COVID-19 Prophylaxis and Treatments: A Comprehensive Overview

By Aman Reddy

Introduction

History of SARS-CoV

SARS-CoV-1 (Severe Acute Respiratory Syndrome) is the designated name of a coronavirus that was first identified in February of 2003 after an outbreak in China. It spread to more than two dozen countries spanning across North and South America, Europe, and Asia. [1] . Despite this worldwide breakout, SARS-CoV-1 only infected approximately 8,000 people and killed ~750 people [1]. While it was not as infectious as its present-day successor, SARS-CoV-2 (aka COVID-19), it was much more deadly, with an estimated death rate of 15% compared to 0.68% of those under 25. [2]. SARS-CoV-2 is a variant of the original SARS-CoV-1, and it was officially discovered in December of 2019 [3,4]. However, unofficial reports claim that SARS-CoV-2 was initially discovered earlier throughout Asia in October/November 2019 [5]. The first domestic case of COVID-19 in the United States wasn’t until January 2020. Interestingly, since 2003, there have been several other coronaviruses that are able to cross the species barrier and infect humans, such as MERS-CoV [6] but none to the degree of SARS-CoV-2 (COVID-19).

SARS-CoV-2 Theories of Origin

SARS-CoV-2 is a coronavirus that originated from SARS. Although the precise origin of COVID-19 is uncertain, it is widely believed that the virus mutated from bats and spread to humans, with plausibility due to the meat market industry in China [7]. However, there is also evidence to suggest that the virus may have originated from Pangolins, who carry a plethora of other coronaviruses similar to SARS-CoV-2 [7]. Scientists that compared spike proteins from smuggled Malaysian Pangolins in China and SARS-CoV-2 found many similarities and proposed that it could spread to humans [7]. An alternative theory has emerged in which the virus originated from the Wuhan Institute of Virology via an infected employee or contaminated object. However, due to limited accessibility and unwillingness to cooperate from the Chinese government, this theory is largely speculative [8]. Despite over 5 million deaths worldwide and a 2-year ongoing pandemic, the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) are still unsure of the precise origin of the virus. An international task force of scientists appointed by the WHO is currently investigating the origin of SARS-CoV-2.

Impact of Covid-19

Covid-19 is quickly becoming one of the most feared diseases in the world. Almost 200 million people have been infected with Covid-19, and more than 4 million of those infected have died [9]. Along with the cost of lives that the virus has taken, there are many economic and social problems that the pandemic has caused. The global economy shrunk by 3.5%, and the global recession is at its biggest since the end of World War II [10]. Furthermore, Mental health issues in the U.S have increased by more than 30% since January of 2019, and substance abuse has similarly become more prevalent [11]. The pandemic has caused harm to society in many ways, and it is important we find effective treatment and prevention to prevent more harm from being done.

This is the first pandemic that has emerged in the age of social media, and as a result, there is an overabundance of information on the internet about Covid-19 and its treatments. It is important to have accurate and reliable information surrounding the treatment and prevention of Covid-19. This review paper acts as a compact, yet detailed guide on the treatments and prevention of Covid-19.

Methods

Databases

PubMed and Google Scholar databases were used for our search. Relevant citations from articles found are also included in our review.

Key Terms

The Key Terms used were: Covid-19 Treatment, Covid-19 Vaccine, Covid-19 Prevention, Coronavirus Treatment, SARS-CoV-2 Treatment, SARS-CoV-2 Drugs, SARS-CoV-2 Prevention, Covid-19 Prophylaxis, Coronavirus Prophylaxis.

Results

Vaccines

There are three vaccines currently authorized for use within the United States: Pfizer-BioNTech, Moderna, and Johnson & Johnson. [31] These vaccines all work in different ways, but they all are highly effective at preventing Covid-19. The Pfizer-BioNTech vaccine is a 2-stage mRNA vaccine, where two doses of the vaccine are needed to get the full efficacy [12]. A study published in The New England Journal of Medicine found that vaccine efficacy between the first and second doses was 52%. The study also reported that seven or more days after the second dose, efficacy rose to 95% [13]. The Moderna vaccine is also a 2-stage mRNA vaccine, and it has a similar efficacy of 95% [12,14].

