The contributory role of lymphocyte subsets, pathophysiology of lymphopenia and its implication as prognostic and therapeutic opportunity in COVID-19.

The incidence of the novel coronavirus disease (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought daunting complications for people as well as physicians around the world. An ever-increasing number of studies investigating the characteristics of the disease, day by day, is shedding light on a new feature of the virus with the hope that eventually these efforts lead to the proper treatment. SARS-CoV-2 activates antiviral immune responses, but in addition may overproduce pro-inflammatory cytokines, causing uncontrolled inflammatory responses in patients with severe COVID-19. This condition may lead to lymphopenia and lymphocyte dysfunction, which in turn, predispose patients to further infections, septic shock, and severe multiple organ dysfunction. Therefore, accurate knowledge in this issue is important to guide clinical management of the disease and the development of new therapeutic strategies in patients with COVID-19. In this review, we provide a piece of valuable information about the alteration of each subtype of lymphocytes and important prognostic factors associated with these cells. Moreover, through discussing the lymphopenia pathophysiology and debating some of the most recent lymphocyte- or lymphopenia-related treatment strategies in COVID-19 patients, we tried to brightening the foreseeable future for COVID-19 patients, especially those with severe disease.

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey.

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

COVID-19 infection in symptomatic pregnant women at the midpoint of the pandemic in Spain: a retrospective analysis.

OBJECTIVES: Determine the strengths and weakness of a symptomatic screening for COVID-19 in pregnant women. Analyze the clinical presentation, management, and outcomes. DESIGN: Descriptive retrospective observational study. SETTING: Mancha-Centro Hospital (Spain). MATERIAL AND METHODS: Population: Symptomatic pregnant women with confirmed diagnosis of COVID-19. Between the 12th of March and 17th of April 2020, all the symptomatic pregnancies were screened with diagnostic test for SARS-CoV-2. Data collection was done by reviewing the medical records and telephone interviews. MAIN OUTCOME MEASURES: Clinical characteristics, management, treatment, and obstetric and neonatal outcomes. RESULTS: Twenty patients with positive COVID-19 diagnostic test out of thirty-four suspected. The most common symptoms were fever (70%), cough (65%) and myalgia (35%). A unique symptom of presentation in 20% of cases. COVID-19 pneumonia was diagnosed in 30% by chest X-ray and one case had pulmonary embolism associated diagnosed by CT-Scan. Thromboprophylaxis was indicated in 16 out of 20 patients. Eight women finished their pregnancy during the observation period. Type of birth: 25% natural birth, 12.5% assisted vaginal delivery and 62.5% caesarean section. We had three severe cases, two of them with intensive care support. All neonates had negative test for COVID 19 infection. CONCLUSIONS: We recommend universal screening of all pregnant woman for COVID-19 during the pandemic because of the limits of the symptomatic screening seen in this studio and the ratio of asymptomatic pregnancies with positive test for COVID-19 recently published.

Evaluation of the clinical profile, laboratory parameters and outcome of two hundred COVID-19 patients from a tertiary centre in India.

COVID-19 is a pandemic with over 5 million cases worldwide. The disease has imposed a huge burden on health resources. Evaluation of clinical and epidemiological profiles of such patients can help in understanding and managing the outbreak more efficiently. This study was a prospective observational analysis of 200 diagnosed COVID-19 patients admitted to a tertiary care center from 20th march to 8th May 2020. All these patients were positive for COVID-19 by an oro-nasopharyngeal swab-rtPCR based testing. Analyses of demographic factors, clinical characteristics, comorbidities, laboratory parameters, and the outcomes were performed. The mean age of the population was 40 years with a slight male predominance (116 patients out of 200, 58%). A majority of the patients (147, 73.5 %) were symptomatic, with fever being the most common symptom (109, 54.5%), followed by cough (91, 45.5%). An older age, presence of symptoms and their duration, leukocytosis, a high quick SOFA score, a high modified SOFA score, need for ventilator support, an AST level more than 3 times the upper limit of normal (ULN), and a serum creatinine level of 2 mg/dl or greater were at a significantly higher risk of ICU admission and mortality. Presence of diabetes mellitus, AST > three times ULN, serum creatinine 2 mg/dl or higher, and a qSOFA score of 1 or higher were all associated with significantly greater odds of critical care requirement. Triage and severity assessment helps in deciding the requirement for a hospital stay and ICU admission for COVID-19 which can easily be done using clinical and laboratory parameters. A mild, moderate and severe category approach with defined criteria and treatment guidelines will help in judicious utilization of health-care resources, especially for developing countries like India.   *Other members of the Safdarjung Hospital COVID-19 working group: Balvinder Singh (Microbiology), MK Sen (Pulmonary Medicine), Shibdas Chakrabarti (Pulmonary Medicine), NK Gupta (Pulmonary medicine), AJ Mahendran (Pulmonary Medicine), Ramesh Meena (Medicine), G Usha (Anaesthesiology), Santvana Kohli (Anaesthesiology), Sahil Diwan (Anaesthesiology), Rushika Saksena (Microbiology), Vikramjeet Dutta (Microbiology), Anupam Kr Anveshi (Microbiology).

