Antimicrobial resistance (AMR) has been declared one of the top ten global threats to human public health, and it has not disappeared with the emergence of the COVID-19 pandemic.
So far, only Catastrophic Effects
Instead, it has worsened as infection control measures and hand hygiene with antimicrobial gels have become ubiquitous.
AMR causes about 700,000 deaths worldwide each year, but researchers estimated in mid-2020 that there would be an additional 130,000 AMR deaths in 2020 due to the COVID-19 pandemic. AMR deaths are likely to exceed COVID-19 deaths by at least threefold by 2050. Some estimates suggest that AMR deaths could reach as many as 10 million deaths per year.
Prior to the pandemic, antibiotic stewardship programs were established around the world to stop the improper use of antibiotics in hospitals, nursing homes, and other settings. However, a study by scientists at Shahid Beheshti University of Medical Sciences in Iran published in Frontiers in Microbiology predicts that overuse of antibiotics, biocides and disinfectants to combat COVID-19 “can have catastrophic effects.” In addition, overuse of antibiotics may also directly affect the immune response.
Antibiotics given to COVID-19 Patients “Just in Case
Remember that COVID-19 is caused by the SARS-CoV-2 virus, which means that antibiotics are useless against this virus. Nevertheless, antibiotics were used prophylactically in COVID-19 patients throughout the pandemic, typically with the logic that this might prevent bacterial co-infections.
However, the rate of secondary bacterial co-infection was generally low, while antibiotic use remained high. In a study of 38 Michigan hospitals, 56.6% of patients with COVID-19 were given antibiotics at the start of their stay, but only 3.5% of them had a bacterial infection.
“For every patient who eventually tested positive for both SARS-Cov2 and a coexisting bacterial infection, 20 other patients received antibiotics, which turned out to be unnecessary,” said Dr. Valerie Vaughn, the study’s lead author. Other studies have found similar evidence of rampant overuse of antibiotics.
In a study of 99 COVID-19 patients in Wuhan, China, 71% were treated with antibiotics, but only 1% had bacterial co-infections. Overall, it is estimated that 1% to 10% of patients with COVID-19 develop bacterial co-infections, yet antibiotics remained the mainstay of treatment in the majority of cases.
Antibiotics as a ” Routine” Part of COVID-19 Treatment
Despite decades of efforts to reduce unnecessary antibiotic use, one of the largest studies of antibiotic use in hospitalized COVID-19 patients found that these drugs are used indiscriminately and inappropriately in COVID-19. More than half (52%) of the approximately 5000 patients included in the study received antibiotics, and more than one antibiotic was given in 36% of cases.
In most cases, 96% of the time, the antibiotics were given before a bacterial infection was confirmed, either on admission or within the first 48 hours of hospitalization. As it turned out, only 20% actually had a suspected or confirmed bacterial infection for which the antibiotics would have been indicated. The rest received them unnecessarily. The Frontiers in Microbiology researchers stated:
“It is worth highlighting that the inappropriate use of antibiotics during this global outbreak could significantly and silently lead to the development of AMR. Unfortunately, recent studies show that in several countries, frequent and extensive use of antibiotics in COVID-19 hospitalized patients is considered part of the routine treatment package.”
Even the World Health Organization made it clear that countries were at risk of accelerated spread of AMR due to the COVID-19 pandemic. They cited data showing that antibiotic use increased during the pandemic. About 79% to 96% of people who reported taking antibiotics did not have COVID-19 but were taking them in hopes of preventing infection, even though antibiotics are not effective against viral infections.
Overuse of Antibiotics Can Damage Immunity
Antibiotics can cause a number of serious adverse effects, a little-known one being damage to your mitochondria, which are closely linked genetically to bacteria. Your mitochondria are responsible for most of your cellular energy production and also play a role in antibacterial and antiviral immune responses – and they are an external target of certain antibiotics known to inhibit mitochondrial activity, DNA synthesis and biogenesis.
“Thus, antibiotic therapy could be an important and not well appreciated cause of mitochondrial dysfunction. This, in turn, may weaken the immune response against COVID-19 infection,” the review paper presented. In April 2020, the researchers called for an “urgent rethink” when it comes to antibiotics against COVID-19, noting:
…mitochondria are vulnerable to antibacterial treatments and disrupt their physiology. Inhibiting these processes with antibiotics could make the immune system less able to fight acute viral infections with COVID-19.”
Excessive use of Biocides and Disinfectants
The COVID-19 pandemic will drive up antimicrobial-resistant diseases because the overuse of antibiotics has been accompanied by the excessive and generous use of antimicrobial products such as household and industrial disinfectants, hand sanitizers, and other cleaning products.
The implications are immense and only beginning to be understood. There are potential adverse human health effects from inhalation of disinfectants, as such chemicals are known to accumulate in the lungs, liver, kidneys, stomach, brain, and blood. Exposure was certainly elevated during the pandemic for many people who were exposed to disinfectants via the inhalation and oral routes, as well as through the skin and eyes.
There are also significant environmental concerns due to the “unusual release and dispersal of higher concentrations of biocide-based products into surface and groundwater and wastewater treatment systems” during the pandemic. When disinfectants and biocides enter the environment, they can wipe out beneficial bacterial species that keep drug-resistant microorganisms at bay.
“When biocide concentrations reach the subminimum inhibitory concentration (sub-MIC), this event can increase selection pressure, promote horizontal gene transfer (HGT), and drive AMR evolution,” the scientists warn.
