The severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) omicron sub-variants in Bangladesh cause mild COVID-19 and associate with similar antibody responses irrespective of natural infection or vaccination history.

Objective: Genomic surveillance and seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) in Bangladesh is paramount for COVID-19 pandemic preparedness yet lagging the high-income countries due to limited resources. Methods: SARS-CoV-2 variants, COVID-19 symptoms, and serology were prospectively evaluated in a cross-sectional study of Bangladeshi adults testing RT-PCR positive in 2021 and 2022. Results: SARS CoV-2 Omicron variants of asymptomatic or mild COVID-19 in 2022 replaced Delta variant infections requiring hospitalization and oxygen support. The omicron XBB became predominant in July 2022 and associated with cough, headache or body ache and loss of smell; 47 of 68 (69 %), 30 of 68 (44 %) and 27 of 68 (40 %) respectively at higher frequency than BA.1/BA.2; 16 of 88 (18 %), 13 of 88 (15 %) and 0 of 88 (0 %) p < 0.01, p < 0.01 and p < 0.0001. Linear regression analysis reveals no associations between the number of previous infections and the number of symptoms, r = -0.084, p = 0.68. The anti-nucleoprotein (N)-protein IgG post COVID-19 and anti-Spike (S) protein IgG post-COVID-19 vaccination were similar between BA.2, BA.4/BA.5 and XBB and significantly lower than the levels in delta variant infections (p < 0.001). Conclusions: Omicron XBB subvariants emerged in Bangladesh two months prior to previous reports and include unique patterns of S-protein mutations not assigned in PANGO lineage. The SARS CoV-2 omicron break-through infections persist in the presence of sustained antibody responses and vaccinations, underscoring the importance of molecular surveillance in low-income countries.

Antibody responses after two doses of SARS-CoV-2 mRNA-1273 vaccine in an individual with history of COVID-19 re-infection.

We present a case of a 58-year-old Japanese man with a history of 2 previous COVID-19 infections, who received 2 doses of mRNA-1273 vaccine. We are not aware of any previous study regarding antibody tendency after 2 infections and 2 vaccinations. We evaluated his IgG titer of antispike protein and neutralizing activity from the first infection before and after 2 doses of vaccine. Both antispike IgG titer and neutralizing activity showed a tendency to decline almost 1 year after initial infection; they rapidly increased after the first vaccination, and they remained high after the second vaccination. Although this is a single case report, it seems to have generalizability because the findings are consistent with previous reports regarding single infections or 3 doses of vaccination. Our findings suggest that a single booster shot may provide sufficient protection and aid the understanding of immunologic responses of vaccination in patients with COVID-19 with history of re-infection.

Monitoring of anti-SARS-CoV-2 IgG antibody immune responses in two cohorts of Hungarian healthcare workers following infection or immunization / Az anti-SARS-CoV-2-IgG-antitest-immunválaszok monitorozása magyarországi egészségügyi dolgozók két kohorszában fertozést, illetve immunizálást követoen.

