Want to prevent long COVID? Prevent COVID-19

The House of Representatives’ Standing Committee on Health, Aged Care and Sport will inquire into and report on long COVID and repeated SARS-CoV-2 infections, at the direction of the Minister for Health and Aged Care, the Hon Mark Butler MP. Submissions to the inquiry closed on 18 November 2022. The following is an edited version of the submission of Dr Benjamin Veness, co-founder of Health Care Workers Australia, advocating for improved health care worker and patient safety from COVID-19, and a founding member of OzSAGE.

LONG COVID is a syndrome that follows some cases of COVID-19, ranging from very mild acute COVID-19 disease to the most severe forms.

The most effective way to prevent long COVID is to prevent COVID-19. A primary objective of the Australian health response to COVID-19 ought therefore be to minimise the number of cases of COVID-19, as opposed to merely aiming to minimise severe acute disease and death.

COVID-19 is caused by SARS-CoV-2, a virus that is primarily transmitted by the airborne route (here and here). As Lazarus and colleagues conclude in their multinational Delphi consensus paper published in Nature: “Public health authorities contribute to the dissemination of false information when their communications do not reflect current scientific understanding that transmission of SARS-CoV-2 is primarily airborne.”

It is imperative that Australian public health authorities heed this lesson and act immediately to improve public awareness of what airborne transmission of SARS-CoV-2 means in terms of risk of infection and effective risk mitigation. For example, it could become a public health objective that public awareness and acceptance of the following facts are maximised through educational campaigns and overt role modelling by authorities:

“SARS-CoV-2 is an airborne virus that presents the highest risk of transmission in indoor areas with poor ventilation.”

The analogy of cigarette smoke posing a passive health risk, especially in poorly ventilated environments, may be helpful as a communication tool.

Given this airborne mode of transmission, much greater emphasis should be placed on mitigating it through the use of a “vaccines plus” approach in Australia, which would include broader access to vaccination plus “testing, surveillance, treatment, community engagement and implementation of social prevention measures (such as facemasks, distancing [and isolation] and quarantine), structural interventions (such as ventilation and air filtration) and financial incentives (eg, support measures)”.

Measures used at the individual level, such as vaccination, testing, treatment, facemasks, isolation and quarantine, must be easily accessible in order to maximise voluntary uptake. Ideally these measures would be readily available at no cost to all persons, or at least they must be subsidised or compensated for persons for whom cost would otherwise inhibit access.

Vaccination

Vaccination has been a core focus of the Australian public health response to COVID-19. Access to vaccination, however, has been restricted based on a combination of factors including vaccine stock availability, Therapeutic Goods Administration (TGA) approval and Australian Technical Advisory Group on Immunisation (ATAGI) advice.

For example, whereas the US has offered COVID-19 vaccination for all children aged 6 months and older since June 2022, ATAGI advice effectively restricts access to vaccination for most children until age 5 years, regardless of caregiver preference.

Similarly, the US recommends the bivalent BA.4/5 COVID-19 booster for all persons aged 5 years and older, whereas ATAGI advice effectively limits bivalent booster doses to persons aged 18 years and over, again regardless of patient or caregiver preference.

For older persons who are “up to date” with their vaccination schedule yet received their last (monovalent) booster many months ago, ATAGI advice effectively prohibits them from accessing the bivalent booster, regardless of patient preference and in contrast to what is recommended in the US.

The rationale for the US’s approach has been detailed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices and is supported by recently published data.

It is not clear why the Australian advice is so divergent from that of the US, especially because ATAGI’s meetings are held in camera, minutes are not published, and advice is often unreferenced, with limited rationale provided.

Usual medical practice in Australia involves discussion between doctor and patient about available preventive health options, and both the doctor’s clinical judgment and the patient’s autonomy are respected as far as practicable. With other vaccinations, for example, typically if a doctor and patient agree that it is in the patient’s best interest to have the vaccination, this may proceed even if not perfectly aligned to Australian guidance such as the National Immunisation Program Schedule. The patient may be required to purchase the vaccine via private script, but the vaccine is nonetheless available to them.

It is unclear why a similar scenario does not exist for COVID-19 vaccinations, particularly in this current era of so-called personal responsibility to protect oneself against infection, as many politicians have espoused.

Face masks

Given SARS-CoV-2 spreads primarily via the airborne route, widespread use of high filtration and well-fitting respirators (eg, P2, N95, KF94, KN95, FFP2/3) is important to reduce transmission, particularly in high risk settings. It therefore follows that use of such respirators should be encouraged via educational campaigns and overt role modelling by authorities. As per AS/NZS 1716:2012 “Respiratory protective devices” and manufacturer recommendations, respirators should ideally be fit-tested to ensure the wearer is obtaining maximal protection from the device, however lay people could easily be taught to perform a fit-check, which is better than nothing.

