Seroprevalence of SARS-CoV-2 in Croatian solid-organ transplant recipients

IntroductionThe data on the coronavirus disease (COVID-19) in solid-organ transplant recipients (SOTRs) in Croatia is unknown. The aim of this study was to analyze the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Croatian SOTRs.Materials and methodsFrom 7 September to 27 November 2020 (beginning of the second COVID-19 pandemic wave), a cross-sectional screening for COVID-19 was performed in the adult outpatient liver (LTRs; N = 280) and kidney transplant recipients (KTRs; N = 232). Serum samples were initially tested for SARS-CoV-2 IgG antibodies using a commercial enzyme-linked immunosorbent assay (ELISA; Vircell Microbiologists, Granada, Spain). All positive samples were confirmed using a virus neutralization test (VNT). Data on risk exposure and COVID-19 related symptoms were collected using a questionnaire.ResultsThe transplanted cohort’s seroprevalence detected by ELISA and VNT was 20.1% and 3.1%, respectively. Neutralizing (NT) antibodies developed in 15.6% of anti-SARS-CoV-2 ELISA IgG positive SOTRs. The difference in seropositivity rates between LTRs and KTRs was not statistically significant (ELISA 21.1% vs. 19.0%, P = 0.554; VNT 3.6% vs. 2.6%, P = 0.082). Overall VNT positivity rates were higher in patients who reported participation in large community events (5.9% vs. 1.0%; P = 0.027) as well as in patients who reported COVID-19 related symptoms in the past six months. In addition, symptomatic VNT positive patients showed significantly higher (P = 0.031) NT antibody titers (median 128, interquartile range (IQR) = 32-128) compared to asymptomatic patients (median 16, IQR = 16-48).ConclusionsThis study showed that 15.6% of anti-SARS-CoV-2 ELISA positive Croatian SOTRs developed NT antibodies indicating protective immunity. Further studies are needed to determine the dynamic of NT antibodies and COVID-19 immunity duration in immunocompromised populations such as LTRs and KTRs.     

Combined Analysis of Anti SARS-CoV-2 IgG and IgM Responses in COVID19 Patients in India

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health problem, India being the second most affected country. The kinetics of antibody response to SARS-CoV-2 in Indian population is not studied yet. To understand serological response in relation to age, gender, time period and severity of disease, Roche Elecsys anti-SARS-CoV-2 test was used which analysed both IgM and IgG. One hundred and three COVID-19 patients were enrolled. Seropositivity was seen in 64% of patients, with 33% at ≤ 7 days, 62% between 8 and 15 days and 81% at ≥ 16 days from the time of admission. Men (65%) showed higher antibody response than women (59%), whereas no difference was observed in seropositivity with respect to age of the patients. Dynamics of antibody responses revealed individual variations. Patients in ICU had higher antibody reactivity with 67% positivity as compared to 60% positivity in non-ICU patients. Kinetics of antibody response during COVID-19 disease varied in relation to gender, age, time period and severity and these factors might play an important role in treatment and control of COVID-19.     

Sequential Profiling of Anti-SARS CoV-2 IgG Antibody in Post COVID-19 Patients

Upon SARS CoV-2 infection, humoral immune system triggers production of anti-SARS CoV-2 IgM and IgG antibodies. Currently, antibodies against SARS CoV-2 spike protein receptor binding domain play a central role in disease protection, making them potential target for in vitro diagnostics applications. This study determines the expression level and sustainability of anti-receptor binding domain (RBD) SARS CoV-2 IgG in post COVID-19 patients. Anti-RBD SARS CoV-2 IgG antibodies in patient serum were analysed by standardised indirect ELISA using SARS CoV-2 spike receptor binding domain protein and HRP conjugated anti-human IgG antibody (anti-h IgG). The study was conducted using 35 adult patient samples with confirmed SARS CoV-2 infection. Additionally, correlation between antibody response after each stage and disease symptoms in post COVID-19 patients were studied. Maximum antibody titre was seen at Day 40 and decreased relatively to Day 180 in antibody positive samples when compared with controls. Overall, more IgG antibody expression is observed in patients who suffered from loss of smell and taste at Day 40. 71% of the positive subjects in this study showed high SARS CoV-2 IgG antibody concentration of above 10 ng/mL and 37% showed strong antibody concentration above 20 ng/mL at the peak of seroconversion.     

