The association of breastfeeding and other factors on respiratory virus positivity and severity in hospitalized children.

Acute respiratory infections (ARIs) are the most prevalent diseases in children under 5 years old, and viruses are the leading cause. ARIs arise due to numerous factors, including age, contact with siblings or other children in daycare centers, and environmental pollution. Breastfeeding reportedly confers protection against ARIs through bioactive components related to mucous epithelial immunity. This study aimed to evaluate the frequency and severity of viral ARIs in hospitalized children, together with the status and duration of exclusive breastfeeding (EBF) and other associated factors. It comprised an epidemiological surveillance study to investigate respiratory viruses in hospitalized children, in which demographic and clinical data were collected. Overall, 279 patients were included, 190 (68%) had positive viral results, and 132 (47%) were exclusively breastfed. In an adjusted analysis, it was observed that older children, the parents' educational level, and the presence of chronic disease were significantly related to EBF for more than 6 months. No significant differences were observed in viral positivity and disease severity concerning EBF. Whereas the EBF status was associated with a positive rate of virus detection, the significance did not remain after adjustment, and it was not considered a protective factor against ARIs. On the other hand, young age and exposure to tobacco were confirmed as risk factors of frequency and severity, respectively. Such confounding factors can impact the analysis and should be considered in future studies.

Large-Scale Screening of Asymptomatic Persons for SARS-CoV-2 Variants of Concern and Gamma Takeover, Brazil.

We performed a large-scale severe acute respiratory syndrome coronavirus 2 screening campaign using 2 PCR-based approaches, coupled with variant genotyping, aiming to provide a safer environment for employees of Federal University in Curitiba, Brazil. We observed the rapid spread of the Gamma variant of concern, which replaced other variants in <3 months.

Intrauterine Transmission of SARS-CoV-2.

We documented fetal death associated with intrauterine transmission of severe acute respiratory syndrome coronavirus 2. We found chronic histiocytic intervillositis, maternal and fetal vascular malperfusion, microglial hyperplasia, and lymphocytic infiltrate in muscle in the placenta and fetal tissue. Placenta and umbilical cord blood tested positive for the virus by PCR, confirming transplacental transmission.

Simultaneous enterovirus EV-D68 and CVA6 infections causing acute respiratory distress syndrome and hand, foot and mouth disease.

BACKGROUND: Although most enterovirus (EV) infections can be asymptomatic, these viral agents can cause serious conditions associated with central nervous system, respiratory disease and uncommon manifestations of hand, foot and mouth disease (HFMD). EV-coinfections have been rarely reported with development of complications and severe clinical outcome. An atypical case of a child presenting HFMD and severe acute respiratory syndrome, co-infected with EV-D68 and CVA6, is reported herein. CASE PRESENTATION: A 3-year-old boy was admitted in the emergency department unit showing fever, abdominal pain and tachycardia. Twenty-four hours after hospitalization the child developed severe clinical symptoms associated with HFMD and was discharged after recovery. Two days later, the child was readmitted with fever, cough and respiratory distress. RT-PCR and Sanger sequencing confirmed positivity for EV-D68 and CVA6 in oro and nasopharynges swabs and vesicles fluid, respectively. Phylogenetic analysis based on VP1 gene sequences suggested that CVA6 was closely related with HFMD viruses circulating in Turkey, while EV-D68 was genetically related to a Chinese strain. CONCLUSIONS: To the best of our knowledge, this case is the first report of a double infection caused by CVA6 and EV-D68, which shed light on the pathogenesis of enterovirus infections. Further studies must be conducted to ascertain the role and clinical significance of EV co-infections, as well as a potential synergistic pathway between these viruses.

Mortality among pediatric hematopoietic stem cell transplantation patients: Report from a single center in southern Brazil.

INTRODUCTION: HSCT has grown in number in recent years. This treatment in children has its particularities and has been characterized in previous studies only on a limited basis. There are important causes of morbidity and mortality in this group of patients, including evolution of primary disease, graft failure, infectious diseases, and GVHD. The aim of this study was to report case series of TRM within 100 days after transplantation and associated factors. METHODS: Retrospective cohort. All children transplanted between January 1, 2010 and December 31, 2017 were included and those who underwent the first HSCT in another center were excluded. RESULTS: Data from 292 children were analyzed. TRM in 100 days was 5.8%, being significantly higher in patients with umbilical cord blood as the cell source. Infectious complications were frequent in this sample (bacterial infections in 27%, viral infections in 75.3%, and fungal infections in 12%) and both the presence of fungal disease and more than one infection during the follow-up (viral and bacterial, viral and fungal or bacterial and fungal) had statistically significant association with the outcome. CONCLUSIONS: The prognosis in allogeneic HSCT is influenced by the origin of the stem cells, the presence of acute GVHD and the occurrence of infectious diseases. Studies that evaluate pediatric individuals undergoing HSCT and analyze their mortality profile, can improve the management of these patients, possibly leading to a reduction in TRM.

