COVID-19 deaths detected in a systematic post-mortem surveillance study in Africa
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Abstract
Objectives
Limited SARS CoV 2 testing in many African countries has constrained availability of data on the impact of COVID-19 (CV19). To address this gap, we conducted a systematic post-mortem surveillance study to directly measure the fatal impact of CV19 in an urban African population.
Design
We enrolled deceased individuals at the University Teaching Hospital (UTH) Morgue in Lusaka, Zambia. We obtained nasopharyngeal swabs for testing via reverse-transcriptase quantitative PCR (RT-qPCR) against the SARS-2 Coronavirus. We stratified deaths by CV19 status, by location, age, sex, and underlying risk factors.
Setting
UTH is Zambia’s largest tertiary care referral hospital and its morgue registers ∼80% of Lusaka’s deaths.
Participants
Participants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent.
Results
We enrolled 372 participants between June and September 2020, and had PCR results for 364 (99.5%). CV19 was detected in 70/364 (19.2%). The median age for CV19+ deaths was 48 years (IQR 36-72 years) and 70% were male. Most CV19+ deaths (51/70, 72.8%) occurred in the community; none had been tested for CV19 antemortem. Among the 19/70 facility deaths, six were tested antemortem. Among the 52/70 CV19 deaths with symptoms data, 44/52 had typical symptoms of CV19 (cough, fever, shortness of breath), of whom only five were tested antemortem. We identified CV19 among seven children; only one had been tested antemortem. The proportion of CV19+ deaths increased with age, but 75.7% of CV19+ deaths were aged <60 years. The five most common co-morbidities among CV19+ deaths were: tuberculosis (31.4%); hypertension (27.1%); HIV/AIDS (22.9%); alcohol use (17.1%); and diabetes (12.9%).
Conclusions
Contrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare. If our data are generalizable, the impact of CV19 in Africa has been vastly underestimated.
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SciScore for 10.1101/2020.12.22.20248327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical oversight for ZPRIME and the CV19 expansion were provided by the Institutional Review Boards at Boston University and the University of Zambia.
Consent: Written informed consent was obtained from the deceased’s family members or representatives.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Runs 17-18 used a different kit that targeted a consensus sequence of the nucleocapsid gene [NCBI Reference Sequence: NC_045512.2] and the gene sequence encoding an overlapping polyprotein that is later cleaved in vivo into PP1ab and … SciScore for 10.1101/2020.12.22.20248327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethical oversight for ZPRIME and the CV19 expansion were provided by the Institutional Review Boards at Boston University and the University of Zambia.
Consent: Written informed consent was obtained from the deceased’s family members or representatives.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Runs 17-18 used a different kit that targeted a consensus sequence of the nucleocapsid gene [NCBI Reference Sequence: NC_045512.2] and the gene sequence encoding an overlapping polyprotein that is later cleaved in vivo into PP1ab and PP1a polyproteins [NCBI Gene ID: 43740578] (Wuhan NCBI Genesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our analysis had several limitations. First, our data were collected over a short span of several months. Within this period, we saw dynamic shifts in the bi-weekly prevalence of CV19+ deaths. There is no way to predict how CV19’s patterns of transmission might shift in the future, which justifies our ongoing surveillance work. Second, our study could only infer links between deaths and CV19 when a PCR signal was detectable. This would fail to identify deaths indirectly due to CV19, such as heart attacks or strokes, that were separated in time from the CV19 infection. In an attempt to quantify the degree of excess mortality indirectly attributable to CV19, we are currently collecting age- and season-specific burial records from Lusaka from the past several years. Third, our assessment of underlying risk factors was limited by the completeness and accuracy of medical chart data and the possibly faulty recall of the next of kin. Hence, there was no way to verify these conditions, nor to assess their duration and severity. An analysis of the association between potential risk factors and CV19 deaths is currently underway in our group. Fourth, because the consequences of CV19 infection are age-specific, our data cannot be used to infer the incidence of CV19 in the larger population, but can only tell us about the prevalence of CV19 deaths across age groups. Lastly, our results came from one city, in one African country, over a short three-month span. In conclusion, contradicting ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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Our take
This study, available as a preprint and thus not yet peer reviewed, enrolled 364 deceased individuals, whose deaths were registered at the University Teaching Hospital in Lusaka, Zambia of whom 19.2% tested positive for SARS-CoV-2. Most of these deaths occurred in the community and the median age of deaths was 48 years. While this method of testing post-mortem provides a period-prevalence estimate for SARS-CoV-2 infection among decedents between June and September 2020, it does not provide detailed information on the cause of death.
Study design
cross-sectional
Study population and setting
Post-mortem SARS-CoV-2 testing (nasopharyngeal swab, RT-qPCR) was performed on 372 deceased individuals at the University Teaching Hospital in Lusaka, Zambia between June and September 2020. In order to be …
Our take
This study, available as a preprint and thus not yet peer reviewed, enrolled 364 deceased individuals, whose deaths were registered at the University Teaching Hospital in Lusaka, Zambia of whom 19.2% tested positive for SARS-CoV-2. Most of these deaths occurred in the community and the median age of deaths was 48 years. While this method of testing post-mortem provides a period-prevalence estimate for SARS-CoV-2 infection among decedents between June and September 2020, it does not provide detailed information on the cause of death.
