The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2), has led to millions of confirmed cases and deaths worldwide. Efficient diagnostic tools are in high demand, as rapid and large-scale testing plays a pivotal role in patient management and decelerating disease spread. This paper reviews current technologies used to detect SARS-CoV-2 in clinical laboratories as well as advances made for molecular, antigen-based, and immunological point-of-care testing, including recent developments in sensor and biosensor devices. The importance of the timing and type of specimen collection is discussed, along with factors such as disease prevalence, setting, and methods. Details of the mechanisms of action of the various methodologies are presented, along with their application span and known performance characteristics. Diagnostic imaging techniques and biomarkers are also covered, with an emphasis on their use for assessing COVID-19 or monitoring disease severity or complications. While the SARS-CoV-2 literature is rapidly evolving, this review highlights topics of interest that have occurred during the pandemic and the lessons learned throughout. Exploring a broad armamentarium of techniques for detecting SARS-CoV-2 will ensure continued diagnostic support for clinicians, public health, and infection prevention and control for this pandemic and provide advice for future pandemic preparedness.

https://cmr.asm.org/content/cmr/34/3/e00228-20.full.pdf

Tools and Techniques for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/COVID-19 Detection.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) poses several challenges to clinicians. Timely diagnosis and hospitalization, risk stratification, effective utilization of intensive care services, selection of appropriate therapies, monitoring and timely discharge are essential to save the maximum number of lives. Clinical assessment is indispensable, but laboratory markers, or biomarkers, can provide additional, objective information which can significantly impact these components of patient care. COVID-19 is not a localized respiratory infection but a multisystem disease caused by a diffuse systemic process involving a complex interplay of the immunological, inflammatory and coagulative cascades. The understanding of what the virus does to the body and how the body reacts to it has uncovered a gamut of potential biomarkers. This review discusses the different classes of biomarkers - immunological, inflammatory, coagulation, hematological, cardiac, biochemical and miscellaneous - in terms of their pathophysiological basis followed by the current evidence. Differences between children and adults are highlighted. The role of biomarkers in the diagnosis and management of Multisystem Inflammatory Syndrome in Children (MIS-C) is reviewed. The correlation of biomarkers with clinical and radiological features and the viral load, temporal evolution and the effect of treatment remain to be studied in detail. Which biomarker needs to be evaluated when and in whom, and how best this information can contribute to patient care are questions which currently lack convincing answers. With the evidence currently available broad guidelines on the rational use of available biomarkers are presented. Integrating clinical and laboratory data, monitoring trends rather than a single value, correlating with the natural course of the disease and tailoring guidelines to the individual patient and healthcare setting are essential.

/pdf/biomarkers-in-covid-19-an-up-to-date-review-4vazv4jgs1.pdf

Biomarkers in COVID-19: An Up-To-Date Review

Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm.

/pdf/multisystem-inflammatory-syndrome-in-children-and-kawasaki-4piihypv48.pdf

Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison.

Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.

/pdf/sars-cov-2-related-mis-c-a-key-to-the-viral-and-genetic-qhtiv8svb9.pdf

SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?

Although data on the incidence and severity of new coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection showed more significant disease among adults and the elderly, a clinical manifestation characterized by a multisystem inflammatory syndrome was described in children (MIS-C). It was initially thought to be specific to children, but recent reports have shown that it can also occur in adults. MIS-C is characterized by a number of multisystemic manifestations resembling other known previously described illnesses, mainly Kawasaki disease, especially in cases with shock, toxic shock syndrome, and macrophage activation syndrome. Available literature shows that our knowledge of MIS-C is largely incomplete. Its development in strict relation with SARS-CoV-2 infection seems documented and, in most cases, can be considered a post-infectious manifestation secondary to an abnormal immune response for some aspects, similar to that seen in adults several days after SARS-CoV-2 infection. However, in a minority of cases, a clinical picture with symptoms fulfilling criteria for MIS-C diagnosis develops during the acute phase of SARS-CoV-2 infection. It is highly likely that the criteria currently used to diagnose MIS-C are too broad, meaning that children with different diseases are included. As clarity on the pathogenesis of MIS-C is lacking, different therapeutic approaches have been used, but no specific therapy is currently available. Further studies are urgently needed to improve our definition of MIS-C, to define the real impact on child health, and to elucidate the best clinical and therapeutic approach and true prognosis.

/pdf/multisystem-inflammatory-syndrome-in-children-related-to-42qy4ch7av.pdf

Jonathan Weale

Papers

Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation.