Association between COVID-19 infection and herpes zoster: A case series

Abstract

Herpes zoster (HZ) is a manifestation of the reactivation of latent varicella zoster virus (VZV) infection in the dorsal root ganglion. The occurrence of HZ has been reported in association with COVID-19. Herein, we describe 10 cases who developed classic HZ within 2–3 weeks of acquiring COVID-19 infection. The triggers in these patients could be severe stress (related to quarantine issues, fear of hospitalisation and death) immune dysregulation and systemic steroid therapy in treating COVID-19. The clinical patterns and therapeutic responses observed were similar to HZ in immunocompetent persons. Increased expression of NKG2A on NK and CD8+ T cells has been proposed as a pathophysiologic mechanism in triggering HZ at the molecular level in COVID-19 patients. Primary physicians should be aware of this association to counsel and treat such patients appropriately, as initiating early treatment could minimise the risk of complications like postherpetic neuralgia.

Introduction

Herpes zoster (HZ), also known as shingles, presents with a dermatomal rash consisting grouped vesicles over an erythematous base. The precipitating factors for reactivation of varicella zoster virus (VZV) lying dormant in the dorsal nerve root ganglion include infections, malignancies, chemotherapy, immunosuppressive drugs, severe emotional stress, and even sunburn.[1]

The most common complication is postherpetic neuralgia (PHN), which refers to pain persisting beyond 1 month after resolution of the rash.[2] Several infectious and noninfectious cutaneous manifestations have been documented in association with SARS-CoV-2 infections. HZ caused by reactivation latent VZV has been reported by many authors in association with SARS-CoV-2 infection. In many anecdotal reports during the pandemic, many patients with HZ were found to have subclinical or asymptomatic COVID-19 infection.[3] This case series, describing 10 cases of HZ occurring within 1 month of COVID-19 infection confirmed by a positive RT-PCR test on a nasal swab, is reported to highlight the probable role of SARS-CoV-2 infection as a trigger for HZ in patients of different age groups. We have observed and reported the clinical features, complications and therapeutic response of HZ occurring in association with COVID-19 infection.

Case Report

Ten cases of HZ following SARS-CoV-2 virus infection were documented from April 2021 to September 2021. The diagnosis of HZ was based on history, physical examination and a Tzanck smear test.

The average age in our study was 46.3 years. The youngest patient was 11 years old, while the oldest was 77 years old. Seven patients (70%) were above 45 years of age. There were four females and six males in the study group. In 60% patients, skin lesions occurred within the first 2 weeks following the onset of COVID-19 infection, while 40% patients presented 2–4 weeks after the infection. One of the patients required hospitalisation for COVID-19 infection due to a drop in oxygen saturation while all others had mild disease, only requiring home-based care and symptomatic treatment. Comorbidities like diabetes mellitus (20%) and hypertension (20%) were noted in 40% of patients. Prodromal symptoms of burning and tingling sensation were noted in 50% of the cases. At the time of presentation, 80% had moderate-to-severe pain while 20% had very severe excruciating pain. The dermatomes involved were T3 and T4 dermatomes (30%), other thoracic (10%), trigeminal (30%) [Figure 1a], and cervical (30%) [Figures 2a and 3a]. All patients presented to the hospital within 5 days of onset of vesicles and 50% of them presented within 3 days. Seven patients received Valacyclovir 1 g thrice daily and three patients received Acyclovir 800 mg five times a day for 7 days. All patients responded well to therapy with lesions drying up and resolving with postinflammatory hyperpigmentation in 7–21 days [Figures 1b, 2b, 3b]. The patients were followed up for a period of 3 months after presentation. The neuralgic pain persisted in 60% patients even after 1 month. These patients were treated with pregabalin 75 mg and 750 mcg of methyl cobalamin once daily, thereby achieving adequate pain relief.

Figure 1.

(a): Multiple vesicles and bullae on an erythematous base noted over the left side of forehead, tip of the nose, left malar area involving V1 and V2 dermatomes with eye-lid swelling. (b): Complete healed lesions with postinflammatory hyperpigmentation noted over the left side of face

Figure 2.

(a): Multiple vesicles noted over the left upper limb involving C5 and C6 dermatomes. (b): Healing lesions with crusting noted over the left upper limb

Figure 3.

(a): Multiple vesicles noted over the chest involving C4 and C5 dermatomes. (b): Healing lesions with crusting noted over the chest

The relevant details of all 10 cases are depicted in Table 1.

Table 1.

