covid-19 blood
216055272
Impact of blood analysis and immune function on the prognosis of patients with COVID 19
Introduction: This retrospective study investigated the implications of changes in blood parameters and cellular immune function in patients with 2019 coronavirus infected disease (COVID 19) Methods: Records were reviewed of 85 patients with COVID 19 between February 4 and 16, 2020. The primary outcome was in hospital mortality at 28 days. Results: Fourteen patients died. The baseline leukocyte count, neutrophil count and hemoglobin was significantly higher in non survivors compared with survivors, while the reverse was true of lymphocyte count, platelet, PaO2/FiO2, CD3+ count and CD4+ count. The percentage of neutrophil count 6.3*109/L in death group was significantly higher than that in survival group, and multivariate logistic regression showed neutrophil count was independently associated with mortality. However, there were not significant difference in IgG, IgM, IgA, C3, C4 and the percentage of IgE 100 IU/ml between the death group and survival group. Areas under the receiver operating characteristic curves of the following at baseline could significantly predict mortality: leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts. Conclusions: For patients with COVID 19, lymphocyte, CD3+ and CD4+ counts that marked decrease suggest a poor outcome. A high neutrophil count is independently associated with mortality. At admission, leukocyte, neutrophil, lymphocyte, CD3+ and CD4+ counts should receive added attention.
medRxiv
Yue-qiang Fu Yue-lin Sun Si-wei Lu Yunpeng Yang Feng Xu
212738941
Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID 19) is urgently needed
Diabetes Research and Clinical Practice
Aihong Wang Weibo Zhao Zhang-rong Xu Jianwen Gu
214733440
Clinical and virological data of the first cases of COVID 19 in Europe: a case series
Summary Background On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID 19) with the first patient diagnosed with the disease on Jan 24, 2020. Methods In this case series, we followed five patients admitted to Bichat Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID 19 by semi quantitative RT PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples) which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France) where RNA extraction, real time RT PCR, and virus isolation and titration procedures were done. Findings The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years) all of Chinese origin, who had travelled to France from China around mid January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS CoV 2 within the first 24 h of the illness onset (5*2 and 7*4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80 year old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80 year old patient died on day 14 of illness (Feb 14, 2020) all other patients had recovered and been discharged by Feb 19, 2020. Interpretation We illustrated three different clinical and biological types of evolution in five patients infected with SARS CoV 2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. Funding REACTing (Research Action Emerging Infectious Diseases)
The Lancet Infectious Diseases
Francois-Xavier Lescure Lila Bouadma Duc Minh Nguyen Marion Parisey Paul-Henri Wicky Sylvie Behillil Alexandre Gaymard Maude Bouscambert-Duchamp Flora Donati Quentin Le Hingrat Vincent Enouf Nadhira Houhou-Fidouh Martine Valette Alexandra Mailles Jean-Christophe Lucet France Mentre Xavier Duval Diane Descamps Denis Malvy Jean-Francois Timsit Bruno Lina Sylvie van-der-Werf Yazdan Yazdanpanah
212718598
Breadth of concomitant immune responses prior to patient recovery: a case report of non severe COVID 19
