ABSTRACT
BackgroundThe inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. MethodsIn a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (median 190 days, IQR165-232), we measured anti-Spike IgG titers on paired serum samples taken before and 28 days after a 100g mRNA-1273 (Moderna) booster. We performed correlations and multivariable ordinal regressions. FindingsAmong 304 participants, the median age was 31 years (range 21-59), 235 (77.3%) were women, 197 (64.8%) had one or more previous SARS-CoV-2 infections (including 155 [51.0%] who had a post-CoronaVac breakthrough infection. Pre-boost IgG titers correlated negatively with the time since the latest documented "virus exposure" (either by the second CoronaVac or SARS-CoV-2-infection whichever most recent). Previous SARS-CoV-2 infection and a longer time interval between second vaccine and mRNA-1273 boost were associated with a higher pre-boost IgG titer. Post-booster, the median IgG titer increased 9.3-fold, from 250 (IQR32-1389) to 2313 (IQR1226-4324) binding antibody units (BAU/mL) (p<0.001). All participants, including seven whose pre-boost IgG was below assay detection limits, became seropositive and all reached a substantial post-boost titer ([≥]364 BAU/mL). Post-boost IgG was not associated with pre-boost titer or previous SARS-CoV-2 infection. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living (ADL). InterpretationA heterologous, high-dose mRNA-1273 booster after two-dose CoronaVac was highly immunogenic and safe, including in those most in need of improved immunity. FundingWellcome Trust, UK Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide, at around 2 billion doses in 54 countries. Concerns that CoronaVac has lower immunogenicity than virus vector or mRNA vaccines, with pronounced decreases of neutralising antibody titres within a few months, and reduced effectiveness in the older population, highlight the urgent need for immunogenic, safe and well-tolerated booster schedules, especially with Omicron rapidly emerging. We used the terms "SARS-CoV-2", "COVID-19", "vaccine", "booster" to search PubMed and medRxiv up to Dec 22th, 2021, with no language or date restrictions, to identify clinical trials and real-world studies reporting on the immune responses and reactogenicity to a "third booster" of currently approved COVID-19 vaccines. Previous research reported that neutralising antibody responses elicited by all currently approved vaccines (mRNA, adenovirus-vectored, inactivated, and protein subunit) declined to varying degrees after 6-8 months after full-schedule vaccination. Several clinical trials have evaluated heterologous ("mix and match") vaccination schedules, demonstrating robust immune responses in adults. After two-dose CoronaVac, BNT162b2 (Pfizer-BioNTech) boost was significantly more immunogenic than a homologous booster against wild-type and Variants of Concern (VOCs) Beta, Gamma and Delta, and AZD1222 boost increased spike RBD-specific IgG 9-10-fold, with high neutralizing activity against the wild type and VOCs. Compared to previous SARS-CoV-2 variants, current vaccine boosters appeared to neutralise Delta to a slightly lesser degree, and Omicron to a substantially lesser degree, although preliminary data from Moderna found that the authorised dose (50g) of the mRNA-1273 boost increased antibodies 37-fold and the high-dose (100g) boost 83-fold. Added value of this studyTo our knowledge, this study is the first to provide critical real-world evidence that heterologous boosting with high-dose mRNA-1273 vaccine after CoronaVac is highly immunogenic, safe and well-tolerated in adults. After a primary course of two-dose CoronaVac, we found that a high-dose (100g) mRNA-1273 booster was immunogenic for all participants in a highly exposed cohort of hospital staff in Jakarta, Indonesia, in the context of Delta predominance, particularly for those with the lowest pre-boost antibody levels. All participants became seropositive and all reached a substantial post-boost titer ([≥]364 BAU/mL), up to a median 9.3-fold increase. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living Implications of all the available evidenceThe study findings contribute to informing policy makers on flexible options in deploying COVID-19 vaccines in mix-and-match schedules, with particular relevance for countries that are largely dependent on inactivated vaccines. Further trials are warranted that assess clinical endpoints of optimized doses of mRNA-1273 booster, and variant-specific or multivalent vaccines in response to decreased protection against emerging SARS-CoV-2 VOCs.
