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Background: COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel beta-coronavirus that is responsible for the 2019 coronavirus pandemic. Acute infections should be diagnosed by polymerase chain reaction (PCR) based tests, but serology tests can demonstrate previous exposure to the virus., Methods: We compared the performance of the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays using 179 negative participants to determine negative percentage agreement (NPA) and in 60 SARS-CoV-2 PCR-confirmed positive patients to determine positive percentage agreement (PPA) at 3 different time frames following a positive SARS-CoV-2 PCR result., Results: At ≥15 days, the PPA (95% CI) was 100 (86.3-100)% for the Diazyme IgM/IgG panel, 96.0 (79.7-99.9)% for the Roche total Ig assay, and 100 (86.3-100)% for the Abbott IgG assay. The NPA (95% CI) was 98.3 (95.2-99.7)% for the Diazyme IgM/IgG panel, 99.4 (96.9-100)% for the Roche total Ig assay, and 98.9 (96.0-99.9)% for the Abbott IgG assay. When the Roche total Ig assay was combined with either the Diazyme IgM/IgG panel or the Abbott IgG assay, the positive predictive value was 100% while the negative predictive value remained greater than 99%., Conclusions: Our data demonstrates that the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays have similar clinical performances. We demonstrated a low false-positive rate across all 3 platforms and observed that false positives observed on the Roche platform are unique compared to those observed on the Diazyme or Abbott assays. Using multiple platforms in tandem increases the PPVs, which is important when screening populations with low disease prevalence., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: We aimed to describe the clinical characteristics, treatment and outcomes of patients with COVID-19 pneumonia, in particular older patients, admitted to tertiary and partner hospitals in Saitama, Japan., Methods: We retrospectively reviewed the medical records of patients with COVID-19 pneumonia admitted to tertiary and partner hospitals in Saitama, Japan. Twenty-six patients with COVID-19 were categorized into two groups, i.e., older (≥75 years) and younger adults (≤74 years). We evaluated the clinical characteristics, comorbidities, symptoms, laboratory test results, treatments and outcomes of the patients., Results: The majority of the older patients had comorbidities, such as dementia, cardiovascular disease and bone fractures. Comorbidities were significantly more frequent in older patients than younger patients. No association was found between age and body temperature or the incidence of respiratory failure. White blood cell count was significantly lower in older patients (P = 0.018) and the decrease in lymphocytes was greater in younger patients (P = 0.009). Computed tomography (CT) of all patients showed non-segmental, peripherally dominant ground-glass opacities consistent with COVID-19 pneumonia. In older patients, antiviral drugs, anticoagulants and anti-inflammatory drugs were administered on a compassionate use basis. The difference in mortality between the older and the younger patients was not statistically significant., Conclusions: In older patients, typical clinical symptoms and blood test changes were often absent; however, CT always contained typical findings of COVID-19, suggesting that CT may be a useful diagnostic tool. Our report illustrates that appropriate treatment, taking patient background into consideration, may improve their condition regardless of age. Geriatr Gerontol Int 2020; 20: 1044-1049., (© 2020 Japan Geriatrics Society.)

Background: In December 2019, a novel coronavirus (SARS-CoV-2) causing symptomatic illness (COVID-19) occurred in Wuhan, China. Travel-associated cases were reported in many other countries leading to epidemic transmission. The number of cases has increased rapidly but laboratory diagnosis is limited., Methods: We collected samples from two groups of patients diagnosed with COVID-19 for experiments. In one group, 63 serum samples were analyzed IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA) and 35 healthy serum samples were served as controls. In the other group, 91 plasma samples were analyzed by colloidal gold-immunochromatographic assay (GICA) for IgG and IgM antibodies and 35 healthy plasma samples were served as controls. Throat swab samples for nucleic acids retest were collected from 81/91 of these participant., Results: The sensitivity of the combined ELISA IgM and IgG detection was 55/63 (87.3%). Sensitivity of the com-bined GICA IgM and IgG detection was 75/91 (82.4%). Both methods were negative for healthy controls and had a specificity of 100%. In 81 cases, the follow up throat swab samples were retested by RT-PCR, showing that 42 cases were positive. The sensitivity was 51.9% (42/81). The area under the receiver operating characteristic (ROC) curve for IgG (AUC(IgG)) was 0.934. The area under the ROC curve for IgM (AUC(IgM)) was 0.812. The area under the ROC curve for IgG + IgM (AUC(IgG+IgM)) was 0.983., Conclusions: The serological test of SARS-CoV-2 can be used as an important supplement to the existing RT-PCR test for the specific and rapid diagnosis of COVID-19. AUC(IgG) > AUC(IgM) indicates that IgG has better classification performance than IgM. AUC(IgG + IgM) > AUC(IgG) indicates that the combination of IgG and IgM has better classification performance than IgG alone.

