Prevention and disinfection in COVID-19

Farhan Shaikh

doi:10.4103/JPCC.JPCC_64_20

REVIEW ARTICLE

Year : 2020 | Volume : 7 | Issue : 7 | Page : 56-64

Prevention and disinfection in COVID-19

Farhan Shaikh
Pediatric Intensive Care Unit and Department of Quality and Accreditation, Rainbow Children's Hospital, Banjara Hills, Hyderabad, India

Date of Submission	20-Apr-2020
Date of Decision	25-Apr-2020
Date of Acceptance	01-May-2020
Date of Web Publication	29-May-2020

Correspondence Address:
Dr. Farhan Shaikh
Pediatric Intensive Care Unit and Department of Quality and Accreditation, Rainbow Children's Hospital, Banjara Hills, Hyderabad
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JPCC.JPCC_64_20

Abstract

The global pandemic involving severe acute respiratory syndrome – coronavirus-2 has tested the capacities of the best of the health-care system worldwide. We are in the middle of the pandemic and the knowledge and science regarding the prevention and treatment of this disease is evolving every minute. This review is an attempt to summarize and simplify the knowledge about preventive and personal protective aspects of management of covid-19 infection. It encompasses the approach to infection prevention and personal protection from the admission of patient to the management in the intensive care units.

Keywords: COVID19, disinfection, personal protective equipments, prevention

How to cite this article:
Shaikh F. Prevention and disinfection in COVID-19. J Pediatr Crit Care 2020;7, Suppl S1:56-64

How to cite this URL:
Shaikh F. Prevention and disinfection in COVID-19. J Pediatr Crit Care [serial online] 2020 [cited 2023 Jun 8];7, Suppl S1:56-64. Available from: http://www.jpcc.org.in/text.asp?2020/7/7/56/285374

Introduction

In November–December 2019, a novel coronavirus was identified in Wuhan city, of the Hubei Province of China.

Virology

Full-genome sequencing and phylogenic analysis indicated that the coronavirus that causes COVID-19 is a beta-coronavirus in the same subgenus as the severe acute respiratory syndrome (SARS) virus (as well as several bat coronaviruses), but in a different clade.

Its receptor-binding gene region is similar to that of the SARS coronavirus, and it uses the same angiotensin-converting enzyme 2 (ACE2) receptor for cell entry.^[1],[2]

Transmission

Person-to-person spread is mainly through respiratory droplets. Droplets usually do not travel beyond six feet (around two meters) and do not remain suspended in the air for long durations. SARS-CoV-2 RNA has also been detected in blood and stool specimens.^[3],[4]

Live virus has been cultured from stool in some cases,^[5] but fecal-oral transmission did not appear to be a significant factor in the spread of infection.^[6]

Environmental contamination

In one study, it is reported that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1. The authors also found that aerosol and fomite transmission of SARS-CoV-2 was possible, because the virus can remain viable and infectious in aerosols for hours and on surfaces up to days.^[7]

In a study by Kampf G et al., various disinfectants (including ethanol at concentrations between 60% and 71%) inactivated a number of coronaviruses related to SARS-CoV-2 within one minute.^[8] Duration of viral persistence on surfaces also depends on the room temperature, relative humidity, and the size of the initial inoculum.^[9]

Immunity

Antibodies to the virus are produced in the infected individuals. Available evidence suggests that these antibodies may be protective. FDA has granted emergency use authorization for tests that qualitatively identify antibodies against SARS-CoV-2 in serum or plasma.^[10]

Preventive Aspects (In the Health Care Setting)

Measures for all patients, visitors, and personnel

The Centers for Disease Control and Prevention (CDC) recommends^[11] the following approach.

Reduce facility risk

Cancel elective procedures, use telemedicine when possible, limit points of entry and manage visitors, screen everyone entering the facility for COVID-19 symptoms, implement source control for everyone entering the facility, regardless of symptoms.

Isolate symptomatic patients as soon as possible. Set up separate, well-ventilated triage areas, place patients with suspected or confirmed COVID-19 in private rooms with the door closed and with private bathrooms (if possible)
Reserve Airborne Infection Isolation Room or Negative pressure room (AIIRs) (negative pressure isolation rooms) for patients with COVID-19 undergoing aerosol-generating procedures and for care of patients with pathogens transmitted by the airborne route (e.g., tuberculosis, measles, and varicella)
Protect healthcare personnel. Emphasize hand hygiene, install barriers to limit contact with patients at triage, cohort patients with COVID-19, limit the numbers of staff providing their care, and prioritize respirators for aerosol-generating procedures.

