Covid Cold Sore: New Clues About Viral Coinfections

Cold sores, caused by herpes simplex virus (HSV-1), are a common infection that can reactivate under stress, illness, or immune suppression. Since COVID-19 emerged, some individuals have reported more frequent outbreaks, raising questions about SARS-CoV-2’s role in triggering latent viral infections.

Researchers are investigating whether COVID-19 reactivates herpes family viruses and its implications for long-term immune health. Understanding these interactions could provide insights into viral coinfections and potential complications following SARS-CoV-2 infection.

Herpes Family Viruses

The herpesvirus family includes several viruses capable of lifelong infections in humans. These viruses can remain dormant for years and reactivate under specific conditions. Three particularly relevant in the context of viral coinfections are herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Each has distinct characteristics but shares the ability to persist in host cells and reactivate in response to various triggers.

HSV-1

Herpes simplex virus type 1 primarily causes oral cold sores but can also lead to genital infections. It establishes latency in the trigeminal ganglia and may reactivate due to fever, UV exposure, or hormonal changes. A 2021 study in Frontiers in Medicine highlighted that viral reactivation often occurs under physiological stress, including infections by other viruses. HSV-1 replication during reactivation produces painful, fluid-filled lesions around the mouth. The virus spreads through direct contact with infected saliva or lesions, and asymptomatic shedding contributes to its widespread prevalence. The World Health Organization estimates over 67% of the global population under 50 carries HSV-1. Antiviral medications such as acyclovir and valacyclovir can reduce outbreak severity but do not eliminate the virus.

VZV

Varicella-zoster virus causes both chickenpox and shingles. After an initial infection, it enters a latent phase in dorsal root or cranial nerve ganglia. Reactivation later in life manifests as shingles, a painful rash following nerve pathways. A study in The Journal of Infectious Diseases (2022) found that individuals experiencing significant immune disruptions, including viral infections, have an increased risk of shingles. Unlike HSV-1, which primarily affects the oral mucosa, VZV reactivation can cause neurological complications such as postherpetic neuralgia. Transmission occurs through respiratory droplets or direct contact with lesions. Vaccination with the recombinant zoster vaccine (RZV) reduces the risk of shingles reactivation by over 90%, according to a 2021 CDC review. Understanding VZV behavior in viral coinfections is critical given its ability to flare up under immune-altering conditions.

EBV

Epstein-Barr virus causes infectious mononucleosis and is linked to chronic conditions, including certain cancers and autoimmune diseases. It establishes latency in B cells and can reactivate under physiological stress. A 2022 study in Nature Microbiology suggested viral interactions, including those with SARS-CoV-2, may influence EBV reactivation patterns. Unlike HSV-1 or VZV, EBV does not cause visible sores, but reactivation can lead to fatigue, lymphadenopathy, and atypical lymphocytosis. The virus spreads primarily through saliva, earning it the nickname “kissing disease.” Research has linked EBV to multiple sclerosis and certain lymphomas, emphasizing its long-term health implications. Current antiviral treatments are limited, with management strategies focusing on symptom relief. Given its persistence in immune cells, EBV remains an important virus to monitor in coinfection scenarios.

Interaction Of SARS-CoV-2 With Latent Herpes Infections

The relationship between SARS-CoV-2 and latent herpesvirus infections has become a focal point of research, as clinicians observe an uptick in herpesvirus reactivations among COVID-19 patients. Several studies have documented increased flare-ups of HSV-1, VZV, and EBV in individuals recovering from SARS-CoV-2. A 2022 study in The Lancet Microbe found that hospitalized COVID-19 patients had a significantly higher incidence of herpesvirus reactivation compared to non-COVID-19 patients with similar comorbidities.

