Deaths from Secondary Infections Are Increasing. What Is Secondary Infection?
Secondary infections are a known complication of infections with many different pathogens, including common respiratory viruses such as influenza, SARS-CoV-2, and RSV. Unfortunately, much remains unclear about the exact consequences of secondary infections concerning SARS-CoV-2. However, secondary respiratory, bloodstream, and urinary infections caused by various bacteria, fungi, and viruses have been increasingly associated with greater severity of disease, greater use of resources, and increased risk of death among patients infected with SARS-CoV-2. Given the unusual patterns observed in the circulation of many pathogens and our waning immunity against these pathogens, secondary infections not only appear to be a significant cause of morbidity and mortality but also complicates the diagnosis of COVID-19 and its challenges the already overburdened healthcare systems around the world. Read along to learn more about secondary infections, their development, along with their potential impact on disease severity and clinical outcome.
What is a secondary infection?
Secondary infection is an infection that occurs after or because of a primary infection. When a primary infection weakens the resistance of the host body, the infected person becomes susceptible to secondary infections with other pathogenic microorganisms. Although these microorganisms may be both newly invaded and originally present in the host body, most secondary infections are caused by endogenous rather than exogenous infections. As secondary infections are often mentioned alongside co-infections, it may also be worthwhile to differentiate these terms. According to the Centers for Disease Control and Prevention (CDC), a coinfection is an infection that occurs concurrently with the initial infection. Thus, multiple infections with no direct relation to each other are generally considered to be co-infections rather than secondary infections.
How does a secondary infection develop?
A secondary infection may develop due to various factors, including changes in the immune system, compromised skin, and treatment for a primary infection. Certain diseases can reduce the ability of the immune system to fight off pathogens and facilitate invasion by other opportunistic infections. Thus, when a primary infection such as AIDS modifies the immune response, the immune system can no longer provide sufficient protection against developing secondary infections. Some skin infections, on the other hand, can cause breaks or sores that may compromise the function of the skin as a barrier against the external environment. Acting as entry points for other pathogens, compromised skin can facilitate secondary infections. Finally, secondary infections may develop due to the treatment used against a primary infection. For instance, antibiotics intended to treat a primary infection can lead other pathogenic microorganisms to invade the host body and multiply without significant interference. Although these are not often considered secondary infections, the infection may also occur at the insertion sites of IVs, catheters, and other medical devices, especially if they are left in for prolonged periods. For example, patients receiving invasive mechanical ventilation were observed often to develop other infections during previous SARS and MERS epidemics.
How do secondary infections affect disease severity and clinical outcome?
The impact of secondary infections may range from insignificant or beneficial to detrimental depending on the combination of various factors, such as the interaction of the involved pathogens, modulation of host response, and the diagnostic or therapeutic interventions applied in the case of viral respiratory diseases. According to Hoffman et al. (2006), pathogens in the host system can both deteriorate disease symptoms, severity, and outcomes by acting synergistically and impair the growth of each other through competition, parasitism, or interference. Combined with the immune response of the host and the applied medical/diagnostic interventions, the interaction between the responsible pathogens can shape disease severity and clinical outcomes for a given patient.
Much about the contribution of secondary infections to COVID-19 severity and mortality remains unclear. However, data on well-studied influenza pandemics and outbreaks of other respiratory viruses similar to COVID-19 suggest that secondary infections may increase disease severity and prolong the duration of the primary infection. Indeed, secondary infections such as bacterial pneumonia significantly cause morbidity and mortality during influenza pandemics, seasonal influenza, and outbreaks of other respiratory diseases. Here, the development of secondary infections is often linked to various factors, such as the disruption of the airway epithelium, the level of viral-induced immune-mediated damage, and the dysregulation of the host immune responses. Although similar mechanisms are thought to apply in the case of SARS-CoV-2, the variation in the testing methodologies, terminology, and treatment modalities adopted in the early studies complicate the analysis of secondary infections.
Still, most early studies on secondary infections among COVID-19 patients have associated secondary infections with increased symptom severity, prolonged infection duration, and a higher risk of death. For instance, in a study involving 14 severe and 24 critical COVID-19 patients, Zhang et al. (2020) found that two severe and 20 acute patients developed secondary infections. Among these 38 patients, 21 had respiratory infections, 13 had bloodstream infections, and 7 had urinary infections. Although a total of 52 different pathogens have been identified, gram-negative bacteria have been observed to be the significant pathogenic agent in all infection types. The most common pathogens included Klebsiella pneumoniae, Enterococcus faecium, Acinetobacter baumannii, and HSV1. In addition, analysis of the clinical outcomes has demonstrated that, compared to those without secondary infections, the patient with secondary infections had significantly longer stays in the ICU, a higher risk of receiving invasive mechanical ventilation, and elevated mortality rates. These findings suggest that secondary bacterial infections may be necessary for the prognosis and treatment of COVID-19 patients.
How to protect yourself against secondary infections?
Testing is one of the most critical strategies against secondary infections associated with COVID-19 and other pathogens. While secondary infections may complicate the diagnosis of infections, efficient diagnostic devices can assist medical professionals in determining the optimal treatment for the case at hand. Alongside laboratory methods, rapid diagnostic assays based on the principle of antigen detection can help minimize the burden on healthcare resources, reduce the turnaround time, and prevent delays in care. In addition, the patient can receive additional treatment against the detected pathogen after determining potential secondary infections. To protect yourself against COVID-linked disease and complications, it is advised to stay up to date with the COVID-19 vaccines, maintain personal hygiene, and follow a healthy lifestyle.
Devi, P., Khan, A. A., Chattopadhyay, P., Mehta, P., Sahni, S., Sharma, S., & Pandey, R. (2021). Co-infections as Modulators of Disease Outcome: Minor Players or Major Players? Frontiers in Microbiology, 12. https://doi.org/10.3389/fmicb.2021.664386
Hoffman, L. R., Déziel, E., D’Argenio, D. Z., Lépine, F., Emerson, J., McNamara, S., Gibson, R. L., Ramsey, B. W., & Miller, S. I. (2006). Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences of the United States of America, 103(52), 19890–19895. https://doi.org/10.1073/pnas.0606756104
U.S. Department of Health and Human Services. (2003). Understanding the Immune System: How It Works.
Zhang, H., Zhang, Y., Wu, J., Li, Y., Zhou, X., Li, X., Chen, H., Guo, M., Chen, S., Sun, F., Mao, R., Qiu, C., Zhu, Z., Ai, J., & Zhang, W. (2020). Risks and features of secondary infections in severe and critical ill COVID-19 patients. Emerging Microbes & Infections, 9(1), 1958–1964. https://doi.org/10.1080/22221751.2020.1812437