Evidence has emerged regarding an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with worse prognosis in elderly male patients with obesity, and blunted growth hormone (GH) secretion represents a feature of this population subgroup. Here, a comprehensive review of the possible links between GH-insulinlike growth factor 1 axis impairment and coronavirus disease 2019 (COVID-19) severity is offered. First, unequivocal evidence suggests that immune system dysregulation represents a key element in determining SARS-CoV-2 severity, as well as the association with adult-onset GH deficiency (GHD); notably, if GH is physiologically involved in the development and maintenance of the immune system, its pharmacological replacement in GHD patients seems to positively influence their inflammatory status. In addition, the impaired fibrinolysis associated with GHD may represent a further link between GH-insulin-like growth factor 1 axis impairment and COVID-19 severity, as it has been associated with both conditions. In conclusion, several sources of evidence have supported a relationship between GHD and COVID-19, and they also shed light upon potential beneficial effects of recombinant GH treatment on COVID-19 patients., (© 2020 The Obesity Society.)

The world is in the midst of a pandemic caused by a novel coronavirus and is desperately searching for possible treatments. The antiviral remdesivir has shown some effectiveness against SARS-CoV-2 in vitro and in a recent animal study. We use data from a study of remdesivir in rhesus macaques to fit a viral kinetics model in an effort to determine the most appropriate mathematical descripton of the effect of remdesivir. We find statistically significant differences in the viral decay rate and use this to inform a possible mathematical formulation of the effect of remdesivir. Unfortunately, this model formulation suggests that the application of remdesivir will lengthen SARS-CoV-2 infections, putting into question its potential clinical benefit., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: On January 30, 2020, WHO declared COVID-19 a pandemic. In this article we describe our experience at Richmond University Medical Center with Chembio serological IgM, IgG testing., Methods: In this prospective cohort study of patients and hospital employees, we utilized Chembio COVID-19 IgM/IgG serological testing in addition to Cepheid RT-PCR analysis., Results: We evaluated the performance of Chembio serological test for IgM and IgG as an employee screening tool in a community hospital setting. The total number of currently asymptomatic employees screened was 1,866 from the Richmond University Medical Center. The non-exposed group included 1,253 (67.1%) employees with no significant clinical history and non-reactive IgM and IgG antibodies. The convalescent group included 255 (13.7%) of the employees with elevation of IgG only, 18 (1%) employees with past history of positive PCR and COVID-19 who currently have non-reactive IgM and IgG antibodies or demonstrate elevated IgG only, followed by 3 employees (< 1%) with no past clinical history who demonstrated reactive IgM and IgG antibodies and negative follow up by PCR. The reported 14.9% exposure/convalescent rate is lower than the reported 20% by the Department of Health and Governor Andrew Cuomo and may represent a better utilization of personal protective equipment, better hand washing techniques, and better disinfection procedures combined with strict social distancing., Conclusions: Chembio's performance is satisfactory; however, hospitals must design their own policies addressing: who needs to be screened and who will interpret the results as well as constructing management algorithms for employees with no previous history and current double positive antibodies.

Background: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients., Methods: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death., Findings: Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47-66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44-84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p<0·0001) and invasive ventilation (30 [20%] vs 32 [5%], p<0·0001) were more frequent in the liver transplant cohort. 28 (19%) patients in the liver transplant cohort died, compared with 167 (27%) in the comparison cohort (p=0·046). In the propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI -7·7 to 10·4]). Multivariable logistic regression analysis showed that age (odds ratio 1·06 [95% CI 1·01 to 1·11] per 1 year increase), serum creatinine concentration (1·57 [1·05 to 2·36] per 1 mg/dL increase), and non-liver cancer (18·30 [1·96 to 170·75]) were associated with death among liver transplant recipients., Interpretation: Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic., Funding: European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the prognostic value of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio and red cell distribution width in type 2 diabetics with COVID-19., Methods: We collected the data of type 2 diabetics with COVID-19 treated in our hospital from January 28 to March 15, 2020 and performed a retrospective analysis. Using severity, duration of hospital stay, and the time required for nucleic acid results became negative as prognostic indicators, we explored the relationship between these inflammation-based markers and prognosis of type 2 diabetics with COVID-19., Results: A total of 134 type 2 diabetics with COVID-19 were selected for this study. Correlation analysis showed that NLR, LMR and RDW were correlated with prognosis ( P  < 0.05). In multivariate regression analysis after controlling for the relevant confounding factors, COVID-19 diabetes patients with higher NLR had heavier severity, longer duration of hospital stay, more time required for nucleic acid results became negative, and heavier hospital expenses ( P  < 0.05). ROC curve result displayed that higher NLR predicted all prognostic indicators with statistical significance, and lower LMR predicted severe and extremely severe with statistical significance ( P  < 0.05)., Conclusions: NLR is a more powerful and practical marker for predicting the prognosis of type 2 diabetic COVID-19 patients that is simple and fast.

