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Supplemento Speciale - Pandemia da SARS-CoV-2 (COVID-19)

The value of laboratory medicine in SARS-CoV-2 outbreak
M. Plebani  | 

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to all heathcare systems. It represents, however, a formidabile opportunity to highlight the value of laboratory medicine. Laboratory tests, in fact, play a key role in allowing the etiological diagnosis thanks to the reverse transcription-plymerase chain reaction (rRT-PCR) to detect the virus in nasopharingeal specimes as well as in other samples collected by using a flocked swab. The second essential contribution that laboratory tests are providing encompasses staging, prognostication and therapeutic monitoring of COVID-19. Finally, serological tests play a central role for surveillance purposes, for using plasma containing antibodies from recovered patients as experimental treatment and for better understanding the immune response to SARS-CoV-2 to eventually address vaccine developments.

TAG: SARS-CoV-2   COVID-19   medicina di laboratorio  
Biochimica Clinica
DOI: 10.19186/BC_2020.053
Pubblicato online il: 18.05.2020
Guida sintetica alla diagnostica della malattia da coronavirus 2019 (COVID-19)
Concise guide to coronavirus disease 2019 (COVID-19) diagnostics

Several months after its emergence, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still prepotently disrupting health, societies and economies worldwide. The current approach for diagnosing SARS-CoV-2 remains based on identification of viral RNA by means of molecular biology techniques in upper or lower respiratory tracts specimens. Nevertheless, the development of immune response against the virus may also provide valuable diagnostic information. The paradigmatic kinetics of anti-SARS-CoV-2 antibodies in patients with COVID-19 would allow to conclude that serological testing shall not replace viral RNA detection in diagnosing acute SARS-CoV-2 infection, but may instead remain an essential tool for identifying patients who have been infected and have developed an immune response, as well as for monitoring the progress of herd immunity. For this purpose, the choice of the antigens used for constructing the immunoassays appears critical, as these shall use epitopes towards which neutralizing antibodies could be generated. Other important aspects in serological testing encompass the absence of cross-reactivity with other coronaviruses, the ability to distinguish the antibody class (i.e. IgG, IgA and/or IgM), quantitative assessment, wide range of linearity and low imprecision at diagnostic thresholds. A finalaspect, almost essential for both clinical and public health purposes, is the evidence of analytical and clinical validation before each method enters clinical practice.

TAG: SARS-CoV-2   COVID-19   diagnostica di laboratorio  
Biochimica Clinica
DOI: 10.19186/BC_2020.052
Pubblicato online il: 18.05.2020
Mortalità da COVID-19: una epidemia senza denominatore. Ma conosciamo il numeratore?
COVID-19 death rate: an epidemic without a denominator. But what do we know about the numerator?
L. Zanolla  | 

Since many COVID-19 patients display few, if any, symptoms, assessing infection rate, hospitalization rate, and mortality rate is very challenging. Not only we do not know the denominator of these ratios, but in assessing the mortality rate, we also have problems to estimate the numerator. Between March and April 2020, Italy recorded 42633 excess deaths compared to the average of the five previous years. In the same period, 27 846 deaths were classified as due to COVID-19. Since the international definition of a COVID-19 case requires a microbiological confirmation of the presence of the virus, 34.7% of the excess deaths remain unexplained. Part of these may be COVID-19 deaths, left unconfirmed for the lack of a microbiological swab; but further deaths may be caused by delayed care of other diseases, due to the reluctance of many patients to visit the hospitals during the pandemic. The same apparent underestimation of COVID-19 deaths emerges for other European countries, with more evident differences in the United Kingdom and in the Netherlands. In other countries, the number of excess deaths is lower than the average of the previous years, probably due to a delay in recording deaths. In conclusion, we have uncertainty about the real number of victims of this pandemic; we will improve our knowledge when numbers will be no longer provisional, but there are areas where it is impossible to get the perfect assessment; however these figures are rather important to better face a possible further epidemic wave.

TAG: SARS-CoV-2   COVID-19   dati epidemiologici  
Biochimica Clinica
DOI: 10.19186/BC_2020.077
Pubblicato online il: 15.07.2020
COVID-19 - Opinions
Iper-infiammazione e squilibrio del sistema renina-angiotensina-aldosterone in corso di COVID-19: una nuova ipotesi per il sospetto clinico di ipercoagulabilità e immuno-trombosi microvascolare
Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis.
BM. Henry  |  J. Vikse  |  S. Benoit  |  EJ. Favaloro  |  G. Lippi  | 

Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.