SARS-CoV-2 in asymptomatic pregnant women in South Brazil: RT-PCR and serological detection.

OBJECTIVES: This study aims to detect the SARS-CoV-2 infection prevalence in asymptomatic pregnant women. METHODS: A group of 195 asymptomatic pregnant women who attended the prenatal care outclinic and to the obstetric emergency department was tested concomitantly for SARS-CoV-2 by RT-PCR and serological tests. RESULTS: The virus was detected by RT-PCR in two (1.02%) cases and 17 (8.71%) patients had antibodies detected by immunochromatographic tests. CONCLUSIONS: Due to the high risk of this emerging infection in the health of pregnant women, fetuses and newborns, we suggest the universal screening of all pregnant women admitted to hospital through the combined method RT-PCR and serological.

Infectious complications in pediatric allogeneic hematopoietic stem cell transplantation recipients-A retrospective clinical and epidemiological cohort study.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an important therapeutic strategy for several hematologic diseases. In the absence of a matched related donor, allogeneic HSCT has been associated with increased risk of infectious complications. Here, we present the clinical and epidemiological characteristics of early infectious complications in children undergoing HSCT from Southern Brazil. METHODS: This is a retrospective unicentric cohort study of infections in all children receiving their first HSCT during the period between 2010 and 2017. RESULTS: Data from 292 patients were analyzed; bone marrow failures (52.7%) comprised most of the baseline diagnosis. Bone marrow (BM) was the stem cell source in 254 (87%), followed by cord blood (CB) in 34 (11.6%) children. The use of alternative donors (77.8%) and presence of acute graft-vs-host disease (GVHD) (23.6%) were associated with an increased risk of viral and fungal infection. Bacterial infection was observed in 79 patients (27%); 220 patients (75.3%) were diagnosed with viral infection, and 35 patients (12%) developed fungal infection. The presence of fungal disease together with the presence of multiple infections during follow-up was associated with an increased risk of death (P < .001). CONCLUSIONS: The clinical profile of HSCT-related infections in this cohort suggests that prognosis in allogeneic HSCT is influenced by the source of stem cells (CB having worse prognosis), presence of acute GVHD and complications arising from fungal infections. The appropriate management of these factors has the potential to improve the overall prognosis rates in pediatric allogeneic HSCT recipients.

Multicenter study of the epidemiology of Clostridioides difficile infection and recurrence in southern Brazil.

Clostridioides (Clostridium) difficile is the main etiology underlying antibiotic-associated diarrhea (AAD). Still, few Brazilian data are available on this infection. The aims of this multicenter study were to identify the prevalence, clinical characteristics, and outcomes of C. difficile infection (CDI) in patients with antibiotic associated diarrhea at eight hospitals in Curitiba, southern Brazil, during the years 2017-2019. Stool samples were tested using enzyme immunoassay for glutamate dehydrogenase antigen (GDH) and A/B toxins. Positive GDH samples were further evaluated by real-time polymerase chain reaction (PCR) for the presence of genes encoding toxin B (tcdB), binary toxin (cdt), and marker of hypervirulent C. difficile strain (tcdC deletion). The prevalence of CDI in 351 patients with AAD included in the study was 17.7% (n = 62). Among the CDI cases, tcdB was positive in all 62 stool samples, while cdt was positive in 10 samples, and tcdC deletion was positive in only two. Carriage of carbapenem-resistant Gram-negative bacilli, previous hospitalization, and use of broad-spectrum cephalosporin and carbapenem were associated with CDI. Among patients with CDI, 64.5% presented with severe diarrhea, and 8% (5/62) progressed with colitis and required intensive care. The 30-day mortality was 24% (15/62), and the CDI-associated mortality was 4.8% (3/62). Overall, 83.8% (52/62) of the patients achieved primary cure, and 20.8% of the evaluated patients (10/48) presented CDI recurrence. The treatment administered was not significantly associated with the 60-day recurrence or mortality. In conclusion, we reported in this study data of prevalence and recurrence rates of CDI in patients with AAD and evaluated the number of severe cases and infection-related mortality, which were up to now unknown in Southern Brazilian hospitals.