One proposed mechanism involves direct viral interactions within host cells. SARS-CoV-2 manipulates cellular pathways that overlap with those used by herpesviruses to maintain latency. Research published in Cell Reports (2021) demonstrated that SARS-CoV-2 infection alters mitochondrial function and disrupts cellular metabolism, conditions that herpesviruses exploit to transition from dormancy to active replication. Additionally, transcriptomic analyses show that SARS-CoV-2 infection changes gene expression, facilitating herpesvirus reactivation in tissues where these viruses establish latency, such as nerve ganglia for HSV-1 and VZV or B lymphocytes for EBV.

Beyond direct cellular effects, systemic factors may contribute to herpesvirus reactivation following SARS-CoV-2 infection. Fever and systemic inflammation, common in COVID-19, are recognized triggers for herpesvirus reactivation. A retrospective cohort study in The Journal of Clinical Virology (2023) reported that patients with severe COVID-19 had a higher likelihood of developing shingles within three months of infection. These findings align with prior research showing that febrile illnesses act as catalysts for herpesvirus reactivation.

Cold Sores In Viral Coinfection Scenarios

Cold sores, typically caused by HSV-1, follow a predictable cycle of dormancy and reactivation. However, additional viral infections can disrupt this pattern. Coinfections with respiratory viruses such as SARS-CoV-2 or influenza have been linked to increased cold sore outbreaks, suggesting that an active virus may influence HSV-1 behavior.

Certain infections create conditions that favor HSV-1 replication. A study in Virology Journal (2022) found that viral coinfections can increase oxidative stress in host tissues, a factor known to promote HSV-1 reactivation. Fever, common in many viral illnesses, also activates stress-related pathways that influence HSV-1 gene expression.

Cold sore severity and frequency in coinfection scenarios vary based on the viruses involved. SARS-CoV-2 has been associated with prolonged viral shedding in some individuals, which may extend HSV-1 outbreaks. Case studies in The British Journal of Dermatology (2023) documented instances where COVID-19 patients experienced unusually large or persistent cold sores, raising questions about whether SARS-CoV-2 alters the healing process. While isolated HSV-1 reactivations typically resolve within 7 to 10 days, some of these cases persisted for weeks, suggesting coinfections could delay resolution.

Immune Dynamics In Post-Infection Phases

Following a viral infection, the immune system undergoes adjustments that can persist beyond acute symptoms. These changes are particularly pronounced after infections that trigger widespread inflammation. One notable shift involves the balance between pro-inflammatory and regulatory immune responses. During acute infection, the body increases inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) to combat viral replication. Once the infection subsides, the immune system must recalibrate to prevent excessive inflammation from damaging healthy tissues.

This rebalancing process does not always occur smoothly, particularly in individuals with preexisting immune dysfunction or those who experienced severe illness. Some patients exhibit lingering immune activation, characterized by elevated inflammatory markers and increased immune cell activity. Others may experience transient immune suppression, making them more susceptible to secondary infections. This phenomenon has been observed in individuals recovering from severe respiratory infections, where post-viral immune exhaustion delays responses to new pathogens.

Emerging Data On Coinfections

Recent research has shed light on the frequency and implications of viral coinfections, particularly involving SARS-CoV-2 and latent herpesviruses. Large-scale genomic sequencing and retrospective patient analyses indicate that individuals with COVID-19 are more likely to experience concurrent viral reactivations than previously thought. A population-based study in Clinical Infectious Diseases (2023) found that nearly 20% of hospitalized COVID-19 patients exhibited detectable levels of reactivated herpesviruses, including HSV-1, VZV, and EBV.

Advancements in molecular diagnostics have improved the ability to detect these interactions. PCR-based viral load assessments and next-generation sequencing provide precise measurements of viral reactivation in real time. A study in Nature Communications (2022) demonstrated that SARS-CoV-2 infection can lead to prolonged herpesvirus shedding in some individuals, raising concerns about extended transmission windows and prolonged symptoms. These findings have prompted further investigations into whether antiviral prophylaxis or immune-modulating therapies could mitigate viral reactivation in susceptible populations.