COVID-19 TREATMENT, PREVENTION AND DEVELOPMENTS: WHERE DO WE STAND NOW

The current global COVID-19 pandemic has created a great need for better treatment options and prevention strategies. Lockdowns have been implemented worldwide alongside precautionary measures that aim to slow the spread of SARS-COV-2.

Trials are already underway to test for antiviral activity amongst readily available medications and therapies. New developments in prevention and treatment are discussed below.

New Developments

• Wastewater monitoring systems are being devised to more accurately keep track of SARS-COV-2 outbreaks^[1]. They may also be used in future to monitor the progress of other viral threats.
• Mask wearing and social distancing are being explored in the context of other viral diseases in order to lower the risk of future pandemics.
• Zinc-embedded fabrics are currently being developed to slow the spread of COVID-19 and other viruses. Preliminary tests suggest that facemasks made of these fabrics are highly effective at inactivating both H1N1 and SARS-COV-2 viral particles for up to 50 washes.^[2]
• New vaccines have been created in response to SARS-COV-2 variant strains.
• Protective compounds are being explored to enhance prevention and treatment. Examples include anticoagulants, protease inhibitors, antiviral medications, and supportive nutrients such as zinc.
• Mild hyperbaric oxygen therapy may be a more effective treatment than intubation in severe cases of COVID-19 respiratory distress.^[3]

COVID-19 Prevention Measures

Currently approved SARS-COV-2 prevention measures include:

1. Social Distancing. Common guidelines advocate for 6ft distances between people to reduce potential SARS-COV-2 transmission. In spite of current guidelines, the virus has been proven to spread beyond distances of 6ft.
2. Reducing Potential Exposures. Minimizing entry into public areas, confined spaces with people and social gatherings can help to improve the efficacy of social distancing. Travel has been restricted in most areas of the world on both national and international levels.
3. Frequent Use of Disinfectants. Infectious particles can remain intact on surfaces for several hours up to several weeks. This has been proven true of SARS-COV-2. Disinfecting hands and surfaces are important strategies for reducing viral spread. Toilets, sinks, and drains deserve special attention in this regard, as do frequently touched surfaces including light switches and door handles.
4. Mask Wearing. Wearing a facemask reduces the spread of respiratory particles and potentially reduces SARS-COV-2 transmission. It has been shown to lower the risk for other respiratory infections by between 70-80%, however evidence pertaining to SARS-COV-2 is lacking^[4]. Effectiveness can be improved when used in combination with other prevention measures.
5. Increasing Air Ventilation and Purity. This can help to reduce the concentration of potentially infectious particles in the air, lowering the risk of infection. On the other hand, air ventilation and air conditioning systems may promote viral spread depending on how they are designed and positioned in a building^[5]. Routine cleaning of air purification systems is important.
6. Decreasing Humidity. The virus is more infectious in humid conditions. Those that live in humid areas may benefit from dehumidifiers. Wet clothing and facemasks should be changed for clean and dry alternatives.

Potential COVID-19 Treatment Options

The following treatment options are currently being explored for treating COVID-19. Strategies involve viral inhibition, antibody enhancement, and immune stabilization.

Anti-Viral Drugs

There are no antiviral drugs that have been tested for their safety and efficacy in the context of preventing or treating SARS-COV-2 infections or COVID-19. More than 400 drugs are being investigated. The potential antivirals that have been singled out are noted to have inhibitory effects in highly experimental lab studies or have been shown to improve symptoms in animals.

All of the drugs being currently tested for antiviral potential are commonly prescribed for other health conditions. Many of them have potentially deleterious side effects and are not recommended for casual use by healthy individuals, often requiring a prescription to take.

