Management of Refractory/Resistant Herpes Simplex Virus Infections in Haematopoietic Stem Cell Transplantation Recipients: A Literature Review.

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

Seroprevalence of human herpes viruses in France, 2018-2022: a multilevel regression and poststratification approach.

BACKGROUND: Information related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden. METHOD: We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights. RESULTS: The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses. LIMITATIONS: Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table. IMPLICATIONS: The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies.

Efficacy and Safety of Amenamevir, a Helicase-Primase Inhibitor for the Treatment of Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis.

PURPOSE: The purpose of this study was to describe the efficacy and tolerance of amenamevir (AMNV), an inhibitor of the viral helicase-primase, for the treatment of recalcitrant herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) herpes simplex virus 1 strains. METHODS: In this retrospective case series, 6 consecutive patients with HSK caused by an ACVR herpes simplex virus 1 strain with a failure of conventional antiviral therapy were included after having been treated with AMNV (there was no control group of comparable patients for whom previous treatment would have been continued despite its inefficacy). Medical files were assessed for clinical data including reason(s) for AMNV introduction (frequent recurrences despite appropriate preventive antiviral treatment and/or clinical resistance to suppressive antiviral treatment of an ongoing clinical relapse), genotypical resistance to herpes simplex virus 1 documentation, immune status, clinical types and number of HSK episodes before and during AMNV treatment, adverse effects observed during AMNV treatment, and best corrected visual acuity. RESULTS: Of 6 patients, 4 (66%) did not experience a single recurrence during AMNV therapy while 2 others had recurrences (1 over 24 months of treatment and 2 over 23 months, ie two-fold less frequently than with conventional preventive treatment). On the overall history of these 6 patients, AMNV appeared to be associated with a reduction in HSK recurrences, with a mean of only 0.02 ± 0.04 episodes/month during follow-up under AMNV as compared to 0.14 ± 0.04 episodes/month in the year preceding AMNV introduction (P = 0.03). Improvement in vision acuity was also observed (mean best corrected visual acuity 0.17 ± 0.12 logarithm of the minimum angle of resolution at the end of follow-up vs. 0.30 ± 0.35 before AMNV onset), albeit nonsignificant probably due to the limited number of patients (P = 0.38). Neither clinical nor biological adverse effects were observed while under AMNV during the follow-up (16.5 ± 5.8 months). CONCLUSIONS: Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences.

Detection of varicella zoster virus DNA in blood from immunocompromised patients during the week preceding the onset of herpes zoster rash.

OBJECTIVE: To assess whether varicella zoster virus (VZV) DNA can be detected in blood before herpes zoster (HZ) rash onset. METHOD: Monocentric retrospective study from January 2019 to March 2023 including patients with HZ and stored blood samples performed during the week preceding the onset of HZ rash. Blood samples were retrospectively analyzed for VZV DNA by quantitative PCR. RESULTS: Among the 138 patients with HZ during the study period, stored blood samples performed during the week preceding the onset of HZ rash were available for 13 of them. Twelve (92 %) patients were immunosuppressed, mostly due to solid organ transplantation (38 %), solid malignancy (31 %) or autoimmune disease (23 %). During the week preceding HZ onset, VZV DNA was detected in blood from 10 (77 %) patients, with a median value of 3.6 log (copies/mL) (IQR 3.3-3.9). At the time of HZ onset, all VZV PCR performed in available blood samples were positive. CONCLUSION: Our findings demonstrates that VZV DNA can be commonly detected in blood from immunocompromised patients during the prodromal phase of HZ. Early screening of VZV DNA in blood from high-risk immunocompromised patients might improve HZ therapeutic management.

Point-of-care multiplex molecular diagnosis coupled with procalcitonin-guided algorithm for antibiotic stewardship in lower respiratory tract infection: a randomized controlled trial.