There is recent evidence that interleukin-6 (IL-6) levels are elevated in cases of complicated COVID-19, but it is also possible that this cytokine may have a far more important role in the pathogenesis of viral infection. IL-6 is known to be modulated by Vitamin D, and there is preliminary evidence that deficiency of this vitamin is linked to poorer outcomes. To identify whether IL-6 levels prior to infection might predict outcome, early data on COVID-19 mortality from Italy and the UK were compared with previously published results of mean IL-6 levels from these countries as well as from the USA. There was a highly significant correlation (r = 0.9883; p = 0.00025) between age-stratified mortality rates and IL-6 levels from previously published data on healthy individuals. To determine whether Vitamin D may be beneficial at lowering IL-6 levels in patients, a limited analysis of trials examining the relationship between these entities published since 2015 was undertaken. Eight out of 11 studies described a significant lowering effect of Vitamin D on IL-6. Given that IL-6 likely facilitates viral cell entry and replication, levels prior to infection may predict mortality. This provides a rationale for prophylactic and therapeutic measures directed at lowering IL-6, including Vitamin D prescription., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Coronavirus Disease 2019 (COVID-19) convalescent plasma (CCP) was approved by the FDA for use in severe cases of COVID-19 under an emergency Investigational New Drug (IND) protocol. Eligibility criteria for CCP donors includes documentation of evidence of COVID-19 either by viral RNA detection at the time of illness or positive SARS-CoV-2 IgG after recovery if diagnostic testing for COVID-19 was not performed at the time of illness. In addition to analysis of CCP, analysis of SARS-CoV-2 IgG provides information for possible past exposure and may support diagnosis when SARS-CoV-2 PCR is negative and clinical suspicion for COVID-19 is high. Furthermore, assays with high sensitivity and specificity for SARS-CoV-2 IgG are critical for understanding community exposure rates to SARS-CoV-2. Currently, there are several assays that test for antibodies to SARS-CoV-2 using a variety of methods, including point-of-care lateral flow-based devices, high throughput immunoassay analyzers, and manual methods such as ELISA. These assays target a number of SARS-CoV-2 antigens, including the nucleocapsid protein (N), full length spike protein (S), S1 subunit, or receptor binding domain (RBD) of the S protein. Given the heterogeneity among methods for, and antigenic targets used in SARS-CoV-2 antibody assays, it is necessary for careful evaluation of these assays prior to implementation for clinical use. We compared two assays that had received the CE mark of regulatory approval and that used either the N antigen or S1-RBD antigen as the target for analysis of a large set of CCP samples. Our data indicates that sensitivity and specificity vary between these assays and that more than one antigenic target may be required to improve the sensitivity and specificity of IgG detection to SARS-CoV-2., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The clinical false negative rate of reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on a single upper respiratory tract sample was calculated using convalescent antibody testing as a comparator. The sensitivity in symptomatic individuals was 86.2% (25/29). Of the missed cases, one (3.5%) was detected by repeat RT-PCR, one by CT thorax and two (7.1%) by convalescent antibody. The clinical false negative rate of a single RT-PCR on an upper respiratory tract sample of 14% in symptomatic patients is reassuring when compared to early reports. This report supports a strategy of combining repeat swabbing, use of acute and convalescent antibody testing and CT thorax for COVID-19 diagnosis., (© 2020 Royal College of Physicians 2020. All rights reserved.)

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2-3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.

Aims: The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability., Methods and Results: Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level., Conclusions: Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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.

