An analysis of lung samples collected during this flu pandemic showed that most deaths were likely due to bacterial pneumonia, which was rampant in the absence of antibiotics. Even in more recent history, such as the 1957 H2N2 and 2009 H1N1 influenza pandemics, nearly 18% of patients with viral pneumonia had additional bacterial infections that increased the risk of death. And the COVID-19 pandemic is no different. With another flu season fast approaching amid the ongoing COVID-19 pandemic, reducing the damage caused by these viruses is important to prevent deaths and reduce infections. However, many deaths related to influenza and COVID-19 are not caused by the virus alone. Rather, it is a secondary bacterial infection that is often at the root of the devastating consequences attributed to an initial viral infection. I am an immunologist who studies why and how cells die during bacterial and viral infections. Understanding the synergy between these microbes is critical not only for effective diagnosis and treatment, but also for managing current pandemics and preventing future ones. My colleagues and I have published a study showing how an immune system protein that is crucial for fighting viruses also plays an essential role in fighting bacteria. A Texas man who died in March 2020 tested positive for COVID-19, strep throat and the flu.
Viruses and bacteria unite
Many pathogens can cause multiple infections in different ways. Scientists distinguish each type based on the time of onset of each infection. Coinfection refers to two or more different pathogens causing infections at the same time. Secondary or superinfections, on the other hand, refer to successive infections that occur after an initial infection. They are often caused by pathogens resistant to the antibiotics used to treat the primary infection. The way viral and bacterial infections interact increases the potential damage they can cause. Viral respiratory infections can increase the chance of bacterial infections and lead to worse illness. The reason why this happens is often multifaceted. Inside your respiratory tract, the epithelial cells that line your airways and lungs serve as the first line of defense against inhaled pathogens and debris. However, viruses can kill these cells and disrupt this protective barrier, allowing inhaled bacteria to invade. They can also alter the surface of epithelial cells to facilitate bacterial attachment. Viruses can also alter the surface of epithelial and immune cells by reducing the number of receptors that help these cells recognize and respond to pathogens. This reduction means that fewer immune cells report to the site of the viral infection, giving the bacteria an opening to launch another infection.
Influenza, COVID-19 and bacterial infections
Patients who have a bacterial infection at the same time they are fighting the seasonal flu are more likely to end up in the hospital. Almost a quarter of patients admitted to the ICU with severe influenza also have a bacterial infection. A study of the 2010 to 2018 flu seasons found that nearly 20% of patients admitted to the hospital with flu-related pneumonia acquired bacterial infections. Another study of patients hospitalized with viral or bacterial infections found that almost half had co-infection with another pathogen. These patients were also almost twice as likely to die within 30 days compared to those with a single infection. Staphylococcus aureus, or MRSA, is a common source of bacterial co-infections. Janice Haney Car/Centers for Disease Control and Prevention Interestingly, the two types of bacteria most commonly involved in flu virus co-infections are Streptococcus pneumoniae and Staphylococcus aureus, which are usually present in the respiratory tract without causing illness. However, the influenza virus can damage the cell barrier of the lungs and disrupt immune function enough to make patients vulnerable to infection by these otherwise benign bacteria. Secondary bacterial infections also exacerbate the COVID-19 pandemic. A 2021 review estimated that 16% to 28% of adults hospitalized for COVID-19 also had a bacterial infection. These patients stayed in the hospital twice as long, were four times more likely to need mechanical ventilation, and were three times more likely to die compared to patients with only COVID-19.
Treatment of secondary and co-infections
The immune system responds differently to viruses and bacteria. Antivirals do not work on bacteria and antibiotics do not work on viruses. A better understanding of the pathways the body uses to regulate both antiviral and antibacterial infections is critical to treating secondary and co-infections. Recent work by my colleagues and I may provide a clue. We sequenced the RNA of one type of immune cell, macrophages, in mice to determine which molecules were present in cells that were either protected or died due to bacterial infection. We identified Z-DNA binding protein (ZBP1), a molecule already known to play a regulatory role in how the immune system responds to influenza. Specifically, ZBP1 detects influenza viruses inside the lungs and signals infected epithelial and immune cells to self-destruct. This induced cell death eliminates the virus and promotes the recruitment of additional immune cells to the site of infection. Programmed cell death takes several forms, two of which include apoptosis and necrosis. Building on this finding that ZBP1 is important in fighting viral infection, we found that macrophages infected with Yersinia pseudotuberculosis, a type of bacteria that causes foodborne illness, also use this protein to initiate cell death. This limits the replication of the bacteria, while also sending inflammatory signals that help remove the bacteria. These findings raise the possibility that ZBP1 may play a dual role in how the body responds to viral and bacterial infections. It is possible that treatments that increase ZBP1 in certain cell types may be useful in the management of bacterial and viral co-infections.