Current status of the lateral flow immunoassay for the detection of SARS-CoV-2 in nasopharyngeal swabs

Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and diagnosis of coronavirus disease 2019 (COVID-19) are priorities during the pandemic. Symptomatic and suspected asymptomatic individuals should be tested for COVID-19 to confirm infection and to be excluded from social interactions. As molecular testing capacity is overloaded during the pandemic, rapid antigen tests, such as lateral flow immunoassays (LFIAs), can be a useful tool as they allow greater test availability and obtain results in a very short time. This short review aims to present the analytical properties of LFIAs in the detection of SARS-CoV-2 in nasopharyngeal swabs. Lateral flow immunoassay is a method that combines thin-layer chromatography and indirect immunochemical sandwich method and allows the detection of a specific SARS-CoV-2 antigen in nasopharyngeal swabs. Swab specimens should be adequately collected and tested as soon as possible. Users should pay attention to quality control and possible interferences. Antigen tests for SARS-CoV-2 show high sensitivity and specificity in cases with high viral loads, and should be used up to five days after the onset of the first symptoms of COVID-19. False positive results may be obtained when screening large populations with a low prevalence of COVID-19 infection, while false negative results may happen due to improper specimen collection or insufficient amount of antigen in the specimen. So as to achieve reliable results, a diagnostic accuracy study of a specific rapid antigen test should be performed.     

Review on COVID-19 Etiopathogenesis,Clinical Presentation and Treatment Available with Emphasis on ACE2

In December 2019, Wuhan city in the Hubei province of China reported for the first time a cluster of patients infected with a novel coronavirus, since then there has been an outburst of this disease across the globe affecting millions of human inhabitants. Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), is a member of beta coronavirus family which upon exposure caused a highly infectious disease called novel coronavirus disease-2019 (COVID-19). COVID-19, a probably bat originated disease was declared by World Health Organization (WHO) as a global pandemic in March 2020. Since then, despite rigorous global containment and quarantine efforts, the disease has affected nearly 56,261,952 laboratory confirmed human population and caused deaths of over 1,349,506 lives worldwide. Virus passes in majority through respiratory droplets and then enters lung epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and there it undergoes replication and targeting host cells causing severe pathogenesis. Majority of human population exposed to SARS-CoV-2 having fully functional immune system undergo asymptomatic infection while 5–10% are symptomatic and only 1–2% are critically affected and requires ventilation support. Older people or people with co-morbidities are severely affected by COVID-19. These categories of patients also display cytokine storm due to dysfunctional immune response which brutally destroys the affected organs and may lead to death in some. Real time PCR is still considered as standard method of diagnosis along with other serology, radiological and biochemical investigations. Till date, no specific validated medication is available for the treatment of COVID-19 patients. Thus, this review provides detailed knowledge about the different landscapes of disease incidence, etiopathogenesis, involvement of various organs, diagnostic criteria’s and treatment guidelines followed for management of COVID-19 infection since its inception. In conclusion, extensive research to recognize novel pathways and their cross talk to combat this virus in precarious settings is our future positive hope.     