Policy in Screening, Admission and Cohorting of Patients

The hospital should screen the patients in a separate clinic setup outside the entry in to the ER or hospital building to screen patients with respiratory illnesses.

All the precautions should be followed to ensure the admitted patients (suspected of COVID-19) are safely shifted to the designated places with minimal risk to the surrounding people. Inform the security staff about such an admission so that they clear the way for shifting this patient, inform the housekeeping department so that they mop the lift clean after the patient is shifted before that lift is used for any other patient. The patient with suspected COVID-19 who is being shifted to respiratory isolation area should wear at least a surgical mask or N-95 respirator (if patient has distress, persistent cough, etc.).

Isolation precautions

Children admitted with suspected COVID-19 but not in need of high oxygen therapy or no significant distress should be placed inside single occupancy rooms with attached toilets.^[12]

Those children admitted with respiratory illnesses with suspected Covid-19 with respiratory distress, frequent need for aerosol-generating procedures (nebulizations, oxygen through high flow nasal canula (HFNC) device, continuous positive airway pressure (CPAP), intubation, extubation, excessively crying child, child with distress and significant cough, cardiopulmonary resuscitation, etc) should be placed in a negative pressure isolation room.^[13]

Environmental Cleaning and Disinfection Strategies

The virus survives on environmental surfaces for varied period of time. The virus has lipid envelope, hence, can easily be disinfected by detergent solutions (e.g., Lysol) or commonly used disinfectants in health-care industry (70% alcohol, 1% sodium hypochlorite, ethylenedioxy dimethanol, benzylkonium chloride, glutaraldehyde, hydrogen peroxide, etc.).^[14]

In noncritical areas where patients with simple respiratory illness are kept who are not suspected of Covid-19, the floors and walls up to 3 feet can be mopped twice in 24 h (once with regular detergent solution and once with an with intermediate level disinfectant (1% sodium hypochlorite and benzylkonium chloride) or high-level disinfectant (glutaraldehyde plus ethylenedioxy dimethanol or glutaraldehyde plus benzylkonium chloride etc.) or hydrogen peroxide-based solution)
In the areas where the suspected or confirmed Covid-19 patients are placed, the floor and walls up to 3 feet height can be mopped three times a day with intermediate level disinfectant (1% sodium hypochlorite and benzylkonium chloride) or high level disinfectant (glutaraldehyde plus ethylenedioxy dimethanol or glutaraldehyde plus benzylkonium chloride, etc., or hydrogen peroxide-based solution)
The surface of patients bed rails, cardiac table, IV stands, syringe and infusion pumps, cardiac monitors, ventilators should be mopped with 60%–70% isopropyl alcohol (bacillol-25) or 0.5% sodium hypochlorite
All used linen pillow covers, etc., used for suspected or confirmed patients of Covid-19 irrespective of whether they were visibly soiled or not, shall be treated as “soiled linen” and shall be sent in yellow bag to sluicing room for the treatment with 1% sodium hypochlorite for 30 min, then washed and sent to laundry
Ambulance should be thoroughly mopped cleaned from inside the patient cabin area with intermediate level disinfectant (1% sodium hypochlorite and benzylkonium chloride) or high level disinfectant (gluteraldehyde plus ethylenedioxy dimethanol or gluteraldehyde plus benzylkonium chloride, etc) once in the morning and subsequently after every patient transport activity.