Context: People who have recently recovered from the threat of deteriorating coronavirus disease-2019 (COVID-19) have antibodies to the coronavirus circulating in their blood. Thus, the transfusion of these antibodies to deteriorating patients could theoretically help boost their immune system. Biologically, two challenges need to be surmounted to allow convalescent plasma (CP) transfusion to rescue the most severe COVID-19 patients. First, convalescent subjects must meet donor selection plasma criteria and comply with national health requirements and known standard routine procedures. Second, multi-criteria decision-making (MCDM) problems should be considered in the selection of the most suitable CP and the prioritisation of patients with COVID-19., Objective: This paper presents a rescue framework for the transfusion of the best CP to the most critical patients with COVID-19 on the basis of biological requirements by using machine learning and novel MCDM methods., Method: The proposed framework is illustrated on the basis of two distinct and consecutive phases (i.e. testing and development). In testing, ABO compatibility is assessed after classifying donors into the four blood types, namely, A, B, AB and O, to indicate the suitability and safety of plasma for administration in order to refine the CP tested list repository. The development phase includes patient and donor sides. In the patient side, prioritisation is performed using a contracted patient decision matrix constructed between 'serological/protein biomarkers and the ratio of the partial pressure of oxygen in arterial blood to fractional inspired oxygen criteria' and 'patient list based on novel MCDM method known as subjective and objective decision by opinion score method'. Then, the patients with the most urgent need are classified into the four blood types and matched with a tested CP list from the test phase in the donor side. Thereafter, the prioritisation of CP tested list is performed using the contracted CP decision matrix., Result: An intelligence-integrated concept is proposed to identify the most appropriate CP for corresponding prioritised patients with COVID-19 to help doctors hasten treatments., Discussion: The proposed framework implies the benefits of providing effective care and prevention of the extremely rapidly spreading COVID-19 from affecting patients and the medical sector., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier B.V.)

Background:  The aim of this meta-analysis is to assess the prevalence of coagulation dysfunction in Chinese COVID-19 patients and to determine the association of coagulopathy with the severity and prognosis of COVID-19., Methods:  A meta-analysis of the prevalence of different abnormal coagulation indicators in COVID-19 patients in China was performed. The difference of coagulation indicators and the incidence of DIC were compared between severe cases and nonsevere cases as well as nonsurvivors and survivors, respectively., Results:  A total of 22 Chinese studies involving 4,889 confirmed COVID-19 inpatients were included. The average D-dimer value of COVID-19 patients is 0.67 µg/mL (95% confidence interval [CI]: 0.56-0.78), and 29.3% (95% CI: 20.1-38.5%) of patients showed elevated D-dimer values. Severe patients had significantly higher D-dimer levels and prolonged prothrombin time (PT) compared with nonsevere patients. Nonsurvivors had significantly higher D-dimer levels, prolonged PT, and decreased platelet count compared with survivors. In total, 6.2% (95% CI: 2.6-9.9%) COVID-19 patients were complicated by disseminated intravascular coagulation (DIC), in which the log risk ratio in nonsurvivors was 3.267 (95% CI: 2.191-4.342, Z  = 5.95, p  < 0.05) compared with that in survivors., Conclusion:  The prevalence of coagulopathy in Chinese COVID-19 inpatients is high, and both the abnormal coagulation indicators and DIC are closely associated with the severity and poor prognosis of these COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Closely monitoring of coagulation indicators and application of appropriate anticoagulation may improve the prognosis of COVID-19 inpatients in China., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The viral shedding duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of coronavirus disease 2019 (COVID-19)., Research Question: What are the shedding durations of SARS-CoV-2 RNA in the upper and lower respiratory tract specimens? What are their associated risk factors?, Study Design and Methods: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020, to March 20, 2020, were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis., Results: SARS-CoV-2 RNA was detected from NPSs in 48 patients (70.6%), and from sputum specimens in 30 patients (44.1%). The median duration of viral shedding from sputum specimens (34 days; interquartile range [IQR], 24-40) was significantly longer than from NPSs (19 days; IQR, 14-25; P < .001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (hazard ratio, 1.71; 95% CI, 1.01-2.93). It was noteworthy that in 9 patients, the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum., Interpretation: These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 reported in pregnant women has occured in late pregnancy, while there are no reports of infection in the first and second trimester. We report two neonates born to mothers with COVID-19 during the second trimester., Case Presentation: Two pregnant women had symptomatic COVID-19 in the second trimester. Throat swabs at delivery for SARS-COV-2 RNA were negative for both women and their newborns. The first woman had positive serum IgM and IgG antibodies to SARS-COV-2 before delivery. Her newborn had negative IgM antibody to SARS-COV-2 but IgG was positive on the 7th day after birth. The second woman had negative serum IgM antibody to SARS-COV-2 but IgG was positive before delivery. Her newborn had negative serum IgM antibody to SARS-COV-2 but IgG was positive at 48 h after birth. None of the neonates developed clinical symptoms of COVID-19., Conclusion: SARS-COV-2 is unlikely to be vertically transmitted in utero as evidenced by the specific antibodies in the serum of the two women and their newborns. The two women with SARS-COV-2 infection in the second trimester did not develop serious complications at delivery and outcomes of the neonates were good.

