Neutrophil-to-lymphocyte ratio is not associated with risk of sarcopenia in elderly COVID-19 patients.

BACKGROUND: To assess the existence of association between neutrophil to lymphocyte ratio (NLR) and the risk of sarcopenia in COVID-19 patients. METHODS: A retrospective cross-sectional study was conducted in a university hospital with patients with an active COVID-19 infection admitted to the nursing ward or intensive care unit (ICU) between September to December 2020. Sarcopenia risk was assessed using the Strength, Assistance for walking, Rise from a chair, Climb stairs and Falls (SARC-F). Biochemical analyses were assessed by circulating of C-reactive protein, D-dimer, neutrophils, lymphocytes count and NLR. Sixty-eight patients were evaluated and divided into tertiles of NLR values and the association between NLR and sarcopenia risk were tested using the linear regression analyses and p<0.05 were considered as significant. RESULTS: Sixty-eight patients were evaluated and divided in NLR tertiles being the 1st (men=52.2%; 71.1±9.0 y; NLR: 1.1-3.85), 2nd (women=78.3%; 73.2±9.1 y; NLR: 3.9-6.0) and 3rd (men=72.7%; 71.7±10.4 y; NLR: 6.5-20.0). There was a difference between the tertiles in relation to the first to the biochemical parameters of total neutrophils count (p=0.001), C-reactive protein (p=0.012), and D-dimer (p=0.012). However, no difference was found in linear regression analysis between tertiles of NLR and SARC-F, if in total sample (p=0.054) or divided by sex, if men (p=0.369) or women (p=0.064). CONCLUSION: In elderly patients hospitalized with COVID-19, we do not find an association between the risk of sarcopenia and NLR.

Evaluation of individual and combined NLR, LMR and CLR ratio for prognosis disease severity and outcomes in patients with COVID-19.

OBJECT: The study aimed to utilize the peripheral blood immunological parameters and resulting individual and combined inflammatory indices [neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR) and C-reactive protein/lymphocyte ratio (CLR)] in predicting the prognosis and mortality in COVID-19 patients. MATERIALS AND METHODS: The measurements of individual and combined inflammatory indices (NLR, LMR and CLR) were performed at hospital admission and at last day of hospitalization for COVID-19 patients. RESULTS: Prominent elevation of NLR and CLR among patients with refractory disease admitted to Intensive Care Unit (ICU) and deceased patients was found when compared with moderate ill patients and healthy controls. Interestingly, NLR and CLR typically returned to near normal value as patients recover from severe infection. By contrast, deceased patients had persistent increased NLR and CLR until last day of hospitalization in ICU. ROC obtained for the above parameters showed that NLR and CLR were the most associated immunological parameters with the severity of COVID-19 disease. Using multivariate logistic regression analysis, CLR > 69.46 is an independent prognostic factors in identifying critically ill COVID-19 cases. Study of the combined markers NLR and CLR showed that most of patients admitted in ICU were characterized with high NLR combined with high CLR, while most of healthy subjects and non-ICU group have low NLR combined with low CLR. CONCLUSION: The combination of NLR and CLR could improve the predictive efficacy compared to individual markers to segregate patients who will develop a severe disease from those with a mild pathology.

Morphologically, immunohistochemically and PCR proven lymphocytic viral peri-, endo-, myocarditis in patients with fatal COVID-19.

BACKGROUND: Despite a reported cardiac injury in patients with new coronavirus infection, the possibility and specifics of genuine viral myocarditis in COVID-19 remains not fully clear. PURPOSE: To study the presence of SARS-CoV-2 in the myocardium and the morphological properties of myocarditis in patients with severe coronavirus infection (COVID-19). METHODS: Autopsy data of eight elderly patients (75.6 ± 7.4 years), four male and four female, with severe new coronavirus infection were studied. The lifetime diagnosis of COVID-19 is based on a positive result of the PCR study. The inclusion criterion was the presence of morphological signs of myocarditis according to the Dallas criteria. A standard histological examination included staining by hematoxylin and eosin, toluidin blue and Van Gieson. An immunohistochemical study was performed using antibodies to CD3, CD 68, CD20, perforin, toll-like receptor (TLR) types 4 and 9. PCR in real-time was performed to determine the viral RNA in the myocardium. RESULTS: All patients had severe bilateral viral pneumonia. In all cases, myocarditis was not clinically diagnosed. Morphological examination of the heart found signs of active lymphocytic myocarditis. PCR identified the SARS-Cov2 RNA in all cases. There were also signs of destructive coronaritis in all cases, thrombovasculitis, lymphocytic pericarditis (in 3 cases) and endocarditis (in 2 cases). The absence of neutrophils confirms the aseptic nature of inflammation. An immunohistochemical study showed the CD3-positive T lymphocytes in the infiltrates. Increased expression of TLR type 4 and less 9 was also detected. CONCLUSION: Morphological and immunohistochemical evidence of myocarditis in COVID-19 was presented. Lymphocytic infiltrations and positive PCR confirm the viral nature of inflammation. Myocarditis in COVID-19 is also characterized by coronaritis with microvascular thrombosis and associated with lymphocytic endo- and pericarditis.