To the Editor We report the kinetics of immune responses in relation to clinical and virological features of a patient with mild to moderate coronavirus disease 2019 (COVID 19) that required hospitalization. Increased antibody secreting cells (ASCs) follicular helper T cells (TFH cells) activated CD4+ T cells and CD8+ T cells and immunoglobulin M (IgM) and IgG antibodies that bound the COVID 19causing coronavirus SARS CoV 2 were detected in blood before symptomatic recovery. These immunological changes persisted for at least 7 d following full resolution of symptoms. A 47 year old woman from Wuhan, Hubei province, China, presented to an emergency department in Melbourne, Australia. Her symptoms commenced 4 d earlier with lethargy, sore throat, dry cough, pleuritic chest pain, mild dyspnea and subjective fevers (Fig. 1a) She traveled from Wuhan to Australia 11 d before presentation. She had no contact with the Huanan seafood market or with known COVID 19 cases. She was otherwise healthy and was a non smoker taking no medications. Clinical examination revealed a temperature of 38.5 degC, a pulse rate of 120 beats per minute, a blood pressure of 140/80 mm Hg, a respiratory rate of 22 breaths per minute, and oxygen saturation 98% while breathing ambient air. Lung auscultation revealed bi basal rhonchi. At presentation on day 4, SARS CoV 2 was detected in a nasopharyngeal swab specimen by real time reverse transcriptase PCR. SARS CoV 2 was again detected at days 5 6 in nasopharyngeal, sputum and fecal samples, but was undetectable from day 7 (Fig. 1a) Blood C reactive protein was elevated at 83.2, with normal counts of lymphocytes (4.3 x 109 cells per liter (range, 4.0 x 109 to 12.0 x 109 cells per liter) and neutrophils (6.3 x 109 cells per liter (range, 2.0 x 109 to 8.0 x 109 x 109 cells per liter) No other respiratory pathogens were detected. Her management was intravenous fluid rehydration without supplemental oxygenation. No antibiotics, steroids or antiviral agents were administered. Chest radiography demonstrated bi basal infiltrates at day 5 that cleared on day 10 (Fig. 1b) She was discharged to home isolation on day 11. Her symptoms resolved completely by day 13, and she remained well at day 20, with progressive increases in plasma SARS CoV 2 binding IgM and IgG antibodies from day 7 until day 20 (Fig. 1c and Extended Data Fig. 1) The patient was enrolled through the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases novel coronavirus substudy (SETREP ID coV) and provided written informed consent before the study. Patient care and research were conducted in compliance with the Case Report guidelines and the Declaration of Helsinki. Experiments were performed with ethics approvals HREC/17/MH/53, HREC/15/MonH/64/2016.196 and UoM#1442952.1/#1443389.4. We analyzed the kinetics and breadth of immune responses associated with clinical resolution of COVID 19. As ASCs are key for the rapid production of antibodies following infection with Ebola virus1,2 and infection with and vaccination against influenza virus2,3, and activated circulating TFH cells (cTFH cells) are concomitantly induced following vaccination against influenza virus3, we defined the frequency of CD3 CD19+CD27hiCD38hi ASC and CD4+CXCR5+ICOS+PD 1+ cTFH cell responses before symptomatic recovery. ASCs appeared in the blood at the time of viral clearance (day 7; 1.48% and peaked on day 8 (6.91% The emergence of cTFH cells occurred concurrently in blood at day 7 (1.98% increasing on day 8 (3.25% and day 9 (4.46% (Fig. 1d) The peak of both ASCs and cTFH cells was markedly higher in the patient with COVID 19 than in healthy control participants (0.61% 0.40% and 1.83% 0.77% respectively (average s.d. n 5) Both ASCs and cTFH cells were prominently present during convalescence (day 20) (4.54% and 7.14% respectively; Fig. 1d) Thus, our study provides evidence on the recruitment of both ASCs and cTFH cells in this patient's blood while she was still unwell and 3 d before the resolution of symptoms. Since co expression of CD38 and HLA DR is the key phenotype of the activation of CD8+ T cells in response to viral infections, we analyzed co expression of CD38 and HLA DR. As per reports for Ebola and influenza1,4, co expression of CD38 and HLA DR on CD8+ T cells (assessed as the frequency of CD38+HLA DR+ CD8+ T cells) rapidly