Background

Background Information

Hypothesis

PI and CHG are being used as antiseptic preventive interventions to decolonize patients’ skin and nares to reduce infections, and as both PI and CHG have broad-spectrum viricidal activity, we hypothesize that antiseptic application of topical nasal PI and oral CHG can protect naso-oropharyngeal viral colonization in healthcare workers, reducing acquisition of SARS-CoV-2 and subsequent COVID-19 infection.

Background

Total positive COVID-19 case count in Wisconsin. dhs.wisconsin.gov

On March 11, 2020 the World Health Organization declared the novel coronavirus (COVID-19) outbreak a global pandemic. Emerging and re-emerging deadly viral infections have significantly affected human health since ancient times and continue to despite recent biomedical advances. The emergence of the novel human coronavirus SARS-CoV-2 (COVID-19) pandemic is a recent example of a deadly virus having significant health effects with its associated high morbidity and mortality. 

As of May 15, 2020, over 4.5 million people worldwide have been infected with COVID-19, with approximately 300,000 deaths. According to the Centers for Disease Control and Prevention (CDC), in the United States alone COVID-19 has infected 1.42 million people with associated 86,386 deaths. The hospitalization rate due to COVID-19 illness is 4.6 per 100,000 population.

Current scientific consensus is that SARS-CoV-2 spreads primarily through respiratory droplets produced by an infected person, which can enter the recipient through the nose and/or mouth. These droplets can also contaminate environments leading to further transmission. Close contact (within about 6 feet) increases the likelihood of transmission. Evidence also suggests transmission occurs from asymptomatic or pre-symptomatic individuals – complicating efforts to contain spread of the virus. Influenza pandemic community mitigation guidelines were recently updated in 2017, which highlights that nonpharmaceutical interventions (NPIs) are the first line of defense, especially until vaccination is available for a novel virus. These NPIs include social distancing and hygienic practices such as personal protective measures for everyday use (e.g., voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene); personal protective measures reserved for influenza pandemics (e.g., voluntary home quarantine of exposed household members and use of face masks in community settings when ill); community measures aimed at increasing social distancing (e.g., school closures and dismissals, social distancing in workplaces, and postponing or cancelling mass gatherings); and environmental measures (e.g., routine cleaning of frequently touched surfaces).

During an influenza pandemic, known antiviral treatments are available, but for novel non-influenza viral pandemics, such as SARS-CoV-2, the community is limited to NPIs. Minimizing transmission of the disease through NPIs is especially critical with the COVID-19 pandemic due to the high percentage of patients who need hospitalization and/or critical care. Severe disease (dyspnea, hypoxia, or >50% lung involvement on imaging) or critical disease (respiratory failure, shock, or multiorgan system dysfunction) occurs in approximately 20% of diagnosed COVID-19 cases. Due to the severity of these symptoms, patients often require critical care in the intensive care unit and the use of specialized lifesaving equipment, such as mechanical ventilation.

Need to Protect Healthcare Workers

In healthcare settings, healthcare workers (HCWs) attend to COVID-19 patients, and may be involved in advanced medical lifesaving technology including medical procedures that can potentially aerosolize micro-organisms. These aerosol-generating procedures can include resuscitation, intubation, respiratory suctioning, bronchoscopy and autopsy. Aerosol-generating procedures are associated with increased risk of infection transmission for those performing them. When HCW perform these procedures during their care of patients with respiratory viral infections such as COVID-19, these HCWs are at high risk of contracting and spreading the virus. CDC and WHO have written infection control prevention practice guidelines for HCW caring for known or suspected COVID-19 patients. HCWs rely on hand hygiene and use of personal protective equipment (PPE). Under routine patient care practices, PPE are a safe and effective barrier to infection transmission.