The Johnson and Johnson vaccine varies from the other two, using traditional virus technology rather than mRNA. It has a lower efficacy rate than the other two, at around 66.3%, according to the CDC [15]. Although it has a lower efficacy rate, this vaccine has some advantages. Only a single dose is needed, reducing the number of vaccine doses needed to be on site. Temperature requirements for storage are not as low as the Pfizer and Moderna vaccines; thus, it can be kept in normal refrigerators, making it more accessible to places that need it [16].

Although the Johnson and Johnson vaccine has been found to cause blood clots in a small minority of people, all 3 of the vaccines have a relatively similar side effect profile [17]. Common side effects are redness, pain, swelling at the injection site, nausea, fatigue, chills, muscle pain, fevers, and headaches. Although less common, if someone has an allergic reaction to the first dose of either the Pfizer-BioNTech vaccine or the Moderna vaccine, it is advised that they do not take the next dose [18].

Currently, the Covid-19 Preventative Guidelines published by the NIH do not recommend the use of any drugs for SARS-CoV-2 pre-exposure prophylaxis, or prevention [19].

Hydroxychloroquine

Several studies have evaluated hydroxychloroquine for pre-exposure and post-exposure prophylaxis of Covid-19. These studies have demonstrated that hydroxychloroquine is not effective for preventing Covid-19. Furthermore, several studies have found that hydroxychloroquine leads to an increased amount of adverse effects. For example, in a study conducted by Barnabas et al. to evaluate the efficacy of hydroxychloroquine for pre-exposure prophylaxis of Covid-19, this group found that mildly adverse effects were more common (45%) among those who had used hydroxychloroquine than those who used a placebo (26%) [19]. Mitjà et al. assessed the use of hydroxychloroquine for post-exposure prophylaxis of Covid-19. Similarly, they found that a greater percentage of patients in the hydroxychloroquine arm experienced adverse events (56.1%) than in the control arm (5.9%). These mild adverse effects included gastrointestinal events, nervous system disorders, myalgia, fatigue, and malaise [20]. Another study conducted by Boulware et al. found similar results. In a randomized, double-blind, placebo-controlled study that spanned across the United States and some of Canada, they concluded that hydroxychloroquine did not reduce the amount of cases of Covid-19 and made side effects more common [21].

Ivermectin

Lately, Ivermectin has become infamous because of its widespread misuse by the public and media coverage. Because of this, it is even more important to understand how this drug works and in what capacity it should be used. Ivermectin has been shown to be able to inhibit the growth of SARS-CoV-2 in a lab setting. Of the 115 participants who were exposed to SARS-CoV-2 and then treated with Ivermectin, 38 became infected with Covid-19, and 77 remained uninfected [19]. However, some meta-analyses determine that the information gathered from clinical studies must be taken with caution, as the quality of evidence supporting Ivermectin received from these studies is low [22]. There are many additional clinical trials currently underway or being planned regarding the clinical use of Ivermectin; however, many of these trials have not published their results as of yet. More research is needed before determining if Ivermectin can be used for the prevention or treatment of Covid-19.

Monoclonal antibodies

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful antigens such as viruses [23]. Currently, the FDA has authorized multiple monoclonal antibodies for emergency use in the treatment of Covid-19, and many others are presently being studied and reviewed for approval. However, there are also novel studies looking at the use of monoclonal antibodies for the prophylaxis of Covid-19. In a recent study published in the New England Journal of Medicine, O’Brien et al. found that subcutaneous REGEN-COV was effective in preventing symptomatic and asymptomatic SARS-CoV-2 infection in household contacts of infected persons [24]. Prophylactic treatment with REGEN-COV reduced the risk of symptomatic infection (Relative risk reduction, 81.4%, P<0.00). The researchers found that REGEN-COV, a prophylactic treatment composed of the monoclonal antibodies casirivimab and imdevimab, prevented symptomatic and asymptomatic infections overall (Relative risk reduction, 66.4%). Furthermore, this study found that of those that were infected, prophylactic treatment with REGEN-COV reduced the duration of symptomatic disease and the duration of high viral load.

REGEN-COV, a prophylactic treatment composed of the combination of the monoclonal antibodies casirivimab and imdevimab, reduced the risk of symptomatic infection by 81.4%, and it has also reduced the risk of symptomatic and asymptomatic infection by 66.4% overall [24]. So far, Monoclonal antibodies seem to be very effective against Covid-19, and it is plausible that these may be used in the future against Covid-19 and other similar diseases.

