COVID 2019—Understanding the potential treatment options

The coronavirus disease was first identified and flagged down as an outbreak in late 2019 (December 31^st, 2019, to be exact). Reported first in Wuhan City, Hubei Province, China, the novel coronavirus—now referred to as SAR-CoV-2.

The virus—which was declared a global health emergency on January 30, 2020, and a full-blown global pandemic on March 11, 2020— has now spread and has become an international pandemic spanning the globe. This resulted in the first global pandemic to arise since the long stretch of absence following the 2009 H1N1 influenza.

The world continues to be deeply affected by the COVID-19 pandemic. At the time of publication, a reported 21.7 million cases were confirmed with a climbing death rate of about 776,000. In the United States alone, a total of 5,382,125 cases and 169,350 deaths were reported by the CDC.

As the months continue to tick by, the number of cases continues to rise—and the death rates continue to rise, too. Why? Because the novel coronavirus responsible for the pandemic continues to largely remain a mystery. Though questions are continuously being answered about sources, spread, and transmissibility, the answers surrounding treatment and prevention continue to evade researchers, scientists, medical professionals, and more.

Currently, there are no solid answers about therapy, treatment, or clinical preventatives approaches to help stop the spread of SARS-Cov-2.

Still, that doesn’t mean research, studies, and other work isn’t being done. Researchers, scientists, and medical professionals are consistently working to uncover treatment options that could suffice as preventative or therapeutic measures.

And while the answers still aren’t readily available, there are a few suggested treatments and investigational therapies that some professionals believe could be the key to preventing or treating SARS-CoV-2 and effectively helping to end the COVID-19 pandemic.

What Exactly is the Coronavirus? A Brief Background on COVID-19

But before we dive into a few of the investigational treatment and management options that are currently being researched, it’s crucial to ensure there’s a solid understanding of what the coronavirus disease 2019 (COVID-19) is, where it comes from, and how it effectively caused one of the most mysterious pandemics in history.

COVID-19—an abbreviation for Coronavirus disease 2019—is an illness that is caused by a novel coronavirus known as severe acute respiratory syndrome coronavirus. Often, this is referred to as SARS-CoV-2.

Coronaviruses themselves comprise an entire family of viruses—only a handful of them (7) are known to cause disease in humans while others invest animals. Coronaviruses can sometimes infect animals and then evolve as viruses that can affect humans.

This specific disease caused by this specific coronavirus (SARS-Cov-2) is characterized by symptoms that include:

Cough
Headache
Fever or chills
Difficulty breathing
Shortness of breath
Diarrhea
Congestion
Runny nose
Sore throat
Vomiting
Muscle aches
Fatigue

Still, however, some of those infected find that they do not experience symptoms—showing that this virus, while highly transmittable, can manifest itself as asymptomatic.

Coronavirus Disease 2019 (COVID-19) Prevention, Treatment, and Management

Treatment and management of coronavirus continue to elude professionals, and while there are no preventative measures that can guarantee a person won’t catch COVID-19, there are a few preventative measures people can take in order to mitigate the risk of catching the disease.

Prevention: Understanding How to Minimize the Spread

Currently, no vaccine exists for SARS-CoV-2, so experts believe that avoidance is the best, most effective method for deterrence. This typically includes a few general measures that you’d take to prevent other viral respiratory infections, including actions like:

Avoiding touching nose, mouth, face, and eyes with unwashed, unsterilized hands
Avoiding sick people and contact with most of the general public
Handwashing with soap and water for 20+ seconds as well as supplementing with alcohol-based sanitizer when hand soap isn’t readily available
Covering coughs and sneezes with tissues (and then throwing tissues in the trash ASAP)
Staying away from people (the general public and those you’re close to) if you feel sick

One of the current and encouraging methods for avoiding catching or spreading the disease is to wear a face-covering that covers your nose and mouth in order to prevent ingesting respiratory droplets and alternatively avoiding others ingesting your respiratory droplets.