OBJECTIVE: We aimed to show that coupling molecular syndromic respiratory panel (RP) testing with procalcitonin (PCT) measurement in the emergency department improves antibiotic (ATB) stewardship in lower respiratory tract infection. METHODS: Open-label, prospective, randomized interventional trial, conducted from 2019 to 2022 in an adult emergency department. Patients with a suspicion of lower respiratory tract infection were randomized into an intervention arm (PCT measurement and point-of-care BIOFIRE RP2.1 plus testing, accompanied by a recommended ATB algorithm) or a standard of care (SOC) arm (PCT allowed as current practice). The primary endpoint was the duration of antibiotic exposure. RESULTS: Four hundred fifty-one patients were randomized, median age 65 years (Q1-Q3: 49-77), the hospitalization rate was 59.9% (270/451), the median length of stay 5 days (Q1-Q3: 3 - 12), and the 28-day mortality rate 5.3% (23/451). The median duration of ATB exposure was 6 days (Q1-Q3: 0-9) and 5 days (Q1-Q3: 0-9) in the SOC and interventional arm respectively (p = 0.71). ATB was started in 29.6 % (67/226) and 33.8% (76/225) respectively (p = 0.54). The BIOFIRE RP2.1 plus identified at least one viral species in 112/225 patients (49.8%) of intervention arm. Two hundred twelve out of two hundred twenty-six (93.8%) SOC patients had PCT measurement. The adherence rate to algorithm in the intervention arm was 93.3 % (210/225). CONCLUSION: Displaying PCT and real-time RP results to emergency physicians failed to significantly reduce ATB exposure in lower respiratory tract infection suspicions. However, the median ATB duration and rate of initiation were already low in the SOC arm using PCT measurement routinely.

Norovirus and sapovirus infections after allogeneic hematopoietic stem cell transplantation: is it worth it to look for them?

Norovirus (NoV) and Sapovirus (SaV) are potential causative agents of diarrhea after allogeneic HSCT but little is known in this population. We performed a retrospective analysis by RT-PCR of calicivirus (NoV and SaV), Human adenovirus (HAdV), rotavirus (RV), Aichi virus (AiV), enterovirus (EV), human parechovirus (HPeV) and Human bocavirus (HBoV) in the diarrheal stools of patients after allogeneic HSCT. 49/162 patients had positive viral assays: HAdV (17%), EV (7%), NoV (4.3%), RV and HBoV (3.1% each), SaV (1.9%), AiV (1.2%), HPeV (0.6%). Seven patients were positive for NoV and 3 for SaV. Among viruses-positive samples, the frequency of caliciviruses cases was 7% in the 6 months post-HSCT compared to 40% after (p < 0.0001). The median duration of symptom was 0.7 months but 2 cases, occurring more than one year after HSCT, were chronic, undiagnosed and strongly contributed to morbidity. Systematic testing of caliciviruses appears especially useful in late chronic diarrhea.

Prevalence and clinical relevance of VZV lung detection in intensive care unit: A retrospective cohort study.

OBJECTIVE: To assess the clinical relevance of varicella zoster virus (VZV) lung detection among patients hospitalized in intensive care unit (ICU). METHODS: We present a monocentric retrospective cohort study from 2012 to 2020. VZV genome was detected in bronchoalveolar lavage (BAL) fluid by real-time PCR. RESULTS: Twelve of 1389 (0.8%) patients exhibited VZV lung detection, corresponding to an incidence of 13.4 (95% confidence interval [CI] 5.8-21.0) per 100 person-years. Immunosuppression and prolonged ICU stay constituted the main risks factors. VZV detection was not associated with pulmonary deterioration but associated with a risk of shingles occurrence during the following days. CONCLUSION: VZV lung detection is a rare event among ICU patients, occurring mostly in immunocompromised patients with prolonged ICU stay. Due to its scarcity and the lack of association with pulmonary failure, a targeted approach to the VZV lung detection diagnosis may allow a significant cost saving without affecting the quality of patients care.

Fatal HSV-2 primary infection most likely acquired by kidney transplantation: A case report.

Herpes simplex virus 2 (HSV-2) rarely causes severe disease, even in solid organ transplant recipients. This paper describes a fatal case of HSV-2 infection, probably transmitted from a donor to a kidney transplant recipient. The donor was seropositive for HSV-2 but not for HSV-1, whereas the recipient was seronegative for both viruses before transplantation, suggesting that the graft was the source of infection. The recipient received valganciclovir prophylaxis due to cytomegalovirus seropositivity. Three months after transplantation, the recipient presented with rapidly disseminated cutaneous HSV-2 infection with meningoencephalitis. The HSV-2 strain was resistant to acyclovir, probably acquired under valganciclovir prophylaxis. Despite early initiation of acyclovir therapy, the patient died. This fatal case of HSV-2 infection, probably transmitted by the kidney graft with acyclovir-resistant HSV-2 from the onset, is uncommon.