TAG: SARS-CoV-2   COVID-19   ipercoagulabilità  
Biochimica Clinica
DOI: 10.19186/BC_2020.067
Pubblicato online il: 13.07.2020
Diagnosi del diabete gestazionale durante l’emergenza COVID-19: semplificazione del protocollo
TAG: SARS-CoV-2   COVID-19   diabete gestazionale  
Biochimica Clinica
DOI: 10.19186/BC_2020.055
Pubblicato online il: 25.05.2020
Importanza dello screening per il deficit di G6PD durante l’emergenza Covid-19
Screening for G6PD deficit during COVID-19 emergency

Hydroxychloroquine, a well known anti-malaria drug, is now widely used in the early treatment of patients infected with SARS-CoV-2. Since chloroquine and its derivatives may cause an acute hemolytic crisis in subjects with glucose 6-phoshpate dehydrogenase (G6PD) deficiency, with different penetrance in men and in women, we recommend that: a) before using these drugs, especially in elderly subjects, the G6PD catalytic activity should be quantitatively estimated; b) all the G6PD deficient subjects treated with chloroquine and its derivatives have to be characterized at molecular level, in order to identify G6PD deficient subjects in their families; c) to be on the safe side, the use of hydoxycholoroquine or chloroquine in carriers of severe G6PD deficiency, and infected by SARS-CoV-2, should be avoided; if treated, the patients should be alerted on the possible hemolytic risks, and care should be paid to the best laboratory indicators of such episodes (whole blood cell count, serum bilirubin, serum LDH, and hemoglobinuria).

TAG: SARS-CoV-2   COVID-19   G6PD  
Biochimica Clinica
DOI: 10.19186/BC_2020.059
Pubblicato online il: 29.05.2020
COVID-19 e coagulazione: un legame indissolubile
TAG: SARS-CoV-2   COVID-19   coagulazione  
Biochimica Clinica
DOI: 10.19186/BC_2020.071
Pubblicato online il: 07.08.2020
Alterazioni dei meccanismi dell’emostasi in corso di infezione da SARS-CoV-2 (COVID-19)
Alterations of hemostasis during SARS-CoV-2 infection (COVID-19)

The corona virus infection (named COVID-19), first identified in December 2019 in Wuhan, China, has contributed to significant mortality in several countries with the number of infected cases increasing exponentially worldwide, in particular in Italy and in the USA. The majority of the most severely ill patients initially presents with single organ failure (i.e. severe respiratory syndrome), but some of them progress to more systemic disease and multiple organ failure (MOF). One of the most significant poor prognostic features in these patients is the development of coagulopathy, similarly to patients who develop sepsis from various infectious agents. Coagulopathy in patients with COVID-19 may be asymptomatic but, in some cases, the septic state may evolve into Sepsis-Induced Coagulopathy (SIC) and overt Disseminated Intravascular Coagulopathy (DIC). In patients with severe clinical manifestations, a cytokine storm occurs that contributes to triggering a greater imbalance of the hemostatic mechanisms by promoting the development of microthrombosis at the level of the pulmonary endothelium. The effectiveness of anticoagulant therapies, performed primarily with low-molecular weight heparin, is greater the earlier the diagnosis is made. This is possible through the adoption of diagnostic protocols that include laboratory tests and clinical scores. The laboratory tests suggested for this purpose by the available Guidelines are prothrombin time, platelet count, D-dimer and fibrinogen. D-dimer appears to be the parameter with the greatest prognostic significance since it also allows a stratification of the thrombotic risk.

TAG: SARS-CoV-2   COVID-19   emostasi  
Biochimica Clinica
DOI: 10.19186/BC_2020.056
Pubblicato online il: 01.06.2020
Il ruolo del laboratorio di coagulazione nel monitoraggio del trattamento eparinico dei pazienti con COVID-19
The role of laboratory monitoring in heparin treatment of COVID-19 patients

