Treatment Options for COVID-19 Patients

5 min readMar 1, 2021

Treatment options greatly depend on identifying the severity of symptoms in patients suffering from COVID-19. A closer look into the pathogenesis of the disease would determine the stage of progression.

Progression from a cell biology perspective is generally divided into three stages, where the severity and risk of mortality increase with every stage.

STAGE I: Asymptomatic State (1–2 days)

The inhaled SARS-Cov-2 virus infects epithelial cells in the nasal cavity & starts replicating. ACE2 is the main receptor for the virus causing COVID-19, and it is a protein found on the surface of many cell types.

The immune response is limited. While the viral burden is low, the patient is infectious. RT-PCR useful to predict viral load and subsequent infectivity as well as the clinical course.

Possible treatment options include:

Therapies to increase immune response
Therapies to disrupt viral genes

STAGE II: Conducting Airway Response (3–7 days)

A more robust innate immune response is triggered as the virus propagates & migrates down the respiratory tract. The level of CXCL10 (or other innate response cytokines) from infected cells may be predictive of the subsequent clinical course.

Taking into consideration that the disease is mild for more than 80% of infected patients. Possible treatment options include:

Therapies to sustain the immune response
Therapies to disrupt viral genes

STAGE III Progression to ARDS (8–12 days)

20% of infected patients will progress to Stage III. The virus reaches the gas exchange units of the lung, infecting the alveolar Type II cells. High amounts of virus released, infecting adjacent units. Subsequent cell apoptosis (and death) triggers epithelial regeneration, activating coagulation pathways.

This leads to hypoxia (a condition where the body is deprived of adequate oxygen supply at the tissue level) and acute respiratory distress syndrome (ARDS). Ground-glass opacity (GGO) can be seen in x-rays and CT scans.

Aberrant wound healing may lead to more severe scarring and fibrosis than other forms of ARDS. Possible treatment options include:

Immunomodulatory therapies to acquire an optimal immune response
Therapies to disrupt viral genes

The Concept of Antiviral Therapies

Antiviral drugs are a class of medication used specifically for treating viral infections. They work by disrupting a specific step in the virus life cycle.

They are different from antibiotics, which are ineffective when treating infections caused by viruses.

Example of antiviral therapies for various diseases. Credit: medillsb.com

Current COVID-19 therapies in development include:

RNA Drugs. A promising therapeutic option that targets viral genes and proteins. It can be used to invoke an immune response. Known mechanisms of RNA drugs:

Blocking the virus from attaching onto the patient’s cell wall by using artificial RNA (aptamers) that bind to viral protein receptors;
Blocking the expression of viral genes by using antisense oligonucleotides (ASO);
Preventing viral replication by using RNA interference molecules (RNAi) that triggers the degradation of viral mRNA which subsequently prevents infected cells from building more viruses.

Known RNA drugs in development for treating COVID-19 include remdesivir (by Gilead Sciences) and favipiravir (marketed as ‘Avigan’ by Fujifilm Toyama).

Polyclonal & Monoclonal Antibodies. Monoclonal antibodies (mAbs) are man-made proteins that act like human antibodies in the immune system. They are made by identical immune cells that are all clones of a unique parent cell.

In the case of COVID-19, mAbs can block the path of coronavirus from attaching onto host cells. In general, antibodies can neutralize viral infectivity by:

Interfering with the virus binding to cell receptors
Blocking uptake of the virus into the host cell
Prevent the uncoating of viral genes
Aggregating virus particles

Comparison between the absence of antibodies (LEFT) and the presence of neutralizing antibodies (RIGHT). Credit: virology.ws

Given the speciﬁcity, consistency & minimal cross-reactivity when compared to polyclonal antibodies, mAbs is the preferred technology platform. It can also be used as an immunomodulatory agent (a substance that stimulates or suppresses the immune system to help the body fight diseases).

Convalescent Plasma. The plasma of COVID-19 survivors contains speciﬁc antibodies and immune agents, making it a viable treatment option for other COVID-19 patients.

The idea is simple: when a patient survives a coronavirus infection, his/her blood becomes ﬁlled with antibody proteins that can help other patients ﬁght the virus. In which case the plasma, or serum (the yellowish liquid component of our blood) can be extracted.

Use of convalescent plasma and its therapeutic effects. Credit: ScienceDirect

Healthcare researchers believe that it can be an eﬀective (albeit rather ‘alternative’) treatment for patients hospitalized with COVID-19 or those who are at high risk of exposure, like healthcare workers.

Stage III Implications: Cytokine Storm

Activation of coagulation pathways during immune response results in overproduction of proinﬂammatory cytokines (such as IL-6 and IL-1β) which leads to multi-organ injury or failure, and eventually death.

Immunomodulatory treatment is critical to achieving the right level of immune response in severe/critical patients. Direct oral anticoagulants (anti-thrombin & anti-factor Xa) might be able to reduce micro thrombosis (obstruction in blood vessels), lung injury, and associated poor outcomes.

Actemra® by Roche (also known as tocilizumab) is a humanized mAb and can be regarded as an immunomodulatory agent, as it can interrupt cytokine release syndrome (CRS).