Mortality among healthcare workers in Indonesia during 18 months of COVID-19

The impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID-19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web-based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39-59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID-19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 - 5.17). The COVID-19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rates is 5-times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and a national systematic surveillance of occupational mortality is urgently needed in this setting.

Serum anti-Spike antibody titers before and after heterologous booster with mRNA-1273 SARS-CoV-2 vaccine following two doses of inactivated whole-virus CoronaVac vaccine

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.

Pandemic inequity in a megacity: a multilevel analysis of individual, community, and health care vulnerability risks for COVID-19 mortality in Jakarta, Indonesia

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.

Excess mortality during the first ten months of COVID-19 epidemic at Jakarta, Indonesia

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.

Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: a hospital-based retrospective cohort study

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.

Quantifying the dynamics of COVID-19 burden and impact of interventions in Java, Indonesia

BackgroundAs in many countries, quantifying COVID-19 spread in Indonesia remains challenging due to testing limitations. In Java, non-pharmaceutical interventions (NPIs) were implemented throughout 2020. However, as a vaccination campaign launches, cases and deaths are rising across the island. MethodsWe used modelling to explore the extent to which data on burials in Jakarta using strict COVID-19 protocols (C19P) provide additional insight into the transmissibility of the disease, epidemic trajectory, and the impact of NPIs. We assess how implementation of NPIs in early 2021 will shape the epidemic during the period of likely vaccine roll-out. ResultsC19P burial data in Jakarta suggest a death toll approximately 3.3 times higher than reported. Transmission estimates using these data suggest earlier, larger, and more sustained impact of NPIs. Measures to reduce sub-national spread, particularly during Ramadan, substantially mitigated spread to more vulnerable rural areas. Given current trajectory, daily cases and deaths are likely to increase in most regions as the vaccine is rolled-out. Transmission may peak in early 2021 in Jakarta if current levels of control are maintained. However, relaxation of control measures is likely to lead to a subsequent resurgence in the absence of an effective vaccination campaign. ConclusionSyndromic measures of mortality provide a more complete picture of COVID-19 severity upon which to base decision-making. The high potential impact of the vaccine in Java is attributable to reductions in transmission to date and dependent on these being maintained. Increases in control in the relatively short-term will likely yield large, synergistic increases in vaccine impact. Key questionsO_ST_ABSWhat is already known?C_ST_ABSO_LIIn many settings, limited SARS-CoV-2 testing makes it difficult to estimate the true trajectory and associated burden of the virus. C_LIO_LINon-pharmaceutical interventions (NPIs) are key tools to mitigate SARS-CoV-2 transmission. C_LIO_LIVaccines show promise but effectiveness depends upon prioritization strategies, roll-out and uptake. C_LI What are the new findings?O_LIThis study gives evidence of the value of syndrome-based mortality as a metric, which is less dependent upon testing capacity with which to estimate transmission trends and evaluate intervention impact. C_LIO_LINPIs implemented in Java earlier in the pandemic have substantially slowed the course of the epidemic with movement restrictions during Ramadan preventing spread to more vulnerable rural populations. C_LIO_LIPopulation-level immunity remains below proposed herd-immunity thresholds for the virus, though it is likely substantially higher in Jakarta. C_LI What do the new findings imply?O_LIGiven current levels of control, upwards trends in deaths are likely to continue in many provinces while the vaccine is scheduled to be rolled out. A key exception is Jakarta where population-level immunity may increase to a level where the epidemic begins to decline before the vaccine campaign has reached high coverage. C_LIO_LIFurther relaxation of measures would lead to more rapidly progressing epidemics, depleting the eventual incremental effectiveness of the vaccine. Maintaining adherence to control measures in Jakarta may be particularly challenging if the epidemic enters a decline phase but will remain necessary to prevent a subsequent large wave. Elsewhere, higher levels of control with NPIs are likely to yield high synergistic vaccine impact. C_LI