Terminal disinfection and body removal from isolation room or area.^[15]

The health worker attending to the dead body should perform hand hygiene, ensure proper use of personal-protective equipment (PPE) (water-resistant apron, goggles, N95 mask, and gloves)
The entire body should be mopped with 1% sodium hypochlorite. Any puncture holes or wounds (resulting from the removal of the catheter, drains, tubes, or otherwise) should be disinfected with 1% hypochlorite and dressed with impermeable material
Plug oral, nasal orifices of the dead body to prevent leakage of body fluids
If the family of the patient wishes to view the body at the time of removal from the isolation room or area, they may be allowed to do so with the application of standard precautions
Place the dead body in a leak-proof plastic body bag. The exterior of the body bag can be decontaminated with 1% hypochlorite
All used linen pillow covers, etc., irrespective of whether visibly soiled or not, should be treated as “soiled linen” and be sent in yellow bag to sluicing room for treatment with 1% sodium hypochlorite for 30 min, then washed and sent to laundry
Used equipment should be autoclaved or decontaminated with disinfectant solutions in accordance with established infection prevention control practices Laryngoscope blades to be mop cleaned with bacillol-25 (ethanol), AMBU bags to be washed and sent for gas sterilization/autoclaving. Suction bottles to be washed with soap solution, and then, 1% bacillocid extra or 1% hypochlorite before using for next patient
Ventilator tubing, bain circuits, oxygen masks, etc., are “single patient use” and shall not be used for any other patient
Instruments such as artery forceps, needle holder, and scissors shall be washed with 1% hypochlorite and sent for autoclaving
All medical waste must be handled and disposed of in accordance with biomedical waste management rules
The room will be subjected to “terminal cleaning”, whereby entire floor, entire walls, and ceiling shall be mopped with intermediate level disinfectant (1% sodium hypochlorite, benzylkonium chloride) or high level disinfectant (gluteraldehyde plus ethylenedioxy dimethanol or gluteraldehyde plus benzylkonium chloride, etc.) TWICE at 1-h interval.

Use of Personal Protective Equipment

^[15],[16]

PPE refers to equipment designed to protect the wearer from injury or the spread of infection or illness.

Procedure of hand hygiene, sequence of donning and doffing of PPE and masks is extensively covered on many platforms; hence, will not be discussed in this document.

Components of Personal Protective Equipment

Face shield and goggles

The flexible frame of goggles should provide good seal with the skin of the face, covering the eyes, and the surrounding areas and even accommodating for prescription glasses. Reprocessing of goggles and face-shield can be done by soap/detergent and water followed by disinfection using either sodium hypochlorite 0.5% (followed by rinsing with clean water) or 70% alcohol wipe.

Masks

Respirator/facemask should be extended under chin. Both the mouth and nose should be protected. Do not wear respirator/facemask under the chin (over neck) or store in scrubs pocket between the patients.

There are three types of masks:

Linen mask
Triple layer surgical mask
N-95 respirator mask.

Linen/cloth mask

The members of the public and those not working in patient care areas; use simple cloth face coverings when in a public setting to slow the spread of the virus.

Triple-layer surgical mask

A triple-layer surgical mask is a disposable mask, fluid-resistant, provide protection to the wearer from droplets of infectious material emitted during coughing/sneezing/talking having filter efficiency of 90% for 5 μ particle size. Surgical masks are not intended to be used more than once.

N-95 Respirator mask

An N-95 respirator mask is a respiratory protective device with high filtration efficiency to airborne particles. “N” indicates non-oil based uses, while “95” means up to 95% filtration of 0.3 micron size test particles. To provide the requisite air seal to the wearer, such masks are designed to achieve a very close facial fit. Since these provide a much tighter air seal than triple-layer surgical masks, they are designed to protect the wearer from inhaling airborne particles.

Gloves

Nitrile gloves are preferred over latex gloves because they resist chemicals, including certain disinfectants such as chlorine. There is a high rate of allergies to latex and contact allergic dermatitis among health workers. However, if nitrile gloves are not available, latex gloves can be used. FDA banned powdered gloves.

Gowns

Gowns are designed to protect torso of health-care providers from exposure to virus. They must be made from nonwoven water-resistant material. A plastic apron can also be worn over or under the gown for the entire time the health worker is in the treatment area.

Shoe covers

Shoe covers should be made up of impermeable fabric to be used over shoes to facilitate the personal protection and decontamination. It should ideally cover shoes along with ankles and lower part of legs.

Head covers

Cover-all gowns have provision to cover the head by a hoody or additional head cover piece. Those using plain gowns without in-built hoody or head cover should use a head cover that covers the head and neck while providing clinical care for patients.

Suggested Rational Use of Personal Protective Equipment

The PPEs are to be used based on the risk profile of the health-care worker. The following [Table 1] describes the PPEs to be used in different settings.