Study design
cross-sectional
Study population and setting
Post-mortem SARS-CoV-2 testing (nasopharyngeal swab, RT-qPCR) was performed on 372 deceased individuals at the University Teaching Hospital in Lusaka, Zambia between June and September 2020. In order to be included in this study, individuals had to have died in the 48 hours before enrollment and next of kin had to provide written, informed consent (~99% consented). The study used quasi-random sampling (enrolling every 5th death in July and every 3rd death in August with daily cap of 5 deaths; and without a daily cap in September). Deaths were included regardless of age or cause. Testing results were described by month, by whether the death occurred at a facility or in the community, by age, and by sex.
Summary of main findings
Testing results were obtained for 364/372 of the deceased (97.8%) (n=10 samples could not be matched to enrollment, and n=2 tested positive antemortem outside of the study). A two-week period in September 2020 accounted for n=59 deaths (~16%) enrolled, while a two-week period in July accounted for n=30 deaths(~8%). Among the 364 deaths with test results, about a quarter were deaths that happened in a facility/health center (n=96) and 74.2% were deaths the occurred in the community (n=268). 19.2% of deceased in this sample tested positive for SARS-CoV-2 (70/364). The greatest proportion of deaths were documented in late July and early August. 70% of those testing positive for SARS-CoV-2 were male, while in the burial registry overall, about 60% were male. The median age among those testing positive for SARS-CoV-2 was 48 years (IQR: 36-72).
Study strengths
Enrollment of the deceased took place from the University Teaching Hospital in Lusaka, Zambia, where close to 80% of all deaths in the city are registered, including those that occur at the hospital itself and from the community. The investigators took steps during enrollment to get a representative sample of the deceased registered at the facility.
Limitations
The authors switch between using the terminology of “CV19 deaths” and “CV19+ deaths.”; this study did not ascertain whether deaths were caused by COVID-19 (COVID-19 attributable deaths) and, therefore, the use of “CV19 deaths” could be misleading. The authors cite US CDC guidance indicating that in deaths where SARS-CoV-2 is detected the virus should be assumed to be underlying cause of death or a contributor. Given competing risks of death in low-income communities in Zambia (e.g. tuberculosis, HIV, etc.), US CDC guidance may not be directly applicable and attributing deaths to COVID-19 may be incorrect. Additionally, because of the sampling strategy, the prevalence estimate will weighted more heavily towards periods in which enrollment was the highest (i.e. September 2020).
Value added
This study uses post-mortem SARS-CoV-2 testing to ascertain prevalence among recently deceased. This strategy may be particularly useful to determine burden of disease in places where antemortem testing is not done.
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SciScore for 10.1101/2020.12.22.20248327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Participants Participants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Distribution of COVID-19 deaths by sex and facility vs. community setting COVID-19 was detected far more often among males than females. 74% of all deaths occurred in the community, and therefore were systematically excluded from antemortem CV19 testing. Table 2: Resources
Software and Algorithms Sentences Resources Runs 17-18 used a different kit that targeted a consensus sequence of the nucleocapsid gene [NCBI … SciScore for 10.1101/2020.12.22.20248327: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Participants Participants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Distribution of COVID-19 deaths by sex and facility vs. community setting COVID-19 was detected far more often among males than females. 74% of all deaths occurred in the community, and therefore were systematically excluded from antemortem CV19 testing. Table 2: Resources
Software and Algorithms Sentences Resources Runs 17-18 used a different kit that targeted a consensus sequence of the nucleocapsid gene [NCBI Reference Sequence: NC_045512.2] and the gene sequence encoding an overlapping polyprotein that is later cleaved in vivo into PP1ab and PP1a polyproteins [NCBI Gene ID: 43740578] (Wuhan NCBI Genesuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
Our analysis had several limitations. First, our data were collected over a short span of several months. Within this period, we saw dynamic shifts in the bi-weekly prevalence of CV19+ deaths. There is no way to predict how CV19’s patterns of transmission might shift in the future, which justifies our ongoing surveillance work. Second, our study could only infer links between deaths and CV19 when a PCR signal was detectable. This would fail to identify deaths indirectly due to CV19, such as heart attacks or strokes, that were separated in time from the CV19 infection. In an attempt to quantify the degree of excess mortality indirectly attributable to CV19, we are currently collecting age- and season-specific burial records from Lusaka from the past several years. Third, our assessment of underlying risk factors was limited by the completeness and accuracy of medical chart data and the possibly faulty recall of the next of kin. Hence, there was no way to verify these conditions, nor to assess their duration and severity. An analysis of the association between potential risk factors and CV19 deaths is currently underway in our group. Fourth, because the consequences of CV19 infection are age-specific, our data cannot be used to infer the incidence of CV19 in the larger population, but can only tell us about the prevalence of CV19 deaths across age groups. Lastly, our results came from one city, in one African country, over a short three-month span. In conclusion, contradicting ...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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