Surgical facemasks, face coverings, and other options that mask your nose and mouth can help to prevent the transmission of coronavirus and influenza when work by an asymptomatic person.

Treatment and Management Options: Investigational Suggestions

While no current therapy, treatment, or management options exist, there are several investigational options out there. Researchers, scientists, medical professionals, and more are consistently working to uncover and develop treatment and management options that could cure, prevent, and help maintain the spread of COVID-19.

Investigational Antiviral Agents

Remdesivir

Considered a broad-spectrum antiviral agent, Remdesivir acts as a nucleotide analog prodrug. The US FDA issued EUA of remdesivir to allow emergency use of the agent for severe COVID-19 in both hospitalized adults and children on May 1, 2020.

Then, in late June 2020, a phase 1b trial of an inhaled, nebulized version of remdesivir was initiated to help determine if this antiviral agent could be used on an outpatient basis to help at earlier stages of the disease.

This antiviral drug seemed to be a good candidate for the coronavirus because it was studied in clinical trials for Ebola virus infections. While the drug showed minimum benefit in these sceneries, it has been shown to inhibit the replication of other human coronaviruses that are associated with high morbidity in certain tissue culture (including SARS-CoV).

The initial EUA of this antiviral drug was based on preliminary data collected in the analysis of the Adaptive COVID-19 Treatment Trial (ACTT) on April 29, 2020. It included about 1,000 hospitalized patients with advanced COVID-19 and lung involvement. Those who received remdesivir recovered faster than similar patients who received a placebo. The initial results showed that patients who received remdesivir had a 31% faster time to recover than others.

Several other studies have been opened to better understand how this antiviral drug can help patients who have COVID-19. One published report stated that compassionate use of remdesivir was associated with improvement in 36 out of 53 hospitalized patients who had severe COVID-19 (about 68% of patients).

Nitazoxanide

Another investigational antiviral, Nitazoxanide, is an extended-release tablet that inhibits the replication of a broad range of respiratory viruses in cell cultures—this includes SARS-CoV-2.

There were two recent phases 3 trials conducted in the prevention of COVID-19 in high-risk populations (including the elderly in long-term care facilities and healthcare workers). As it stands, the third trial for early treatment of COVID-19 using Nitazoxanide is planned.

Ivermectin

Traditionally used as an antiparasitic drug, Ivermectin showed in vitro reduction of viral RNA in Vero-hSLAM cells 2 hours post-infection with SARS-Cov-2.

However, this study also stated that the results might not necessarily translate to human use and the effective dose studied is not established at this early in discovery. There’s a need for more research to determine if an antiviral effect could be elicited in humans from the concentrations that were tested or a similar concentration.

Immunomodulators & Other Investigational Therapies

One of the strategies that researchers and professionals are taking to quickly solve the mystery of COVID-19 are examining and repurposing existing drugs through methods of immunomodulation. Right now, the drugs in clinical trials that most accurately represent these include Interleukin (IL) inhibitors, Janus Kinase Inhibitors, and interferons—however, this is just a small sample of the therapies being investigated.

Interleukin Inhibitors

IL inhibitors could ameliorate severe damage to lung tissue caused by cytokine release in patients who are suffering from serious COVID-19 symptoms and infections. The disease can—and in many cases, do—cause an increased pulmonary inflammatory response that may result in increased alveolar-capillary gas exchange. Which, in turn, makes oxygenation incredibly difficult—especially with severely ill patients infected with COVID-19.

Studies are currently investigating Interleukin-6 inhibitors and Interleukin-1 inhibitors. IL-6, a pleiotropic pro-inflammatory cytokine produced by various cell types, includes lymphocytes, monocyte, and fibroblasts. As of June 2020, the NIH guidelines noted insufficient data to recommend for or against the use of IL-6 inhibitors to fight the SARS-CoV-2 infection-induced dose-dependent production of IL-6 from bronchial epithelial cells.