Table 1: The personal protective equipments to be used in different settings

Click here to view

During an epidemic and pandemic THERE IS NO EMERGENCY! Wear you PPE first!!

Even if the patient is gasping or in cardiac arrest, the team of doctors and nurses must wear complete PPE before examining the patient or attempting cardiopulmonary resuscitation (CPR).

Just because it is an “emergency “ if the doctors and nurses do not observe personal safety practices they themselves may get infected and subsequently infect their other colleagues. If they get infected, they are sent in quarantine for 15 days; hence, hospital loses its skilled workforce. If they become sick, then they occupy hospital bed and equipment. If they die and then again a great loss of trained individuals. Thus, during an epidemic there is NO “Emergency”!!

During CPR use 3–4 members in full PPE for CPR and avoid overcrowding. First connect the chest lead to assess cardiac rhythm and if shockable then deliver the shock. In the meantime, the rest of team members shall wear PPE and join the CPR using chest compression.

Some units are using a large transparent hood box which can be kept over patient's head to prevent aerosol spread. Intubation should be attempted by most senior member. Video laryngoscopy helps intubation by maintaining some distance away from the patient's face.^[17]

Clamp the ETT as soon as intubation is done to prevent aerosols coming out through ETT.

Use a bacterial/viral (HEPA) filter between ET adaptor and the AMBU bag to prevent aerosolization during ET bagging. Avoid using high flow devices such as Bain circuits which can produce more aerosols.

Reuse of masks and N-95 respirator:

The linen masks can be washed in a detergent solution and dried outside for re-use
Surgical masks are best disposed-off after single use
N-95 masks or respirators have been in short supply due to overwhelming demand across the world.

The CDC offers guidance on optimizing the supply of PPE when sudden increases in patient volume threaten a facility's PPE capacity which is as follows.^[16]

Extended use of N95 mask: Wear a surgical mask or face shield so that N95 is protected from direct exposure.

Decontamination of respirators: The CDC has highlighted three methods for decontamination of respirators (crisis standards).^[18]

Ultraviolet (UV) light – decontamination with UV irradiation was observed to reduce H1N1 influenza viability on N95 respirator surfaces at doses below the threshold observed to impair the integrity of the respirator.^[19],[20] Nebraska Medicine has implemented a protocol for UV irradiation of N95 respirators in the context of the COVID-19 pandemic^[21]
Hydrogen peroxide vapor – hydrogen peroxide vapor has been observed to inactivate other non-coronavirus single-stranded RNA viruses on environmental surfaces.^[22],[23] Duke University Health System and some other centers have created an in-house protocol using hydrogen peroxide vapor for N95 decontamination^[24],[25]
Moist heat has been observed to reduce the concentration of H1N1 influenza virus on N95 respirator surfaces.^[26] In this study, moist heat was applied by preparing a container with 1 L of tap water in the bottom and a dry horizontal rack above the water; the container was sealed and warmed in an oven to 65°C/150°F for at least three hours; it was then opened, the respirator placed on the rack, and the container resealed and placed back in the oven for an additional 30 min. No residual H1N1 infectivity was found.

5-days reuse strategy (Centers for Disease Control and Prevention)

Recently, CDC has recommended to issue five respirators to each HCW working in COVID area. The HCW will wear one respirator each day (shift) and store it in a breathable paper bag at the end of each shift. The order of N95 mask use should be repeated after minimum of 5 days gap before reusing the same N95 mask (i.e., on the 6^th day the first day N95 mask can be repeated). This will result in each HCW requiring a minimum of five N95 mask for 25 working days. This practice is extremely dangerous; should be used as LAST RESORT, when no other options are available.

One strategy which may be followed can be a combination of two strategies (keeping for 4 days and then subjecting to heat on day 5)

Keep the used N95 masks which were not used in sick patients and during aerosol-generating procedures, in dry place for 4 days (with name of the user stuck on mask) and then keep them inside an oven (not microwave) for 30 min at 7°C. The masks should not touch the metal parts of oven.

Microwave oven not recommended as this can damage the fibers of N95 masks.

Gas (ETO) sterilization is not recommended due to possible harm from the toxic gas.

These N95 masks which are subjected to the above method are now fit for re-uses in low-risk areas where aerosol-generating procedures are not done (in ER/respiratory wards where aerosol-generating procedures are not used/respiratory clinic etc.)