A 53-Year-Old Man Presents to the ED With Shortness of Breath, Cough, and Fever.

CASE PRESENTATION: A 53-year-old man presented to the ED at a time of low severe acute respiratory syndrome coronavirus 2, also known as coronavirus disease 2019 (COVID-19), prevalence and reported 2 weeks of progressive shortness of breath, dry cough, headache, myalgias, diarrhea, and recurrent low-grade fevers to 39°C for 1 week with several days of recorded peripheral capillary oxygen saturation of 80% to 90% (room air) on home pulse oximeter. Five days earlier, he had visited an urgent care center where a routine respiratory viral panel was reportedly negative. A COVID-19 reverse transcriptase polymerase chain reaction test result was pending at the time of ED visit. He reported a past medical history of gastroesophageal reflux disease that was treated with famotidine. Travel history included an out-of-state trip 3 weeks earlier, but no recent international travel.

Hematological changes in patients with COVID­19 (Review).

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.

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.

Analysis of clinical features and imaging signs of COVID-19 with the assistance of artificial intelligence.

OBJECTIVE: To explore the CT imaging features/signs of patients with different clinical types of Coronavirus Disease 2019 (COVID-19) via the application of artificial intelligence (AI), thus improving the understanding of COVID-19. PANTIENTS AND METHODS: Clinical data and chest CT imaging features of 58 patients confirmed with COVID-19 in the Fifth Medical Center of PLA General Hospital were retrospectively analyzed. According to the Guidelines on Novel Coronavirus-Infected Pneumonia Diagnosis and Treatment (Provisional 6th Edition), COVID-19 patients were divided into mild type (7), common type (34), severe type (7) and critical type (10 patients). The CT imaging features of the patients with different clinical types of COVID-19 types were analyzed, and the volume percentage of pneumonia lesions with respect to the lung lobes (where the lesion was located) and to the whole lung was calculated with the use of AI software. SPSS 21.0 software was used for statistical analysis. RESULTS: Common clinical manifestations of COVID-19 patients: fever was found in 47 patients (81.0%), cough in 31 (53.4%) and weakness in 10 (17.2%). Laboratory examinations: normal or decreased white blood cell (WBC) counts were observed in 52 patients (89.7%), decreased lymphocyte counts (LCs) in 14 (24.1%) and increased C-reactive protein (CRP) levels in 18 (31.0%). CT imaging features: there were 48 patients (94.1%) with lesions distributed in both lungs and 46 patients (90.2%) had lesions most visible in the lower lungs; the primary manifestations in patients with common type COVID-19 were ground-glass opacities (GGOs) (23/34, 67.6%) or mixed type (17/34, 50.0%), with lesions mainly distributed in the periphery of the lungs (28/34, 82.4%); the primary manifestations of patients with severe/critical type COVID-19 were consolidations (13/17, 76.5%) or mixed type (14/17, 82.4%), with lesions distributed in both the peripheral and central areas of lungs (14/17,82.4%); other common signs, including pleural parallel signs, halo signs, vascular thickening signs, crazy-paving signs and air bronchogram signs, were visible in patients with different clinical types, and pleural effusion was found in 5 patients with severe/critical COVID-19. AI software was used to calculate the volume percentages of pneumonia lesions with respect to the lung lobes (where the lesion was located) and to the whole lung. There were significant differences in the volume percentages of pneumonia lesions for the superior lobe of the left lung, the inferior lobe of the left lung, the superior lobe of the right lung, the inferior lobe of the right lung and the whole lung among patients with different clinical types (p<0.05). The area under the ROC curve (AUC) of the volume percentage of pneumonia lesions for the whole lung for the diagnosis of severe/critical type COVID-19 was 0.740, with sensitivity and specificity of 91.2% and 58.8%, respectively. CONCLUSIONS: The clinical and CT imaging features of COVID-19 patients were characteristic to a certain degree; thus, the clinical course and severity of COVID-19 could be evaluated with a combination of an analysis of clinical features and CT imaging features and assistant diagnosis by AI software.

Prostaglandin D2 as a mediator of lymphopenia and a therapeutic target in COVID-19 disease.

A characteristic feature of COVID-19 disease is lymphopenia. Lymphopenia occurs early in the clinical course and is a predictor of disease severity and outcomes. The mechanism of lymphopenia in COVID-19 is uncertain. It has been variously attributed to the release of inflammatory cytokines including IL-6 and TNF-α; direct infection of the lymphocytes by the virus; and rapid sequestration of lymphocytes in the tissues. Additionally, we postulate that prostaglandin D2 (PGD2) is a key meditator of lymphopenia in COVID-19. First, SARS-CoV infection is known to stimulate the production of PGD2 in the airways, which inhibits the host dendritic cell response via the DP1 receptor signaling. Second, PGD2 is known to upregulate monocytic myeloid-derived suppressor cells (MDSC) via the DP2 receptor signaling in group 2 innate lymphoid cells (ILC2). We propose targeting PGD2/DP2 signaling using a receptor antagonist such as ramatroban as an immunotherapy for immune dysfunction and lymphopenia in COVID-19 disease.