The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients.

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission. Results: A total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001). Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.

Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19.

BACKGROUND: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. OBJECTIVE: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. MATERIALS AND METHODS: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. RESULTS: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. CONCLUSION: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.

Comparisons of the immunological landscape of COVID-19 patients based on sex and disease severity by multi-omics analysis.

OBJECTIVE: To determine the differences in the immune response against SARS-CoV-2 infection of patients based on sex and disease severity. METHODS: We used an analytical framework of 382 transcriptional modules and multi-omics analyses to discriminate COVID-19 patients based on sex and disease severity. RESULTS: Male and female patients overexpressed modules related to the innate immune response. The expression of modules related to the adaptive immune response showed lower enrichment levels in males than females. Inflammation modules showed ascending overexpression in male and female patients, while a higher level was observed in severe female patients. Moderate female patients demonstrated significant overexpression to interferon, cytolytic lymphocyte, T & B cells, and erythrocytes modules. Moderate female patients showed a higher adaptive immune response than males matched group. Pathways involved in metabolism dysregulation and Hippo signaling were upregulated in females than in male patients. Females and moderate cases showed higher levels of metabolic dysregulation. CONCLUSIONS: The immune landscape in COVID-19 patients was noticeably different between the sexes, and these differences may highlight disease vulnerability in males. This study suggested that certain treatments that increase or decrease the immune responses to SARS-CoV-2 might be necessary for male and female patients at certain disease stages.

Early Prediction of Disease Progression in Patients with Severe COVID-19 Using C-Reactive Protein to Albumin Ratio.

BACKGROUND: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. METHODS: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. RESULTS: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. CONCLUSION: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.

The role of inflammatory indices in the outcome of COVID-19 cancer patients.

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients' outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19-2253) in non-survivors, compared to 27.4 (0.8-681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Clinical characteristics of COVID-19 patients in three consecutive generations of spread in Zhejiang, China.

OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.

The Associations of Lymphocyte Ratio and Neutrophil Ratio on Liver Dysfunction in COVID-19 Patients.

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.

Prognostic value of neutrophil-to-lymphocyte ratio, lactate dehydrogenase, D-dimer, and computed tomography score in patients with coronavirus disease 2019.

BACKGROUND: This study aimed to explore the significance of neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), D-dimer, and CT score in evaluating the severity and prognosis of coronavirus disease 2019 (COVID-19). METHODS: Patients with laboratory-confirmed COVID-19 were retrospectively enrolled. The baseline data, laboratory findings, chest computed tomography (CT) results evaluated by CT score on admission, and clinical outcomes were collected and compared. Logistic regression was used to assess the independent relationship between the baseline level of the four indicators (NLR, LDH, D-dimer, and CT score) and the severity of COVID-19. RESULTS: Among the 432 patients, 125 (28.94%) and 307 (71.06%) were placed in the severe and non-severe groups, respectively. As per the multivariate logistic regression, high levels of NLR and LDH were independent predictors of severe COVID-19 (OR=2.163; 95% CI=1.162-4.026; p=0.015 for NLR>3.82; OR=2.298; 95% CI=1.327-3.979; p=0.003 for LDH>246 U/L). Combined NLR>3.82 and LDH>246 U/L increased the sensitivity of diagnosis in patients with severe disease (NLR>3.82 [50.40%] vs. combined diagnosis [72.80%]; p=0.0007; LDH>246 [59.2%] vs. combined diagnosis [72.80%]; p<0.0001). CONCLUSIONS: High levels of serum NLR and LDH have potential value in the early identification of patients with severe COVID-19. Moreover, the combination of LDH and NLR can improve the sensitivity of diagnosis.

