratio. Other potential markers included HPV-specific lymphocyte response, cytokine profile, expression of immune-blocking antigens on cell surfaces, and tumor-associated lymphocyte, macrophage, and neutrophil infiltration. Studies of immunosuppressed patients described more severe cytopenic changes overall and concluded that viral suppression led to improved outcomes. CONCLUSIONS: The immunologic interplay at work in cervical cancer development, progression, and treatment is complex. Strong evidence was found in favor of lymphopenia and elevated neutrophil-to-lymphocyte ratio being prognostic for worse outcomes with other markers showing potential associations as well. Although the interpretation of immune status with regard to treatment approach remains unclear, future studies should aim to tailor treatment that minimizes possible detrimental immune effects.

Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients.

Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.

Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

Preoperative lymphopaenia, mortality, and morbidity after elective surgery: systematic review and meta-analysis.

BACKGROUND: In the general adult population, lymphopaenia is associated with an increased risk for hospitalisation with infection and infection-related death. The quality of evidence and strength of association between perioperative lymphopaenia across different surgical procedures and mortality/morbidity has not been examined by systematic review or meta-analysis. METHODS: We searched MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane databases from their inception to June 29, 2020 for observational studies reporting lymphocyte count and in-hospital mortality rate in adults. We defined preoperative lymphopaenia as a lymphocyte count 1.0-1.5×109 L-1. Meta-analysis was performed using either fixed or random effects models. Quality was assessed using the Newcastle-Ottawa Scale. The I2 index was used to quantify heterogeneity. The primary outcome was in-hospital mortality rate and mortality rate at 30 days. RESULTS: Eight studies met the inclusion criteria for meta-analysis, comprising 4811 patients (age range, 46-91 yr; female, 20-79%). These studies examined preoperative lymphocyte count exclusively. Studies were of moderate to high quality overall, ranking >7 using the Newcastle-Ottawa Scale. Preoperative lymphopaenia was associated with a threefold increase in mortality rate (risk ratio [RR]=3.22; 95% confidence interval [CI], 2.19-4.72; P<0.01, I2=0%) and more frequent major postoperative complications (RR=1.33; 95% CI, 1.21-1.45; P<0.01, I2=6%), including cardiovascular morbidity (RR=1.77; 95% CI, 1.45-2.15; P<0.01, I2=0%), infections (RR=1.45; 95% CI, 1.19-1.76; P<0.01, I2=0%), and acute renal dysfunction (RR=2.66; 95% CI, 1.49-4.77; P<0.01, I2=1%). CONCLUSION: Preoperative lymphopaenia is associated with death and complications more frequently, independent of the type of surgery. PROSPERO REGISTRY NUMBER: CRD42020190702.

Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

Coronavirus Disease 2019 (COVID-19): A Haematologist's Perspective.

Coronavirus disease 2019 (COVID-19) is affecting millions of patients worldwide. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the family Coronaviridae, with 80% genomic similarities to SARS-CoV. Lymphopenia was commonly seen in infected patients and has a correlation to disease severity. Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors. This pandemic has caused disruption in communities and hospital services, as well as straining blood product supply, affecting chemotherapy treatment and haematopoietic stem cell transplantation schedule. In this article, we review the haematological manifestations of the disease and its implication on the management of patients with haematological disorders.

Hyperglycemia associated with lymphopenia and disease severity of COVID-19 in type 2 diabetes mellitus.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been declared a global pandemic. COVID-19 is more severe in people with diabetes. The identification of risk factors for predicting disease severity in COVID-19 patients with type 2 diabetes mellitus (T2DM) is urgently needed. METHODS: Two hundred and thirty-six patients with COVID-19 were enrolled in our study. The patients were divided into 2 groups: COVID-19 patients with or without T2DM. The patients were further divided into four subgroups according to the severity of COVID-19 as follows: Subgroup A included moderate COVID-19 patients without diabetes, subgroup B included severe COVID-19 patients without diabetes, subgroup C included moderate COVID-19 patients with diabetes, and subgroup D included severe COVID-19 patients with diabetes. The clinical features and radiological assessments were collected and analyzed. We tracked the dynamic changes in laboratory parameters and clinical outcomes during the hospitalization period. Multivariate analysis was performed using logistic regression to analyze the risk factors that predict the severity of COVID-19 with T2DM. RESULTS: Firstly, compared with the nondiabetic group, the COVID-19 with T2DM group had a higher erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and procalcitonin (PCT) but lower lymphocyte counts and T lymphocyte subsets, including CD3+ T cells, CD8+ T cells, CD4+ T cells, CD16 + CD56 cells, and CD19+ cells. Secondly, compared with group A, group C had higher levels of Fasting blood glucose (FBG), IL-6, TNF-α, and neutrophils but lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts. Similarly, group D had higher FBG, IL-6 and TNF-α levels and lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts than group B. Thirdly, binary logistic regression analysis showed that HbA1c, IL-6, and lymphocyte count were risk factors for the severity of COVID-19 with T2DM. Importantly, COVID-19 patients with T2DM were more likely to worsen from moderate to severe COVID-19 than nondiabetic patients. Of note, lymphopenia and inflammatory responses remained more severe throughout hospitalization for COVID-19 patients with T2DM. CONCLUSION: Our data suggested that COVID-19 patients with T2DM are more likely to develop severe COVID-19 than those without T2DM and that hyperglycemia associated with the lymphopenia and inflammatory responses in COVID-19 patients with T2DM.

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients.

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.