increased in this patient from day 7 (3.57% to day 8 (5.32% and day 9 (11.8% then decreased at day 20 (7.05% (Fig. 1e) Furthermore, the frequency of CD38+HLA DR+ CD8+ T cells was much higher in this patient than in healthy individuals (1.47% 0.50% n 5) CD38+HLA DR+ T cells were also recently documented in a patient with COVID 19 at one time point5. Similarly, co expression of CD38 and HLA DR on CD4+ T cells (assessed as the frequency of CD38+HLA DR+ CD4+ T cells) increased between day 7 (0.55% and day 9 (3.33% in this patient, relative to that of healthy donors (0.63% 0.28% n 5) although at lower levels than that of CD8+ T cells. CD38+HLA DR+ T cells, especially CD8+ T cells, produced larger amounts of granzymes A and B and perforin ~34 54% higher) than did their parent cells (CD8+ or CD4+ populations; Fig. 1e) Thus, the emergence and rapid increase in activated CD38+HLA DR+ T cells, especially CD8+ T cells, at days 7 9 preceded the resolution of symptoms. Details on data reproducibility are in the Life Sciences Reporting Summary. Analysis of CD16+CD14+ monocytes, which are related to immunopathology, showed lower frequencies of CD16+CD14+ monocytes in the blood of this patient at days 7, 8 and 9 (1.29% 0.43% and 1.47% respectively) than in that of healthy control donors (9.03% 4.39% n 5) (Fig. 1f) possibly indicative of the efflux of CD16+CD14+ monocytes from the blood to the site of infection. No differences in activated HLA DR+CD3 CD56+ natural killer cells were found. As pro inflammatory cytokines and chemokines are predictive of severe clinical outcomes for influenza6, we quantified 17 pro inflammatory cytokines and chemokines in plasma. We found low levels of the chemokine MCP 1 (CCL2) in the patient's plasma (Extended Data Fig. 2a) although this was comparable to results obtained for healthy donors (22.15 13.81; n 5) patients infected with influenza A virus or influenza B, assessed at days 7 9
Nature Medicine
Irani Thevarajan Thi H O Nguyen Marios Koutsakos Julian D Druce Leon Caly Carolien E van de Sandt Xiaoxiao Jia Suellen Nicholson Michael G Catton Benjamin C Cowie Steven Y C Tong Sharon R Lewin Katherine Kedzierska
213228186
Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID 19)
BACKGROUND The outbreak of coronavirus disease 2019 (COVID 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID 19 patients remain largely unclear. METHODS We retrospectively reviewed the counts of total T cells, CD4+ CD8+ T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory confirmed COVID 19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD 1 and Tim 3 were measured by flow cytometry in the peripheral blood of 14 COVID 19 cases. RESULTS The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID 19 patients, especially among elderly patients =60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+T cells or CD4+T cells lower than 800/mL, 300/mL, or 400/mL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL 6, IL 10 and TNF a concentration, with patients in decline period showing reduced IL 6, IL 10 and TNF a concentrations and restored T cell counts. Finally, T cells from COVID 19 patients have significantly higher levels of the exhausted marker PD 1 as compared to health controls. Moreover, increasing PD 1 and Tim 3 expression on T cells could be seen as patients progressed from prodromal to overtly symptomatic stages, further indicative of T cell exhaustion. CONCLUSIONS T cell counts are reduced significantly in COVID 19 patients, and the surviving T cells appear functionally exhausted. Non ICU patients, with total T cells, CD8+T cells CD4+T cells counts lower than 800/mL, 300/mL, and 400/mL, respectively, may still require aggressive intervention even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
medRxiv
Bo Diao Chenhui Wang Yi-ran Tan Xiewan Chen Yanjun Liu Lifeng Ning Li Chen Min Li Yueping Liu Gang Wang Zilin Yuan Zeqing Feng Yuzhang Wu Yongwen Chen
212568150
CT Features of Coronavirus Disease 2019 (COVID 19) Pneumonia in 62 Patients in Wuhan, China.
OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory confirmed coronavirus disease (COVID 19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory confirmed COVID 19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann Whitney U test was used to compare lesion distribution and CT scores. The chi square test was used to compare the CT signs of early phase versus advanced phase COVID 19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean SD] age, 52.8 12.2 years; range, 30 77 years) with COVID 19 pneumonia were evaluated. Twenty four of 30 patients who underwent routine blood tests (80.0% had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high sensitivity C reactive protein level assessed, 18 (66.7% had an increased erythrocyte sedimentation rate, and all 27 (100.0% had an elevated high sensitivity C reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9% Forty eight of 62 patients (77.4% had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 3.4) was significantly lower than that for the middle (4.5 3.8) and lower (4.5 3.7) zones (p 0.022 and p 0.020, respectively) and there was no significant difference in the mean CT score of the middle and lower zones (p 1.00) The mean CT score for the anterior area (4.4 4.1) was significantly lower than that for the posterior area (7.7 6.3) (p 0.003) CT findings for the patients were as follows: 25 patients (40.3% had ground glass opacities (GGO) 21 (33.9% consolidation; 39 (62.9% GGO plus a reticular pattern; 34 (54.8% vacuolar sign; 28 (45.2% microvascular dilation sign; 35 (56.5% fibrotic streaks; 21 (33.9% a subpleural line; and 33 (53.2% a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6% had air bronchogram, and 11 (17.7% had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4% had pleural thickening, 35 (56.5% had pleural retraction sign, and six (9.7% had pleural effusion. Compared with early phase disease 7 days after the onset of symptoms) advanced phase disease (8 14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced phase disease. CONCLUSION. CT examination of patients with COVID 19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early phase disease. CT signs of aggravation and repair coexisted in advanced phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high sensitivity C reactive protein level were the most common laboratory findings.
AJR. American journal of roentgenology
Shu-chang Zhou Yujin Wang Ting-ting Zhu Liming Xia
211214818
Preparing for the Most Critically Ill Patients With COVID 19: The Potential Role of Extracorporeal Membrane Oxygenation.
The novel coronavirus has now infected tens of thousands of people in China and has spread rapidly around the globe.1 The World Health Organization (WHO) has declared the disease, coronavirus disease 2019 (COVID 19) a Public Health Emergency of International Concern and released interim guidelines on patient management.2 Early reports that emerged from Wuhan, the epicenter of the outbreak, demonstrated that the clinical manifestations of infection were fever, cough, and dyspnea, with radiological evidence of viral pneumonia.3,4 Approximately 15% to 30% of these patients developed acute respiratory distress syndrome (ARDS) The WHO interim guidelines made general recommendations for treatment of ARDS in this setting, including that consideration be given to referring patients with refractory hypoxemia to expert centers capable of providing extracorporeal membrane oxygenation (ECMO).2 ECMO is a form of modified cardiopulmonary bypass in which venous blood is removed from the body and pumped through an artificial membrane lung in patients who have refractory respiratory or cardiac failure.5 Oxygen is added, carbon dioxide is removed, and blood is returned to the patient, either via another vein to provide respiratory support or a major artery to provide circulatory support. ECMO is a resource intensive, highly specialized, and expensive form of life support with the
JAMA
Graeme MacLaren Dale A Fisher Daniel Brodie
214756052
Kidney disease is associated with in hospital death of patients with COVID 19
In December 2019, a coronavirus 2019 (COVID 19) disease outbreak occurred in Wuhan, Hubei Province, China, and rapidly spread to other areas worldwide. Although diffuse alveolar damage and acute respiratory failure were the main features, the involvement of other organs needs to be explored. Since information on kidney disease in patients with COVID 19 is limited, we determined the prevalence of acute kidney injury (AKI) in patients with COVID 19. Further, we evaluated the association between markers of abnormal kidney function and death in patients with COVID 19. This was a prospective cohort study of 701 patients with COVID 19 admitted in a tertiary teaching hospital that also encompassed three affiliates following this major outbreak in Wuhan in 2020 of whom 113 (16.1% died in hospital. Median age of the patients was 63 years (interquartile range, 50 71) including 367 men and 334 women. On admission, 43.9% of patients had proteinuria and 26.7% had hematuria. The prevalence of elevated serum creatinine, elevated blood urea nitrogen and estimated glomerular filtration under 60 ml/min/1.73m2 were 14.4, 13.1 and 13.1% respectively. During the study period, AKI occurred in 5.1% patients. Kaplan Meier analysis demonstrated that patients with kidney disease had a significantly higher risk for in hospital death. Cox proportional hazard regression confirmed that elevated baseline serum creatinine (hazard ratio: 2.10, 95% confidence interval: 1.36 3.26) elevated baseline blood urea nitrogen (3.97, 2.57 6.14) AKI stage 1 (1.90, 0.76 4.76) stage 2 (3.51, 1.49 8.26) stage 3 (4.38, 2.31 8.31) proteinuria 1+ (1.80, 0.81 4.00) 2+~3+ (4.84, 2.00 11.70) and hematuria 1+ (2.99, 1.39 6.42) 2+~3+ (5.56,2.58 12.01) were independent risk factors for in hospital death after adjusting for age, sex, disease severity, comorbidity and leukocyte count. Thus, our findings show the prevalence of kidney disease on admission and the development of AKI during hospitalization in patients with COVID 19 is high and is associated with in hospital mortality. Hence, clinicians should increase their awareness of kidney disease in patients with severe COVID 19.
