4 'long-haul' viruses and what to expect

By Naveed Saleh, MD, MS
Published February 8, 2022

Key Takeaways

  • Chronic viral infections can take months, years, or decades to develop.

  • Some viruses can lead to atherosclerosis, diabetes, and cancer.

  • Chronic coxsackievirus infection has been linked to type 1 diabetes and chronic cardiomyopathies.

Chronic viral infections can develop over months, years, or decades. Although recent antiviral therapies have been successful in treating such diseases, many viruses select for drug resistant progeny in their long-term host.

Chronic viral infections are linked to cancer, diabetes, and atherosclerotic disease, according to the Emory Vaccine Center. These associations, as well as the impact on long-term health and quality of life, make chronic viral infection important to any physician. Long-haul COVID-19 has been dominating the news lately, but we've been battling other long-term viruses for much longer.

Genital herpes

This lifelong viral infection is caused by two variants: HSV-1 and HSV-2. While most cases are caused by HSV-2, an increasing number of anogenital herpes infections are being caused by HSV-1—especially in young women and men who have sex with men.

About 12% of people in the United States between the ages of 14 and 49 years are estimated to be infected, according to the CDC. Most people with HSV-2 infection are undiagnosed, with many having mild symptoms that spread from the anogenital region. Consequently, many people who do spread the virus do so unknowingly. 

Management addresses chronicity vs acute episodes. Antiviral drugs, such as acyclovir, valacyclovir, and famciclovir, can help mitigate the signs/symptoms of genital herpes, and they are prescribed at the first clinical occurrence and with recurrent episodes. 

They can also be used as daily suppressive therapy. However, these drugs don’t clear the virus or decrease the risk or severity of recurrence following discontinuation. 

All initial presentations of genital herpes should be treated with antiviral therapy. Initial genital herpes infections can present with severe genital ulcerations and neurological involvement. Moreover, mild initial infections can lead to severe and prolonged recurrence.

Related: Why was there a rabies spike in the US in 2021?


Infection with this agent typically results in an acute presentation (eg, common cold symptoms) or more serious illness (eg, meningitis, encephalitis, hand-foot-and-mouth disease), but persistent disease can occur. Chronic disease has been linked to type 1 diabetes and chronic cardiomyopathies. Young kids are at highest risk for severe infection.

Experts hypothesize that persistence is established in two ways. First, there is steady-state persistence, which results from non-lytic replication that affects nearly all cells. 

The second way—a carrier-state-type persistent infection—occurs when a small subpopulation of cells is infected despite a relatively high titer of the virus produced by the infected cells. Pancreatic cells have been observed to express a carrier state. In the aggregate, the host cells and virus co-evolve.

Researchers publishing in iScience found that extensive transcriptional responses in persistently infected pancreas cells, as well as changes to the pancreatic microenvironment, could play a role in predisposition to diabetes.


Although there is a vaccine for HPV, its efficacy in previously infected women remains to be fully elucidated. In a meta-analysis published in the Journal of Gynecologic Oncology, researchers performed what they believe is the first systematic review of data investigating vaccine efficacy among seropositive, DNA-negative women.

The investigators found high serotype-specific efficacy for HPV vaccination in cohorts of women with previous HPV16/18 infections. These results include 87% efficacy against HPV16/18 cervical dysplasia.

“These findings strengthen the case for vaccination of all DNA-negative women aged between 15–45, regardless of serostatus, on the basis that DNA-negative women must either be seropositive or seronegative, and efficacy among women defined as DNA negative seronegative (such as sexually naive women) has already been conclusively established,” they wrote.

Related: 4 biggest risk factors for chronic disease, according to science


Long-haul COVID—also known as post-acute COVID-19 syndrome—appears to affect one in four people infected with the SARS-CoV-2 virus. Factors such as age, severity of infection, and previous medical history do not seem to impact development, according to research cited by UC Davis Health

Researchers are still endeavoring to define what exactly constitutes post-acute COVID-19 syndrome. According to the results of a meta-analysis published in Clinical Microbiology and Infection, this syndrome is highly heterogeneous.

Investigators assessed 63 studies involving 257,348 participants. The following are the most commonly reported symptoms between 3 and 6 months:

  • Fatigue (32%)

  • Dyspnea (25%)

  • Sleep disorder (24%)

  • Concentration impairment (22%)

Between 6 and 9 months, the most common symptoms include:

  • Effort intolerance (45%)

  • Fatigue (36%)

  • Sleep disorder (29%)

  • Dyspnea (25%)

Between 9 and 12 months follow-up, fatigue (37%) and dyspnea (21%) were most common. After 12 months, symptoms such as fatigue (41%), dyspnea (31%), sleep disorder (30%), and myalgia (22%) persisted. 

Factors that play a role in long-haul symptoms included world region, male sex, diabetes mellitus, and disease severity. In total, five of six studies exhibited a relationship between COVID-19 and long-term symptoms after adjusting for covariates.

What this means for you

All people are susceptible to viral infections. Some of these viral infections can have long-term systemic effects that impact general health and quality of life. It is worth considering persistent infection in certain patients based on clinical presentation and previous medical history. 


  1. Alkodaymi MS. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis. Clinical Microbiology and Infection.

  2. Buchacher T. Persistent coxsackievirus B1 infection triggers extensive changes in the transcriptome of human pancreatic ductal cells. iScience.

  3. Eochagain, CM. HPV vaccination among seropositive, DNA negative cohorts: a systematic review & meta-analysis. Journal of Gynecologic Oncology.

  4. Sexually Transmitted Infections Treatment Guidelines, 2021. CDC.

  5. Studies show long-haul COVID-19 afflicts 1 in 4 COVID-19 patients, regardless of severity. UC Davis Health.

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