Epidemiology of enteric viruses in children with gastroenteritis in Ogun State, Nigeria.

Acute gastroenteritis (AGE) remains a global public health concern and Nigeria is one of the two countries accounting for 42% of global under-5 deaths attributable to gastroenteritis. This study aimed to determine the prevalence, seasonality, and risk factors of enteric viruses (EVs) in children with AGE in Ogun State, Nigeria. Stool samples collected from children under-5 from three different hospitals between February 2015 and April 2017 were analyzed using molecular methods for the presence of four EVs (group A rotavirus [RVA], norovirus [NoV], human astrovirus [HAstV], and human adenovirus [HAdV]). Among the 175 samples analyzed, 63 (36%) were positive for at least one EV. The most prevalent was HAstV (19.4%), followed by RVA (16.6%), NoV (5.1%), and HAdV (5.1%). Mixed infections were found in 17 cases. No significant association was observed with age, sex, and risk factors. Though not significant, EV prevalence was higher in the dry season. Positive cases (asides HAdV) had no correlation with temperature and/or humidity. This study provides information on the prevalence and seasonal fluctuations of EVs, which will be of value in the effective management of patients and control strategies for viral gastroenteritis in the country.

Human adenovirus meningoencephalitis: a 3-years' overview.

Human adenovirus (HAdV) has been recognized as a significant viral pathogen implicated in neurological diseases, particularly in immunocompromised patients. However, its involvement in meningoencephalitis remains unclear. The aim of this study was to investigate HAdV and other viral co-infections in the cerebrospinal fluid (CSF) of patients suspected of having either meningoencephalitis or encephalitis. A total of 373 CSF samples from patients under clinical suspicion of neurological viral infection were included in this study. HAdV was investigated by conventional or multiplex real-time PCR, for different time periods. The frequency of HAdV central nervous system (CNS) infection was 1.08%, predominating in female patients with a predisposing condition, and presented with HAdV encephalitis. HAdV CNS infection was found to occur during the months of autumn and winter. The frequency of HAdV detected in CSF positive samples increased after the change in the diagnostic method from conventional to multiplex real-time PCR. There were no specific NMRI or EEG characteristics and two CSF samples with HAdV encephalitis had normal CSF WBC count. There were two cases of co-infection with HIV; no other co-infections with enterovirus or herpes family viruses were detected. All patients had good outcome. Although HAdV is rarely observable in CNS infectious syndromes, it must be investigated particularly in immunocompromised patients.

High frequency of multiple HPV types detection in Fanconi anemia patients oral swabs.

BACKGROUND: Fanconi anemia (FA) is a rare genetic disease usually characterized by bone marrow failure and congenital malformations. The risk of development of malignancies in the oral cavity of FA patients, such as squamous cell carcinoma (SCC), increases significantly after a hematopoietic stem cells transplant (HSCT), and may also be linked with the presence of human papillomavirus (HPV) infections in the oral cavity. We investigated the prevalence and the HPV genotypes in oral mucosa of Brazilian FA patients. METHODS AND RESULTS: Oral swabs of 49 FA patients were collected. The median age of patients was 20 years (range 5-44) and 57% were over 18 years. Oral lesions were present in 20% of all patients, being 90% leukoplakia. HPV DNA was detected in 28% (14/49) of patients, and one of them also reported genital HPV lesions. Sixty-seven percent of all patients had undergone HSCT, including 12 patients (86%) of those with HPV results. Multiple HPV types were detected in 78% and 71% of HPV samples by Sanger sequencing and reverse hybridization methods, respectively. The most prevalent HPV types detected were 6, 11, 18, and 68. CONCLUSIONS: HPV prevalence in the oral mucosa of the assessed FA patients was higher than reported in the general population. Additional studies with collection of sequential samples are needed to know the natural history of the presence of multiple HPV types in these individuals and its association with the development of tumors, to evaluate the implementation of preventive measures, such as vaccination, and to guide early treatment.

Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid of patients infected with HIV-1 subtypes B and C.

Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aß) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and ß (sAPPα, sAPPß), Aß oligomers 38, 40, 42, and Aß-total; phosphorylated tau (P-tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aß-42 and Hulstaert (P-tau181) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau181 (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aß-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau181/Aß-42, T-tau/Aß-42, P-tau181/T-tau, sAPPα/ß (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aß-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau181) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.

Molecular characterization and clinical epidemiology of human respiratory syncytial virus (HRSV) A and B in hospitalized children, Southern Brazil.

Human respiratory syncytial virus (HRSV) is a major etiologic agent of pediatric respiratory infections. Genetic variability of its glycoprotein G enables HRSV to evade the immune response and determines its seasonal dissemination. This study reports genetic variability and clinical profiles of HRSV-infected patients from Southern Brazil. Seventy positive samples, 78% type A and 22% type B, were analyzed. Of the patients (median age, 6 months; interquartile range, 2-11 years), 16% had co-morbidities and 17% developed severe disease. The ON1 HRSV genotype first appeared in 2012, and patients infected with this genotype showed an increased tendency to develop severe disease.

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil.

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p < 0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p = 0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV-. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.

Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs.

Background: CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness. Methods: We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%. Findings: 1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases. Interpretation: Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination. Funding: Research supported by Sanofi.

Neurocognitive impairment in HIV-1 clade C- versus B-infected individuals in Southern Brazil.

HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C-infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV- participants were recruited from the same geographic region in Southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale (IHDS)), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV-associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid were collected from all HIV+ participants. HIV+ and HIV- participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV- by the IHDS and the GDS. Clade B- and C-infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis.

IgA antibody dynamics in healthcare workers after CoronaVac® vaccination and heterologous Comirnaty® booster dose.

BACKGROUND: This study is aimed at calculating the IgA antibody dynamic range in healthcare workers (HCWs) after immunization with CoronaVac® and Comirnaty® booster dose. METHODS: A total of 118 HCW serum samples from Southern Brazil were collected the day before the first vaccine dose (day 0) and + 20, + 40, + 110, + 200 days following the vaccine's first dose, and + 15 days after a Comirnaty® booster dose. Immunoglobulin A (IgA) was quantified using immunoassays for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). RESULTS: Seroconversion for the S1 protein occurred in 75 (63.56%) and 115 (97.47%) HCWs by day + 40 and day + 15 after the booster dose, respectively. There was an absence of IgA antibodies after the booster dose in two (1.69%) HCWs undergoing biannual rituximab administration and one (0.85%) HCW for no apparent reason. CONCLUSION: Complete vaccination showed a significant IgA antibody production response, and the booster dose considerably increased this response.

Influenza A, like Omicron SARS-CoV-2, Is Similarly Detected in Saliva or Nasopharyngeal Samples via RT-qPCR.

After the Coronavirus pandemic, the importance of virus surveillance was highlighted, reinforcing the constant necessity of discussing and updating the methods for collection and diagnoses, including for other respiratory viruses. Although the nasopharyngeal swab is the gold-standard sample for detecting and genotyping SARS-CoV-2 and Influenza viruses, its collection is uncomfortable and requires specialized teams, which can be costly. During the pandemic, non-invasive saliva samples proved to be a suitable alternative for SARS-CoV-2 diagnosis, but for Influenza virus the use of this sample source is not recognized yet. In addition, most SARS-CoV-2 comparisons were conducted before the Omicron variant emerged. Here, we aimed to compare Influenza A and Omicron RT-qPCR analysis of nasopharyngeal swabs and saliva self-collection in paired samples from 663 individuals. We found that both nasopharyngeal swab and saliva collection are efficient for the diagnosis of Omicron (including sub-lineages) and for Influenza A, with high sensitivity and accuracy (>90%). The kappa index is 0.938 for Influenza A and 0.905 for SARS-CoV-2. These results showed excellent agreement between the two samples reinforcing saliva samples as a reliable source for detecting Omicron and highlighting saliva as a valid sample source for Influenza detection, considering this cheaper and more comfortable alternative.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

Antibody response following a Comirnaty booster dose in CoronaVac vaccinated individuals.

Serum samples from 106 health care workers were analyzed by enzyme-linked immunosorbent assay (ELISA) test 15 days after a booster dose. A total of 99% of the participants showed a significant increase in the anti-S1 IgG index. The significant humoral response was observed 15 days after the heterologous dose of Comirnaty in most the subjects, regardless of having comorbidities. The administration of a third booster dose is suggested 5 months after the second vaccine dose of the initial vaccine.