COVID-19 has almost paralyzed the world. This pandemic has taken more than 3 million lives worldwide till April 2021 and still continues to kill. It is a highly transmissible disease and has shaken the world’s healthcare structure. Coronavirus was is said to arise from a seafood market from Wuhan city, china in mid-December 2019 and was declared as a “public health emergency of international concern” (PHEIC) on 30th January 2020 and then a pandemic on 11th March 2020.
SARS-CoV-2 or COVID-19 is an RNA beta coronavirus that is linked to severe acute respiratory syndrome (SARS) virus. It spreads through direct person-to-person transmission. After close contact mainly through respiratory droplets produced during a cough or the sneeze, even the asymptomatic patient can shed virus, this virus enters the body through eyes, nose, mouth, or rarely through the perforated eardrum. However, there were studies that showed fico-oral transmission as well. The average incubation period is around 5 days and for how long one person remains infectious is uncertain. As per observations period of infectivity starts 2 days before the onset of symptoms and lasts up to 8 days.
Symptoms of covid-19 (as per WHO)
Most common symptoms:
- Fever
- Dry cough
- Tiredness
Less common symptoms:
- Aches and pains
- Sore throat
- Diarrhea
- Conjunctivitis
- Headache
- Loss of taste or smell
- A rash on the skin, or discoloration of fingers or toes
Serious symptoms:
- Difficulty breathing or shortness of breath
- Chest pain or pressure
- Loss of speech or movement
There are other symptoms as well which are atypical and seen in older, immunosuppressed patients:
- Fatigue
- Reduced alertness
- Reduced mobility
- Loss of appetite
- Delirium
- Absence of fever
A small proportion of covid-19 patients progress to acute respiratory distress syndrome (ARDS) or multiorgan failure. It’s wondering how few people don’t even develop symptoms while some patients deteriorate fast and die is and the explanation is very high levels of cytokines (immune system proteins) in the blood a hyperimmune response called “cytokine storm” leading to irreversible cellular damage and multiorgan failure. Scientists are trying many different ways to target coronavirus, the most common is vaccination. But still, there is evidence of people being infected even after taking the covid vaccine.
What is a cytokine storm?
Our immune system has been naturally set to react and respond upon entry of any outside pathogen into the body. In the case of SARS-CoV-2, there can be a hyper response via activation of inflammatory pathways of the host immune system. This uncontrolled hyper response and flood of cytokines rather than benefitting severely damages the body. Cytokines are a kind of signaling molecule which are protein, peptide, or glycoprotein in nature and are responsible for immune modulation. Cytokine itself means movement related to cell, cyto- meaning cell, and kine-meaning movement. After activation of the immune system, they are produced transiently by several immune cells, macrophages, natural killer cells, dendritic cells, B and T lymphocytes.
These cytokines have the ability to trigger cell death. In case of an infection with coronavirus there occurs rapid dividing and very fast proliferation of virus after its entry into the host cell. This rapid increase in viral load is taken as a threat by the body and our cells start to send signals which lead to activation of the immune system to trigger cell death so that the infection doesn’t spread to another cell. Some researchers have claimed that the number of cytokines produced after COVID-19 infection is as much as 50 times higher than few other deadly viral diseases like Zika or West Nile virus.
For the immune system to get activated after virus invasion there are specific receptors called PRRs (pattern recognition receptors) and they recognize the invading virus by identifying some molecular structures that are characteristic of the virus. PRRs are present on immune cells like macrophages and dendritic cells. The characteristic molecular structures of invading virus are called as PAMPs (pathogen-associated molecular patterns) and once they are recognized by PRRs there occurs an activation of various signaling pathways through which genes encoding inflammatory cytokines are expressed and cytokines are released.
Cytokines rush to the site of infection and attract macrophages, neutrophils, and T cells which have destructive effects on human tissues like endothelial damage, vascular barrier damage, capillary, and alveolar damage and it all leads to multiorgan failure and death. The three most important pro-inflammatory cytokines are interleukin-1 (IL-1), tumor necrotic factor-alpha (TNF- α), and interleukin-6 (IL-6).
In the case of covid as this reaction is happening inside the lungs there occurs acute lung injury, ARDS (acute respiratory distress syndrome), pneumonia and lung failure, and falling saturation leads to death. Till now there is no surety on why some covid-19 affected experience cytokine storm and become severely ill and others don’t, and also there are other emerging causes of covid-19 related deaths such as irregular heartbeat or cardiac arrhythmias.
So, scientist and researches are focusing on how to recognize cytokine storm at an early stage and treating promptly to stop cytokine release or reduce covid-19 related mortality. There are examples and stories on how some severely ill patients even after being on ventilators and ECMO survived after receiving a drug called “Actemra”. Actemra is also known as “tocilizumab” is an interleukin-6 receptor antagonist which helps in reducing IL-6 related damage.
These drugs are declared experimental for covid-19 and their use should be under strict medical supervision as we are still not sure in what manner this drug can help or harm covid-19 patients. Another emerging thought is to block catecholamine release, catecholamine is the chemical that triggers cytokine release, and few are already in support of this as they observed that people who were taking drugs that reduce catecholamines for other reasons (like some blood pressure medicines), less often needed ICU or ventilators.
EXO-CD24
The most recent breakthrough is EXO-CD24. Israel’s Tel Aviv Sour sky Medical Centre (TASMC) brings some hope as they found EXO-CD24 to be almost 97% effective to save lives of moderate to severely ill patients who were in ICUs. EXO-CD24 has been researched for ovarian cancer. In the case of covid-19, it targets the cytokine storm rather than acting as antiviral. It lets cancer cells escape the body’s immune system. It prevented tumor cells from being killed by white blood cells by sending out “don’t eat me” signals. Since then, because of its ability to hide from the immune system researchers believed it can be used in immunotherapy. In covid patients, CD24 can be used to prevent damage from cytokine storms similarly by sending “don’t eat me” signals.
Another challenge was how to deliver this to the body cells and Dr. Arber made a step forward discovery! Dr. Arber used Exosomes to deliver CD24 protein that too directly to the lungs by a very simple mean which is Inhalation. Exo in EXO-CD24 stands for exosome. Exosomes are in all body cells and they carry out the function of transport of material from one cell to another and they have also been claimed to have an effect on immune regulation.
This exosome-assisted delivery of CD24 protein directly to lungs reduced or prevented cytokine storm. Other benefits were easy administration to the patient (once a day inhalation for 5 minutes), economical, and without any significant side effects. 29 out 30 moderate to severely ill patients who received this treatment recovered from covid within three to five days, and the 30th patient also recovered over a longer duration of treatment.
Though this research is still continued for phase 2 trial on the larger group of covid-19 patients for more understanding of its benefits and possible harms, it gives hope to the covid affected the world. And for more widespread use emergency authorization might also be given to this drug.
But till the cure arrives let us not forget to take all mandatory precautions! Please follow covid-19 appropriate behavior, follow SMS that is sanitization, mask, and social distancing. Never panic, remember around 85-90% of patients recover easily without any hospital admission, and also it is very important that you don’t rush unnecessarily to medical centers for testing, not every fever is the corona, and if you have fever isolate yourself, follow a healthy diet and say no to corona!