Long pentraxin 3 as a marker of COVID-19 severity: evidences and perspectives

IntroductionSeveral laboratory tests are characteristically altered in Coronavirus Disease 2019 (COVID-19), but are not totally accurate in predicting the disease outcome. The long pentraxin 3 (PTX3) is quickly released directly at inflammation sites by many immune cell types. Previous studies have shown that PTX3 correlated with disease severity in various inflammatory conditions. Our study investigated the use of PTX3 as a potential marker of COVID-19 severity and compared its performance in detecting a more severe form of the disease with that of routine laboratory parameters.Materials and methodsStored serum samples of RT-PCR confirmed COVID-19 cases that had been obtained at hospital admission were retrospectively analysed. Intensive care unit (ICU) stay was considered a surrogate endpoint of severe COVID-19. Pentraxin 3 was measured by a commercial enzyme-linked immunosorbent assay.ResultsA total of 96 patients were recruited from May 1st, 2020 to June 30th, 2020; 75/96 were transferred to ICU. Pentraxin 3 was higher in ICU vs non-ICU patients (35.86 vs 10.61 ng/mL, P < 0.001). Univariate and multivariate logistic regression models demonstrated that the only significant laboratory predictor of ICU stay was PTX3 (OR: 1.68 (1.19-2.29), P = 0.003), after controlling for comorbidities. The Receiver Operator Characteristic curve analysis showed that PTX3 had a higher accuracy compared to C-reactive protein (CRP), lactate dehydrogenase (LD), ferritin in identifying ICU patients (AUC of PTX3 = 0.98; CRP = 0.66; LD = 0.70; ferritin = 0.67, P < 0.001). A cut-off of PTX3 > 18 ng/mL yielded a sensitivity of 96% and a specificity of 100% in identifying patients requiring ICU.ConclusionHigh values of PTX3 predict a more severe COVID-19.     

Notable and Emerging Variants of SARS-CoV-2 Virus: A Quick Glance

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a highly contagious pathogenic coronavirus to emerge and spread in human populations. Although substantial exertions have been laid to avert spread of COVID-19 by therapeutic and preventive countermeasures, but emergence of SARS-CoV-2 variants as a result of mutations make the infection more ominous. New viral confers a higher nasopharyngeal viral load, increased viral transmissibility, higher infectiousness, immune escape, increased resistance to monoclonal/polyclonal antibodies from convalescence sera/vaccine, and an enhanced virulence. Thus, it is pertinent to monitor evolving mutations and genetic diversity of SARS-CoV-2 as it is decisive for understanding the viral variants. In this review we provide an overview of colloquial nomenclature and the genetic characteristics of different SARS-CoV-2 variants in the context of mutational changes of the circulating strains, transmissibility potential, virulence and infectivity.     

Comparison of diagnostic accuracy for eight SARS-CoV-2 serological assays

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population. We compared the diagnostic performance of eight commercial serological assays for IgA, IgM, and IgG antibodies to the SARS-CoV-2 virus.Materials and methodsThe comparison study was performed on a total of 76 serum samples: 30 SARS-CoV-2 polymerase chain reaction (PCR)-negative and 46 SARS-CoV-2 PCR-positive patients with asymptomatic to severe disease and symptoms duration from 3-30 days. The study included: three rapid lateral flow immunochromatographic assays (LFIC), two enzyme-linked immunosorbent assays (ELISA), and three chemiluminescence immunoassays (CLIA).ResultsAgreement between IgM assays were minimal to moderate (kappa 0.26 to 0.63) and for IgG moderate to excellent (kappa 0.72 to 0.92). Sensitivities improved with > 10 days of symptoms and were: 30% to 89% for IgM; 89% to 100% for IgG; 96% for IgA; 100% for IgA/IgM combination; 96% for total antibodies. Overall specificities were: 90% to 100% for IgM; 85% to 100% for IgG; 90% for IgA; 70% for IgA/IgM combination; 100% for total antibodies. Diagnostic accuracy for IgG ELISA and CIA assays were excellent (AUC ≥ 0.90), without significant difference. IgA showed significantly better diagnostic accuracy than IgM (P < 0.001).ConclusionThere is high variability between IgM assays independently of the assay format, while IgG assays showed moderate to perfect agreement. The appropriate time for testing is crucial for the proper immunity investigation.     

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.     

Serology in COVID: Light the Lantern and Pave the Way to Unexplored…

International Guidelines have voted for PCR as the Gold Standard in COVID diagnosis. Nasoparyngeal swab is the preferred specimen for PCR. It has a high probability of diagnosing early infection. But the diagnostic sensitivity of nasopharyngeal PCR decreases with increase in lapse between the infection and presentation to hospital. This might lead to dire consequences of labelling these patients as false negative, though such patients have been proved to be potentially infective since viral shedding occurs through other body fluids (stools) for long. COVID infection reveals that the IgM antibodies start to appear as early as 5th day of infection and switches over to IgA within 2–3 days. The aim of the study was to see if COVID antibody testing be coupled with PCR for diagnosis especially in patients presenting late (more than 14 days) of onset of infection? And if the antibodies are giving values, hence can them be reported quantitatively rather than in qualitative fashion? The second objective was to see if the COVID antibody levels be used to monitor the disease severity? And if the antibody levels of SARS CoV 2 be used an indicator to monitor the recovery?     

On the syndemic nature of crises: A Freeman perspective

In this paper we draw a parallel between the insights developed within the framework of the current COVID-19 health crisis and the views and insights developed with respect to the long term environmental crisis, the implications for science, technology and innovation (STI) policy, Christopher Freeman analyzed already in the early 90′s. With at the time of writing, the COVID-19 pandemic entering in many countries a third wave with a very differentiated implementation path of vaccination across rich and poor countries, drawing such a parallel remains of course a relatively speculative exercise. Nevertheless, based on the available evidence of the first wave of the pandemic, we feel confident that some lessons from the current health crisis and its parallels with the long-term environmental crisis can be drawn. The COVID-19 pandemic has also been described as a “syndemic”: a term popular in medical anthropology which marries the concept of ‘synergy’ with ‘epidemic’ and provides conceptually an interesting background for these posthumous Freeman reflections on crises. The COVID-19 crisis affects citizens in very different and disproportionate ways. It results not only in rising structural inequalities among social groups and classes, but also among generations. In the paper, we focus on the growing inequality within two particular groups: youngsters and the impact of COVID-19 on learning and the organization of education; and as mirror picture, the elderly many of whom witnessed despite strict confinement in long-term care facilities, high mortality following the COVID-19 outbreak. From a Freeman perspective, these inequality consequences of the current COVID-19 health crisis call for new social STI policies: for a new “corona version” of inclusion versus exclusion.     

疫情之下的数据治理及人工智能应用边界探索

梳理欧美相关法律中的相关条款,专注于分析疫情爆发初期主要国家采用科技抗疫的案例,提出在疫情等公共安全事件突发时,各国应在内部明确数据保护与公共利益优先的临界点,并尽快建立平衡数据保护与公共利益的国际合作机制.     

The rise in preanalytical errors during COVID-19 pandemic

IntroductionThe COVID-19 pandemic has posed several challenges to clinical laboratories across the globe. Amidst the outbreak, errors occurring in the preanalytical phase of sample collection, transport and processing, can further lead to undesirable clinical consequences. Thus, this study was designed with the following objectives: (i) to determine and compare the blood specimen rejection rate of a clinical laboratory and (ii) to characterise and compare the types of preanalytical errors between the pre-pandemic and the pandemic phases.Materials and methodsThis retrospective study was carried out in a trauma-care hospital, presently converted to COVID-19 care centre. Data was collected from (i) pre-pandemic phase: 1^st October 2019 to 23^rd March 2020 and (ii) pandemic phase: 24^th March to 31^st October 2020. Blood specimen rejection rate was calculated as the proportion of blood collection tubes with preanalytical errors out of the total number received, expressed as percentage.ResultsTotal of 107,716 blood specimens were screened of which 43,396 (40.3%) were received during the pandemic. The blood specimen rejection rate during the pandemic was significantly higher than the pre-pandemic phase (3.0% versus 1.1%; P < 0.001). Clotted samples were the commonest source of preanalytical errors in both phases. There was a significant increase in the improperly labelled samples (P < 0.001) and samples with insufficient volume (P < 0.001), whereas, a significant decline in samples with inadequate sample-anticoagulant ratio and haemolysed samples (P < 0.001).ConclusionIn the ongoing pandemic, preanalytical errors and resultant blood specimen rejection rate in the clinical laboratory have significantly increased due to changed logistics. The study highlights the need for corrective steps at various levels to reduce preanalytical errors in order to optimise patient care and resource utilisation.     