Coronavirus disease 2019 (COVID-19) can be associated with serious clinical complications such as acute respiratory distress syndrome (ARDS), sepsis and multiple organ failure (MOF). A key event in the pathophysiology of ARDS is immunothrombosis, a process initiated by the innate immune system that provides a first line of defense for local control of infection. In its physiological form, immunothrombosis is intended to facilitate the recognition, containment and destruction of pathogens, thus protecting the integrity of the host without inducing significant collateral damage. The cytokine storm that occurs during COVID-19 induces often venous and arterial thrombotic events affecting different organs, not limited to the respiratory system. It is therefore necessary to introduce an anticoagulant treatment in patients with COVID-19 to prevent the onset and the extension of thrombotic events. The low molecular weight heparin (LMWH) is the first-choice drug recommended by the main international scientific societies; alternatively, unfractionated heparin (UFH) or fondaparinux can be used. The dosage of these drugs in patients with COVID-19 is still under discussion. The coagulation testing plays an important role in monitoring the efficacy and safety of UFH treatment; in the case of LMWHs, these usually do not require monitoring but, if alterations of renal function occur, it is important to perform the chromogenic determinations of the anti-Xa activity, paying a particular attention to the timing of sampling, the pre-analytical variables, calibration of the test and reference ranges.

TAG: SARS-CoV-2   COVID-19   trattamento eparinico  
Biochimica Clinica
DOI: 10.19186/BC_2020.073
Pubblicato online il: 13.07.2020
Al “cuore” del quadro clinico di COVID-19
To the “heart” of the clinical picture of COVID-19

Several studies document cardiac involvement in COVID-19 patients, as evidenced by cardiac biomarkers elevation. Hospitalized patients with cardiac involvement have a poorer prognosis, in terms of need for intensive care unit, or mortality. This paper provides a review of the wealth of literature on heart involvement in COVID 19. The majority of the available papers reports data from the Chinese experience and it is not clear at the moment whether the observations are related to really different populations of patients. The mechanism of the cardiac injury is likely multifactorial. There could be direct myocardial damage by the virus, but the few heart histologic specimens available do not evidence the presence of virus RNA in myocytes. The infection in the lungs may produce a cytokine storm which in turn could damage myocytes. Coagulation system is also affected by COVID-19: D-dimer is increased, while platelets are reduced in most studies, and both parameters relate directly with the risk of death. These alterations are probably the cause of the many cases of pulmonary embolism, venous thromboembolisms, and arterial embolism reported. Hypertension and previous cardiovascular diseases are also likely involved in the severity of the observed cardiac injury. Although all these mechanisms may play a role in cardiac involvement, the severe lung infection alone could justify cardiac damage, due to the simultaneous reduced supply and increased demand of myocardial oxygen. We still know very little about this new viral disease, but as knowledge is accumulating, the medical community will pinpoint the mechanism of cardiac involvement and find the optimal strategy to prevent its severe consequences.

TAG: SARS-CoV-2   COVID-19   troponine cardiache  
Biochimica Clinica
DOI: 10.19186/BC_2020.063
Pubblicato online il: 13.07.2020
Valutazione di IgG e IgM anti-SARS-CoV-2 su Maglumi 800 (Snibe)
Evaluation of Anti-SARS-CoV-2 immunoglobulin G and M on Snibe Maglumi 800

Introduction: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a due to new beta-coronavirus causing the pandemic called Coronavirus disease 2019 (COVID-19). The evaluation of the presence of immunoglobulin G and M anti-SARS-CoV-2 (IgG and IgM) is important to understand the epidemiology of the disease and to confirm the presence of the disease when clinical signs are present, but RNA is not detected.
Methods: leftover serum samples from different types of patients were used: sera from biobank collected in 2018 as negative controls; patients recovering from the disease as positive controls; patients presenting at the Emergency Room with a positive rhino-pharyngeal swab; patients in Intensive Care Units. Anti-SARS-CoV-2 IgG and IgM were measured with MAGLUMI 2019-nCoV IgM/IgG Kits on Maglumi 800.
Results: one out of 61 expected negative resulted positive, and 2 were borderline for IgG (95% specificity, 95%CI 89.6-100), 1 positive for IgM (98.4% specificity, 95%CI 95.2-100); one out of 41 expected IgG positive resulted negative (97.6% sensitivity, 95%CI 92.8-100). All the 13 Intensive Care patients were positive for IgG, 11 for IgM. IgG were negative in 50.9% of the 55 swab positive from Emergency Room patients, while IgM were negative in 87.3%.
Discussion: sensitivity and specificity of the test appear good for IgG, some false positive is expected and low antibody titles in subjects with no disease story should be rechecked with an alternative method. IgM show a good specificity, but the unexpected low percentage of positivity in Emergency Room patients compared to IgG, pose some relevant doubts on the sensitivity of the test.

