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Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities.

ABSTRACT: Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the pandemic. Although asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals-unaware they are infected-transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the decrease in symptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing that intermediate levels of nonsymptomatic transmission lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants. In particular, when immunity provides protection against symptoms, but not against infections or deaths, epidemic trajectories can have faster growth rates and higher peaks, leading to more total deaths. Conversely, even modest levels of protection against infection can mitigate the population-level effects of asymptomatic spread.

SUBMITTER: Park SW

PROVIDER: S-EPMC10118396 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities.

Park Sang Woo SW Dushoff Jonathan J Grenfell Bryan T BT Weitz Joshua S JS

PNAS nexus 20230329 4

Asymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the pandemic. Although asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals-unaware they are infected-transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the decre ...[more]

PMID: 37091542

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Project description:Earlier work demonstrated that ACGME duty hour reform did not adversely affect mortality, with slight improvement noted among specific subgroups.To determine whether resident duty hour reform differentially affected the mortality risk of high severity patients or patients who experienced post-operative complications (failure-to-rescue).Observational study using interrupted time series analysis with data from July 1, 2000 - June 30, 2005. Fixed effects logistic regression was used to examine the change in the odds of mortality or failure-to-rescue (FTR) in more versus less teaching-intensive hospitals before and after duty hour reform.All unique Medicare patients (n = 8,529,595) admitted to short-term acute care non-federal hospitals and all unique VA patients (n = 318,636 patients) with principal diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal bleeding, stroke or a DRG classification of general, orthopedic or vascular surgery.We measured mortality within 30 days of hospital admission and FTR, measured by death among patients who experienced a surgical complication. The odds of mortality and FTR generally changed at similar rates for higher and lower risk patients in more vs. less teaching intensive hospitals. For example, comparing the mortality risk for the 10% of Medicare patients with highest risk to the other 90% of patients in post-reform year 1 for combined medical an OR of 1.01 [95% CI 0.90, 1.13], for combined surgical an OR of 0.91 [95% CI 0.80, 1.04], and for FTR an OR of 0.94 [95% CI 0.80, 1.09]. Findings were similar in year 2 for both Medicare and VA. The two exceptions were a relative increase in mortality for the highest risk medical (OR 1.63 [95% CI 1.08, 2.46]) and a relative decrease in the high risk surgical patients within VA in post-reform year 1 (OR 0.52 [95% CI 0.29, 0.96]).ACGME duty hour reform was not associated with any consistent improvements or worsening in mortality or failure-to-rescue rates for high risk medical or surgical patients.

Project description:IntroductionCombined genotyping/whole genome sequencing and epidemiological data suggest that in endemic settings only a minority of Clostridium difficile infection, CDI, is acquired from other cases. Asymptomatic patients are a potential source for many unexplained cases.MethodsWe prospectively screened a cohort of medical inpatients in a UK teaching hospital for asymptomatic C. difficile carriage using stool culture. Electronic and questionnaire data were used to determine risk factors for asymptomatic carriage by logistic regression. Carriage isolates were compared with all hospital/community CDI cases from the same geographic region, from 12 months before the study to 3 months after, using whole genome sequencing and hospital admission data, assessing particularly for evidence of onward transmission from asymptomatic cases.ResultsOf 227 participants recruited, 132 provided ?1 stool samples for testing. 18 participants were culture-positive for C. difficile, 14/132(11%) on their first sample. Independent risk factors for asymptomatic carriage were patient reported loose/frequent stool (but not meeting CDI criteria of ?3 unformed stools in 24 hours), previous overnight hospital stay within 6 months, and steroid/immunosuppressant medication in the last 6 months (all p?0.02). Surprisingly antibiotic exposure in the last 6 months was independently associated with decreased risk of carriage (p?=?0.005). The same risk factors were identified excluding participants reporting frequent/loose stool. 13/18(72%) asymptomatically colonised patients carried toxigenic strains from common disease-causing lineages found in cases. Several plausible transmission events to asymptomatic carriers were identified, but in this relatively small study no clear evidence of onward transmission from an asymptomatic case was seen.ConclusionsTransmission events from any one asymptomatic carrier are likely to be relatively rare, but as asymptomatic carriage is common, it may still be an important source of CDI, which could be quantified in larger studies. Risk factors established for asymptomatic carriage may help identify patients for inclusion in such studies.

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Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities.

Publications

Intermediate levels of asymptomatic transmission can lead to the highest epidemic fatalities.

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