How should our testing behaviour change with time in children in current COVID-19 pandemic?

BACKGROUNDS: More paediatric-confirmed cases have been reported with the global pandemic of COVID-19. This study aims to summarize the key points and supply suggestions on screening paediatric COVID-19 patients more appropriately. MATERIALS AND METHODS: We retrospectively included paediatric patients who have accepted SARS-CoV-2 RT-PCR testing in Children's Hospital of Chongqing Medical University (30 January 2020 to 13 February 2020) and compared them with paediatric-confirmed COVID-19 cases. Besides, a review was carried out by analysing all current literature about laboratory-confirmed paediatric cases with COVID-19. RESULTS: There were 46 suspected cases included in the descriptive study. The results of SARS-CoV-2 RT-PCR testing were all negative. Compared with paediatric-confirmed cases, the incidence of epidemic history was lower in suspected cases (P < .001). The rate of fever (P < .001), cough (P < .001), headache or dizziness (P < .001), vomiting (P < .001) and abdominal discomfort or distention (P = .01) were more observed in the included suspected children. There were more children having decreased WBC count in the confirmed group. In the literature review, twenty-nine studies were obtained with 488 paediatric COVID-19 cases. 88.6% of them had epidemiological history. Cough and fever were the most common symptoms. Compared with older patients, the incidence of fever, respiratory symptoms, lethargy and headache or dizziness was lower, while gastrointestinal symptoms were reported more. CONCLUSIONS: Children with a history of close contact with confirmed cases, manifested as cough and fever should be paid more attention to after excluding infection of other common pathogens. Atypical symptoms should not be over-emphasized in screening paediatric COVID-19. More studies are needed for guiding efficient recognition in paediatric COVID-19.

COVID-19 and the clinical hematology laboratory.

The ongoing COVID-19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID-19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID-19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID-19 infection, (c) summarize the current state of biomarker analysis in COVID-19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID-19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide.

Meta-analysis investigating the relationship between clinical features, outcomes, and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

OBJECTIVE: We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 pneumonia. METHODS: We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and nonsevere (non-ICU) groups. RESULTS: We included 12 cohort studies including 2,445 patients with COVID-19. Compared with nonsevere (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P = .003) and comorbidities including chronic obstructive pulmonary disease (OR = 5.08, P < .001), diabetes (OR = 3.17, P < .001), hypertension (OR = 2.40, P < .001), coronary heart disease (OR = 2.66, P < .001), cerebrovascular diseases (OR = 2.68, P = .008), and malignancy (OR=2.21, P = .040). We found significant differences between the 2 groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P < .05). Significant differences were also observed for multiple treatments (P < .05). Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with nonsevere (non-ICU) disease (P < .05). CONCLUSIONS: Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness.

Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures.

By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID-19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R0 ) of COVID-19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future.

Clinical Presentation of COVID-19: A Systematic Review Focusing on Upper Airway Symptoms.

AIM: Pharyngodynia, nasal congestion, rhinorrhea, smell, and taste dysfunctions could be the presenting symptoms of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2. The aim was to perform a systematic review of current evidences on clinical presentation of COVID-19, focusing on upper airway symptoms in order to help otolaryngologists identifying suspected cases. METHODS: We searched PubMed and Web of Science electronic databases. RESULTS: We included 5 retrospective clinical studies for a total of 1556 hospitalized patients with COVID-19, 57.5% were male and mean age was 49.1 years. Pooled data revealed that pharyngodynia was present in 12.4% of patients, nasal congestion in 3.7%, and rhinorrhea was rare. No reports on COVID-19 and olfactory/gustative disorders matched inclusion criteria but preliminary evidences suggested they could be present. Common symptoms were fever (85.6%), cough (68.7%), and fatigue (39.4%). Frequent comorbidities were hypertension (17.4%), diabetes (3.8%), and coronary heart disease (3.8%); 83% of patients had alterations on chest computed tomography that were bilateral in 89.5% of cases. Ground-glass opacity was the most common finding (50%). Lymphopenia (77.2%) and leucopenia (30.1%) were common. Critical cases with complications were 9%, intensive care unit admission was required in 7.3%, invasive ventilation in 3.4%, and mortality was 2.4%. CONCLUSION: Otolaryngologists should know that pharyngodynia, nasal congestion, olfactory, and gustative disorders could be the presenting symptoms of COVID-19. Clinical presentation together with radiological and laboratory findings could help to identify suspected cases.

COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis.

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).