Herpes simplex virus, varicella-zoster virus and cytomegalovirus keratitis: Facts for the clinician.

Keratitis due to Herpes simplex virus (HSK), Varicella-Zoster virus (VZK) and Cytomegalovirus remains a frequent source of concern for many ophthalmologists. They are a frequent cause of emergency consultations at eye care centers and carry the risk of permanent loss of visual acuity or visual quality and/or chronic neurotrophic keratitis, resulting in a significant decrease in the quality of life. HSK and VZK can affect the corneal epithelium, stroma, or endothelium or a combination of layers. In contrast, most cases of CMV keratitis present as isolated endothelitis (CMVE), a clinical entity that has been described within the last 2 decades. These three types of viral keratitis are characterized by a high frequency of recurrences and each new episode increases the risk of sequelae. Hence, ophthalmologists must adapt the treatment to the clinical presentation of each recurrent episode in order to mitigate the immediate consequences of viral replication and the immune response on corneal transparency. In patients with frequent recurrences, preventive long-term antiviral treatment is strongly recommended. However, in some rare cases, continuous exposure to antivirals may promote the emergence of resistant viral strains, which can be difficult to manage. In the future, the introduction of new antiviral drugs, with differing modes of action compared to current medical therapy, could be an alternative until a truly effective preventive solution, such as a vaccine, is available.

Herpesviridae lung reactivation and infection in patients with severe COVID-19 or influenza virus pneumonia: a comparative study.

BACKGROUND: Lung reactivations of Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) have been reported in COVID-19 patients. Whether or not those viral reactivations are more frequent than in other patients is not known. METHODS: Retrospective monocentric cohort study of 145 patients with severe COVID-19 pneumonia requiring invasive mechanical ventilation and who were tested for HSV and CMV in bronchoalveolar lavage performed during fiberoptic bronchoscopy for ventilator-associated pneumonia suspicion. Rates of HSV and CMV lung reactivations, and HSV bronchopneumonitis were assessed and compared with an historical cohort of 89 patients with severe influenza pneumonia requiring invasive mechanical ventilation. RESULTS: Among the 145 COVID-19 patients included, 50% and 42% had HSV and CMV lung reactivations, respectively, whereas among the 89 influenza patients, 63% and 28% had HSV and CMV lung reactivations, respectively. Cumulative incidence of HSV lung reactivation (taking into account extubation and death as competing events) was higher in influenza than in COVID-19 patients (p = 0.03), whereas the rate of HSV bronchopneumonitis was similar in both groups (31% and 25%, respectively). Cumulative incidence of CMV lung reactivation (taking into account extubation and death as competing events) was similar in COVID-19 and influenza patients (p = 0.07). Outcomes of patients with HSV or CMV lung reactivations were similar to that of patients without, whatever the underlying conditions, i.e., in COVID-19 patients, in influenza patients, or when all patients were grouped. CONCLUSIONS: HSV and CMV lung reactivations are frequent in COVID-19 patients, but not more frequent than in patients with influenza-associated severe pneumonia, despite a higher severity of illness at intensive care unit admission of the latter and a longer duration of mechanical ventilation of the former. Although no impact on outcome of HSV and CMV lung reactivations was detected, the effect of antiviral treatment against these Herpesviridae remains to be determined in these patients.

Phylogeographic analysis reveals an ancient East African origin of human herpes simplex virus 2 dispersal out-of-Africa.

