Introduction

Hantaviruses are a viral RNA group that is known to have very severe consequences following infection. There are three common European hantaviruses known as 

Puumala, Dobrava and Saaremaa.Hantavirus is transmitted by rodents, and each type of Hantavirus is unique to a rodent species. Puumala is spread by a rodent known as a Bank vole, yellow-necked mice are responsible for Dobrava transmission, and the striped field mouse carries Saaremaa and spreads this virus.¹ Hantavirus leads to two diseases: haemorrhagic fever with renal syndrome (HRFS), which causes severe kidney damage and human pulmonary syndrome (HPS), which causes severe lung complications. Puumala is known to lead to Nephropathia epidemica, which is a less severe HRFS.² Patients are typically immunocompromised in instances of HIV and AIDS, as well as when patients have undergone organ transplants or if they have cancer. Immunocompromised patients are much more susceptible to bacterial infections, such as pneumonia, as well as viral infections.³ This is because, in organ transplant cases immunosuppressant drugs are used to prevent the body from rejecting the new organ.⁴ Cancer is associated with a weakened immune system, as this typically increases the chance of cancer development, and HIV weakens the immune system over time, leading to AIDS.⁵ Immunocompromised patients are at higher risk of developing severe symptoms and contracting Hantavirus; therefore, it is of utmost importance to understand how certain populations are vulnerable. This article will explore the mechanisms behind immunocompromised individuals and delve into how this leads to a higher prevalence. Treatment methods and future directions will also be explored.

Hantavirus overviews

The virions that lead to hantavirus are very small and spherical, and the composition of the genome is three different segments that differ in size. The segments are therefore characterised as small, medium and large. As aforementioned, the virus is formed of RNA, and this type of RNA is negative-sense. The segments serve different roles, with the large segment encoding polymerases that are required for replication, and the other segments encoding the G1 and G2 glycoproteins that facilitate binding to target cells.⁶ As aforementioned, there are different hantavirus strains, with the most well-documented strains being Puumala, Dobrava and Saaremaa. The Puumala strain that is spread by the Bank vole is very common throughout different parts of Europe, including Russia and Finland. Bank voles are commonly found in Eastern Europe and Scandinavia; thus, these regions are particularly susceptible to this strain.⁷ Dobrava is associated with regions of Southeast Europe, such as the Balkans, as it is mainly exclusive to this region; however, there have been some instances in other European countries, such as Germany.⁸ Yellow-necked mice are commonly found in Romania and other parts of Southeast Europe; hence, these rodents dictate the high prevalence in this region.⁹ Saaremaa is spread by the striped field mouse that is found in many 

different regions in Central Europe, the Far East, as well as the Korean Peninsula and East Asia, thus leading to cases in Europe as well as in China, Japan and Mongolia.¹⁰ Hantavirus is spread by rodents as previously mentioned and is airborne, The virus is transmitted through many different modes, including droppings and faeces, saliva and urine. Arthropods are also capable of spreading this virus, however, rodents are the most common hosts for this virus.¹¹ Although Hantavirus leads to HFRS and HPS, which are very severe, the initial symptoms are similar to any other type of viral infection, with symptoms being tiredness, headaches and a fever along with muscle aches; therefore, it is difficult to distinguish between Hantavirus and other illnesses in the early stages.¹²

Immunocompromised patients: definition and common causes

Patients are immunocompromised when their immune system is weakened, thus, it cannot respond to pathogens such as viruses, leading to higher infection susceptibility.¹³ Autoimmune disorders and diseases, such as HIV and AIDS, lead to patients being immunocompromised as HIV weakens the immune system, and cancer also weakens the immune system.⁵ In organ transplant cases, immunosuppressants intentionally weaken the immune system; however, the caveat is increased susceptibility.⁴ Autoimmune diseases, such as psoriasis, are treated with steroids to reduce the immune system being overactive, but once again, this leads to lower overall immunity for infections, making these patients more susceptible to viral infections.¹⁴

