Do We Need to Worry About Asymptomatic COVID-19 Infection?

Christy Leung

Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, emerged in late 2019 and has become a pandemic. Although SARS-CoV-2 primarily attacks host respiratory tracts, as suggested by its name, the virus can also cause inflammation-mediated multi-organ injury upon binding to angiotensin-converting enzyme 2 (ACE2) receptors in other host cell types. This condition is described as multi-system inflammatory syndrome in children (MIS-C) or adults (MIS-A). 

From its wild-type strain, the virus has undergone mutations to form variants, of which the Alpha, Delta, and Omicron ones led to outbreaks. The latest variant, Omicron, has reportedly caused lower morbidity and mortality rates compared to its preceding variants. Together with the implementation of population-wide COVID-19 vaccination which confers immunological protection, it is reported that as many as one-third of COVID-19—infected individuals are asymptomatic. Individuals may then be tempted to underestimate the health consequences, subsequently becoming more complacent with personal hygiene measures. Recent studies, however, warn an increased likelihood of developing “long COVID” or even sinister chronic medical conditions in COVID-19—infected individuals, compared to the uninfected. This sparks debate as to whether any asymptomatic presentation is just the sugar-coated tip of a troublesome iceberg. 

Long COVID

“Long COVID”, otherwise described as “Post COVID-19 Syndrome”, implies the onset or persistence of COVID-19-related signs and symptoms for a long period following infection; some studies define the cut-off onset as 4 weeks, with others as 12 weeks. Common manifestations of “long COVID” include anosmia (inability to smell) and ageusia (inability to taste), in addition to fatigue, shortness of breath and dyscognition (brain fog). In some cases, such symptoms may persist even after 6 months post-infection. While these symptoms may seem trivial, they bring about significant impacts on individuals themselves, as well as society. For example, healthcare workers, a high-risk group for “long COVID”, may have impaired work productivity. Consequently, the day-to-day functioning of clinics and wards may also be affected. At the same time, their loss of ability to taste deprives them of the opportunities to enjoy their cuisine. Ultimately, stagnant operation in different sectors may halt economic growth at the national level.

Since “long COVID” symptoms can be debilitating to some, the scientific community is investigating ways to reduce the chance of progression to “long COVID”. For example, Hong Kong researchers propose that the intake of probiotics may aid the regulation of the gut microbiome, lowering the likelihood of developing a clinical presentation consistent with “long COVID”.

The abovementioned “long COVID” symptoms are mostly subjective. However, objective investigation methods can be obtained to quantify the extent of impairment. For example, dyscognition may be measured by the Montreal Cognitive Assessment (MoCA), assessing aspects such as working memory and attention. On the other hand, shortness of breath may be measured by lung function tests to look for any abnormalities, such as restrictive or obstructive lung disease-like patterns.

Lung Function Impairment

Munker et al. conducted a study measuring the lung functions of COVID-19 patients, from asymptomatic to symptomatic, to the hospitalised. The most striking finding for mild or asymptomatic COVID-19 patients was a decrease in partial pressure of oxygen in arterial blood (PaO2); 5 out of 23 experienced PaO2 decrease, with an overall value of 78.7±6.6 (p<0.01). This aligns with our current understanding that COVID-19 infection causes low arterial oxygenation; the extent of hypo-oxygenation correlates with disease severity. Although its overall value only slightly deviates from the reference range of 80 to 100 mmHg, hypo-oxygenation leads to hypoxaemia (low blood oxygen concentration) and subsequent chronic tissue hypoxia (insufficient oxygen delivery to tissues) (Rabi, 2017). Ultimately, it may take its toll on patients’ activities of daily life, subjectively. However, additional evidence on the impact of reduced arterial oxygenation will require more long-term follow-up of COVID-19 survivors.

Cardiovascular Risk

The heart is responsible for pumping blood to all organs through blood vessels, so it is important to assess for any increased risk of cardiovascular complications following COVID-19 infection. According to Ziyad Al-Aly from the Veteran Affairs St. Louis Health Care System, even asymptomatic COVID-19 patients experience a higher likelihood of arrhythmias, myocarditis and, pericarditis, in addition to systemic thromboembolism and cerebrovascular accidents; in particular, myocardial infarction, stroke and hospitalisation from heart failure belong to the “major adverse cardiovascular events” category, reflecting their severity and potential for acute clinical deterioration. These findings may be attributed to incomplete viral clearance, followed by SARS-CoV-2 entry into host cardiac muscle cells or cells lining vessel walls, then inflammation. 

Autoimmune Diseases

Apart from non-specific “long COVID” symptoms, studies have shown the increased incidence of autoimmune diseases following COVID-19 infection. 

Upon COVID-19 infection, host neutralising antibodies form immune complexes with COVID-19—specific antigens. This immune response is present even in asymptomatic COVID-19 individuals. The circulation of immune complexes and viral presence in the lower gastrointestinal tract persist in hosts for months, suggesting the possibility of host immune response chronically. Sometimes, the host immune system may incorrectly recognise self-antigens from blood vessel wall cells as foreign antigens, triggering a Type III hypersensitivity reaction characterised by complement activation. This accounts for vasculitis — inflammation of blood vessels. Examples of vasculitis triggered by COVID-19 are IgA vasculitis (small-vessel vasculitis), Kawasaki Disease-like vasculitis (medium-vessel vasculitis) and, giant cell arteritis (large-vessel vasculitis); asymptomatic COVID-19 patients are not spared from this risk. Examples of subsequent complications are coronary artery aneurysms from Kawasaki-like presentation, blindness from giant cell arteritis, or  kidney insufficiency from IgA vasculitis.

In conclusion, asymptomatic COVID-19 infection does not imply the lack of long-term complications. Patients may still encounter systemic health consequences, such as the increased risk of cardiovascular diseases, lung function impairment, neurological consequences like dyscognition, and autoimmune conditions, along with reduced quality of life. Therefore, all efforts should be made to control SARS-CoV-2 transmission by performing personal hygiene and complying with quarantine measures. Nonetheless, for the already-infected asymptomatic individuals, there is no need for excessive worry; close monitoring of their own signs and symptoms should suffice.

References

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