Background: While molecular techniques remain the gold standard for diagnosis of acute SARS-CoV-2 infection, serological tests have the unique potential to ascertain how much of the population has been exposed to the COVID-19 pathogen. There have been limited published studies to date documenting the performance of SARS-CoV-2 antibody assays., Methods: We compared the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Diagnostics Elecsys Anti-SARS-CoV-2 assays using 228 samples spanning patients with positive PCR for SARS-CoV-2, patients with compatible symptoms but negative PCR, pre-COVID specimens, and potential cross-reactives., Results: Both assays detected antibodies in 18/19 samples collected at least one week after a positive PCR result. Neither method consistently detected antibodies in specimens collected within one week of a positive PCR result (sensitivity < 50%), but antibodies were detected by only Roche in four samples in this time frame. Using 139 pre-COVID and 35 PCR-negative samples, the Roche and DiaSorin assays demonstrated specificities of 100.0% and 98.9%, respectively. Neither assay demonstrated cross-reactivity from other coronaviruses (229E, HKU1, NL63, OC43), respiratory pathogens (adenovirus, metapneumovirus, rhinovirus/enterovirus), or antibodies to other viruses (HIV, EBV, CMV, HBV, HCV, HAV)., Discussion: Overall, the qualitative interpretations afforded by the Roche and DiaSorin assays agreed for 97% of samples evaluated. Minor discrepancies in sensitivity and specificity were observed between methods, with the differences in specificity more clinically significant for our low-prevalence population. For the DiaSorin assay, all disagreements with the Roche assay occurred in samples with quantitative signals near the cut-off determining positivity., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.

Background: COVID-19 disease affects the nervous system and led to an increase in neurological consults for patients at admission and through the period of hospitalization during the peak of the pandemic., Methods: Patients with clinical and laboratory diagnosis of COVID-19 that required a neurologic consultation or those who presented with neurological problems on admission that led to a diagnosis of SARS-CoV-2 infection during a 2-month period at the peak of the pandemic were included in this study. Demographic and clinical variables were analyzed., Results: Thirty-five patients were included. The presenting neurologic manifestations on admission led to the diagnosis of COVID-19 in 14 patients (40%). The most common reasons for consultation during the hospitalization period were stroke (11), encephalopathy (7), seizures (6), and neuropathies (5) followed by a miscellaneous of syncope (2), migraine (1), anosmia (1), critical illness myopathy (1), and exacerbation of residual dysarthria (1). The most common neurological disturbances were associated with severe disease except for neuropathies. Patients with encephalopathies and seizures had markedly increased D-dimer and ferritin values, even higher than stroke patients. RT-PCR was performed in 8 CSF samples and was negative in all of them., Conclusion: Neurological disturbances represent a significant and severe burden in COVID-19 patients, and they can be the presenting condition that leads to the diagnosis of the viral infection in a high percentage of patients. Evidence of direct viral mechanisms was scarce, but the pathogenesis of the diverse manifestations remains enigmatic.

Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 215 countries, with over 11.91 million reported cases and more than 540,000 deaths. Rapid diagnosis remains a bottleneck for containing the epidemic. We used an automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to the 2019-nCoV in 742 subjects, so as to observe the dynamic process of antibody production in COVID-19 disease and seroepidemiology in different populations. Patients with COVID-19 were reactive (positive) for specific antibodies within 3-15 days after onset of symptoms. Specific IgM and IgG levels increased with the progression of the disease. The areas under the receiver operating characteristic curves for IgM and IgG were 0.984 and 1.000, respectively. This antibody detection assay had good sensitivity and specificity. The understanding of the dynamic serological changes of COVID-19 patients and the seroepidemiological situation of the population will be helpful to further control the epidemic of COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Population-based data on COVID-19 are essential for guiding policies. There are few such studies, particularly from low or middle-income countries. Brazil is currently a hotspot for COVID-19 globally. We aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence by city and according to sex, age, ethnicity group, and socioeconomic status, and compare seroprevalence estimates with official statistics on deaths and cases., Methods: In this repeated cross-sectional study, we did two seroprevalence surveys in 133 sentinel cities in all Brazilian states. We randomly selected households and randomly selected one individual from all household members. We excluded children younger than 1 year. Presence of antibodies against SARS-CoV-2 was assessed using a lateral flow point-of-care test, the WONDFO SARS-CoV-2 Antibody Test (Wondfo Biotech, Guangzhou, China), using two drops of blood from finger prick samples. This lateral-flow assay detects IgG and IgM isotypes that are specific to the SARS-CoV-2 receptor binding domain of the spike protein. Participants also answered short questionnaires on sociodemographic information (sex, age, education, ethnicity, household size, and household assets) and compliance with physical distancing measures., Findings: We included 25 025 participants in the first survey (May 14-21) and 31 165 in the second (June 4-7). For the 83 (62%) cities with sample sizes of more than 200 participants in both surveys, the pooled seroprevalence increased from 1·9% (95% CI 1·7-2·1) to 3·1% (2·8-3·4). City-level prevalence ranged from 0% to 25·4% in both surveys. 11 (69%) of 16 cities with prevalence above 2·0% in the first survey were located in a stretch along a 2000 km of the Amazon river in the northern region. In the second survey, we found 34 cities with prevalence above 2·0%, which included the same 11 Amazon cities plus 14 from the northeast region, where prevalence was increasing rapidly. Prevalence levels were lower in the south and centre-west, and intermediate in the southeast, where the highest level was found in Rio de Janeiro (7·5% [4·2-12·2]). In the second survey, prevalence was similar in men and women, but an increased prevalence was observed in participants aged 20-59 years and those living in crowded conditions (4·4% [3·5-5·6] for those living with households with six or more people). Prevalence among Indigenous people was 6·4% (4·1-9·4) compared with 1·4% (1·2-1·7) among White people. Prevalence in the poorest socioeconomic quintile was 3·7% (3·2-4·3) compared with 1·7% (1·4-2·2) in the wealthiest quintile., Interpretation: Antibody prevalence was highly heterogeneous by country region, with rapid initial escalation in Brazil's north and northeast. Prevalence is strongly associated with Indigenous ancestry and low socioeconomic status. These population subgroups are unlikely to be protected if the policy response to the pandemic by the national government continues to downplay scientific evidence., Funding: Brazilian Ministry of Health, Instituto Serrapilheira, Brazilian Collective Health Association, and the JBS Fazer o Bem Faz Bem., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study was to evaluate the applicability of bedside ultrasonography for the diagnosis of deep venous thrombosis (DVT) in patients infected with corona virus disease 2019 (COVID-19) with and without treatment with low molecular weight heparin (LMWH)., Methods: We retrospectively analyzed the records of deceased and surviving patients in whom ultrasonography detected or not a DVT, and in whom LMWH was or not prescribed., Results: The incidence of DVT is higher in the deceased (33/35) than in the surviving (22/46) patients. LMWH was administered in a larger proportion of surviving (18/22) than of deceased (18/33) patients. D-dimer concentrations decreased in patients who received LMWH in both groups., Conclusions: There was a high incidence of DVT in patients who succumbed to COVID-19. Bedside ultrasonography can detect the presence of DVT as early as possible and help assessing the risk of venous thromboembolism, allowing early and reasonable use of LMWH., (© 2020 Wiley Periodicals LLC.)

Background: Novel coronavirus disease-19 (COVID-19) has spread worldwide, and to date presence of the virus has been recorded in 215 countries contributing 0.43 million of death. The role of blood groups in susceptibility/resistance to various infectious diseases has been reported. However, the association of blood groups with susceptibility to COVID-19 infections or related death are limited. In the present report, we performed an epidemiological investigation in the Indian population to decipher the importance of blood groups concerning susceptibility or mortality in COVID-19 infection., Materials and Methods: Data on COVID-19 infection and mortality was obtained from the website of the Government of India. Prevalence of ABO blood groups in different states and union territories of India were searched using different databases such as PubMed and Google Scholar. Relevant articles were downloaded, and data were extracted. Spearman's rank coefficient analysis was employed to study the correlation between blood group frequencies and COVID-19 infection or mortality rate., Results: A significant inverse correlation was observed between the frequency of O blood group and the COVID-19 mortality rate (Spearman r=-0.36, P=0.03), indicating a possible protective role of O blood group against COVID-19 related death. In contrast, the prevalence of blood group B was positively correlated with COVID-19 death/million (Spearman r=0.67, P<0.0001), suggesting B blood type as a deleterious factor in COVID-19 infection., Conclusions: ABO blood group system is associated with poor prognosis of COVID-19 infection. Blood group O may protects, and subjects with blood type B could be susceptible to COVID-19 mortality. However, further studies on COVID-19 infected patients in different population are required to validate our findings., (Copyright © 2020 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background: Amidst the coronavirus disease 2019 (COVID-19) pandemic, continuous glucose monitoring (CGM) has emerged as an alternative for inpatient point-of-care blood glucose (POC-BG) monitoring. We performed a feasibility pilot study using CGM in critically ill patients with COVID-19 in the intensive care unit (ICU)., Methods: Single-center, retrospective study of glucose monitoring in critically ill patients with COVID-19 on insulin therapy using Medtronic Guardian Connect and Dexcom G6 CGM systems. Primary outcomes were feasibility and accuracy for trending POC-BG. Secondary outcomes included reliability and nurse acceptance. Sensor glucose (SG) was used for trends between POC-BG with nursing guidance to reduce POC-BG frequency from one to two hours to four hours when the SG was in the target range. Mean absolute relative difference (MARD), Clarke error grids analysis (EGA), and Bland-Altman (B&A) plots were calculated for accuracy of paired SG and POC-BG measurements., Results: CGM devices were placed on 11 patients: Medtronic ( n  = 6) and Dexcom G6 ( n  = 5). Both systems were feasible and reliable with good nurse acceptance. To determine accuracy, 437 paired SG and POC-BG readings were analyzed. For Medtronic, the MARD was 13.1% with 100% of readings in zones A and B on Clarke EGA. For Dexcom, MARD was 11.1% with 98% of readings in zones A and B. B&A plots had a mean bias of -17.76 mg/dL (Medtronic) and -1.94 mg/dL (Dexcom), with wide 95% limits of agreement., Conclusions: During the COVID-19 pandemic, CGM is feasible in critically ill patients and has acceptable accuracy to identify trends and guide intermittent blood glucose monitoring with insulin therapy.