Impact of hantavirus on immunocompromised patients

Many studies, including clinical trials and experimental studies, have shown that immunocompromised individuals due to the various aforementioned causes are more susceptible to hantavirus infections, as the immune system is weaker and unable to respond appropriately to the virus.¹⁵ Immunocompromised patients tend to exhibit severe symptoms such as HFRS and HPS quickly than patients with a functioning immune system, which can lead to many complications.¹⁶ The effects on the lungs due to HPS can cause acute respiratory distress syndrome, which in many cases can cause multi-organ failure (MOF). HFRS causes chronic kidney disease, which further contributes to the development of MOF.¹⁷ Hantavirus is hard to diagnose in immunocompromised individuals due to symptoms developing quickly in these patients and symptoms not being typical of other instances, hence, some patients are not correctly diagnosed.¹⁸ As the initial symptoms of fever and headaches are indicative of other opportunistic infections, making a distinction is difficult, making diagnosis extremely difficult for the most part.¹⁹ It is more difficult to treat these patients effectively.

Management and treatment strategies

There are many ways to treat and manage hantavirus. Firstly, preventing exposure to certain rodents, particularly in households, is a very effective prevention measure. Removing sources of food and using traps as well as ensuring areas are ventilated will decrease airborne transmission and reduce rodent exposure. A good standard of hygiene to deter rodents is necessary.²⁰ Treatments include oxygen therapy, such as extracorporeal membrane, for those with HPS; this has proved beneficial in severe and critical cases.²¹ To support renal function during HFRS, fluid treatments help maintain homeostasis and electrolyte levels despite renal function being affected. Fluid and oxygen therapy are the two main modes of treatment.²² Antivirals are also effective, but are not as useful in immunocompromised patients, as the immune system is utilised to treat these viruses.²⁰ Monitoring IgG and IgM antibody levels, which are indicative of immunity, is a way to monitor how immunocompromised patients are dealing with the virus. Symptom monitoring over an extended period of time is crucial in these patients.²³ Rehabilitation has led to a full recovery in severe hantavirus cases, and managing the long-term effects.²⁴ Lymphoma is a common long-term risk following hantavirus infection thus, these effects must be monitored alongside rehabilitating the affected patients.²⁵

Case studies and research findings

Immunocompromised individuals tend to present with more severe symptoms than those with a functioning immune system. For example, patients have developed acute kidney injuries at a very fast rate and develop HPS quicker, which leads to the higher mortality rates that are typically associated with immunocompromised patients.²² Animal studies have shown high mortality rates and symptoms mimicking HPS, and respiratory distress has been noted as a major cause of death.²⁶ Treatment efficacy is generally lower, and the disease tends to progress at a faster rate; therefore, increased monitoring is key to prevent a sudden decline in immunocompromised patients.

Future directions and research needs

In the future, due to pulmonary symptoms being severe in hantaviruses that lead to HPS, there is a need for increased diagnostic testing. This would greatly improve detection, which would allow treatments to be introduced to patients earlier, and this would likely improve survival rates.²⁷

Immunotherapies are not effective in patients with a compromised immune system due to the immune system not being active hence, although this is useful in some use cases, special treatments tailored to immunocompromised individuals must be developed.²⁰ Increasing awareness of rodents and exposure risk in regions of the world that have a high hantavirus prevalence is integral in ensuring that viral spread is reduced. Education will prove to be key in the near future as a prevention measure for hantavirus infections and protecting immunocompromised individuals.²⁸

Conclusion

To conclude, hantavirus tends to be more severe in immunocompromised individuals overall and can easily lead to death, particularly the strains that lead to HPS in HFRS in the majority of cases. Respiratory distress and multi-organ failure are more common in immunocompromised patients; those affected may have a lower functioning immune system due to a plethora of reasons. Cancer, infections such as HIV and AIDS, as well as autoimmune diseases and the treatments associated with these conditions, can increase infection susceptibility; therefore, infection likelihood and severity greatly increase simultaneously. In order to combat this, there needs to be more research and treatments developed that are specific to immunocompromised patients and those who are vulnerable need to take extra measures to ensure they avoid being affected through rodent transmission. Increased education and awareness, alongside research, will all be key in the near future as we look to reduce the number of people that die or have severe long-term complications due to hantaviruses across the world. Diagnosis and treatment are more difficult in these patients however, the goal is to make the difficulties associated with immunocompromised patients a thing of the past.