N95 respirators should be discarded, if there is increased resistant in breathing through N95 mask or it is visibly dirty, damaged, or soiled.

Note: N95 respirators will not be considered for disinfection and re-use when contaminated with blood, respiratory or nasal secretions, etc., or physically damaged (torn etc.) or used for a managing a confirmed COVID-19 patient involving aerosol-generating procedure.

Infection Control Aspects of Intensive Care Units

^[27]

Staff allocation in high-risk areas

Hospital should designate an intensive care unit (ICU) and HDU to provide care to COVID-19 suspected/confirmed cases, rather than admitting them randomly in different locations of hospital or ICUs.

Staff selected for such patient care should not have comorbidities or risk factors which are likely to make them susceptible to severe disease
Staff should be made aware of the risk of infection and infection control practices to be followed on such patients. Adequate numbers of nurses (nurse: patient ratio) should be maintained to ensure efficiency at work and adequate rest for the staff
Housekeeping department should provide adequate workforce to ensure environmental cleaning and disinfection strategies are not compromised
Training all staff (including X-ray technicians, housekeeping staff, and other ancillary staff) in infection control precautions and appropriate use of PPE.

Hand hygiene must be performed by all staff (including ancillary staff) in accordance with World Health Organization's [WHO's] “5 Moments of Hand Hygiene.”

Isolation precautions

Follow the standard infection control precautions for all patients, with additional contact and droplet isolation precautions for patients with COVID-19 admitted to the ICU.
If there is more than one patient in the room then separation of at least 1 m (3 feet) between patients beds to be maintained.
Thorough cleaning and disinfection of the environment and equipment per institutional policy (mopping of entire floor and walls up to 3 feet height with intermediate level or high level disinfectant at least three times every day. All equipments (ventilators, pumps, monitors, etc.), IV stands, patient bed rails to be mopped by 60%–70% alcohol at least 2-three times daily)
Limit transport of patients outside the ICU. Limit shifting of any equipment (for example, portable X-Ray machine, portable ultrasound machine, syringe pump, etc.) outside the isolation area of patient and if that is unavoidable, then the equipped should be thoroughly mopped with 60%–70% alcohol after moving out and before using for next patient
Avoid/limit aerosol-generating procedures (e.g., intubation, extubation, CPR before intubation, bronchoscopy, noninvasive ventilation [NIV], tracheostomy, etc.), if they are essential, airborne isolation precautions to be followed
Restricted entry of staff to the designated ICU for COVID-19 patients, so that only those directly involved in patient care are provided entry
Limit visitors to the ICU where COVID-19 patients are admitted
For negative pressure isolation air-handling systems delivering >12 air-changes per hour with 1–2 fresh air exchanges per hour, preferably with HEPA filter, are mandatory. For isopressure isolation rooms, 6–12 air exchanges with 1-2 fresh air exchanges should suffice.

Infection Control Aspects of Mechanical Ventilation

^[17]

If available, CPAP or bi-level NIV as a first-line approach is recommended rather than high-low nasal cannula (HFNC), in patients with SpO₂/FiO₂>221 and <264. Intubation should not be further delayed if SpO₂/FiO₂<221. CPAP/NIV bears increased risk of aerosol contamination, if there is a leak.

For NIV, prefer use of a certified helmet because leaks are minimized or a non-vented oronasal or full-face mask, a double-limb circuit (or a single limb with filter before the leak site) and appropriate bacterial/viral filters.

Intubation must be recommended if there is no improvement in oxygenation (target SpO₂92%–97% and FiO₂<0.6) within 60–90 min. One adult report suggests considering adding the ROX index (SpO2/FiO2 divided by the respiratory rate) in the decision-making for intubation (i.e., ROX <5). However, with SpO₂/FiO₂<221 intubation should not be further delayed.

High-flow nasal cannula (HFNC) might be considered as an option if CPAP/NIV is unavailable for patients with SpO₂/FiO₂>264 (FiO₂<0.35–0.40).

Like CPAP/NIV, with interfaces others than helmets, HFNC bears increased risk of aerosol contamination. Escalation of therapy (i.e., non-invasive ventilation or intubation) should not be delayed, if there is no improvement in oxygenation within 30-60 min (target for HFNC treatment success: SpO₂92%–97% with FiO₂<0.4).