(Photo by Bryce Richter / UW-Madison)

However, under circumstances of a global pandemic, access to PPE has become limited resulting in prolonged use and reuse of PPE and in some instances, ‘home-made’ PPE. A recent CDC report identified 11%-19% of reported COVID-19 cases as healthcare workers in which over 50% indicated their only contact was in a healthcare setting. The report notes 90% of these HCWs were symptomatic and 8% were asymptomatic with 8-10% hospitalization, 2-5% admitted to ICU and 27 deaths (0.3-0.6%).

It has become clear that at the intersection of a novel viral pandemic requiring care of critically ill patients, many of which are requiring these high-risk aerosol generating procedures, and limited access to PPE, HCWs have become at risk for acquiring SARS-CoV-2 and getting COVID-19 and its potential serious health outcomes. Adjunct interventions to improve safety of HCWs are urgently needed to protect them, and their family members, from becoming ill and possibly developing devasting consequences of these infections. As important, is the need to keep HCW at work to care for infected community members requiring advanced medical care.

Povidone Iodine and Chlorhexidine as COVID-19 Antiseptic Agents

The skin and mucous membranes are considered first line of defense against infection and harbor both beneficial and pathogenic microorganisms. Often, life-saving medical treatments, especially invasive procedures, interrupt this first line of defense. A common infection prevention strategy is to disinfect the skin or mucous membrane prior to medical procedures to prevent infections.

Antiseptics have been extensively used in healthcare settings to disinfect skin, mucous membranes and wounds to kill microorganisms that may cause infections. There is a wide variety of chemical agents (or biocides) that can be used at antisepsis, many which have been used for hundreds of years. Povidone iodine (PI) and chlorhexidine gluconate (CHG) are two common antiseptics that have been used safely in healthcare for over 50 years. CHG and PI skin antisepsis have long been used prior to surgery and other invasive procedures. More recently, CHG has been used to decolonize skin and oropharynx of critically ill patients with invasive devices (e.g., central lines and mechanical ventilation). In addition, application of nasal PI is being used for bacterial decolonization of nares prior to surgery. CHG and PI are also used extensively in hand antisepsis in healthcare. Antiseptics have a broad spectrum of activity and have multiple nonspecific cellular targets. Despite widespread use, antiseptic resistance is not common. PI and CHG are known to be safe, effective, affordable and have minimal adverse effects.

CHG is a divalent cationic biguanide molecule that has been incorporated into many products such as hand rubs, body washes, surgical skin preparation and antiseptic mouthwashes and is regarded as an extremely safe topical agent. Mild adverse effects include skin irritation and more rarely allergic reactions. CHG is easy to use and the oral application takes less than a minute to rinse. In addition to broad spectrum biocide activity, CHG has residual activity when compared to other antiseptics. It is most active against gram-positive bacteria but also has activity against gram-negative, some enveloped viruses and fungi but shows poor activity against nonenveloped viruses and is inactive against bacterial spores. CHG is positively charged and binds to the negatively charged cell membrane and cell wall, leading to inhibition of cellular respiration and ultimately cell death at high enough concentrations.

PI is an iodophor complex and is used for skin disinfection prior to surgery and other invasive procedures, hand rubs, mouthwashes; more recently it is being applied topically to the nares to prevent surgical site infections. PI has the broadest spectrum of activity of any antiseptic and has good activity against a range of bacterial, fungi and protozoa as well as virucide activity including influenza, HIV and Ebola virus. PI releases free iodine near cell membrane which can penetrate cell wall via oxidation. PI also a safe topical product and there are no reports of resistance. PI is easy to use and takes approximately 30 seconds for an individual to apply. Recent evidence suggests that PI can effectively inhibit multiple viruses. This includes coronavirus (SARS-CoV and MERS-CoV) and influenza (H1NI).

Although SARS-CoV-2 pathogenesis is being studied, based on other respiratory viral infections likely passes through the mucous membranes, especially nasal and larynx mucosa, then enters the lungs through the respiratory tract. Current evidence suggests that viral detection of SARS-CoV-2 is best obtained from upper respiratory specimens, especially from naso- oropharyngeal mucosa.