About the author:
Saurabh Mandal is a Ph.D. student at the Manipal Institute of Regenerative Medicine (MIRM), Manipal Academy of Higher Education (MAHE), Bangalore. He completed his M.Sc. in Biotechnology from VIT University, Vellore. Post his master’s, he worked as a project assistant at the Institute of Nano Science and Technology (INST), Department of Science and Technology (DST), Mohali. At MIRM, Saurabh is currently pursuing his doctoral research focusing broadly on cardiovascular diseases and breast cancer stem cells (bCSCs).
His Ph.D. research centers on generating functional cardiomyocytes. He investigates the roles of small molecules and microRNAs in the differentiation of Wharton’s Jelly-derived mesenchymal stem cells (WJMSCs) into cardiomyocytes. He also evaluates various microRNAs as molecular therapeutics against cancer drug-induced cardiotoxicity. In the area of bCSC research, he has reported the anti-cancer effects of WJMSCs and described the anti-CSC properties of ursolic acid and the role of miR-499a-5p in bCSCs.
India is facing an aggressive second wave of Covid-19, recording the world’s highest number of new coronavirus cases daily. A significant concern in this wave is the surge in asymptomatic cases, prompting experts to call for an accelerated vaccination campaign.
A distinctive symptom in the second wave has been a sudden drop in patients’ blood oxygen levels, leaving them gasping for breath. This surge has led to an unprecedented demand for medical oxygen across the country, exposing the fragile healthcare infrastructure. Reports of oxygen cylinder shortages have caused panic among citizens. Although the government is trying hard to manage the crisis, it continues to face logistical challenges.
Why is low blood oxygen such a critical complication in India’s second wave?
SARS-CoV-2 primarily affects the human respiratory system, damaging the lungs and alveoli, which are responsible for transferring oxygen to red blood cells. The virus harms the alveolar walls, thickening them and obstructing oxygen flow. This leads to inflammation, fluid build-up, and pneumonia.
An Overlooked Clinical Entity
The increase in cases with low oxygen saturation suggests that hypoxemia plays a significant role in disease progression. Hypoxemia is a condition where oxygen levels in the blood drop below normal (95–100%). When levels fall to 92% or lower, it becomes critical. Interestingly, patients may not experience breathlessness, but a pulse oximeter can detect low oxygen levels—a phenomenon known as silent hypoxemia.
A few key studies from India indicate that hypoxemia was present during the first wave as well but was not given due attention. The table below summarizes a few reports:
| Hospital | Date & Time | No. of Patients | Hypoxemia Complication | Drugs Used | References |
|---|---|---|---|---|---|
| Lokmanya Tilak M.M.C., Mumbai | Mar 31–Jul 5, 2020 | 269 | Persistent hypoxia (≤94%) | Tocilizumab | DOI:10.1186/s12879-021-05912-3 |
| RG Kar Medical College, Kolkata | Apr 23, 2020 | 1 | Oxygen saturation 78% | Hydroxychloroquine, Azithromycin | DOI:10.1136/bcr-2020-237207 |
| Vallabhbhai Patel Chest Institute, Delhi | May 8–Jul 3, 2020 | 35 | 51% with hypoxemia | NA | DOI:10.4081/monaldi.2020.1568 |
| Deenanath Mangeshkar Hospital, Pune | Mar 22–May 31, 2020 | 134 | 77.2% with shortness of breath | Multiple drug combinations | DOI:10.5005/jp-journals-10071-23599 |
These studies suggest that India’s medical community may have underestimated hypoxemia’s significance, failing to anticipate its potential for widespread complications.
The Vicious Cycle of Infection
Once SARS-CoV-2 enters the body, it can trigger hypoxemia, which in turn activates Hypoxia-Inducible Factor-1 (HIF-1). HIF-1 increases the expression of the ACE2 receptor, which facilitates viral entry. Moreover, HIF-1 influences coagulation pathways by altering levels of Tissue Factor, PAI-1, thrombomodulin, and others—resulting in blood clots (microvascular thrombosis) that damage vital organs and exacerbate respiratory issues.
Hypoxemia also induces immune cells like macrophages to produce a ‘cytokine storm’—overproduction of inflammatory cytokines (TNF, IL-6, IFN-γ, IL-1β)—leading to severe lung cell injury.
Ultimately, hypoxemia contributes to respiratory distress and oxygen deficiency, aggravating the severity of Covid-19.
What Next?
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Hypoxemia profiling: Using RT-PCR and RNA sequencing to study how gene expression changes under hypoxic conditions during Covid-19 infection.
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Intermittent Hypoxia/Hyperoxia Training (IHHT): A potential therapy using controlled oxygen deprivation (hypoxia) and restoration (hyperoxia) to stimulate alveolar recovery and improve respiratory function.
Regular use of a pulse oximeter (at least thrice a day) and self-proning (MOHFW guide) can also help maintain oxygen levels.
Above all, both central and state governments must ensure oxygen and ventilation availability. Hospitals must be proactive in preparedness, not reactive.
India must accelerate vaccination efforts before hypoxemia compromises vaccine efficacy. Monitoring viral mutations that may favor hypoxemia is also vital to prevent further fatalities.
Written by: Saurabh Mandal
Edited by: Vikramsingh Gujar
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