Introduction: Abnormal coagulation function has been demonstrated to be involved in the disease progression of COVID-19. However, the association between D-dimer levels and the severity of COVID-19 is not clear. The study was aimed to investigate the association between D-dimer levels and the severity of COVID-19 based on a cohort study and meta-analysis., Materials and Methods: Demographic and clinical data of all confirmed cases with COVID-19 on admission to Tongji Hospital from January 27 to March 5, 2020, were collected and analyzed, and coagulation function parameters were described and compared between patients with severe infection and those with non-severe infection. Cohort studies reporting risk estimates for the D-dimer and severity of COVID-19 association were searched and included to perform a meta-analysis., Results: In our cohort study, patients with severe disease were more likely to exhibit dysregulated coagulation function, and a significantly higher D-dimer level (median 1.8 μg/ml [interquartile range 0.9-4.6] vs 0.5 [0.3-1.1], p < 0.001) was found in severe cases than the mild ones, on admission. In the meta-analysis of 13 cohort studies (including the current study), patients with severe disease had an increase in mean D-dimer value by 0.91 (95% confidence interval, 0.51-1.31, p < 0.001) μg/ml compared to those with non-severe disease, and odds of severe infection was associated with D-dimer greater than 0.5 μg/ml (odds ratio = 5.78, 95% confidence interval, 2.16-15.44, p < 0.001) on admission., Conclusions: Patients with severe COVID-19 have a higher level of D-dimer than those with non-severe disease, and D-dimer greater than 0.5 μg/ml is associated with severe infection in patients with COVID-19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Infection rates, severity, and fatalities due to COVID-19, the pandemic mediated by SARS-CoV-2, vary greatly between countries. With few exceptions, these are lower in East and Southeast Asian and Sub-Saharan African countries compared with other regions. Epidemiological differences may reflect differences in border closures, lockdowns, and social distancing measures taken by each county, and by cultural differences, such as common use of face masks in East and Southeast Asian countries. The plasma serine protease inhibitor alpha-1 antitrypsin was suggested to protect from COVID-19 by inhibiting TMPRSS2, a cell surface serine protease essential for the SARS-CoV-2 cell entry. Here, we present evidence that population differences in alpha-1 antitrypsin deficiency allele frequencies may partially explain national differences in the COVID-19 epidemiology. Our study compared reported national estimates for the major alpha-1 antitrypsin deficiency alleles PiZ and PiS (SERPINA1 rs28929474 and rs17580, respectively) with the Johns Hopkins University Coronavirus Resource Center dataset. We found a significant positive correlation (R = .54, P = 1.98e-6) between the combined frequencies of the alpha-1 antitrypsin PiZ and PiS deficiency alleles in 67 countries and their reported COVID-19 mortality rates. Our observations suggest that alpha-1 antitrypsin deficiency alleles may contribute to national differences in COVID-19 infection, severity, and mortality rates. Population-wide screening for carriers of alpha-1 antitrypsin deficiency alleles should be considered for prioritizing individuals for stricter social distancing measures and for receiving a SARS-CoV-2 vaccine once it becomes available., (© 2020 Federation of American Societies for Experimental Biology.)

During the COVID-19 pandemic, the antimicrobial stewardship module in our electronic medical record was reconfigured for the management of COVID-19 patients. This change allowed our subspecialist providers to review charts quickly to optimize potential therapy and management during the patient surge.

