Pathophysiology of COVID-19 Infection:
SARS-CoV-2 is a single-stranded RNA virus that belongs to the Orthocoronavirinae subfamily. It consists of 16 nonstructural proteins and 4 structural components: spike glycoprotein (S), envelope protein, membrane glycoprotein, and nucleocapsid phosphoprotein (N). However, the viral types can differ across infections at different times and at least 116 mutations have been identified in the beginning of 2021. The S proteins are critical for binding to the host cell surface receptors, whereas the N proteins are essential for viral survival and expansion.
How Virus Works:
SARS-CoV-2 is transmitted through exposure to respiratory droplets from a person with COVID-19 that are inhaled or deposited on the host’s mucous membranes. Respiratory droplets may be airborne or can land on surfaces and objects, which when exposed to a host cell with the entry receptor ACE2 (angiotensin-converting enzyme 2) in the presence of TMPRSS2 (transmembrane protease serine 2) interacting with its spike protein to gain entry. Upon binding to the ACE2 receptor, the SARS-CoV-2 spike protein is activated through proteolytic cleavage by TMPRSS2, inserted into the cell membrane, and fuses the viral and cellular membranes so that transfer of the viral RNA into the host cell cytoplasm can occur, followed by viral replication. The cell then releases the new viruses to infect more cells.
In addition to varying entry routes into host cells, questions remain regarding how SARS-CoV-2 gains access into the central nervous system (CNS), referred to as neurotropism or the ability to infect nerve tissue. The nasal-olfactory nerve route, blood-nervous stem barrier breakdown, blood-nerve barrier or blood-cerebrospinal fluid barrier permeability, lymphatic drainage system of the brain, retrograde transmission from the enteric, lung, or kidney nerve routes, or macrophage/ monocyte cargo routes have all been suggested pathways by which the SARS-CoV-2 virus reaches the CNS.
The immune system has several layers of defense, including killer T cells, which attack cells overcome by viruses. Eventually, new antibodies are created that can neutralize viruses before they infect cells. When reproducing viruses can make mistakes in their genetic material or even reassort with other viruses. Mutation can create new viruses that the immune system can’t recognize.
For now, general precautions (masks, social distancing, and frequent handwashing) remain in place to control the virus, as COVID-19 vaccinations are taking place worldwide. Testing for COVID-19 infection remains a critical component of the COVID-19 detection and surveillance efforts. In the meantime, we have learned to live with the pandemic, which has changed our lives in ways large and small.
Symptoms reported during COVID 19 infection:
- Cough
- Fever
- Anosmia (loss of smell)
- Ageusia (loss of taste)
- Anosmia or ageusia
- Sore throat
- Myalgia
Acute Phase of Illness (Days 0-10 from time of a positive resulte on a COVID-19 test) 5 Symptom Clusters:
- Dyspnea-anxiety (dyspnea, anxiety, tachycardia, headache, and abdominal pain)
- Cough-fatigue (cough, fatigue, muscle pain, dysgeusia, and nausea)
- Fever-headache (fever, headache, muscle pain, tachycardia, and abdominal pain)
- Chest pain-tachycardia (chest pain, tachycardia, anxiety, muscle pain, and insomnia)
- Diarrhea-abdominal pain (diarrhea, abdominal pain, fatigue, nausea, and headache)
The possibility that specific symptoms could correspond with more severe infection has been discussed with symptoms of chest pain, myalgia, and abdominal pain being suggested as precursors to severe illness.
Post-Acute COVID-19 Syndrome:
- Fatigue
- Brain fog
- Headaches
- Numbness/ tingling
- Dysgeusia
- Anosmia
- Myalgias – one of the most common symptoms associated with COVID-19 infection, and it is thought to result from the inflammatory response due to viral invasion with release of cytokines such as interleukin-6 (IL-6) that are known to cause hyperalgesia.
A mechanism by which SARS-CoV-2 infection may lead to the development and maintenance of pain is through CNS activation of microglia, resulting in release of pain-related proinflammatory mediators and initiating inflammasomes.
Theory 1: Post-acute COVID-19 syndrome is caused when fregments of the virus are not cleared and continue to maintain an environment of low-grade inflammation.
Theory 2: Post-acute COVID-19 syndrome is caused by the autoimmune response in which immune cells damage the body’s organs and tissues.
Follow-up Management for individuals affected by COVID 19: Based on the patient’s disease course and symptoms, referrals may be made to pulmonary medicine, cardiology, neurology, and/or kidney specialists for disgnostic evaluation and follow-up care. Psychologists and counselors may be needed to address mental health issues and symptom management, including anxiety and sleep disturbances. Due to potential cardiac and pulmonary sequelae from COVID-19 infection, long-term surveillance and monitoring of symptoms are recommended to detect impaired function and provide treatment when indicated.
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Ivermectin is widely used across the world. Ivermectin is derived from the avermectins, a class of highly active broad-spectrum, antiparasitic agents primarily metabolized by CYP3A4. Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, which leads to an increase in the permeability of cell membranes to chloride ions with hyperpolarization of the nerve or muscle cell. The result is paralysis and death of the parasite. Oral ivermectin is a powerful anthelmintic and insecticide for ruminants, pigs, horses, or humans with action against gastrointestinal parasitic nematodes (roundworms), lung worms, lice, and manga.
As the COVID-19 pandemic continues, articles continue to flood the literature. Scientists, clinicians, patients, and governments face significant challenges in interpreting evidence to drive practices. In addition, disconcerting is the rise in false information in social media as well as the literature that continues to drive vaccine hesitance, fear, and use of unproven products for the prevention and treatment of COVID-19. The current claims for ivermectin have possible antiviral, antimalarial, antimetabolic, and anticancer actions and offers preventative and illness treatment of COVID-19, is only a “possible” opinion, and not yet evidence.
Multiple current registered clinical trials are in progress evaluating ivermectin for the treatment of COVID-19, and during this time, it is necessary to remember pharmacological principles in the design and process of invitro and clinical testing to safely repurpose drugs for use in the COVID-19 pandemic. As the current in vitro studies by Caly et al. in 2020, found that ivermectin reduced viral load nearly 100% at 48 hours in the test tube but only a suggestion that ivermectin could reduce viral loads in infected patients, and however, there is no evidence that ivermectin doses used in the vitro can be replicated in vivo. Recently, use of ivermectin for the prevention or treatment of COVID-19 has demonstrated harmful effects. Healthcare professionals should counsel patients against use of ivermectin as a treatment of COVID-19, emphasizing the potential toxic effects of this drug, including nausea, vomiting, and diarrhea. Overdoses are associated with hypotension and neurologic effects such as decreased consciousness, confusion, hallucinations, seizures, coma, and death.
Again, Ivermectin has approval from the US FDA for human use to treat infections caused by internal and external parasites. Ivermectin is not approved to prevent or treat COVID-19.
References:
Eze, B., & Starkweather, A. (2021) COVID-19 Pain and Commorbid Symptoms
O’Malley, P. A. (2021) Ivermectin – 21st Century “Snake Oil” or Safe and Effective for COVID 19?