While respirator fit-testing has historically been provided by employers of workers in industries such as mining and construction, and was eventually provided by most clinical health services to employees working in clinical spaces, it remains difficult to access for members of the general public – even persons at significantly increased risk of severe acute COVID-19 or death.

An obvious opportunity exists for fit-testing to be made available to the public through local public health units and similar services. Ideally, this would be coupled with a program of free distribution of respirators for everyone who wants them, or at least they could be subsidised for persons for whom cost would otherwise inhibit access. Of note, a fit-tested respirator provides very high level protection not just for the wearer but also for others, thus conferring a public health benefit by mitigating disease transmission.

Isolation and quarantine

Isolation of cases and quarantine of close contacts is a standard public health measure for mitigating the spread of an infectious disease, and in this case would assist with reducing the incidence of long COVID and repeated COVID-19 infections.

It remains unclear why mandatory isolation and quarantine were ceased in Australia, and the public health rationale and modelling of impact ought to be made transparent in the interests of both science and maintaining public confidence in public health and government institutions.

In the US, there remains a minimum 5-day isolation period for persons diagnosed with COVID-19, followed by a minimum 5-day period of mandated mask-wearing unless the person tests negative on serial rapid antigen tests (RATs) taken 48 hours apart.

Given the availability of RATs, Australia could consider requiring isolation of cases until two serial negative RATs have been achieved (a “test to cease” approach). Serial tests are important to account for false negatives, due for example to poor specimen collection or test error, which the US Food and Drug Administration has warned is more likely with the Omicron variants. A test to cease approach would appear to be a more scientific method of determining when to cease isolation compared with relying on self-judgement or symptom resolution, neither of which corresponds as well with infectivity, which is the reason for requiring isolation in the first place.

Indoor air quality

As Lazarus and colleagues articulate well:

“Relying on individual, voluntary compliance with transmission prevention measures is insufficient to end COVID-19 as a public health threat.”

They therefore recommend countries adopt a “vaccines plus” approach, including that:

“Governments should regulate and incentivise the development and deployment of structural prevention measures (eg, ventilation, air filtration) to mitigate airborne transmission of SARS-CoV-2, with an early emphasis on high risk settings.”

Further,

“Prevention of SARS-CoV-2 transmission in the workplace, educational institutions and centres of commerce should remain a high priority, reflected in public health guidance and supported through multiple social measures and structural interventions (eg, remote work/schooling policies, ventilation, air filtration, facemask wearing).”

This advice makes sense not only for mitigation of SARS-CoV-2 transmission but also as a public health intervention to protect against a variety of other airborne pathogens, including as part of a pandemic preparedness strategy for future threats.

Ventilation can be monitored with carbon dioxide meters, which are relatively inexpensive and easy to use and interpret. Belgium provides an example of a jurisdiction in which public display of such meters in public places will soon be required (here and here). Their plan also includes risk assessments, carbon dioxide targets, indoor air quality labelling, and a centralised database.

In the US, the White House recently launched “The Clean Air in Buildings Challenge”, which they describe as “a call to action for organizational leaders and building owners and operators of all types to assess their indoor air quality and make ventilation, air filtration, and air cleaning improvements to help keep building occupants safe. As part of the Challenge, the Environmental Protection Agency (EPA) published a best practices guide for improving indoor air quality and reducing the risk of spreading dangerous airborne particles”.

The Challenge involves an online pledge with four key commitments for leaders, owners, and operators of businesses, schools, and other buildings. They include creating a clean indoor air action plan, optimising fresh air ventilation, enhancing air filtration and cleaning, and engaging the building community. Once the pledge has been taken, building managers can download and print a digital “Clean Indoor Air Champion” pledge badge for public display.

Australia could use a combination of education, regulation and incentives to improve indoor air quality and encourage the use of outdoor spaces where practicable; for example, outdoor learning and meeting spaces, including for concerts and other forms of mass entertainment. Regulation could be informed by The Lancet COVID-19 Commission’s Task Force on Safe Work, Safe School, and Safe Travel, which recently published proposed non-infectious air delivery rate targets.

Diagnosis

Community testing options need to include both RATs and gold-standard polymerase chain reaction (PCR) tests in order to optimise case ascertainment and opportunities for effective isolation and treatment of cases.

Testing should continue to be encouraged before mass private or public gatherings, to reduce the likelihood of preventable infections. Both RATs and PCR testing options must be easily accessible for this to occur, especially for lower socio-economic groups and persons for whom the personal risk of infection is perceived as low, but who nonetheless pose a significant public health risk (ie, socially mobile younger people).

