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BackgroundImmunity acquired from natural SARS-CoV-2 infection and vaccine wanes overtime. This longitudinal prospective study compared the effect of a booster vaccine (BNT162b2) in inducing the mucosal (nasal) and serological antibody between Covid-19 recovered patients and healthy unexposed subjects with two dose of mRNA vaccine (vaccine-only group). MethodEleven recovered patients and eleven gender-and-age matched unexposed subjects who had mRNA vaccines were recruited. The SARS-CoV-2 spike 1 (S1) protein specific IgA, IgG and the ACE2 binding inhibition to the ancestral SARS-CoV-2 and omicron (BA.1) variant receptor binding domain were measured in their nasal epithelial lining fluid and plasma. ResultIn the recovered group, the booster expanded the nasal IgA dominancy inherited from natural infection to IgA and IgG. They also had a higher S1-specific nasal and plasma IgA and IgG levels with a better inhibition against the omicron BA.1 variant and ancestral SARS-CoV-2 when compared with vaccine-only subjects. The nasal S1-specific IgA induced by natural infection lasted longer than those induced by vaccines while the plasma antibodies of both groups maintained at a high level for at least 21 weeks after booster. ConclusionThe booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against Omicron BA.1 variant.
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Conjunctival and nasal mucosal antibody responses in thirty-four paediatric and forty-seven adult COVID-19 patients were measured. The mucosal antibody was IgA dominant. In the nasal epithelial lining fluid (NELF) of asymptomatic paediatric patients, SARS-CoV-2 spike protein 1 (S1) specific immunoglobulin A (IgA) was induced early. Their plasma S1-specific IgG levels were higher than symptomatic patients. More adult with mild disease had NELF S1-specific IgA than those with severe/critical illness. Within the first week of diagnosis, higher S1-specific antibodies in NELF and plasma and lower vial loads were detected in paediatric than adult patients with mild disease. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF neutralizing S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. This study highlights the effect of nasal IgA in limiting the SARS-CoV-2 replication and provides complementary information to the serum antibody measurements.
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Vaccines that elicit mucosal immune responses against SARS-CoV-2 could potentially be of exceptional importance in providing first line defense at the site of viral entry. The serological antibody response induced by SARS-CoV-2 vaccines have already been well characterized. In order to understand the mucosal immune response profiles of SARS-CoV-2 vaccines, we examined both the mucosal and systemic responses of subjects vaccinated by two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac). Serial nasal epithelial lining fluid (NELF) and peripheral blood samples were collected in ten subjects who had received CoronaVac and thirty-two subjects who had received Comirnaty. We quantified IgA and IgG specific to SARS-CoV-2 S1 protein by ELISA in NELF and plasma samples. The neutralization effect of these two sample types were evaluated by surrogate ACE-SARS-CoV-2 Spike protein ELISA. Only Comirnaty induced nasal SARS-CoV-2 S1 protein-specific (S1-specific) IgA and IgG responses, which were evident as early as on 14{+/-}2 days after the first dose. The NELF samples of 72% of subjects became IgA+IgG+, while in 62.5% of subjects the samples were neutralizing by 7{+/-}2 days after the second dose. In 45% of the subjects their NELF remained neutralizing 50 days after the booster of Comirnaty. In plasma, 91% and 100% Comirnaty subjects possessed S1-specific IgA+IgG+ on 14{+/-}2 days after the first dose and 7{+/-}2 days after booster, respectively. The plasma collected on 7{+/-}2 days after booster was 100% neutralizing. The induction of S1-specific antibody by CoronaVac was IgG dominant, and 70% of the subjects possessed S1-specific IgG by 7{+/-}2 days after booster and were all neutralizing. This study reveals that Comirnaty is able to induce S1-specific IgA and IgG response with neutralizing activity in the nasal mucosa in addition to a consistent systemic response. The clinical implications and the biological mechanism of an additional nasal immune response induced by vaccines such as Comirnaty warrant further investigation. One Sentence SummarymRNA vaccine (CoronaVac) elicits mucosal IgA and IgG in the nasal epithelial lining fluid together with ELISA-detected anti-wild-type spike neutralizing antibodies as early as day 14 post vaccination.
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INTRODUCTION@#Respiratory virus (RV) infections have been implicated in acute exacerbation cardiopulmunary conditions. This study aimed to determine the prevalence of RV infections in patients admitted to the cardiology unit with acute decompensated heart failure (ADHF) in a tertiary hospitals in Singapore.@*MATERIALS AND METHODS@#This was a single-centre, prospective observational study. A total of 194 adults (aged >21) admitted to the Singapore General Hospital with ADHF were recruited. A nasopharyngeal swab was taken for multiplex polymerase chain reaction (PCR) detection of influenza virus, rhinovirus, parainfluenza virus (HPIV), human coronavirus (HcoV), adenoviurs, human bocavirus (HboV), human metapneumovirus (hMPV), and respiratory syncytial virus (RSV).@*RESULTS@#Twenty-five (13%) had RVs detected by RV multiplex PCR. There comprised 9 rhinoviruses (36%), 4 influenza A viruses (16%), 3 HPIV (12%), 3 HCoV (12%), 2 adenoviruses (8%), 1 human HBoV (4%), 1 hMPV (4%), and 1 RSV (4%). Symptoms-wise, cough was significantly more common in the PCR-positive group (48% vs 24%, = 0.02). There were no statistically significant differences in laboratory investigations (haemoglobin, leukocytes, platelets, creatine kinase, creatine kinase-muscle/brain, troponin T), and radiology findings between RV PCR-positive and -negative groups. The PCR-positive group did not have increased mortality or length of hospital stay.@*CONCLUSION@#This study identified a considerable burden of RVs in our ADHF cohort, and highlights the need for prevention of RVs in this group of patients. We also recognised the difficulty with clinical diagnosis of RVs in ADHF patients.