Some options being investigated in this regard include^[6]:

• Chloroquine and hydroxychloroquine are anti-malarials that have antiviral potential against SARS-COV-2, as well as potential anti-inflammatory benefits. It was used experimentally with success in China and France early on in the pandemic. Nonetheless, after large scale trials, it was revoked for emergency use by the US FDA due to adverse effects. A study from New York implies that when combined with azithromycin, it may worsen prognosis in COVID patients and increase the risk of having a heart attack^[7].
• Umifenovir (Arbidol) is prescribed in Russia and China for treating respiratory viral infections. It has been shown to have inhibitory actions against SARS-COV-2 in a lab, and may improve symptoms in those with COVID-19. Other studies indicate that it is not effective at promoting viral clearance in COVID patients, preventing mortality or improving symptoms^[8]. In severe cases, may also promote liver damage in those with COVID-19^[9]. Studies are currently confirming its efficacy in COVID-19 treatment.^[10]
• Lopinavir is a protease inhibitor and antiretroviral used to treat HIV patients. It has been shown to have in vitro antiviral activity against SARS-COV-2 and is used as an emergency treatment together with ritonavir in order to inhibit replication. However, results from trials are contradictory, with these drugs appearing to either improve outcomes dramatically or provoke severe complications and mortality^[11]. Some studies showed no benefit.
• Camostat mesylate is approved for use in Japan for pancreatitis and postoperative gastric reflux. As a serine protease 2 inhibitor, it proved to block this form of viral entry via ACE2 receptors in the lungs^[12]. The efficacy of this drug has not been tested in patients and no data supporting its efficacy exists. Protease inhibitors tend to incur negative side effects and are not recommended for general use. This drug has been associated with inducing edema and severe allergic reactions.^[13]
• Remdesivir inhibits viral RNA from interacting with the host genome, potentially putting an end to replication. Positive results have been confirmed in limited trials on infected patients and the drug has been approved for emergency use by the FDA. It may also lower the need for oxygen support in those with COVID-19 and lower recovery time^{[14] [15]}. The European Union has approved the drug prior to the pandemic for treating pneumonia in adults and adolescents requiring oxygenation. Several international trials are evaluating the safety and efficacy of this drug for COVID-19 treatment and prevention.
• Favilavir is a Japanese antiviral drug that has been approved in China, Russia and India for treating COVID-19. It may serve to reduce symptom severity in COVID patients, revealing less fibrosis in the lungs and enhanced viral clearance. Studies indicate dramatic results in both mild and severe COVID-19 cases taking favilavir, with improvements ranging between 40 and 87% over the course of 1-2 weeks.
• Meplazumab appears to be protective against viral entry and spike protein adherence to CD147 receptors^[16]. Very small clinical trials show promising results, implying that the drug may speed the resolution of pneumonia in COVID-19 patients.^[17]
• Plitidepsin (aplidin) is an anti-tumor drug approved for treating multiple myeloma in Australia. It was shown to have considerable antiviral actions against SARS-COV-2 in animals and humans^[18]. Further research is required to assess dosage, long-term safety and potential toxicity.

Anticoagulants

Blood thinners, such as heparin, are administered intravenously to hospitalized patients at an increased risk of blood clots and thrombosis. This therapy has proven controversial and may increase mortality risk. ^[19]

August, 2020. A recent trial concluded that anticoagulant administration improves outcomes in moderately ill patients and serve to lower the need to implement intensive respiratory or cardiac support. In critically ill patients where ventilation and intensive care are required, blood thinning medications are likely to increase the risk of mortality due to vascular damage and internal bleeding.^[20]

Immune Support Strategies

It is currently unclear if SARS-COV-2 is able to erode immune responses over time and with repeat infections^[21]. Nevertheless, the pathways it affects in the cell suggest that it is able to contribute towards immune dysfunction.

Thus, promoting optimal immune function is another important aspect of prevention.

The following strategies are being explored for optimizing immune support for COVID patients:

Antibody Production

Individuals with stronger immune systems are able to generate quicker antibody responses to the virus than those with weaker immune systems. The level of neutralizing antibodies is associated with the degree of immunity towards SARS-COV-2 infection, with higher amounts predicting protection^[22].