ABSTRACT
BackgroundThe 33 recognized megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and health care factors associated with COVID-19-related mortality in a megacity of Jakarta, Indonesia, during two epidemic waves spanning March 2, 2020, to August 31, 2021. MethodsThis retrospective cohort included all residents of Jakarta, Indonesia, with PCR-confirmed COVID-19. We extracted demographic, clinical, outcome (recovered or died), vaccine coverage data, and disease prevalence from Jakarta Health Office surveillance records, and collected sub-district level socio-demographics data from various official sources. We used multi-level logistic regression to examine individual, community and sub-district-level health care factors and their associations with COVID-19-mortality. FindingsOf 705,503 cases with a definitive outcome by August 31, 2021, 694,706 (98{middle dot}5%) recovered and 10,797 (1{middle dot}5%) died. The median age was 36 years (IQR 24-50), 13{middle dot}2% (93,459) were <18 years, and 51{middle dot}6% were female. The sub-district level accounted for 1{middle dot}5% of variance in mortality (p<0.0001). Individual-level factors associated with death were older age, male sex, comorbidities, and, during the first wave, age <5 years (adjusted odds ratio (aOR) 1{middle dot}56, 95%CI 1{middle dot}04-2{middle dot}35; reference: age 20-29 years). Community-level factors associated with death were poverty (aOR for the poorer quarter 1{middle dot}35, 95%CI 1{middle dot}17-1{middle dot}55; reference: wealthiest quarter), high population density (aOR for the highest density 1{middle dot}34, 95%CI 1{middle dot}14-2{middle dot}58; reference: the lowest), low vaccine coverage (aOR for the lowest coverage 1{middle dot}25, 95%CI 1{middle dot}13-1{middle dot}38; reference: the highest). InterpretationIn addition to individual risk factors, living in areas with high poverty and density, and low health care performance further increase the vulnerability of communities to COVID-19-associated death in urban low-resource settings. FundingWellcome (UK) Africa Asia Programme Vietnam (106680/Z/14/Z). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed on November 22, 2021, for articles that assessed individual, community, and healthcare vulnerability factors associated with coronavirus disease 2019 (COVID-19) mortality, using the search terms ("novel coronavirus" OR "SARS-CoV-2" OR "COVID-19") AND ("death" OR "mortality" OR "deceased") AND ("community" OR "social") AND ("healthcare" OR "health system"). The 33 recognized megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. At individual-level, studies have shown COVID-19-related mortality to be associated with older age and common underlying chronic co-morbidities including hypertension, diabetes, obesity, cardiac disease, chronic kidney disease and liver disease. Only few studies from North America, and South America have reported the association between lower community-level socio-economic status and healthcare performance with increased risk of COVID-19-related death. We found no studies have been done to assess individual, community, and healthcare vulnerability factors associated with COVID-19 mortality risk, especially in lower-and middle-income countries (LMIC) where accessing quality health care services is often challenging for substantial proportions of population, due to under-resourced and fragile health systems. In Southeast Asia, by November 22, 2021, COVID-19 case fatality rate had been reported at 2{middle dot}2% (23,951/1,104,835) in Vietnam, 1{middle dot}7% (47,288/2,826,853) in Philippines, 1{middle dot}0% (20,434/2,071,009) in Thailand, 1{middle dot}2% (30,063/2,591,486) in Malaysia, 2{middle dot}4% (2,905/119,904) in Cambodia, and 0{middle dot}3% in Singapore (667/253,649). Indonesia has the highest number of COVID-19 cases and deaths in the region, reporting 3{middle dot}4% case fatality rate (143,744 /4,253,598), with the highest number of cases in the capital city of Jakarta. A preliminary analysis of the first five months of surveillance in Jakarta found that 497 of 4265 (12%) hospitalised patients had died, associated with older age, male sex; pre-existing hypertension, diabetes, or chronic kidney disease; clinical diagnosis of pneumonia; multiple (>3) symptoms; immediate intensive care unit admission, or intubation. Added value of this studyThis retrospective population-based study of the complete epidemiological surveillance data of Jakarta during the first eighteen months of the epidemic is the largest studies in LMIC to date, that