by Molly Sargen
figures by Molly Sargen, Buse Aktaş, and Aparna Nathan

COVID-19 is unarguably devastating from any perspective. Even as we struggle to overcome the present challenges of the pandemic, COVID-19 is paving the way for other infectious agents to cause damage in the future. Although SARS-CoV-2 is a virus that cannot be treated with antibiotics, antibiotic usage has significantly increased throughout the pandemic. With increased antibiotic usage, the prevalence of antibiotic resistance, which was already a global problem prior to COVID-19, has also accelerated. 

What is antibiotic resistance? 

Antibiotics are drugs that inhibit the growth of or kill microorganisms such as bacteria or fungi by damaging important cellular structures or blocking processes microbes require to survive. Antibiotic resistance is the ability of microorganisms to evade the effects of antibiotics. Specific changes in a microbe, such as gaining the ability to pump an antibiotic out of the cell, destroy the antibiotic, or modify the target of the antibiotic, can make the microbe insusceptible to the harmful effects of the antibiotic. Whenever microbes are exposed to a condition that inhibits growth, such as antibiotics, they are pressured to make changes that will help them survive. Microbes that acquire resistance can multiply rapidly and spread the resistance to other microbes, resulting in exponential spread of resistance. 

How is the response to COVID-19 increasing antibiotic resistance? 

Antibiotic resistance increases with heightened antibiotic usage as microbes exposed to antibiotics face more pressure to develop resistance. Since February 2020, antibiotic use has risen drastically across the globe, largely tied to changes in medical practices due to SARS-CoV-2 (1, 2). Several studies estimate that 70-97% of hospitalized patients with COVID-19 receive antibiotic therapy (3, 4, 5). This high usage is striking because antibiotics cannot directly treat COVID-19. Viruses like SARS-CoV-2 are non-living infectious particles and therefore unaffected by antibiotics, which target essential features of living bacteria and fungi. Overall antibiotic usage has increased since the start of the pandemic and the surplus exposure to antibiotics fuels a parallel threat of resistant microbes.

Two factors of the COVID-19 response have driven increased antibiotic usage: an increase in standard antibiotic usage and several forms of misguided antibiotic usage.

Increased standard antibiotic usage: 

Before widespread testing and diagnosis of COVID-19, patients presenting symptoms of respiratory infections were often given antibiotics that might treat bacterial or fungal lung infections in the absence of or prior to a diagnosis. Even though diagnosis of COVID-19 is now more efficient, antibiotic treatment is often initiated as a precaution prior to receiving a test result. Early and precautionary antibiotic treatment is a standard of care that is often beneficial in the case of true bacterial or fungal infections. However, during the COVID-19 pandemic, the number of patients presenting with these symptoms and thus receiving this standard antibiotic therapy has drastically increased. 

Similarly, antibiotics have been used as preventative therapy against further bacterial or fungal infections, known as secondary infections. Severe illness, like cases of COVID-19 that require hospitalization, increases the risk of secondary infections as patients may have weakened immune systems or require invasive procedures, such as intubation. Secondary infections can be devastating or even lethal for these critically ill patients, so preventative antibiotics are standard protocol for many procedures. Critically, irrespective of preventative antibiotic treatment, only ~10% of patients hospitalized with COVID-19 also acquire secondary infections, indicating that a significant portion of antibiotic therapy for COVID-19 patients is unnecessary.  

Misguided antibiotic usage:

Early in the pandemic, in the absence of well-defined treatments for the novel disease, doctors tried to use drugs that were already clinically approved for use in patients. For example, azithromycin is a well characterized antibiotic that has been used for decades to treat bacterial illnesses including ear infections, bronchitis, and some sexually transmitted diseases.  Although classified as an antibiotic, azithromycin’s mechanism of action against bacteria and potential anti-inflammatory effects suggested it could have some impact on replication of SARS-CoV-2 and inflammatory symptoms. It has now been confirmed that azithromycin and closely related drugs have no effect on COVID-19. Nonetheless, increased resistance to these drugs stemming from heightened use early in the pandemic is projected as researchers continue to collect antimicrobial resistance data from the end of 2020. 