Összefoglaló. Bevezetés: A SARS-CoV-2-fertozések és az anti-SARS-CoV-2-vakcinák által kiváltott immunvédelem tartóssága, nagysága és különbségeinek háttere nem teljesen tisztázott, az oltási protokollok optimális idozítése vitatott. Célkituzés: A humorális immunválaszok nagyságát, idobeli változását, a reinfekciók gyakoriságát, demográfiai és klinikai paraméterekkel való összefüggését vizsgáltuk magyarországi egészségügyi dolgozóknál. Módszerek: Megyei egyetemi oktató kórházunkban prospektív, longitudinális vizsgálatot végeztünk egészségügyi dolgozók két csoportjában. 1. kohorsz: SARS-CoV-2-fertozésen átesett, oltatlan 42 dolgozó (no: 100%) antinukleokapszid-IgG-szintjét mértük 8 hónapon keresztül (2020. június-2021. február). Az immunválasznak a változását és az életkorral, a krónikus betegségekkel, a vércsoporttal és a tünetek súlyosságával való összefüggését vizsgáltuk. 2. kohorsz: két dózis mRNS-vakcinával (Pfizer-BioNTech) végzett immunizálást követoen, fertozésnaiv 49 dolgozó (no: 73%) anti-spike-RBD-protein-IgG-szintjét monitoroztuk 8 hónapig (2020. december-2021. augusztus). Medián analízis, lineáris regresszió, ANCOVA, Kruskal-Wallis- és Skillings-Mack-teszt-elemzéseket végeztünk. Eredmények: 1. kohorsz: az IgG-szintek átlagosan a betegség 4-es súlyossági kategóriájában voltak a legmagasabbak, a negatív tartományba csökkenés medián ideje 6 hónap volt. 2. kohorsz: a második vakcina hatására az IgG-szint a 25-szörösére nott, majd 210 nap után a csúcsszint 6%-ra csökkent. Az ellenanyagtiter negatív összefüggést mutatott az idosebb életkorral és a férfinemmel. Tünetmentes (újra)fertozodést valószínusítettünk a fertozésen átesettek 17%-ánál és az immunizált kohorsz 14%-ánál. Az érintettek magas kockázatú osztályokon dolgoztak. Következtetés: 6 hónap után mind a fertozésen átesettek, mind az immunizáltak jelentosen csökkeno IgG-védelmet mutattak. A (re)infekciók átlagosan 15%-ban, tünetmentesen zajlottak. Az eredmények megerosítik az oltás hatékonyságát a betegség megelozésében, a harmadik emlékezteto vakcina fontosságát 6 hónap után és az anti-SARS-CoV-2-IgG-monitorozás potenciális értékét. Orv Hetil. 2022; 163(12): 455-462. INTRODUCTION: The length, level and variation of immune responses to infection with SARS-CoV-2 or following anti-SARS-CoV-2 vaccination remains unclear, optimal (re)vaccination protocols remain debated. OBJECTIVE: We investigated the magnitude of humoral immune responses, their over-time changes, the frequency of (re)infections and the association with demographic and clinical parameters in Hungarian healthcare workers. METHODS: We conducted a prospective, longitudinal study in two groups of healthcare workers of a public, county-level teaching hospital. Cohort 1: The anti-nucleocapsid IgG levels of 42 workers (female: 100%) were followed up over 8 months after SARS-CoV-2 infection (June 2020-February 2021). The change in humoral immune response and its associations with age, existing chronic conditions, blood type and severity of symptoms were investigated. Cohort 2: The anti-spike-RBD protein IgG levels of 49 workers (female: 73%) with no prior COVID-19 infection were monitored over 8 months (December 2020-August 2021) following immunisation with two doses of mRNA vaccine (Pfizer-BioNTech). Analyses included median analysis, linear regression, ANCOVA, Kruskal-Wallis and Skilling-Mack tests. RESULTS: Cohort 1: IgG levels were on average the highest among those in illness severity category 4, the median time of IgG level reduction below the positive test cut-off was 6 months. Cohort 2: The IgG levels increased 25-fold between the first and second immunisations, but decreased to 6% of the peak level after 210 days. They showed an overall negative association with older age and male sex. The suspected levels of (re)infections were 17% and 14% within the infected and the immunised cohorts, respectively, all symptomless. Those affected all worked on high-risk wards. CONCLUSION: Both the infected and the immunised cohorts showed significantly declining IgG protections beyond 6 months. The average observed rate of (re)infections was 15%, all asymptomatic. Our findings are confirmative of the effectiveness of vaccination to prevent illness, the importance of booster vaccination due to declining humoral immune protection beyond 6 months, and the potential value of anti-SARS-CoV-2 IgG monitoring. Orv Hetil. 2022; 163(12): 455-462.

Improved immunologic response to COVID-19 vaccine with prolonged dosing interval in haemodialysis patients.

Vaccination against 2019 coronavirus disease (COVID-19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID-19 vaccines in haemodialysis patients. All patients within a Swedish haemodialysis network, vaccinated with two doses of COVID-19 vaccine 2-8 weeks before inclusion, were eligible for this cross-sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antibody levels were determined by EliA SARS-CoV-2-Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty-nine patients were included. Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA-1273, 23,6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43-50) days after the second dose. A previous COVID-19 infection associated with higher antibody titres (median (25th-75th percentile) 1558.5 (814.5-3,763.8) U/mL vs 87 (26-268) U/mL, P = .002), while time between vaccine doses did not differ between groups (P = .7). Increasing SARS-CoV-2 antibody titres were independently associated with increasing time between vaccine doses (B 0.241, P = .02), decreasing serum calcium levels (B -0.233, P = .007) and previous COVID-19 (B 1.078, P < .001). In conclusion, a longer interval between COVID-19 mRNA vaccine doses, lower calcium and a previous COVID-19 infection were independently associated with a stronger immunologic vaccination response in haemodialysis patients. While the response rate was good, only a minority developed high antibody titres, 47 (43-50) days after the second vaccine dose.

Molecular and Serological Characterization of the SARS-CoV-2 Delta Variant in Bangladesh in 2021.