comprehensively analysed the individual, community, and healthcare vulnerability associated with COVID-19-related mortality among individuals diagnosed with PCR-confirmed COVID-19. The overall case fatality rate among general population in Jakarta was 1{middle dot}5% (10,797/705,503). Individual factors associated with risk of death were older age, male sex, comorbidities, and, during the first wave, age <5 years (adjusted odds ratio (aOR) 1{middle dot}56, 95%CI 1{middle dot}04-2{middle dot}35; reference: age 20-29 years). The risk of death was further increased for people living in sub-districts with high rates of poverty (aOR for the poorer quarter 1{middle dot}35, 95%CI 1{middle dot}17-1{middle dot}55; reference: wealthiest quarter), high population density (aOR for the highest density 1{middle dot}34, 95%CI 1{middle dot}14-2{middle dot}58), and low COVID-19 vaccination coverage (aOR for the lowest coverage 1{middle dot}25, 95%CI 1{middle dot}13-1{middle dot}38; reference: the highest). Implications of all available evidenceDifferences in socio-demographics and access to quality health services, among other factors, greatly influence COVID-19 mortality in low-resource settings. This study affirmed that in addition to well-known individual risk factors, community-level socio-demographics and healthcare factors further increase the vulnerability of communities to die from COVID-19 in urban low-resource settings. These results highlight the need for accelerated vaccine rollout and additional preventive interventions to protect the urban poor who are most vulnerable to dying from COVID-19.
ABSTRACT
Excess mortality during the COVID-19 epidemic is an important measure of health impacts. We examined mortality records from January 2015 to October 2020 from government sources at Jakarta, Indonesia: 1) burials in public cemeteries; 2) civil death registration; and 3) health authority death registration. During 2015-2019, an average of 26,342 burials occurred each year from January to October. During the same period of 2020, there were 42,460 burials, an excess of 61%. Burial activities began surging in early January 2020, two months before the first official laboratory confirmation of SARS-CoV-2 infection in Indonesia in March 2020. Analysis of civil death registrations or health authority death registration showed insensitive trends during 2020. Burial records indicated substantially increased mortality associated with the onset of and ongoing COVID-19 epidemic in Jakarta and suggest that SARS-CoV-2 transmission may have been initiated and progressing at least two months prior to official detection. Article summary lineAnalysis of civil records of burials in Jakarta, Indonesia showed a 61% increase during 2020 compared to the previous five years, a trend that began two months prior to first official confirmation of SARS-CoV-2 transmission in the city.
ABSTRACT
BackgroundData on COVID-19-related mortality and associated factors from low-resource settings are scarce. This study examined clinical characteristics and factors associated with in-hospital mortality of COVID-19 patients in Jakarta, Indonesia, from March 2 to July 31, 2020. MethodsThis retrospective cohort included all hospitalised patients with PCR-confirmed COVID-19 in 55 hospitals. We extracted demographic and clinical data, including hospital outcomes (discharge or death). We used Cox regression to examine factors associated with mortality. FindingsOf 4265 patients with a definitive outcome by July 31, 3768 (88%) were discharged and 497 (12%) died. The median age was 46 years (IQR 32-57), 5% were children, and 31% had at least one comorbidity. Age-specific mortalities were 11% (7/61) for <5 years; 4% (1/23) for 5-9; 2% (3/133) for 10-19; 2% (8/638) for 20-29; 3% (26/755) for 30-39; 7% (61/819) for 40-49; 17% (155/941) for 50-59; 22% (132/611) for 60-69; and 34% (96/284) for [≥]70. Risk of death was associated with higher age; pre-existing hypertension, cardiac disease, chronic kidney disease or liver disease; clinical diagnosis of pneumonia; multiple (>3) symptoms; and shorter time from symptom onset to admission. Patients <50 years with >1 comorbidity had a nearly six-fold higher risk of death than those without (adjusted hazard ratio 5{middle dot}50, 95% CI 2{middle dot}72-11{middle dot}13; 27% vs 3% mortality). InterpretationOverall mortality was lower than reported in high-income countries, probably due to younger age distribution and fewer comorbidities. However, deaths occurred across all ages, with >10% mortality among children <5 years and adults >50 years.
