Thoughts on COVID-19 Beyond the Circle of Expertise

A tiny nanoparticle consisting of ribonucleic acid surrounded by a protective protein ring has created havoc in the entire world. First reported in mid-December 2019, the SARS-CoV-2 virus caused COVID-19, as named by WHO. Lighter than air it made its way from Wuhan (China) traveling all over the globe causing panic and pandemic by destroying human lives, exhausting the healthcare system and life as we know. Scientists say that the weight of the virus is about 0.85 atto or about one-millionth of a trillion grams¹!

Original research from Wuhan Scientists demonstrated that – this disease rapidly alters the dynamic parameters of the body like biochemical and immunological specifications, but the accurate picture of the disease emerged a little later that warrants the need for early intervention as the resuscitation efforts proved futile later in the disease The novel nature of the disease, lack of its understanding, and nonexistence of specific COVID-19 anti-viral therapies, raised controversies in the treatment options initially, and despite the voluminous literature piling up in the initial 18 months of the pandemic, more studies were needed to accurately identify risk factors and biomarkers of COVID-19. Many Indian Labs and Institutes in several countries globally are working hard to develop a vaccine to beat the pandemic and to know its epidemiology. I don’t know about epidemiology, but Vaccines have appeared on the global horizon. Reluctantly people have come to accept this as the only solution making the rush for any type of vaccine².

Controversies on its mode of action of drugs and vaccines are keeping the discussions alive among scientists and medico’s for treatment options! Currently, most research about this virus includes the pulmonary, cardiac, and hematologic symptoms of this novel disease. The long-term hematologic, cardiac, and pulmonary effects/complications of COVID-19 are still under research, but the major concern is the efficacy of the vaccine against emerging variants of coronavirus. B.1.617.2 or Delta variant (by WHO) is linked to India’s surge in infection, similarly, other variants are emerging in different countries, that WHO is trying to keep the track of and scientists are working on understanding. Recent focus has been on sequencing the genome of the coronavirus (COVID-19), to establish it’s mutational frequency. Researchers are concerned with the potential of these variants to drive the next wave of the pandemic. WHO has classified certain ‘variants of concern’ of coronavirus based on their transmissibility, harmful change, enhanced virulence, altered clinical presentation, and potential of the limited effectiveness of current therapeutic and preventive (vaccine, etc) measures³.

All viruses acquire minute genetic changes as they reproduce and spread. Those changes rarely impact fitness or the ability to compete. The SARS-CoV-2 variant that circulated in the earliest regional outbreaks lacked the D614G mutation now dominating much of the world. Scientists also warn that experiments in serum aren’t a good guide about variant dodging vaccine-based immunity in the real world, so a dip in potency can be insignificant due to the production of a variety of antibodies secondary to vaccination. Moreover, other parts of the immune system, such as T cells, might not be affected^4,5.

Whether the changes they observed also translate to increased transmissibility in the real world requires additional epidemiological studies. Our earlier therapies were based on symptomatic treatment or the race to prevent and treat this deadly disease had led to the “off-label” re-purposing of drugs such as hydroxychloroquine and lopinavir/ritonavir with the potential for unwanted QT interval prolongation, and a risk of drug-induced sudden cardiac death. Also, no specific drugs to SARS-CoV-2 were confirmed by the official guideline at the very early stage of the epidemic outbreak. Therefore, the front-line doctors treated the patients mainly by their clinical experience alone. However recent times have seen the evolution of better treatment and supply of ventilators and oxygen to the more severe cases in ICU^6,7.

After much investigation - it was confirmed that mostly immuno-compromised persons and individuals with co-morbidities were found to be more vulnerable to COVID-19. Some stats have shown that the most common chronic pre-existing disease in the patients who died were arterial hypertension (76%), followed by ischemic heart disease (37%), atrial fibrillation (26%), and active cancer within the previous 5 years (19%)⁸. Further, reports from some health professionals recorded a surge in diabetic conditions immediately after COVID-19 infections. Additionally, most recent complication of COVID-19 was the increase in Mucormycosis or black fungus in COVID-19 patients, which was attributed to uncontrolled diabetes, surprisingly a report found that 82 of the 101 cases were from India and only 19 were from other countries⁹. A poosibility exists that this increase in mucormycosis could be related to some steam inhalation procedures adopted by some Indian communities to destroy SARS-CoV-2 from their nostrils. Whatever their reasons it is now declared as an epidemic in India . Computational Scientists have identified hundreds of FDA approved drugs as possible candidates for repurposing against COVID-19 given that these drugs are well-established, they could be rapidly advanced into clinical trials to prevent or treat the virus.

Recently a very interesting and important concept has emerged which is worth noting: Scientists in collaboration with Olink are rapidly identifying the protein and pathways involved in COVID-19 pathophysiology to enhance disease understanding (Fig. 1). Each Olink proseek panel allows the simultaneous measurement of 92 markers and is already used in a large number of ongoing and planned COVID-19 studies including prediction, prognosis, and comorbidity across continents. Its 1.3 million protein data points and associated clinical parameters are enabling the wider scientific community to augment previous findings, accelerate the discovery of new therapies in unpinning the mysteries of COVID-19. So far, Olink Explore has succeeded in identifying proteins to predict the severity and outcomes of admitted COVID-19 patients¹⁰.

Current number of planned/ongoing studies using Olink = 47

We have witnessed that this pandemic has brought the world to a standstill. The struggle ahead is long and will not end in a few months. Furthermore, tests that are faster than the current nasopharyngeal swab or serum tests would be desirable, especially in the asymptomatic population. Recently, the US FDA has approved the first coronavirus diagnostic test that can be conducted entirely at the point of care¹¹.

ACKNOWLEDGEMENT

Thanks to Chairman and Management of Bhagwan Mahavir Medical Research Center, Hyderabad and Research Director of BMMRC for their encouragement and support. Thanks to ACSE Team for their continued support and encouragement.

REFERENCES

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