Laboratory medicine in pandemic of COVID-19

After the outbreak in China in the year 2019, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) quickly spread around the world causing a protracted pandemic. Approximately one-third of infections appear to be asymptomatic. Symptomatic disease is characterized primarily by symptoms of respiratory tract infection of varying severity. But Coronavirus Disease 2019 (COVID-19) is much more than an acute respiratory disease because SARS-CoV-2 affects many organs inducing a vast number of symptoms such as cardiovascular, neurological, gastrointestinal, dermatological, with numerous complications. Short and long-term effects of infection, severe ones, and especially mild forms of the disease which affect a huge number of patients need to be further investigated. Laboratory medicine has a crucial role in early diagnosis of the disease, recognition of the patients who need hospital care, and close monitoring of hospitalized patients to timely identify associated clinical complications as well as follow-up of patients with long-term COVID-19.     

Can people hear others’ crying?: A computational analysis of help-seeking on Weibo during COVID-19 outbreak in China

Social media like Weibo has become an important platform for people to ask for help during COVID-19 pandemic. Using a complete dataset of help-seeking posts on Weibo during the COVID-19 outbreak in China (N = 3,705,188), this study mapped their characteristics and analyzed their relationship with the epidemic development at the aggregate level, and examined the influential factors to determine whether and the extent the help-seeking crying could be heard at the individual level using computational methods for the first time. It finds that the number of help-seeking posts on Weibo has a Granger causality relationship with the number of confirmed COVID-19 cases with a time lag of eight days. This study then proposes a 3C framework to examine the direct influence of content, context, and connection on the responses (measured by retweets and comments) and assistance that help-seekers might receive as well as their indirect effects on assistance through the mediation of both retweets and comments. The differential influences of content (theme and negative sentiment), context (Super topic community, spatial location of posting, and the period of sending time), and connection (the number of followers, whether mentioning others, and verified status of authors and sharers) have been reported and discussed.     

新冠疫苗核心免疫原的专利分析

本文基于已公布的新冠病毒(COVID-19)疫苗专利或文献,分析了我国目前研发的新型冠状病毒疫苗核心免疫原,着重关注其中可能涉及的S-2P知识产权风险,并对我国利用该技术发展相关疫苗提出了建议.     

Determining the SARS-CoV-2 serological immunoassay test performance indices based on the test results frequency distribution

IntroductionCoronavirus disease 2019 (COVID-19) is known to induce robust antibody response in most of the affected individuals. The objective of the study was to determine if we can harvest the test sensitivity and specificity of a commercial serologic immunoassay merely based on the frequency distribution of the SARS-CoV-2 immunoglobulin (Ig) G concentrations measured in a population-based seroprevalence study.Materials and methodsThe current study was conducted on a subset of a previously published dataset from the canton of Geneva. Data were taken from two non-consecutive weeks (774 samples from May 4-9, and 658 from June 1-6, 2020). Assuming that the frequency distribution of the measured SARS-CoV-2 IgG is binormal (an educated guess), using a non-linear regression, we decomposed the distribution into its two Gaussian components. Based on the obtained regression coefficients, we calculated the prevalence of SARS-CoV-2 infection, the sensitivity and specificity, and the most appropriate cut-off value for the test. The obtained results were compared with those obtained from a validity study and a seroprevalence population-based study.ResultsThe model could predict more than 90% of the variance observed in the SARS-CoV-2 IgG distribution. The results derived from our model were in good agreement with the results obtained from the seroprevalence and validity studies. Altogether 138 of 1432 people had SARS-CoV-2 IgG ≥ 0.90, the cut-off value which maximized the Youden’s index. This translates into a true prevalence of 7.0% (95% confidence interval 5.4% to 8.6%), which is in keeping with the estimated prevalence of 7.7% derived from our model. Our model can provide the true prevalence.ConclusionsHaving an educated guess about the distribution of test results, the test performance indices can be derived with acceptable accuracy merely based on the test results frequency distribution without the need for conducting a validity study and comparing the test results against a gold-standard test.