A team from Plymouth University in England also conducted a risk assessment to determine the potential environmental impact of prescribing antibiotics to COVID-19 patients. They concluded, “The data for amoxicillin suggest a potential environmental problem for AMR selection.” The team urged that such assessments be conducted in the future to keep track of the potentially catastrophic effects of prescribing habits on AMR.
Gut Microbiome Affects Immune Response to COVID
Antibiotics disrupt the gut microbiome, which has far-reaching implications for overall health, including the immune system’s ability to fight COVID-19 – further evidence that indiscriminate antibiotic use is counterproductive.
When researchers from the Chinese University of Hong Kong analyzed the composition of the gut microbiome of 100 patients with COVID-19, they found that gut bacteria known to modulate the immune system were low compared to people without the infection. The composition of the patients’ gut bacteria – both quantity and diversity – influenced the severity of COVID-19 infection as well as the immune response.
An imbalanced gut microbiome could also contribute to the inflammatory symptoms associated with “long COVID,” in which symptoms persist for months after infection.
According to the Study:
“Given reports that a subset of recovered patients with COVID-19 have persistent symptoms of fatigue, dyspnea, and joint pain, some beyond 80 days after the initial onset of symptoms, we postulate that the dysbiotic gut microbiome may contribute to immune-related health problems after COVID-19.”
In the study, 50% to 75% of patients received antibiotics, while less than 7% had bacterial infections. While the researchers found no difference in outcomes with or without antibiotics, the drugs were not associated with improved patient outcomes and, they noted, “it is still possible that a higher prevalence of antibiotic administration in severe and critical patients could exacerbate inflammation.
Isolation Disrupts Your Immune Response
Of all the negative effects of social isolation during the pandemic, the impact on your immune system may be the last to come to mind, even though it’s among the most important for your future health. What does staying home have to do with your immune system?
It changes the 24-hour light-dark cycle your body is designed to respond to. When you spend more time indoors, you are less exposed to sunlight and have less opportunity to produce vitamin D, which activates the macrophages in your lungs that act as the first line of defense against respiratory infections, among other immune activities.
It’s true that taking vitamin D supplements can compensate for this somewhat, provided your vitamin D levels are optimized, but other negative effects of being on lockdown are less easily remedied. Take exercise, another critical component of a well-oiled immune response, which can reduce stress levels and diseases like heart disease and type 2 diabetes that are associated with worsening COVID-19 outcomes.
But even beyond that, staying indoors means you’re not spending regular time in nature, which has its own benefits for the immune system. Trees release phytoncides that humans inhale and are known to alter natural killer cells. For this reason, in Japan, shinrin-yoku, or forest bathing, is said to improve immune function – but it’s hard to spend much time in the forest when you’re cooped up at home.
The other factor that can’t be ignored is the lack of exposure to everyday dirt and germs, which you miss if you stay at home, socially distant and sanitized. “Our immune system needs a job,” Dr. Meg Lemon, a Denver dermatologist, told The New York Times. “We’ve evolved over millions of years to have our immune systems under constant attack. Now they have nothing to do.
What’s perhaps most troubling is that this comment was made in March 2019 – before the pandemic. Now it’s exponentially worse, and your immune system is likely missing interactions with bacteria and other microorganisms that teach it, train it how to respond, and keep it on standby for life.
Without regular “training,” your immune system can overreact when triggered by normally harmless substances, leading to allergies and inflammation. Could a generation of children kept isolated and masked have immunological effects when exposed to common childhood viruses after a pandemic?
Already, cases of respiratory syncytial virus (RSV), which normally circulates in winter, have emerged in the summer months, suggesting a possible increased immunological vulnerability.
New Antibiotics Likely Won’t Save Us
There are 43 antibiotics in clinical development, but none of them show promise for solving the rapidly increasing AMR because innovation has stagnated-most of the “new” antibiotics being brought to market are variations of drug classes that have been around since the 1980s. In addition, according to the WHO’s annual Antibacterial Pipeline Report, the antibiotics currently in development are insufficient to combat AMR:
“The 2020 report shows a nearly static pipeline with only a few antibiotics approved by regulatory agencies in recent years. Most of these agents in development offer limited clinical benefit compared to existing treatments, with 82% of recently approved antibiotics being derivatives of existing antibiotic classes with well-established drug resistance. Therefore, rapid development of resistance to these new agents can be expected.”
Another problem is that hospital reimbursement systems make it difficult to use expensive new antibiotics because they are only reimbursed up to a certain point. That means patients may be given older drugs that don’t work as well to protect the hospital from financial loss.
Legislation to reform this situation – the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act – has been introduced to allow the use of new, targeted antibiotics against superbug infections. Preserving the efficacy of existing antibiotics are also important, and the overuse of antibiotics in agriculture cannot be ignored in this equation.
Globally, most antibiotics are used not for human diseases or pets, but for farm animals. In the International Journal of Antimicrobial Agents, researchers noted that “the ongoing pandemic is pushing the limits of optimal antibiotic stewardship and called for an end to unnecessary antimicrobial use.
So be sure to avoid antibiotics whenever they are not absolutely necessary. In addition, by choosing organic foods, including grass-fed meats and dairy products, you can avoid exposure to antibiotic residues in your diet while supporting food producers who do not contribute to AMR.
You should also be careful when using disinfectants and sanitizers, using them sparingly and only when really necessary, which – if you are outside of a hospital – is unlikely to be the case.
17. BBC May 21, 2020