Novel SARS-CoV-2 variants are emerging at an alarming rate. The delta variant and other variants of concern (VoC) carry spike (S)-protein mutations, which have the potential to evade protective immunity, to trigger break-through infections after COVID-19 vaccination, and to propagate future waves of COVID-19 pandemic. To identify SARS CoV-2 variants in Bangladesh, patients who are RT-PCR-positive for COVID-19 infections in Dhaka were screened by a RT-PCR melting curve analysis for spike protein mutations. To assess the anti-SARS CoV-2 antibody responses, the levels of the anti-S -proteins IgA and IgG and the anti-N-protein IgG were measured by ELISA. Of a total of 36 RT-PCR positive samples (75%), 27 were identified as delta variants, with one carrying an additional Q677H mutation and two with single nucleotide substitutions at position 23029 (compared to Wuhan-Hu-1 reference NC 045512) in the genome sequence. Three (8.3%) were identified as beta variants, two (5.5%) were identified as alpha variants, three (8.3%) were identified as having a B.1.1.318 lineage, and one sample was identified as an eta variant (B.1.525) carrying an additional V687L mutation. The trend of higher viral load (lower Cp values) among delta variants than in the alpha and beta variants was of borderline statistical significance (p = 0.045). Prospective studies with larger Bangladeshi cohorts are warranted to confirm the emergence of S-protein mutations and their association with antibody response in natural infection and potential breakthrough in vaccinated subjects.

Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life.

Background: Development of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority. Children living in low and lower-middle income settings are at the highest risk of contracting and dying from these diseases. Improved vaccines with broader coverage are required. Data on the natural development of antibodies to putative vaccine antigens, especially in high-risk settings, can inform the rational selection of the best antigens for vaccine development. Methods: Serum IgG titres to four pneumococcal proteins (PspA1, PspA2, CbpA, and Ply) and five NTHi antigens (P4, P6, OMP26, rsPilA and ChimV4) were measured in sera collected from 101 Papua New Guinean children at 1, 4, 9, 10, 23 and 24 months of age using multiplexed bead-based immunoassays. Carriage density of S. pneumoniae and H. influenzae were assessed by quantitative PCR on genomic DNA extracted from nasopharyngeal swabs using species-specific primers and probes. All data were log-transformed for analysis using Student's unpaired t-tests with geometric mean titre (GMT) or density (GMD) calculated with 95% confidence intervals (CI). Results: Serum -pneumococcal protein-specific IgG titres followed a "U" shaped pattern, with a decrease in presumably maternally-derived IgG titres between 1 and 4 months of age and returning to similar levels as those measured at 1 month of age by 24 months of age. In contrast, NTHi protein-specific IgG titres steadily increased with age. There was no correlation between antibody titres and carriage density for either pathogen. Conclusion: This longitudinal study indicates that the waning of maternally- derived antibodies that is usually observed in infants, after infants does not occur for NTHi antigens in Papua New Guinean infants. Whether NTHi antigen IgG can be transferred maternally remains to be determined. Vaccines that are designed to specifically increase the presence of protective NTHi antibodies in the first few months of life may be most effective in reducing NTHi disease. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT01619462.

Asymptomatic COVID-19 re-infection in a Japanese male by elevated half-maximal inhibitory concentration (IC50) of neutralizing antibodies.

INTRODUCTION: "Re-infection" with COVID-19 is a growing concern; re-infection cases have reported worldwide. However, the clinical characteristics of SARS-CoV-2 re-infection, including the levels and role of anti-SARS-CoV-2 Spike protein IgG antibodies and the half-maximal concentration (IC50) of neutralizing antibodies remain unknown. METHODS: Both the epidemiological and clinical information has been collected during two episodes of COVID-19 in a patient. Laboratory results, including RT-PCR, Ct values, anti-SARS-CoV-2 Spike protein IgG antibodies, and the IC50 of neutralizing antibodies levels were analyzed on the patient. RESULTS: The patient was a 58-year-old man who developed moderate COVID-19 pneumonia with oxygen demand (cannula 2 L/min) in the first episode. By day 30, he recuperated and was discharged after testing negative for SARS-CoV-2. After two and a half months, his three family members showed COVID-19 symptoms and tested positive for SARS-CoV-2. He tested positive for SARS-CoV-2 once again and was asymptomatic (the second episode). The IC50 of neutralizing antibodies against SARS-CoV-2 greatly increased from 50.0 µg/mL (after the first episode) to 14.8 µg/mL (after the second episode), and remained strongly reactive (20.1 µl/mL) after 47 days of the second episode. CONCLUSIONS: Epidemiological, clinical, and serological analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest that SARS-CoV-2 re-infection may manifest as asymptomatic with increased neutralizing antibody levels. Further studies such as the virus characteristics, immunology, and epidemiology on SARS-CoV-2 re-infection are needed.