TAG: SARS-CoV-2   COVID-19   indagini epidemiologiche  
Biochimica Clinica
DOI: 10.19186/BC_2020.054
Pubblicato online il: 25.05.2020
Prevalenza di anticorpi anti-SARS-CoV-2 in una popolazione di operatori sanitari e amministrativi di un ospedale toscano
Serum prevalence of anti-SARS-CoV-2 antibody in a population of health care and administrative workers in a hospital in Tuscany (Italy).
F. Balboni  |  A. Baldini  |  G. Forgeschi  |  F. Sequi  |  S. Burbui  |  G. Lippi  | 

Introduction: the challenges due to COVID-19 pandemic forced scientific community to focus their efforts to improve diagnosis and management of patients. The recognized gold standard for the diagnosis is the reverse transcription polymerase chain reaction (RT-PCR) on orofaringeal and nasal swabs. Recently, the antibody detection surge to attention with the aim of estimating the epidemiological impact of the pandemic.
Methods: the Screen Test COVID-19 2019-nCov IgG/IgM (Screen Italia, Perugia, Italy) an immunochromatographic lateral flow test has been used to assess the immunological status of 356 asymptomatic healthcare and administrative workers of our hospital.
Results: only 26 (7.3%) of the screened subjects was positive for IgM and/or IgG anti SARS-CoV-2 virus although the beginning of the epidemic in Tuscany can be dated two months before. The RT-PCR performed on these samples revealed that only 5 (19%) of them were positive for viral RNA on orofaringeal swab.
Conclusions: antibody detection will be of great value in the near future to assess global pandemic impact on population and to drive health policy for the lock down release.

TAG: SARS-CoV-2   COVID-19   screening  
Biochimica Clinica
DOI: 10.19186/BC_2020.057
Pubblicato online il: 01.06.2020
Determinazione degli anticorpi IgM e IgG anti-SARS-CoV-2 mediante piattaforma iFlash1800 CLIA in una casistica italiana
Detection of IgG and IgM anti-SARS-CoV-2 by iFlash1800 CLIA analyser in an Italian population

Introduction: World Health Organization guidance dated 17 January 2020 indicates the need to associate the detection of antibodies anti-SARS-CoV-2 to real time reverse transcriptase PCR test (rRT-PCR) for the diagnosis of the new coronavirus infection. Aim of this study is to acquire information about the prevalence of IgG and IgM anti-SARS-CoV-2 antibodies in a population of health workers (control group) and in patients affected by COVID-19.
Methods: the control group includes 190 asymptomatic health workers; the patient group includes 44 affected patients. Serum IgM and IgG antibodies to SARS-CoV-2 were measured by using iFlash1800, a fully automatic chemiluminescence immunoassay analyser. rRT-PCR was performed with CFX96 TouchTM system (Bio-Rad, Hercules, California, USA) and LightCycler 480 Real-Time PCR System (Roche Diagnostics, Mannheim, Germania).
Results 186 out of 190 asymptomatic health workers were negative for rRT-PCR. Among these, 3 were positive for IgG antibodies (98% specificity, 95%CI 96-99) and 5 for IgM antibodies (97,3% specificity, 95%CI 95-98). 40 out of 44 patients were positive for rRT-PCR. Among these, 39 were positive for IgG (97,5 sensibility, 95%CI 91-100); 30 were positive for IgM anti-SARS-CoV-2 (75%).
Discussion: rRT-PCR is a routine method for the diagnosis and confirmation of COVID-19 infection. However, false negative and positive results from rRT-PCR were found in a number of healthcare workers. They were possibly due to sample collection, storage conditions, difference of virus load in the infection site, RNA extraction methods and kit quality, contaminations and test performed in patients from areas with low prevalence of the infection. These rRT-PCR failures can determine an important negative impact on the diagnosis. The high sensitivity of IgG and IgM detection in the patient group indicates that serological tests are of great help in improving the clinical sensitivity of COVID-19 diagnosis. Our results show that anti-SARS-CoV-2 IgG and IgM antibody detection is a very effective tool, in association with molecular test for diagnosis, and epidemiologic studies of this severe disease.

TAG: G6PD   NADPH   chemiluminescenza  
Biochimica Clinica
DOI: 10.19186/BC_2020.073
Pubblicato online il: 13.07.2020