Those with healthy immune functions, quicker antibody responses and higher neutralizing antibody levels tend to have milder symptoms or be asymptomatic^[23]. Patients with a worse prognosis due to comorbidities are likely to have weaker or compromised immune functions, resulting in less protection. Increased antibody production is also seen in patients with increased disease severity and this is linked to better protection post infection.

• Vaccines

Vaccines are currently the most effective treatment option for increasing antibody synthesis in those who are not immune compromised and still able to produce antibodies.

It should be noted that SARS-COV-2 has a unique ability for spike protein mutation, which has given rise to several new strain variants. Strain variants require unique types of antibodies, as their spike proteins are more adept at immune evasion and thus may warrant slower immune responses^{[24] [25]}. Some reports suggest that spike proteins are able to use natural antibodies to more efficiently bind to cell receptors. Contracting the virus may increase one’s risk of contracting it again in future, as suggested by a slower antibody response towards repeat infections.^[26]

This suggests that natural immunity will become less effective with each mutation of this virus, highlighting the need for vaccines in prevention and treatment^{[27] [28]}.

According to WHO reports, natural infections pose a similar degree of immunity as currently available vaccines. Antibody responses to the virus have been reported to last for 6-8 months, reducing the risk of reinfection by 80-90% and the risk of acquiring symptomatic infection by up to 94%^[29].

More details on currently available vaccines can be found here.

Herd Immunity

Small subsets of infected people are unable to produce antibodies, while some produce fewer antibodies upon reinfection; possibly lowering the potential effectiveness of vaccines in immune-compromised individuals.

According to the WHO, if enough people get vaccinated, herd immunity will protect those rare few that are unable to get vaccinated and who are at a high risk of contracting COVID.^[30]

• Convalescent Plasma and Monoclonal Antibody Treatment

Convalescent plasma is blood plasma that has been extracted from previously ill patients who recovered successfully from an infectious illness. It contains antibodies (immunoglobulins or “immune proteins”) that can neutralize viral particles. Transfusion of convalescent plasma is FDA approved^[31] and has been used as a standard emergency treatment since the start of the pandemic with some successful outcomes. In spite of this, evidence promoting its use is limited^[32] and trials are still underway to confirm its safety and efficacy^[33].

Monoclonal antibody treatments are also currently being devised. These are singular antibodies that are lab-generated in tissue cultures. They are often administered in what is referred to as a monoclonal antibody cocktail, which offers a combination of protective antibodies. Many people appear to have improved their symptoms and recovery through making use of this treatment^[34]. Investigations of the efficacy of monoclonal antibodies for SARS-COV-2 are also being conducted.

Which is more effective?

It is uncertain which type of antibody transfusion works best for treating COVID-19 virus infection. Convalescent plasma is not a standard product and may be susceptible to contamination, just like any other blood transfusion. Monoclonal antibody production dispenses with these issues and may be more effective as antibody levels and ratios can be controlled. However it is a lot more time consuming and expensive.

Currently, convalescent plasma is expected to out-perform monoclonal antibody therapy, as there is currently a limited understanding of the antibodies that can neutralize viral particles. This is particularly true of novel viral protein mutations. Plasma transfusions may also serve dual purposes for those who contracted hemolytic anemia as a result of SARS-COV-2 infection. As the current understanding increases, the efficacy and accuracy of monoclonal antibodies will improve and likely overtake that of convalescent plasma.

History tells us that antibody transfusions don’t always work. In spite of promising preliminary trials, both treatments performed dismally in large scale clinical studies in the context of treating severe influenza A.^[35] Time will tell if the same applies to SARS-COV-2 or not.

Inflammation Control

It should be noted that mortality is associated with low oxygen status and majorly inflammatory cytokine storms, which may occur irrespective of increased antibody production in susceptible individuals with severe COVID-19.

As a result, therapeutics that control for systemic inflammation are likely to improve prognosis and be synergistic with antibody-boosting treatments.

Currently, anti-inflammatory drugs are being explored for their antiviral potentials against SARS-COV-2.

