key: cord-0043380-xc6sz085
authors: Gharote, Mukul Arvind
title: Role of Nasopharyngeal lactate dehydrogenase as a possible economical mass screening test for the detection and segregation of SARS-CoV-2 (COVID-19) cases in India
date: 2020-04-30
journal: Indian J Med Sci
DOI: 10.25259/ijms_25_2020
sha: 182f97b5c1417220a7473fdf4fbf572a668a34c3
doc_id: 43380
cord_uid: xc6sz085

COVID-19 pandemic is affecting almost every country in the world. Every country must test all the individuals with suspected clinical presentation of COVID-19. Unfortunately, the symptoms are mild and often the incubation period is 5–7 days. Hence, the detection of COVID-19 takes time and is costly even, many resource-constrained nations are not testing their citizens due to cost incurred. That is why we need an economical mass screening test to detect and help the health-care system to segregate cases needing their attention. Nasopharyngeal lactate dehydrogenase (LDH) is raised in viral upper respiratory infections, it can be easily tested and raised serum LDH in addition to nasopharyngeal LDH can predict stormy outcome of disease. Such prediction will help health-care system for effective resource allocation.

Lactate dehydrogenase (LDH) is a membrane associated enzyme and is released in extracellular environment during inflammation as a result of cellular injury. [1] Few studies established direct correlation between concentrations of LDH and acute-phase cytokines. LDH is a reliable biomarker of acute inflammatory injury associated with upper respiratory infections (URI). Unlike LDH, these cytokines in themselves do not directly represent cellular injury -the acute-phase cytokines are the mediators of inflammation, whereas LDH is the product of inflammatory injury. [2] LDH is enzyme released in the bronchoalveolar space on damage of cytoplasmic cell membrane. Elevated LDH is also indicator of underlying lung injury and inflammation. [3] Serum LDH elevation had direct links to prognosis in this outbreak as well. Cohort of 138 cases of COVID-19 reported LDH elevation in 38% which had 4% mortality [7] whereas cohort of 99 cases reported having LDH elevation in 75% which had 11% mortality. Elevated LDH in the previous studies also was reported to be associated with bad prognosis as was seen in 2003 outbreak. [4] NASOPHARYNGEAL LDH, VIRAL URI, AND COVID-19

Above discussion makes one thing clear that elevated LDH is a marker of viral cytolysis and poor prognosis. Now coming to viral URI and elevated LDH, in a study done on pediatric cases, elevated LDH in nasopharyngeal sample was associated with increased chances of acute otitis media (AOM). LDH was indicator of nasopharyngeal injury and inflammation, leading to Eustachian tube damage which resulted in AOM. [2] COVID-19 starts as URI and in majority presents with same complaints few progresses onto lung injury and eventually ARDS. COVID-19 can be screened by doing nasopharyngeal LDH, even we can predict poor outcome on the basis of nasopharyngeal LDH and serum LDH.

Both nasopharyngeal LDH and serum LDH are economical tests which can help our health-care personnel to segregate patient who can have stormy course of disease. Nasopharyngeal aspirate was used as a surrogate for the lower respiratory tract, as several studies confirm virus titers obtained in nasal washes correlate with disease activity in the lower airways. [8] In fact, cytopathic effects of respiratory syncytial viruses are detected earlier and are economical than isolation of virus itself. [9] WHAT SHOULD BE THE IDEAL TECHNIQUE TO DETECT NASOPHARYNGEAL LDH? Nasal fluid is admixed with lacrimal fluid and water condenses at the mucosal surface during expiration can make an additional contribution.

Nasal secretions contain minute amounts of cytokines and other inflammatory mediators expressed by various epithelial and non-epithelial cells. Because cytokines play a dominant role in the pathophysiology of airway disease, interest has focused on cytokine determinations in nasal secretions. Data on cytokine concentration obtained with different sampling techniques may differ by more than an order of magnitude. [10] Polyurethane foam sampler technique is one of the most reliable and easy methods of detecting nasopharyngeal LDH. [11] 

For a resource-constrained country like ours and considering the demography, the task of applying COVID-19 to all the residents of India will be a daunting task on health care workers, not only that but the cost of such herculean exercise will be exorbitant! Practically, it is impossible. Our nation is being feared of entering Stage III of pandemic, i.e., community spread is highly likely. In such phase contact, tracing may not be possible for health-care system to track. In this phase, it is advisable to test each and every suspected case and isolate them and treat. 

Based on above discussion and evidences, we can apply nasopharyngeal LDH as economical option to do mass screening and it will also help us in segregation of cases requiring urgent health-care support. No study has been done on nasopharyngeal LDH and COVID-19.

Hence, we do not know the false negativity of such approach, but given the cost of applying COVID-19 test kit on each and every suspected URI cases in India, we can give a serious thought to nasopharyngeal LDH.

Patient's consent not required as there are no patients in this study.

Nil.

ere are no conflicts of interest.

be COVID-19 positive as well. While others may be having seasonal flu, without much damage, they may be very well treated at home, of course in home isolation. is will save lot of exchequers money and help the health-care systems to identify potential patients needing health-care assistance and ventilator support as well. Nasopharyngeal LDH -a marker of tissue damage can help us in finding and segregating patients of COVID-19, at much lesser cost as would have been incurred, had the COVID-19 kits applied on every person with URI.

For any screening test to be effective, false-negative rate should be minimal. Based on the study done on nasopharyngeal secretion LDH and development of AOM, higher nasopharyngeal secretion LDH was associated with high chances of AOM, we suggest that LDH-3 and LDH-4 are higher in nasopharyngeal secretion. [12] Furthermore, viral URI causes more rise in LDH as compared to bacterial. [13] Based on the study done by Ede Lin, 2013, [2] nasopharyngeal LDH and its association with various viruses are mentioned in Table 1 . [2] If we study this Table 1 carefully then, you can find that the mean LDH and median LDH concentration in mU/ml was higher in coronavirus patients, we agree that the study population was small and hence is limitation but still given the severity of COVID-19, it is bound to have raised LDH at presentation.

Even the standard deviation is also lower, indicating that the Gaussian curve is steep in case of coronavirus as compared to other viruses.

Serum lactate dehydrogenase isoenzyme and total lactate dehydrogenase values in health and disease, and clinical evaluation of these tests by means of discriminant analysis

Lactate dehydrogenase as a marker of nasopharyngeal inflammatory injury during viral upper respiratory infection: Implications for acute otitis media

Diagnosis of Pneumocystis pneumonia: Evaluation of four serologic biomarkers

Severe acute respiratory syndrome: Clinical outcome and prognostic correlates

Lactate dehydrogenase as a biomarker for prediction of refractory mycoplasma pneumoniae pneumonia in children

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity

Clinically useful method for the isolation of respiratory syncytial virus

Quantification of cytokines and inflammatory mediators in samples of nasopharyngeal secretions with unknown dilution

Biological markers in nasal secretions

How to cite this article: Gharote MA. Role of Nasopharyngeal lactate dehydrogenase as a possible economical mass screening test for the detection and segregation of SARS-CoV-2 (COVID-19) cases in India

e isoenzyme pattern of lactatedehydrogenase in nasal secretions

e enzymology of nasal secretion