IL-1 levels, which are elevated in individuals with COVID-19 and other conditions. As of June 2020, NIH guidelines noted insufficient data to recommend for or against IL-1 inhibitors (just as they did with IL-6 inhibitors).

Corticosteroids

Though corticosteroids are not generally recommended for the treatment of viral pneumonia or similar ailments, the benefit lies in the septic shock results from tempering the host immune response to bacterial toxin release. In a study describing clinical outcomes of patients diagnosed with COVID-19, 84 patients (41.8%) developed ARDS, and of those, 44 of them (52.4%) died. A study in the Netherlands showed that a 5-day course of high-dose corticosteroids accelerated respiratory recovery, lowered hospital mortality rates, and reduced the likelihood of mechanical ventilation for COVID-19 patients with associated cytokine storm syndrome (compared with historical controls).

Convalescent Plasma

Recently, the FDA has posted information for investigators wishing to study convalescent plasms for use in patients with immediately life-threatening COVID-19. These anti-body rich products are collected from eligible donors who have successfully recovered from COVID-19

Interferons

Some lab studies suggest that normal interferon responses are suppressed in some people infected with SARS-CoV-2—in the lab, some type 1 interferon can inhibit SARS-CoV-2 and closely related viruses like MERS-CoV and SARS-CoV.

Nitric Oxide

In 2004, a study was published that suggested inhaling nitric oxide could be a supportive measure for treating infection in patients dealing with pulmonary complications. Currently, a study is underway in patients who are suffering from COVID-10 complications with the sole goal of preventing disease progression of those who already have severe ARDS.

In March 2020, the FDA accepted a phase 3 study in order to evaluate the efficacy and safety in patients diagnosed with COVID-19 who needed additional supplemental oxygen before the progression of the disease to the point of ventilatory support.

JAK and NAK Inhibitors

It’s been suggested that drugs that can target numb-associated kinase (NAK) can mitigate systemic and alveolar inflammation in patients who are suffering from COVID-19 pneumonia. How? By inhibiting essential cytokine signaling involved in the immune-mediated inflammatory response. Further, NAK inhibition has been shown to help reduce viral infection in vitro. Janus kinase inhibitor (JAK) can also be a therapeutic option.

Hydroxychloroquine, Chloroquine, and Lopinavir / Ritonavir

Both hydroxychloroquine and chloroquine were widely used as antimalarial drugs that can help elicit immunomodulatory effects and are also used to treat autoimmune conditions, too. They’re believed to have additional antiviral activity via alkalization of the phagolysosome, which can inhibit the pH-dependent steps of viral replication.

Initially, the FDA had determined an authorization to explore and study the effects of hydroxychloroquine and chloroquine on COVID-19 symptoms. However, on June 15, 2020, the FDA authorization (EUA) of hydroxychloroquine and chloroquine was revoked. Based on its ongoing analysis and emerging scientific data, the FDA determined it was unlikely that hydroxychloroquine was effective in treating COVID-19. While additional trials could help to continue potential evaluation, the FDA Determined the EUA they’d put in place was no longer appropriate

Investigational Devices

Researchers, medical professionals, and scientists are also investigating the use of devices in order to aid with the treatment and maintenance of COVID-19. These devices include nanosponges and blood purification devices.

Cellular nanosponges (often referred to as just nanosponges) are made from plasma membranes that are derived from human lung epithelial type II cells (or human macrophages that have been evaluated in vitro). They display the same protein receptors that are required by SARS-CoV-2 for cellular entry, therefore, they can act as a decoy to bind the virus instead of allowing the virus to bind to a host.

Blood purification devices—also known as blood purification filters—have received emergency use authorization from the FDA for the treatment of COVID-19 patients with severe respiratory failure. They can be used in continuous renal replacement therapy or in the reduction of pro-inflammatory cytokines levels.