Summary of cases

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9	Case 10
Age (in years)	55	77	68	60	25	24	45	50	48	11
Sex	F	M	F	M	M	Female	Male	Female	Male	Male
Comorbidities	Nil	T2DM	HTN	Nil	Nil	Nil	HTN	T2DM	Nil	Nil
Duration after COVID diagnosis	3 weeks	3 weeks	1.5 weeks	2 weeks	2 weeks	3 weeks	2 weeks	1 ½ week	3 weeks	2 weeks
Type of COVID treatment	Home quarantine on oral medication	Hospitalised and on O2 supplementation	Home quarantine on oral medication	Home quarantine on oral medication	Home quarantine on oral medication	Home quarantine on oral medication	Home quarantine on oral medication	Home quarantine on oral mediation	Home quarantine on oral medication	Home quarantine on oral medication
COVID vaccination status	Unvaccinated	Unvaccinated	Covishield 2 doses (last dose 4 months back)	Covishield 1 dose (2 months back)	Covishield 2 doses (last dose 3 months back)	Unvaccinated	Covishield-2 doses (last dose 6 months back)	Unvaccinated	Covishield-2 doses (last dose 5 months back)	Unvaccinated
Prodromal symptoms	Burning sensation	Burning sensation	Tingling sensation	Nil	Nil	Nil	Burning sensation	Tingling sensation	Nil	Nil
Duration of rash	4 days	2 days	3 days	3 days	4 days	7 days	3 days	4 days	3 days	4 days
Grading of pain	Severe	Severe	Severe	Moderate	Moderate	Moderate	Severe	Severe	Moderate	Moderate
Dermatome involved	V1 and V2 dermatomes	V1 and V2 dermatomes	C5 and C6 dermatomes	C4 and C5 dermatomes	C6 and C7 dermatomes	V3 dermatome	T3 and T4 dermatomes	T12 dermatome	T3 and T4 dermatomes	T3 and T4 dermatomes
Types of skin lesions	Vesicles and bullae over the left side of forehead with eye-lid swelling	Bullae over the left side of forehead with eye-lid swelling	Vesicles over the left upper limb	Vesicles over the left side of chest	Vesicles over the left side of back	Multiple grouped crusted erosions over right cheek	Vesicles over the left side of chest and back	Vesicles and bullae over the right back	Vesicles and bullae over the left side of chest and back	Vesicles and bullae over right side of chest and back
Treatment given	Valacyclovir 1 g thrice daily for 10 days, Wysolone 30 mg under tapering doses, lubrex e/d	Valacyclovir 1 g thrice daily for 7 days, lubrex E/D	Valacyclovir 1 g thrice daily for 1 week	Valacyclovir 1 g thrice daily for 1 week	Acyclovir 800 mg 5 t/day for 7 days	Valacyclovir 1 g thrice daily for 7 days	Valacyclovir 1 g thrice daily for 10 days	Valacyclovir 1 g thrice daily for 1 week	Acyclovir 800 mg 5 times/day for 7 days	Acyclovir 800 mg 5t/day for 7 days
Follow-up at 2 weeks	Lesions resolved, pain +	Lesions resolved, pain +	Lesions resolved	Lesions resolved	Lesions resolved	Lesions resolved	Lesions resolved, pain +	Lesions resolved, pain present	Lesions resolved, pain +	Lesions resolved, pain +
Follow-up at 4 weeks	Pain present	Pain present	Nil	Nil	Nil	Nil	Pain present	Pain present	Nil	Nil
Follow-up at 12 weeks	No PHN	No PHN	No PHN	No PHN	No PHN	No PHN	No PHN	No PHN	No PHN	No PHN

Discussion

During the first wave of the COVID-19 pandemic, Recalcati had noted dermatologic manifestations in 18 out of 88 European COVID-19 patients, of whom 1 had varicella-like rash.[4] Another Italian study reported varicella-like exanthem in COVID-19 patients over the course of pandemic.[5] There have been several case reports of the occurrence of HZ preceding or following the onset of respiratory symptoms of COVID-19 infection.

The reactivation is probably due to complement and innate immune system activation which can cause hyperinflammatory states and immune cell dysfunction even in patients with relatively mild SARS-CoV-2 disease.[6,7] The pathophysiology for the reactivation of latent VZV includes increased expression of NKG2A expression in COVID-19 patients on NK and CD8+ T cells. NKG2A is an inhibitory receptor which will induce NK and CD8+ T-cell exhaustion. As cytotoxic T cells and natural killer cells are necessary for the control of viral infection and the exhaustion of cytotoxic lymphocytes is correlated to disease progression.[8] There is also a possibility of severe stress related to the infection because of the necessity for quarantine, fear of hospitalisation, and death contributing in a significant way in precipitating HZ. The use of steroids in the treatment of COVID-19 is another noteworthy factor which can cause the VZV reactivation.

In this case series, we report 10 cases of HZ that presented within 3 weeks following diagnosis of COVID-19. The short interval between the diagnosis of SARS-CoV-2 infection and presentation with HZ in all 10 cases strengthens the probable triggering role of the preceding COVID-19 disease, its treatment or the associated stress in precipitating the reactivation of VZV. Another interesting aspect noted in this case series is that all patients had quite typical skin lesions of HZ and had resolution of skin lesions after 2 weeks postinitiation of valacyclovir or acyclovir therapy. Therefore, though HZ could have been triggered by episode of COVID-19 disease, there was no atypicality in the clinical presentation of HZ and the response to therapy was good as usual.

Proper stress management during COVID-19 disease, and judicious use of systemic steroids only when indicated, may be helpful in reducing the chances of such post-COVID occurrence of HZ. The major limitation of our study was the smaller sample size and lack of molecular studies. Further studies on the immunological changes following COVID-19 infections may throw more light on the immunopathological mechanisms involved in the reactivation of VZV.

Conclusion

COVID-19 is primarily a respiratory virus but can cause various cutaneous manifestations in all age groups. The onset of HZ within 3 weeks of diagnosis of COVID-19 infection in all 10 patients in our case series emphasises the very likely role of SARS-CoV-2 infection in the occurrence of HZ. Immune dysregulation due to COVID-19 infection and stress could play an important role in the activation of different cellular processes that will result in reactivation of latent VZV. Primary-care physicians should be aware of this association, so that they can identify HZ early and initiate prompt treatment, which could reduce the risk of complications like PHN. Knowledge about this probable association can help primary-care physicians to reassure and appropriately counsel patients with COVID-19 infection-associated HZ.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.