New York City offers “COVID-19 Express Testing” in which appointments are available at six public health locations within the city, free to all New Yorkers, regardless of insurance and immigration status. All tests are PCR with a panel that includes not only SARS-CoV-2 but also influenza A, influenza B, and respiratory syncytial virus (RSV). Test results are available within 24 hours, but usually less – sometimes as few as 2 hours. Rapid tests are also freely available for collection from all New York Public Library sites. Testing before and after social gatherings such as Thanksgiving and Christmas is routinely encouraged in public health messaging.

The city also operates a “Test and Treat Corps” that includes a network of mobile and fixed locations for free COVID-19 testing and treatment (eg, prescriptions and dispensing of nirmatrelvir/ritonavir [Paxlovid] antiviral tablets), again regardless of insurance or immigration status. The “Test and Treat Corps” service also includes telephone (212-COVID-19) and video telehealth options so patients with a diagnosis of COVID-19 (made by either RAT or PCR) do not need to break isolation to access treatment.

Treatment

A recent preprint article on the medRxiv server, from researchers in the US using a large Veterans Affairs dataset (participants were predominantly white males with comorbidities and a mean age of 65 years), found evidence that, compared with the control group, treatment with nirmatrelvir/ritonavir (Paxlovid) antiviral tablets was associated with a 26% reduced risk of post-acute sequelae of SARS-CoV-2 (ie, long COVID), “including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath”. Treatment was also associated with a reduced risk of post-acute death and post-acute hospitalisation. Eligibility for treatment was broader than in Australia, with participants only requiring one of the following risk factors for progression to severe acute COVID-19: “age > 60, [body mass index] > 25 km/m², current smoker, cancer, cardiovascular disease, kidney disease, chronic lung disease, diabetes, immune dysfunction and hypertension”.

While not yet peer-reviewed, and limited by its lack of younger, healthier and female subjects, this research provides promising evidence in support of broader use of nirmatrelvir/ritonavir (Paxlovid) in Australia as a treatment for acute COVID-19. The rationale for its use includes a combination of reduced duration of infectivity (here and here) (thus reducing the effective reproductive number of the disease and therefore the number of people each case is likely to infect), reduced severity of symptoms of acute COVID-19, reduced risk of death, and likely also a reduced risk of long COVID. More data are needed on prevention of long COVID by molnupiravir, which reduces viral load and accelerates viral clearance.

However, similar to the case with vaccination, access to antiviral treatment is relatively limited in Australia, especially compared with the US.

In the US, the National Institutes of Health COVID-19 treatment guidelines recommend treatment with nirmatrelvir/ritonavir (Paxlovid) or else remdesivir for patients who do not require hospitalisation or supplemental oxygen but who are at high risk of progressing to severe COVID-19. This treatment is provided for free. The definition of “high risk of progressing to severe COVID-19” is linked to the Centers for Disease Control and Prevention webpage, “Underlying medical conditions associated with higher risk for severe COVID-19”, which provides a long list of conditions, for example, asthma, cancer, diabetes mellitus, mood disorders including depression, obesity, pregnancy, physical inactivity, and current or former smoking, among others, to guide clinician prescribing.

The net result is that a much broader range of people in the US are eligible for treatment with antiviral therapies compared with Australia, where the criteria to access treatment under the Pharmaceutical Benefits Scheme (PBS) are very limited. Treatment in Australia outside of the PBS, on private script, is prohibitively expensive at approximately A$1159.50 for a course of nirmatrelvir/ritonavir (Paxlovid), posing an equity issue as access is effectively limited to those of high socio-economic status or the small fraction of the community eligible for subsidised antivirals.

As with vaccination, especially in this current era of so-called personal responsibility to protect oneself against infection, consideration should be given to widening the PBS criteria for treatment with antiviral therapies, especially where there is emerging evidence of likely benefit against long COVID. That treatment is also likely to reduce the duration of infectivity and symptoms is an added societal benefit in that infected persons are less likely to pose a health risk to others and more likely to be able to return to the workforce quickly.

Summary

The most effective way to prevent long COVID is to prevent COVID-19.

A primary objective of the Australian health response to COVID-19 ought therefore be to minimise the number of cases of COVID-19, as opposed to merely aiming to minimise severe acute disease and death. The COVID-19 and long COVID strategy should be informed by a “vaccines plus” approach and the multinational Delphi consensus article by Lazarus and colleagues published in Nature. Regard must be paid to the social determinants of health, including the ability of individuals to access effective risk mitigants for an airborne virus such as SARS-CoV-2.

Dr Benjamin Veness is a psychiatrist and holds a Master of Public Health from the University of Sydney. In the early phase of the COVID-19 pandemic, he co-founded Health Care Workers Australia to advocate for improved health care worker and patient safety from COVID-19. He was also a founding member of OzSAGE, the Australian Scientific Advisory Group of Experts. Twitter @venessb and Mastodon @venessb@med-mastodon.com

 

 

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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