The increase in telehealth appointments during the pandemic has also increased antibiotic prescriptions. The higher frequency of antibiotic prescriptions during virtual healthcare was well-documented prior to the pandemic. Antibiotics are prescribed for a broader set of symptoms in the absence of physical examinations or laboratory tests to determine whether antibiotics are truly necessary. 

Why is antibiotic resistance a problem? 

Antibiotic resistance makes it more challenging and expensive to treat infections. Resistant infections require testing to determine what drugs are suitable for treating the infection. When the first choice of antibiotics are ineffective, more expensive drugs or a longer treatment regimen may be required. Additionally, microbes resistant to one antibiotic may also be resistant to others, a phenomenon known as multi-drug resistance that further exacerbates challenges in treating resistant infections. 

2.8 million people contract antibiotic-resistant infections every year, resulting in 700,000 deaths. While these numbers may seem small in comparison to the devastating impact of COVID-19 in 2020, antibiotic-resistant infections occur year after year, leading to a sustained impact on healthcare and the economy. Furthermore, trends of increasing antibiotic resistance suggest that the annual death toll from antibiotic resistant infections will be greater than 10 million by 2050. 

How can COVID-19 positively impact the future of antibiotic resistance? 

Despite the numerous negative consequences, COVID-19 has driven shifts in the mindsets of both medical professionals and civilians toward infectious diseases that could improve future management of antibiotic usage. Firstly, a major aspect of managing antibiotic usage is preventing infections, and thus the need for antibiotics, in the first place. One component of infection prevention is general hygiene, which reduces the chances of one’s own infection and the potential to spread the causative microbes. Such practices have been widely adopted during COVID-19 and have been shown to reduce the spread of some commonly transmitted illnesses, like the flu. 

A second critical component of preventing infections is immunization. Immunization can prevent illnesses that might require antibiotic treatment like whooping cough (pertussis), tetanus, and meningitis. However, vaccine hesitancy and refusal leave many people susceptible to these infections. As people eagerly await vaccines against SARS-CoV-2 and praise the vaccines’ effectiveness, vaccination may be more widely accepted. 

An additional aspect of preventing infections is containing antibiotic-resistant infections. Antibiotic resistance spreads especially rapidly within hospitals as resistant microbes are easily transferred among vulnerable patients. Containment of COVID-19 within hospital settings has shown it is possible to prevent the spread of even highly contagious pathogens. Thus, the strict infection containment practices adopted in many communities provide a model for reducing the spread of antibiotic-resistant infections especially within hospitals. 

Lastly, antibiotic resistance will require an integrated approach to global health. COVID-19 has highlighted how health across the globe is connected and affects many other aspects of society. Hopefully, the impact of COVID-19 will promote the adoption of transdisciplinary and international approaches, such as the One Health Approach, which recognizes that human health is connected to a broad range of global economic and environmental factors that must be considered when addressing public health concerns.      

All in all, while altered practices during the COVID-19 pandemic are accelerating the development of antibiotic resistance, the pandemic also offers some procedures that can reduce the spread of antibiotic resistance.  As the antibiotic resistance crisis will continue well beyond the resolution of the COVID-19 pandemic, it’s critical to address antibiotic resistance now with proper antibiotic usage and prevention of infections beyond COVID-19.

---

Molly Sargen is a second-year Ph.D. student in the Biological and Biomedical Sciences Ph.D. Program at Harvard Medical School.

Aparna Nathan is a fourth-year Ph.D. student in the Bioinformatics and Integrative Genomics Ph.D. program at Harvard University. You can find her on Twitter as @aparnanathan.

Buse Aktaş is a fourth-year Ph.D. student in Materials Science & Mechanical Engineering at Harvard University.

Cover Image: “Cocktail” by emilybean is licensed under CC BY-NC-ND 2.0.

For More Information:

• SITN Seminars in 2014 and 2020 addressed antibiotic resistance and strategies to combat this increasing issue. 

• We also discussed the discovery bacteria with extreme antibiotic resistance in this article.

• A recent SITN seminar discussed vaccines for COVID-19. 

• We previously published articles on treatment and prevention of COVID-19 and managing vaccine-preventable illnesses during the pandemic. 

• View an infographic about COVID-19 and antibiotic resistance from the WHO here.

• Check out SITN’s COVID-19 infocomics here.