Human herpes simplex virus 2 (HSV-2) is a ubiquitous, slowly evolving DNA virus. HSV-2 has two primary lineages, one found in West and Central Africa and the other found worldwide. Competing hypotheses have been proposed to explain how HSV-2 migrated out-of-Africa (i)HSV-2 followed human migration out-of-Africa 50-100 thousand years ago, or (ii)HSV-2 migrated via the trans-Atlantic slave trade 150-500 years ago. Limited geographic sampling and lack of molecular clock signal has precluded robust comparison. Here, we analyze newly sequenced HSV-2 genomes from Africa to resolve geography and timing of divergence events within HSV-2. Phylogeographic analysis consistently places the ancestor of worldwide dispersal in East Africa, though molecular clock is too slow to be detected using available data. Rates 4.2 × 10-8-5.6 × 10-8 substitutions/site/year, consistent with previous age estimates, suggest a worldwide dispersal 22-29 thousand years ago. Thus, HSV-2 likely migrated with humans from East Africa and dispersed after the Last Glacial Maximum.

Novel mutations in antiviral multiresistant HSV-2 genital lesion: A case report.

HSV-2 antiviral resistance mainly occurs in immunocompromised patients and especially in HIV-positive individuals receiving long-term antiviral treatment. Those situations can be challenging as few alternatives are available for HSV infection management. To describe clinical and virological significance of two novel potential HSV-2 resistance mutations after treating an obese patient with a pseudotumoral genital HSV-related lesion. Consecutive different antiviral treatments were used: valacyclovir (VACV) then foscarnet (FOS) then topical cidofovir (CDV) and finally imiquimod. Under VACV, genotypic resistance testing revealed a novel mutation within viral thymidine kinase (TK, gene UL23) not previously reported but probably accounting for antiviral resistance: W89G, similar to W88R mutation reported in HSV-1 TK, known to be associated with ACV resistance for HSV-1. Under FOS, while initial mutations were still present, a second genotypic resistance testing performed on persisting lesions showed a novel mutation within viral DNA polymerase (DNA pol, gene UL30): C625R. All three antivirals used in this case are small molecules and pharmacokinetics of VACV, FOS, and CDV have not been evaluated in animals and there are very few studies in human. As small molecules are poorly bound to proteins and distribution volume is increased in obese patients, there is risk of underdosage. This mechanism is suspected to be involved in emergence of resistance mutation and further data is needed to adapt, closely to patient profile, antiviral dosage. This report describes a chronic HSV-2 genital lesion, with resistance to current antivirals and novel mutations within viral TK and DNA pol which may confer antiviral resistance.

Cumulative incidence of SARS-CoV-2 infection and associated risk factors among frontline health care workers in Paris: the SEROCOV cohort study.

With the COVID-19 pandemic, documenting whether health care workers (HCWs) are at increased risk of SARS-CoV-2 contamination and identifying risk factors is of major concern. In this multicenter prospective cohort study, HCWs from frontline departments were included in March and April 2020 and followed for 3 months. SARS-CoV-2 serology was performed at month 0 (M0), M1, and M3 and RT-PCR in case of symptoms. The primary outcome was laboratory-confirmed SARS-CoV-2 infection at M3. Risk factors of laboratory-confirmed SARS-CoV-2 infection at M3 were identified by multivariate logistic regression. Among 1062 HCWs (median [interquartile range] age, 33 [28-42] years; 758 [71.4%] women; 321 [30.2%] physicians), the cumulative incidence of SARS-CoV-2 infection at M3 was 14.6% (95% confidence interval [CI] [12.5; 16.9]). Risk factors were the working department specialty, with increased risk for intensive care units (odds ratio 1.80, 95% CI [0.38; 8.58]), emergency departments (3.91 [0.83; 18.43]) and infectious diseases departments (4.22 [0.92; 18.28]); current smoking was associated with reduced risk (0.36 [0.21; 0.63]). Age, sex, professional category, number of years of experience in the job or department, and public transportation use were not significantly associated with laboratory-confirmed SARS-CoV-2 infection at M3. The rate of SARS-CoV-2 infection in frontline HCWs was 14.6% at the end of the first COVID-19 wave in Paris and occurred mainly early. The study argues for an origin of professional in addition to private life contamination and therefore including HCWs in the first-line vaccination target population. It also highlights that smokers were at lower risk.Trial registration The study has been registered on ClinicalTrials.gov: NCT04304690 first registered on 11/03/2020.

Long-term evolution of humoral immune response after SARS-CoV-2 infection.