Kidney International
Yichun Cheng Ran Luo Kun Wang Meng Zhang Zhixian Wang Lei Dong Junhua Li Ying Yao Shuwang Ge Gang Xu
214749978
Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID 19) in Hubei Province, China
Key Points Question What are the ocular manifestations and conjunctival viral prevalence in patients from Hubei province, China, with coronavirus disease 2019 (COVID 19) Findings In this case series including 38 patients with COVID 19, 12 patients had ocular manifestations, such as epiphora, conjunctival congestion, or chemosis, and these commonly occurred in patients with more severe systemic manifestations. Reverse transcriptase polymerase chain reaction results were positive for severe acute respiratory syndrome coronavirus 2 in 28 nasopharyngeal swabs and 2 conjunctival swabs, and more significant changes in blood test values appeared in patients with ocular abnormalities. Meaning These data may assist ophthalmologists and others to understand the ocular manifestations of COVID 19, thus enhancing the diagnosis and prevention of the transmission of the disease.
JAMA ophthalmology
Ping Wu Fang Duan Chunhua Luo Qiang Liu Xingguang Qu Liang Liang Kaili Wu
212628970
[Analysis of the pregnancy outcomes in pregnant women with COVID 19 in Hubei Province]
Objective: To study the effect of COVID 19 on pregnancy outcomes and neonatal prognosis in Hubei Province. Methods: A retrospective comparison of the pregnancy outcomes was done between 16 women with COVID 19 and 45 women without COVID 19. Also, the results of laboratory tests, imaging examinations, and the 2019 nCoV nucleic acid test were performed in 10 cases of neonatal deliverd from women with COVID 19. Results: (1) Of the 16 pregnant women with COVID 19, 15 cases were ordinary type and 1 case was severe type. No one has progressed to critical pneumonia. The delivery method of the two groups was cesarean section, and the gestational age were (38.7+ 1.4) and (37.9+ 1.6) weeks, there was no significant difference between the two groups (P> 0.05) Also, there wee no significant differences in the intraoperative blood loss and birth weight of the newborn between the two groups (all P>0.05) (2) Ten cases of neonates delivered from pregnant women with COVID 19 were collected. The 2019 nCoV nucleic acid test were all negative. There were no significant differences in fetal distress, meconium stained amniotic fluid, preterm birth, and neonatal asphyxia between the two groups (all P>0.05) (3) In the treatment of uterine contraction fatigue, carbetocin or carboprost tromethamine was used more in cesarean section for pregnant women with COVID 19 (1.3+ 0.6) compared with Non COVID 19 group (0.5+ 0.7) the difference was statistically significant (P=0.001) Conclusions: If there is an indication for obstetric surgery or critical illness of COVID 19 in pregnant women, timely termination of pregnancy will not increase the risk of premature birth and asphyxia of the newborn, but it is beneficial to the treatment and rehabilitation of maternal pneumonia. Preventive use of long acting uterotonic agents could reduce the incidence of postpartum hemorrhage during surgery. 2019 nCoV infection has not been found in neonates deliverd from pregnant women with COVID 19.
Zhonghua fu chan ke za zhi
Li-jing Zhang Y Jiang Min Wei Biheng Cheng X Zhou J Li J H Tian L Q Dong Ruheng Hu