Page 128 - CSIR-IGIB Annual Report 2020-21

with a change in body lipid composition. Because method of choice to detect infected individuals
of the diversity in lipid species within a biological although there were reports of false positive and
system, liquid chromatography-mass negative results. This necessitated the
spectrometry (LCMS/MS) emerged as a powerful development of other methods for detection of
tool for identification and quantification of lipids. this virus with high sensitivity and specificity. The
It is important to identify different lipid species for other issue was that most of the cases were
better understanding the role of vitamin B12 asymptomatic and were not tested and hence the
deficiency in lipid metabolism and further true extent of the disease prevalence could not be
identification of potential lipid biomarkers ascertained. Most importantly, the human
associated with coronary artery disease (CAD) in response to the virus was not known, which could
the Indian population. We developed a targeted- help in prognosis of the disease.
mass spectrometry-based method for large-scale
lipidomics using a combination of variable Using the LC-MS/MS based proteomics technique
retention time window and relative dwell time we developed a sMRM method to detect viral
weightage. Using this, we detected more than peptides from spike protein and replicase
1000 lipid species with the limit of detection polyprotein 1ab on a triple-quadrupole mass
varying from femtomolar to nanomolar range and spectrometer from naso-oropharyngeal swab
the coefficient of variance <30% for 849 lipid samples with a high sensitivity of 90.5% and a
species. This method enabled identification of by 100% specificity. To understand the host response
far the largest number of lipid species with to infection, we identified proteins, metabolites
structural isomers in a single experiment (24 and lipids using the LC-MS/MS based approach.
minutes). Using this method, we found that the Plasma samples were collected from COVID
levels of lipids with ω-3 fatty acid chains decreased patients with asymptomatic, mild, and severe
while those with ω-6 increased in vitamin B12 symptoms at the day of their admission to hospital
deficiency. Further, we found the accumulation of (day 0), day 3 and day 7. We could quantitate 183
triacylglycerides having long chain plasma proteins from these samples with some
polyunsaturated fatty acid in CAD patients (n=92), proteins showing specific patterns in their
suggesting defect in its hydrolysis/transport. expression during the course of disease in
Diacylglycerol, a well-known precursor of asymptomatic to severe cases. Few acyl carnitines
phospholipids, was found to be higher in CAD also show their importance in COVID-19 as
patients, suggesting increase in synthesis of represented in the untargeted metabolomics
phospholipids. SM, known to regulate LCAT, was data. These signatures could be useful in
also high in CAD. Phospholipids including PC were predicting the disease prognosis.
high and LysoPC was low, suggesting the During the pandemic, we built a longitudinal
regulation of phosphocholines through LCAT cohort of CSIR personnel (CSIR cohort) and using
during reverse cholesterol pathway. serology assay estimated the burden of the
Cardiovascular diseases are a major public health disease and also evaluated the stability of the
problem worldwide especially in developing antibodies. We found that by September 2020
countries like India. Conventional markers do not around 10 % of the individuals were sero-positive
add prognostic value to disease identification for anti-SARS-CoV-2 antibody and almost three-
therefore it is important to identify newer markers fourth of them were asymptomatic. The
for complex cardio-metabolic diseases. seropositivity increased to 28% during Feb-March
2021. We also found that about 20% individuals
SARS-CoV-2 detection, biomarker discovery and lost the neutralizing capacity within 6 months of
pan India sero-epidemiological survey for anti- infection.
SARS-CoV-2 antibody
The world is in the midst of the COVID 19 In our effort to understand the systemic outcome
pandemic since April 2020. RT PCR was the of COVID-19 infection, an integrated analysis of

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