ABSTRACT
BackgroundAnalyses of correlates of SARS-CoV-2 infection or mortality have usually assessed individual predictors. This study aimed to determine if patterns of combined predictors may better identify risk of infection and mortality MethodsFor the period of March 2nd to 10th 2020, the first 9 days of the COVID-19 pandemic in Indonesia, we selected all 18 confirmed cases, of which 6 died, and all 60 suspected cases, of which 1 died; and 28 putatively negative patients with pneumonia and no travel history. We recorded data for travel, contact history, symptoms, haematology, comorbidities, and chest x-ray. Hierarchical cluster analyses (HCA) and principal component analyses (PCA) identified cluster and covariance patterns for symptoms or haematology which were analysed with other predictors of infection or mortality using logistic regression. ResultsFor univariate analyses, no significant association with infection was seen for fever, cough, dyspnoea, headache, runny nose, sore throat, gastrointestinal complaints (GIC), or haematology. A PCA symptom component for fever, cough, and GIC tended to increase risk of infection (OR 3.41; 95% CI 1.06-14; p=0.06), and a haematology component with elevated monocytes decreased risk (OR 0.26; 0.07-0.79; 0.027). Multivariate analysis revealed that an HCA cluster of 3-5 symptoms, typically fever, cough, headache, runny nose, sore throat but little dyspnoea and no GIC tended to reduce risk (aOR 0.048; <0.001-0.52; 0.056). In univariate analyses for death, an HCA cluster of cough, fever and dyspnoea had increased risk (OR 5.75; 1.06 - 31.3, 0.043), but no other individual predictor, cluster or component was associated. Other significant predictors of infection were age [≥] 45, international travel, contact with COVID-19 patient, and pneumonia. Diabetes and history of contact were associated with higher mortality. ConclusionsCluster groups and co-variance patterns may be stronger correlates of SARS-CoV-2 infection than individual predictors. Comorbidities may warrant careful attention as would COVID-19 exposure levels.
ABSTRACT
Isolated small bowel perforation is a rare presentation of blunt abdominal trauma, and most cases present immediately following the trauma. Delayed presentation of such cases beyond one week of trauma is extremely rare, and various pathophysiological mechanisms were described for the same. We present a 20-year-old male patient who sustained blunt abdominal and pelvic trauma, underwent open reduction and internal fixation for right acetabular fracture, and later developed features of acute peritonitis after one month. On laparotomy, complete terminal ileal transection was found and an ileostomy was done. Delayed perforation of the intestine following trauma occurs due to ischemic necrosis, either through direct trauma to the intestinal wall or indirectly by injury to the mesenteric vessels. Direct trauma to the bowel can result in large hematomas on the bowel wall, which can later perforate due to ischemia. Surgeons should be aware of this rare presentation as the management is challenging and it poses significant medico-legal sequel. Close monitoring of the patient's vitals and examination for the development of abdominal signs along with repeat imaging at the onset of abdominal signs are cornerstones for successful management of these patients.
ABSTRACT
In children under 5, a hemoglobin (Hb) cutoff of 11 g/dL is recommended by the World Health Organization to define anemia, yet few studies have examined whether this cut point accurately coincides with negative functional consequences. This systematic review and meta-analysis of iron intervention and observational studies aimed to clarify the consequences of low Hb concentration in children under age 5 years on growth, development, and chronic disease (functional outcomes) across the full range of Hb values. A literature search returned 5049 studies; of these, 56 intervention and 20 observational studies fit the inclusion criteria. Among iron supplementation trials, a metaregression indicated significant associations between intervention effects on Hb and their effects on motor and mental development. For each 1 standard deviation (SD) increase in Hb, motor scores increased by 0.28 SD and mental scores increased by 0.24 SD. Iron supplementation trials among children with lower Hb concentrations at baseline showed stronger associations between their effects on Hb and their effects on mental development (P-interaction = 0.008). Heterogeneity among observational studies precluded calculation of pooled associations between Hb and functional outcomes. Available evidence was not able to establish an inflection point at which decreasing Hb begins to be associated with negative functional outcomes. Future research is needed to examine associations of Hb with growth and development in populations with varying levels of Hb, inflammation, and in different ages and settings.