Intubation is performed by an expert in the airway management in a closed environment with a minimal amount of staff.

Video laryngoscopy (if available) should be used. All personnel should have PPE. Preoxygenating the patient with a bag/mask that is equipped with a bacterial/viral filter.

If bag/mask ventilation is necessary use the “two-person technique” to ensure a better seal of the mask around the mouth. The panel recommends rapid sequence induction to avoid bag-mask ventilation which can result more aerosol generation.

Use cuffed endotracheal tubes, inflating the cuff immediately after intubation before verification of the position of the tube by end-tidal CO₂, chest X-ray, auscultation or ultrasound examination.

Minimize ETT disconnections and the use of inline, closed suctioning.

Preference heat moisture exchangers with bacterial/viral filters (not regular HME filters) to reduce the risk of aerosol contamination. Active humidification may bear the risk of aerosol contamination.

The use of bacterial/viral filters on the expiratory limb of the patient circuit (particularly when there is active humidification used) and to replace them every 24–48 h, or earlier if they become wet to ensure full efficiency.

In addition to a bacterial/viral filter in the expiratory limb, some manufacturers (e.g., Maquet and Getinge) are recommending one more bacterial/viral filter in the inspiratory limb as extra precaution for COVID-19 patients. Some ventilators (e.g., GE Carescape R860) have one bacterial/viral filter already in place in the inspiratory limb hence one bacterial/viral filter is needed only in expiratory limb in them.

The endotracheal tube should be immediately clamped in case of disconnection whether expected or unexpected.

Routine chest physiotherapy, use of cough assist is not recommended in the absence of any thick mucus or history of mucus plugs in the airways.

Infection Control Aspects of Ecmo

^[28]

Procedure of cannulation and decannulation are high risk for aerosolization. ECMO patients should ideally be managed in negative pressure isolation rooms (negative pressure of 2–4 Pascals, with 12 air exchanges 92 fresh air exchanges) per hour and preferably with HEPA filter. The mopping and disinfection strategies, visitor and staff and equipment movement policies will be same as for a ventilated patient described earlier.

Risk of aerosolization from the oxygenator in ECMO^[29]

During cardiac surgeries, the oxygenator with microporous membranes is being used. A typical microporous fiber (e.g. Getinge company make) has pore size of up to 200 nm (≤0.2 μm). Based on the reported diameter of the virus 3 (≈60–140 nm), there is a theoretical risk of virus transmission across the gas exchange membrane.

Thus, the virus can leave patients' blood, enter the inner lumen of gas fibers and leave the oxygenator through the gas outlet passing from the blood to the gas side of such oxygenators. This is more likely when this oxygenator is used beyond 6 h and develops plasma leakage (sometimes plasma leak may start even before 6 h of use).

It advisable not to use microporous oxygenators for applications over 6 h. This significantly reduces the risk of plasma leakage and possible aerosolization.

The oxygenators typically used for ECMO in ICU have with polymethylpentene (PMP) fibers with a plasma tight diffusion membrane; hence, there are negligible chances of aerosolization of Covid-19 virus from the PMP oxygenators used in regular ECMOs in the ICUs [Table 2] and [Figure 1].^[30]

Table 2: Approach to exposures in health care workers^[30]

Click here to view

Figure 1: Flowchart on the management of health-care provider's exposure to coronavirus disease (COVID 19). Note: This flowchart is applicable only to HCPs that have provided direct care to a confirmed case of COVID 19. Exposure risk assessment must be conducted by facilities infection control practitioner. *Quarantine ideally for 14 days, but if staff shortage may reduce to at least7 days. In addition, someone who develops symptoms of cold, cough, fever, etc., and had been taking care of COVID-19 patients undergoes screening (nasopharyngeal swabs for COVID19 PCR) and if comes positive, then goes in 14 days quarantine

Click here to view

Conclusion

Even though knowledge regarding the care of patients with COVID-19 is constantly evolving, adhering to basic practices of hand hygiene, isolation practices, use of PPE, and sterilization and disinfection practices are still the corner stone of patient care and personal protection. There is no emergency during an epidemic situation. The use of proper protective equipment before approaching a patient is crucial for self-protection and protection of entire health-care system.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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