Remdesivir

Remdesivir is an antiviral medicine that has proven to inhibit the growth of SARS-CoV-2 in vitro. Many clinical studies also show that it is effective when given to patients with Covid-19. According to the National Institute of Health, it binds to the RNA of a virus and prevents it from replicating, disabling the virus, and allowing the immune system to deal with the remaining viruses [25]. Remdesivir is currently the only antiviral medication approved for use by the FDA and the only treatment approved for hospitalized patients [25]. It is a broad range antiviral medication, which means it can be used for any type of Covid-19 treatment, even if it is asymptomatic. A meta-analysis study found that Remdesivir, along with other anti-inflammatory agents, “were associated with improved outcomes of hospitalized COVID-19 patients” [26]. Based on the randomized clinical trials, this meta-analysis found the risk of progression to severe course and mortality was significantly reduced with Remdesivir in Covid-19 patients. (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) [26]. Remdesivir has shown promising results as a possible treatment for Covid-19 and has been an invaluable treatment during this pandemic.

Convalescent Plasma Therapy

Convalescent Plasma Therapy uses blood from people who have recovered from Covid-19. The blood is cleaned to remove red and white blood cells so it leaves behind only plasma and antibodies, which can combat Covid-19 [28]. A study conducted by Li et al. concluded that convalescent plasma therapy along with standard therapy for Covid-19 had no significant effect compared to standard therapy on its own [27]. However, a report published by the ID society also notes that while convalescent plasma may not be effective at combating Covid-19, it may have merit in increasing the humoral immunity of patients infected with SARS-CoV-2, and that may indirectly help them recover [28]. The report noted a series of case studies where 23 patients received a high concentration of Convalescent Plasma, and subsequently, 87% of those patients experienced a full recovery [28]. While the USDA has authorized emergency use of this treatment, the IDSA advises against its use on patients hospitalized with Covid-19, and only in clinical trials does it support its use [28]. More research needs to be done to determine if these effects can be used practically for the general public.

Interferon Beta

Interferon Beta are types of protein that can have an effect on other immune cells. They have been tested as a treatment for SARS-CoV-2 because of their effects on viruses in vitro. A double-blind, placebo-controlled study conducted in the U.K. quoted by the NIH found that Covid-19 patients who received interferons through inhalation could walk without restrictions after recovering, had a decreased chance of their condition worsening, and had less breathlessness [29]. Another randomized clinical trial conducted by Monafared et al. found that the mortality rate of those given Interferon Beta was much lower than that of the control group (19% versus 43.6%, respectively). It significantly increased the discharge rates of Covid-19 patients [30]. Furthermore, a systematic review and meta-analysis performed by Nakhlband et al. found promising results for the treatment of Covid-19 with Interferon Beta, especially when combined with antiviral drugs [30]. These results show promise for Interferon Beta as a mainstream drug; however, many more studies are currently being conducted, and it will take time for it to be approved.

Discussion

While vaccines have proven to be largely effective in minimizing the burden of Covid-19, it is important to study alternative treatments to better protect the general public. As we find more effective ways of treating and preventing this disease, we can further minimize the burden of Covid-19.  Of the prophylactic treatments listed here, all of these treatments have marginal benefits over others, but overall, the most effective one would be Monoclonal antibodies. There is mixed evidence regarding preventative treatments of Covid-19; however, monoclonal antibodies have recently shown promising results in clinical testing. Our research demonstrates that there is evidence that they drastically reduced the chance of both symptomatic and asymptomatic infection and reduced hospitalization and death in Covid-19 patients. On the other hand, the data regarding Ivermectin has been largely inconclusive. While there is evidence that it may reduce the rate of infection, there is not enough data to support its efficacy in treating or preventing Covid-19. More research needs to be done on this drug and many others, as many treatments are still early on in the research process. Although lots of research has been done, more research is required to find more effective treatments. Lots of research has already been done on the treatment and prevention of this disease; however, it is still a relatively new virus variant, and many uncertainties remain. It remains clear through our literature review that there is a lot to learn regarding the most effective way to combat this disease, and more research needs to be done to help further our knowledge.

Limitations

Although this review provides an overview of the treatments/prophylaxis of Covid-19, there are some limitations. This review only discusses the most prominent and widely discussed treatments for Covid-19 currently available. There are several other experimental treatments being studied that are not included.

Conclusion

This review paper provides a broad overview of the main treatments and prophylaxis for Covid-19. Although there are several promising treatments for Covid-19, it is clear that more research needs to be done to find more effective treatments with fewer side effects.

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