OBJECTIVE: We aimed to characterize the evolution of humoral immune response up to 1 year after SARS-CoV-2 infection in healthcare workers (HCWs) during the first wave of COVID-19 in Paris. METHODS: Serum samples from 92 HCWs were tested at month 0 (M0), M6, and M12 after SARS-CoV-2 infection for IgG targeting the nucleocapsid (N), IgG targeting the receptor-binding domain (RBD) of spike (S) protein, IgA targeting S, and anti-RBD neutralizing antibodies. After M6, 46 HCWs received a single dose of COVID-19 vaccine. RESULTS: We observed a significant decrease in all SARS-CoV-2 immunologic markers at M6 post-infection: median decreases were 0.26 log binding antibody units/mL (M0: 1.9 (interquartile range (IQR) 1.47-2.27); M6: 1.64 (IQR 1.22-1.92)) for anti-RBD IgG; 4.10 (index) (M0: 4.94 (IQR 2.72-6.82); M6: 0.84 (IQR 0.25-1.55)) for anti-N IgG; 0.64 (index) (M0: 2.50 (IQR 1.18-4.62); M6: 1.86 (IQR 0.85-3.54)) for anti-S IgA; and 24.4% (M0: 66.4 (IQR 39.7-82.5); M6: 42.0 (IQR 16.8-68.8)) inhibition activity for the RBD neutralizing antibodies. Between M6 and M12, anti-RBD IgG level, anti-S IgA index, and anti-RBD neutralizing activity significantly increased among COVID-19 vaccinated HCWs, whereas they remained stable among unvaccinated HCWs. Anti-N IgG index significantly decreased between M6 and M12 among both vaccinated (median: 0.73 (IQR 0.23-1.11) at M6 and 0.52 (IQR 0.20-0.73) at M12) and unvaccinated HCWs (median: 0.79 (IQR 0.21-4.67) at M6 and 0.34 (IQR 0.24-2.78) at M12). DISCUSSION: A steady decline in the anti-N IgG response was observed during the first year after SARS-CoV-2 infection among HCWs, whereas the anti-RBD IgG and the anti-S IgA responses remained stable and could be enhanced by COVID-19 vaccination.

Pre-COVID-19 Immunity to Common Cold Human Coronaviruses Induces a Recall-Type IgG Response to SARS-CoV-2 Antigens Without Cross-Neutralisation.

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.

Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis: A Concerning and Emerging Clinical Challenge.

PURPOSE: To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) strains of herpes simplex virus 1 (HSV-1). DESIGN: Multicenter retrospective case series. METHODS: HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments, and HSV-1 genotypic resistance profiles. RESULTS: This study evaluated 18 HSK patients (13 male and 5 female, aged 66.8 ± 4.7 years) with ACVR HSV-1-positive ocular samples. Genotypic resistance testing was performed because of frequent recurrences despite adequate antiviral prophylaxis (AVP) (n = 13, 72%), or poor response to suppressive antiviral therapy (n = 5, 28%). Resistance mutations were found in the TK (n = 15, 83%) or in the DNA pol gene (n = 3, 17%). Prior to the diagnosis of resistance, the duration of disease was 29.8 ± 20.4 years, with more than 10 HSK recurrences in 15 patients (83%). The number of recurrences between the first episode and the diagnosis of resistance was significantly lower in immunocompromised patients (n = 6, 33%) than in immunocompetent patients (n = 12; 67%) (11.5 ± 4.9 vs 16.4 ± 1.9, P = .05). CONCLUSION: HSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with longstanding disease may be particularly at risk for developing resistance.

Neutralization Heterogeneity of UK and South African Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in BNT162b2-Vaccinated or Convalescent Coronavirus Disease 2019 (COVID-19) Healthcare Workers.

There are concerns about neutralizing antibodies' (NAbs') potency against severe acute respiratory syndrome coronavirus 2 variants. Despite decreased NAb titers elicited by BNT162b2 vaccine against VOC202012/01 and 501Y.V2 strains, 28/29 healthcare workers (HCWs) had an NAb titer ≥1:10. In contrast, 6 months after coronavirus disease 2019 mild forms, only 9/15 (60%) of HCWs displayed detectable NAbs against 501Y.V2 strain.