Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, β, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to β and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs

Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals

Background To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps. Methods Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2-blocking antibodies (ACE2-blocking Abs), antibodies to the receptor-binding domain (RBD) of variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort. Results All individuals (100%) had SARS-CoV-2-specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2-blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2-blocking Abs (p Conclusions Both dosing schedules resulted in high antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose

Comparison of the immunogenicity of five COVID-19 vaccines in Sri Lanka

To determine the antibody responses elicited by different vaccines against SARS-CoV-2, we compared antibody responses in individuals 3 months post-vaccination in those who had received different vaccines in Sri Lanka. Abs to the receptor binding domain (RBD) of the ancestral (wild type) virus (WT) as well as to variants of concern (VoCs), and ACE2 blocking Abs, were assessed in individuals vaccinated with Moderna (n = 225), Sputnik V (n = 128) or Sputnik light (n = 184) and the results were compared with previously reported data on Sinopharm and AZD1222 vaccinees. A total of 99.5% of Moderna, >94% of AZD1222 or Sputnik V and >70% of Sputnik light, >60% of Sinopharm vaccine recipients, had a positive response to ACE2 blocking antibodies. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/AZD1222 (had equal levels) > Sputnik light > Sinopharm. All Moderna recipients had antibodies to the RBD of WT, alpha and beta, while positivity rates for delta variant was 80%. The positivity rates for Sputnik V vaccinees for the WT and VoCs were higher than for AZD1222 vaccinees while those who received Sinopharm had the lowest positivity rates (<16.7%). The total antibodies to the RBD were highest for the Sputnik V and AZD1222 vaccinees. The Moderna vaccine elicited the highest ACE2 blocking antibody levels followed by Sputnik V/AZD1222, while those who received Sinopharm had the lowest levels. These findings highlight the need for further studies to understand the effects on clinical outcomes

Seroprevalence of SARS-CoV-2 infection in the Colombo Municipality region, Sri Lanka

Background: As the Municipality Council area in Colombo (CMC) experienced the highest number of cases until the end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak. Methods: SARS-CoV-2 seropositivity was determined in 2,547 individuals between the ages of 10–86 years, by the Wantai total antibody ELISA. We also compared seroprevalence using the haemagglutination test (HAT) to evaluate its usefulness in carrying out serosurveys. Results: The overall seropositivity rate was 24.46%, while seropositivity by HAT was 18.90%. Although The SARS-CoV-2 infection detection rates by PCR were highest in the population between the ages of 20–60 years of age, there was no statistically significant difference in the seropositivity rates in different age groups. For instance, although the seropositivity rate was highest in the 10–20 age group (34.03%), the PCR positivity rate was 9.80%. Differences in the PCR positivity rates and seropositivity rates were also seen in 60–70-year-olds (8.90 vs. 30.4%) and in individuals >70 years (4.10 vs. 1.20%). The seropositivity rate of the females was 29.70% (290/976), which was significantly higher (p < 0.002) than in males 21.2% (333/1,571). Conclusions: A high seroprevalence rate (24.5%) was seen in all age groups in the CMC suggesting that a high level of transmission was seen during this time. The higher PCR positivity rates between the ages of 20–60 are likely to be due to increased testing carried out in the working population. Therefore, the PCR positivity rates, appear to underestimate the true extent of the outbreak and the age groups which were infected

Immune responses to Sinopharm/BBIBP-CorV in individuals in Sri Lanka

As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor-binding domain (RBD) of the wild-type (WT), alpha, beta and delta variants, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 and 6 weeks (2 weeks after the second dose). Ninety-five percent of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p 60 years (93.3%) compared to those who were 20–39 years (98.9%); 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p = 0.44). Vaccinees had significantly less (

Socio-demographic variations in prostate cancer diagnosis recording: Primary care compared to the Cancer Registry in England

IntroductionIn the UK, primary care data are often used for cancer-related research, but the accuracy of cancer information is uncertain. ObjectiveWe investigated socio-demographic variation based on the recording date of prostate cancer diagnosis between primary care and the National Cancer Registry (CR). ApproachWe utilised a data extract of 1,600,000 patients over 65 years from Clinical Practice Research Datalink (CPRD). We extracted prostate cancer diagnoses using Read and SNOMED-CT codes from primary care, and ICD-10 from CR. Initial code entry determined diagnosis dates. We categorised recording timing differences as earlier, same-day or later in primary care than CR and used the chi-squared test and logistic regression (adjusted for recording year) to compare these discrepancies across age, deprivation, and ethnicity. ResultsWe included 26,875 men with prostate cancer diagnoses commonly recorded in both sources during 2000-2016 (1,030 excluded with missing ethnicity). Compared to CR, 1,747 (7%) had diagnoses recorded on the same day in primary care, while 20,615 (77%) had later recordings with a median delay of 21 days (IQR: 13-38). Age at diagnosis was associated with recording discrepancies (p<0.001); older men were more likely to have earlier/same-day recordings. Adjusted ORs for age groups were 1.4 (95%CI: 1.3-1.5) for 60-69, 1.3 (1.2-1.5) for 70-79, and 0.9 (0.8-1.0) for ≥80 compared to <60. No associations were found between deprivation (p=0.096) or ethnicity (p=0.067) and recording differences. Conclusion/ ImplicationsThe discrepancy in prostate cancer information between primary care and CR underscores potential biases in studies relying solely on one data source.</p

Evaluating the quality of prostate cancer diagnosis recording in CPRD GOLD and CPRD Aurum primary care databases for observational research: a study using linked English electronic health records

