The COVID-19 pandemic, undoubtedly one of the greatest healthcare crises in a century, has a silver lining in the world of medical research: it has allowed researchers to conduct experiments in the context of an unprecedentedly aggressive pandemic. There exists a whole body of COVID-19 studies in the medical literature—some conducted at the start of the pandemic when much about the virus was unknown; others conducted when the global situation was more stable. Either way, they all conveyed useful information. 

The boom in scientific research is remarkable, considering that researchers from most nations experienced some form of lockdown that hampered their ability to travel to their place of work and collaborate with other researchers in a physical setting. 

If you read between the lines, medical literature during this era carries with it a sense of confusion and urgency, especially during the early stage, when some of the drugs used on seriously ill patients were rather experimental in nature. We can be grateful for the sense of responsibility that many scientists felt in playing their part to solve the puzzle that was the COVID-19 pandemic, and some of the research that has arisen from that period offers us fascinating ideas that are still relevant today. 


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Some of the studies conducted examined the link between alpha-1 antitrypsin deficiency (AATD) and COVID-19. There is a logic in this: both conditions can contribute to severe respiratory disease. Herth and colleagues wrote a paper that reported on the benefits of the self-administration of alpha-1 antitrypsin (AAT) therapy for AATD patients during the COVID-19 pandemic, when travel to healthcare settings was either impossible or seriously discouraged. 

The Benefits of Continued AAT Therapy 

AAT therapy is usually administered in a healthcare setting through weekly IV infusions, although self-administration is possible with appropriate training. Herth and colleagues commented that many respiratory conditions—including asthma, chronic obstructive pulmonary disease (COPD), and asthma—already allow self-administration of medications.

Self-administration of AAT therapy has 2 main objectives: relieving the patient’s disease burden and extending survival. Herth et al spent the bulk of their study examining the impact of AAT therapy on quality of life (QoL) and mortality.

In terms of QoL, AAT therapy mainly helps in reducing the frequency and severity of exacerbations. Studies have indicated that fewer exacerbations caused patients to rate their QoL higher. There is a solid reason for this: AAT therapy slows deterioration in lung function. Therefore, even in the context of COVID-19, it is imperative that AAT therapy continues to be administered in AATD patients. 

Read more about AATD treatment 

In terms of extending survival, Herth quoted a study that showed AAT therapy significantly improved overall survival in all predicted forced expiratory volume in 1 second (FEV1) deciles (from 10% to 60%), compared to AATD patients who never received AAT therapy. Another study indicated that the switching of patients from placebo to AAT therapy resulted in slower lung density decline after 48 months. 

The Role of AAT Therapy in COVID-19 Care 

Since AATD and COVID-19 both cause pulmonary decline, can AAT therapy be used in COVID-19 patients? This is the subject of a study by Bai and colleagues. 

“No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids,” Bai et al wrote in late 2020. They then asked the question: would AAT therapy work to ameliorate some of the symptoms of COVID-19? 

The study team listed a number of reasons why AAT therapy should theoretically work in COVID-19 patients. Among them are: 

  • AAT makes it more difficult for the COVID-19 virus to gain intracellular entry. 
  • AAT has potent anti-inflammatory properties. 
  • AAT inhibits injurious neutrophils implicated in acute lung injury. 
  • AAT inhibits the formation of thrombin, which is implicated in COVID-19. 

In other words, there are solid scientific grounds as to why AAT therapy should be considered to treat COVID-19.

“AAT is a promising therapeutic for COVID-19,” Bai et al wrote. “It is also important to note that AAT is routinely prescribed to those with AAT deficiency, has an excellent safety profile, and normal plasma AAT levels may be achieved with once weekly intravenous administration.” 

Read more about AATD therapies 

However, Bai and colleagues never tested their hypothesis in real-life. They only recommended, “If mounting evidence shows that AAT does have significant activity against SARS-CoV-2 infection, it can be studied by randomized, placebo-controlled trials in which AAT is administered by different means depending on the severity of the SARS-CoV-2 infection.” 

Looking Ahead 

It is incredible that scientists and physicians are so adept at putting 2 and 2 together; in the case of AATD and COVID-19, there was a speedy recognition that perhaps the 2 diseases share some common pathological pathways and can hence be treated in a similar way. Also, scientists immediately realized that if medications cannot be administered in-person, then a switch to self-administration must occur, and quickly.

This has undoubtedly led to the normalization of the self-administration of drugs (and the boom in telemedicine), which are rather permanent changes even as COVID-19 retreats to become an endemic disease. Progress, ingenuity, commitment, and speed: these are the traits of the best of us who rose up to the challenge in an unprecedentedly dark time. 

References

Herth FJF, Sandhaus RA, Turner AM, Sucena M, Welte T, Greulich T. Alpha-1 antitrypsin therapy in patients with alpha-1 antitrypsin deficiency: perspectives from a registry study and practical considerations for self-administration during the COVID-19 pandemicInt J Chron Obstruct Pulmon Dis. Published online November 1, 2021. doi:10.2147/COPD.S325211

Bai X, Hippensteel J, Leavitt A, et al. Hypothesis: alpha-1-antitrypsin is a promising treatment option for COVID-19. Med Hypotheses. Published online November 12, 2020. doi:10.1016/j.mehy.2020.110394