• Baricitinib may be a good complementary treatment for those with COVID-19 as it does not interfere with liver drug metabolism and may enhance antiviral effects of other treatments^[36].
• NSAIDs (Non-steroidal Anti-Inflammatory Drugs) may improve outcomes in patients with COVID-19 and lower the risk of mortality^[37]. Examples such as ibuprofen and naproxen appear to have antiviral effects against other respiratory infections, including influenza A and the common cold^[38]. Other reports suggest that NSAID use may prolong hospital time. More research is required to verify whether NSAIDs are effective for use in patients with COVID, however current data indicates they are more beneficial than not^{[39] [40]}.
• Glucocorticoids. In spite of their immune-suppressing properties that generally serve to decrease inflammation, glucocorticoids may actually increase the risk of COVID-19 complications, such as lympopenia^[41].

Interferon Enhancement

As part of immunologic strategies to counter the virus, interferon signaling may be a potential immune-boosting target, particularly since SARS-COV-2 may be capable of interfering with this aspect of immunity^[42]. Interferons are important for stimulating a robust immune response towards infections. A lack of interferons is associated with greatly reduced immunity while very high levels are associated with inflammation excess.

Interferon treatment is highly controversial and there is limited evidence of its safety and efficacy in treating COVID-19 and SARS-COV-2 infection. Administration at the wrong time may provoke worse inflammatory symptoms and ultimately a fatal cytokine storm. Test-tube studies indicate that the virus increases interferon signaling in macrophages, which tended to result in their death.^[43]

Nonetheless, early interferon treatment may serve to promote better outcomes in immune-compromised individuals. Interferon beta proved to be more effective against SARS-COV-1 than interferon alpha.

Zinc

Zinc is a vital nutrient, particularly with regard to immune function. SARS-COV-2 interferes with zinc signaling and may promote deficiency.

Zinc deficiency is one of the most common global nutrient deficiencies and does not necessitate mortality or disease susceptibility, as evidenced by epidemiological studies.^[44] However it is likely to increase the risk of COVID-19 severity and viral complications, which are associated with increased mortality risk and prolonged hospitalization^[45].

Viral complications linked to severe zinc deficiency include anemia^[46], disturbances in iron metabolism and transport^[47], systemic infection due to loss of tissue barrier integrity^{[48] [49]}, and chronic COVID-19.

Aside from treating zinc deficiency, zinc may be an appropriate complementary intervention for its multiple synergistic effects. Zinc:

• has direct antiviral effects against respiratory infections and computational models reveal that it may block SARS-COV-2 viral replication in a similar fashion to that of SARS-COV-1.^[50]
• is a prime component of ACE2 and has been shown to have a high affinity for ACE2 receptors. It may therefore exert antiviral actions right at the binding site of SARS-COV-2.^[51]
• is needed to make zinc finger proteins. These work with interferons in the innate antiviral response against SARS-COV-2 in experimental conditions^{[52] [53]}.
• Its antioxidant and immune regulating properties^[54] may also prove relevant in combating symptoms of COVID-19. Further trials are underway to test the efficacy of zinc in this context.^[55]
• is associated with stabilizing membranes and lowering permeability, particularly in the respiratory tract; which may serve to prevent systemic complications.

Conclusion

A lot of promising treatment options have emerged over the course of the pandemic for COVID-19 patients, however their safety and precise efficacy in humans is still being verified.

Vaccines remain to be the best proposed solution for increasing antibody production, with the jury still being out on other antibody-boosting therapies. Antiviral drugs that proved effective for other respiratory conditions and a few anti-inflammatory drugs appear to show the most promise. Zinc is highly indicated in deficient patients or those with comorbidities. Anticoagulants should not be administered to critically ill patients.

Better protective gear and improved pandemic surveillance are suspected to help quickly control future pandemics.

To search for the best healthcare providers that offer either COVID-19 Treatment, or vaccines, please use the Mya Care search engine.

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