Background: Primary care data in the UK are widely used for cancer research, but the reliability of recording key events like diagnoses remains uncertain. Data linkage can mitigate these uncertainties; however, researchers may avoid it due to costs, timelines, and sample size constraints. We evaluated accuracy, completeness, and date concordance of prostate cancer (PCa) diagnosis recording in Clinical Practice Research Datalink (CPRD) GOLD and Aurum compared to linked Cancer Registry (CR) and Hospital Episode Statistics (HES) Admitted Patient Care (APC) in England. Methods: Incident PCa diagnoses (2000-2016) for males aged ≥46 at diagnosis who remained registered with their General Practitioner (GP) by age 65 and were recorded in at least one data source were analysed. Accuracy was the proportion of diagnoses recorded in GOLD or Aurum with a corresponding record in CR or HES. Completeness was the proportion of CR or HES diagnoses with a corresponding record in GOLD or Aurum. Results: The final cohorts for comparisons included 29,500 records for GOLD and 26,475 for Aurum. Compared to CR, GOLD was 86% accurate and 65% complete, while Aurum was 87% accurate and 77% complete. Compared to HES, GOLD was 76% accurate and 60% complete, and Aurum was 79% accurate and 70% complete. Concordance in diagnosis dates improved over time in both GOLD and Aurum, with 93% of diagnoses recorded within a year compared to CR, and 66% (GOLD) and 71% (Aurum) compared to HES. Delays of 2-3 weeks in primary care diagnosis recording were observed compared to CR, whereas most diagnoses appeared at least 3 months earlier in primary care than in HES. Conclusions: Aurum demonstrated better quality for PCa diagnosis recording than GOLD. However, linkage to HES or CR is recommended for improved case capture. Researchers should address the limitations of each data source to ensure research validity.</p

The rising complexity and burden of multimorbidity in a middle-income country.

BackgroundThe limited knowledge on aetiology, epidemiology and risk factors for multimorbidity especially evident from low and middle-income countries curtail the development and implementation of sustainable healthcare models. Sri Lanka, boasting for one of South Asia's most efficient public health systems that is accessible free-of-charge by the citizens is presently transitioning from lower-middle to upper-middle-income tier. Faced with the triple burden of disease, it is imperative for Sri Lanka to incorporate an integrated model to manage multimorbidity.MethodsA descriptive cross-sectional study was carried out in medical clinics of a tertiary care hospital and a University primary care department. Data were extracted on to a form from the clinical records of patients over the age of 20 years with at least one non-communicable disease (NCD) and analysed.ResultsMultimorbidity was present among 64.1% of patients (n = 1600). Nearly 44.44% of the patients aged 20-35 years have a minimum of two disorders, and by the time they reach 50 years, nearly 64% of the patients have two or more non-communicable diseases. Nearly 7% of those aged over 65 years were diagnosed with four or more disorders. A fourth of the sample was affected by co-morbid diabetes mellitus and hypertension, whereas the combinations of coronary heart disease with hypertension and diabetes mellitus were also found to be significantly prevalent. A salient revelation of the binomial logistic regression analysis was that the number of disorders was positively correlated to the presence of mental disorders 7.25 (95% CI = 5.82-8.68).ConclusionMultimorbidity is highly prevalent among this population and seemingly has a detrimental effect on the psychological wellbeing of those affected. Therefore, the need for horizontal integration of all primary to tertiary care disciplines, including mental health, to manage multimorbidity by policymakers is emphasized as a priority task

Immune responses to a single dose of the AZD1222/Covishield vaccine at 16 weeks in individuals in Sri Lanka

Due to limited access to vaccines, many countries have only administered a single dose of the AZD1222, whereas the dosage intervals have increased ≥4 wk. We sought to investigate the immunogenicity of a single dose of vaccine at ≥16 wk postimmunization. Severe acute respiratory syndrome coronavirus 2–specific Abs in 553 individuals and Abs to the receptor-binding domain of the Wuhan virus (wild-type) and the variants of concern, angiotensin-converting enzyme 2 receptor blocking Abs ex vivo and cultured IFN-γ T cell (Homo sapiens) responses and B cell (H. sapiens) ELISPOT responses, were investigated in a subcohort. The seropositivity rates in those >70 y of age (93.7%) was not significantly different compared with other age groups (97.7–98.2; Pearson χ2 = 7.8; p = 0.05). The Ab titers (Ab index) significantly declined (p 60 y. Ex vivo IFN-γ T cell ELISPOT responses were seen in 10 of 66 (15.1%), whereas only a few expressed CD107a. However, >85% had a high frequency of cultured IFN-γ T cell ELISPOT responses and B cell ELISPOTs. Virus-specific Abs were maintained at ≥16 wk after receiving a single dose of AZD1222, although levels were lower to variants of concern, especially in older individuals. A single dose induced a high frequency of memory T and B cell responses

Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers

Several COVID-19 vaccines have received emergency approval. Here we assess the immunogenicity of a single dose of the AZD1222 vaccine, at one month, in a cohort of health care workers (HCWs) (629 naïve and 26 previously infected). 93.4% of naïve HCWs seroconverted, irrespective of age and gender. Haemagglutination test for antibodies to the receptor binding domain (RBD), surrogate neutralization assay (sVNT) and ex vivo IFNγ ELISpot assays were carried out in a sub-cohort. ACE2 blocking antibodies (measured by sVNT) were detected in 67/69 (97.1%) of naïve HCWs. Antibody levels to the RBD of the wild-type virus were higher than to RBD of B.1.1.7, and titres to B.1.351 were very low. Ex vivo T cell responses were observed in 30.8% to 61.7% in naïve HCWs. Previously infected HCWs, developed significantly higher (p