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.

The cytokine storms of COVID-19, H1N1 influenza, CRS and MAS compared. Can one sized treatment fit all?

An analysis of published data appertaining to the cytokine storms of COVID-19, H1N1 influenza, cytokine release syndrome (CRS), and macrophage activation syndrome (MAS) reveals many common immunological and biochemical abnormalities. These include evidence of a hyperactive coagulation system with elevated D-dimer and ferritin levels, disseminated intravascular coagulopathy (DIC) and microthrombi coupled with an activated and highly permeable vascular endothelium. Common immune abnormalities include progressive hypercytokinemia with elevated levels of TNF-α, interleukin (IL)-6, and IL-1ß, proinflammatory chemokines, activated macrophages and increased levels of nuclear factor kappa beta (NFκB). Inflammasome activation and release of damage associated molecular patterns (DAMPs) is common to COVID-19, H1N1, and MAS but does not appear to be a feature of CRS. Elevated levels of IL-18 are detected in patients with COVID-19 and MAS but have not been reported in patients with H1N1 influenza and CRS. Elevated interferon-γ is common to H1N1, MAS, and CRS but levels of this molecule appear to be depressed in patients with COVID-19. CD4+ T, CD8+ and NK lymphocytes are involved in the pathophysiology of CRS, MAS, and possibly H1N1 but are reduced in number and dysfunctional in COVID-19. Additional elements underpinning the pathophysiology of cytokine storms include Inflammasome activity and DAMPs. Treatment with anakinra may theoretically offer an avenue to positively manipulate the range of biochemical and immune abnormalities reported in COVID-19 and thought to underpin the pathophysiology of cytokine storms beyond those manipulated via the use of, canakinumab, Jak inhibitors or tocilizumab. Thus, despite the relative success of tocilizumab in reducing mortality in COVID-19 patients already on dexamethasone and promising results with Baricitinib, the combination of anakinra in combination with dexamethasone offers the theoretical prospect of further improvements in patient survival. However, there is currently an absence of trial of evidence in favour or contravening this proposition. Accordingly, a large well powered blinded prospective randomised controlled trial (RCT) to test this hypothesis is recommended.

Characteristics of patients with kidney injury associated with COVID-19.

To explore the characteristics of COVID-19 infection related kidney injury, we retrospectively collected cases of COVID-19 patients with definite clinical outcomes (discharge or death) and relevant laboratory results from Jan 3 to Mar 30, 2020 in Tongji hospital, Wuhan, China. 1509 patients were included, 1393 cases with normal baseline serum creatinine, and 116 cases with elevated baseline serum creatinine (EBSC). On admission, the prevalence of elevated serum creatinine, elevated blood urea nitrogen (BUN) and estimated glomerular filtration (eGFR) under 60 ml/min/1.73 m2 were 7.7%, 6.6% and 7.2%, respectively. The incidence of in-hospital death in the patients with EBSC was 7.8%, which was significantly higher than those with normal serum creatinine (1.2%). Inflammatory, immunological, and organ damage indices were relatively higher in the EBSC group, in which lymphocytes, albumin, and hemoglobin were significantly lower. Kaplan-Meier analysis revealed age above 65 years, males, comorbidities (especially for cardiovascular disease and tumor patients), lymphocyte count < 1.5 × 109/L, leukocyte count > 10 × 109/L, EBSC, eGFR < 60 ml/min/1.73 m2 were associated with in-hospital death. Multivariate Cox proportional hazard regression confirmed that EBSC (HR: 2.643, 95% CI: 1.111-6.285, P = 0.028), eGFR < 60 ml/min/1.73 m2 (HR: 3.889, 95% CI: 1.634-9.257, P = 0.002), were independent risk factors after adjusting for age, sex, any comorbidity, leukocyte and lymphocyte count. Therefore, the prevalence of kidney injury in patients with COVID-19 was high and associated with in-hospital mortality. Early detection and effective intervention of kidney injury may reduce COVID-19 deaths.

Diffuse interstitial pneumonia-like/macrophage activation syndrome-like changes in patients with COVID-19 correlate with length of illness.

OBJECTIVES: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. METHODS: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. RESULTS: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). CONCLUSIONS: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.