Background: To determine whether abnormal coagulation parameters are associated with disease severity and poor prognosis in patients with 2019 Corona Virus Disease (COVID-19)., Methods: A systematic literature search was conducted using the databases PubMed, Embase, and Web of sciences until April 25, 2020. We included a total of 15 studies with 2277 patients. Platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), and fibrinogen (FIB) were collected and analyzed. The statistical results were expressed as the effect measured by mean difference (MD) with the related 95% confidence interval (CI)., Results: The PLT level of severe cases was lower than that of mild cases, while the levels of PT, D-D, and FIB were higher than those of mild cases (P < 0.05). The level of APTT had no statistical difference between two groups (P > 0.05). PT of ICU patients was significantly longer (P < 0.05) than that of non-ICU patients. In non-survivors, PT and D-D were higher, yet PLT was lower than that of survivors (P < 0.05). There was no significant difference in APTT between survivors and non-survivors (P > 0.05). The funnel plot and Egger's regression test demonstrated that there was no publication bias., Conclusions: Our data support the notion that coagulopathy could be considered as a risk factor for disease severity and mortality of COVID-19, which may help clinicians to identify the incidence of poor outcomes in COVID-19 patients., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Observational evidence suggests that excessive inflammation with cytokine storm may play a critical role in development of acute respiratory distress syndrome (ARDS) in COVID-19. We report the emergency use of immunomodulatory therapy utilizing an extracorporeal selective cytopheretic device (SCD) in two patients with elevated serum interleukin (IL)-6 levels and refractory COVID-19 ARDS requiring extracorporeal membrane oxygenation (ECMO). The two patients were selected based on clinical criteria and elevated levels of IL-6 (>100 pg/ml) as a biomarker of inflammation. Once identified, emergency/expanded use permission for SCD treatment was obtained and patient consented. Six COVID-19 patients (four on ECMO) with severe ARDS were also screened with IL-6 levels less than 100 pg/ml and were not treated with SCD. The two enrolled patients' PaO2/FiO2 ratios increased from 55 and 58 to 200 and 192 at 52 and 50 hours, respectively. Inflammatory indices also declined with IL-6 falling from 231 and 598 pg/ml to 3.32 and 116 pg/ml, respectively. IL-6/IL-10 ratios also decreased from 11.8 and 18 to 0.7 and 0.62, respectively. The two patients were successfully weaned off ECMO after 17 and 16 days of SCD therapy, respectively. The results observed with SCD therapy on these two critically ill COVID-19 patients with severe ARDS and elevated IL-6 is encouraging. A multicenter clinical trial is underway with an FDA-approved investigational device exemption to evaluate the potential of SCD therapy to effectively treat COVID-19 intensive care unit patients.

We conducted a nationwide study of the prevalence of severe acute respiratory syndrome coronavirus 2 infection in the Faroe Islands. Of 1,075 randomly selected participants, 6 (0.6%) tested seropositive for antibodies to the virus. Adjustment for test sensitivity and specificity yielded a 0.7% prevalence. Our findings will help us evaluate our public health response.

In the last decades, coronaviruses have been a major threat to public health worldwide. SARS-CoV-2 is the third known coronavirus that causes fatal respiratory diseases in humans. The initial clinical features of SARS-CoV-2 infection are quite nonspecific and not all suspected patients can be tested to exclude or confirm the diagnosis. Increasing scientific evidence has shown that abnormalities in routine laboratory tests, particularly hematological tests, have the potential to indicate, in a quick, practical and economical way, the need for specific laboratory tests for the diagnosis of SARS-CoV-2 infection, besides assisting in the prognosis of the disease and in the optimization of its clinical monitoring. In order to address in a simple and practical way the various aspects related to SARS-CoV-2 infection, this review reports the history of the virus, the epidemiology and pathophysiology of COVID-19, with emphasis on its laboratory diagnosis, particularly in hematological changes found during the course of the disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Serologic tests are one of the available diagnostic tools in COVID-19. Growing literature highlights their role in the clinical management of the disease. Unfortunately, due to the limited availability of commercial tests and the lack of reliable trials establishing the sensitivity and specificity of the diagnostic method, the clinical application of the test needs to be precisely determined. In this paper, we discuss the utility of anti-SARS-CoV-2 serology testing in a clinical setting and propose diagnostic algorithms that include serological tests in patients with confirmed or suspected COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19., Objectives: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19., Patients/methods: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR)., Results: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 ('PE likely') was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001). In the 'low probability' group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE., Conclusions: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)