Skip to content

Respiratory Infection → Downstream Disease Sequelae

Source prompt: Intercept ("Ending Respiratory Infections"), https://blog.interceptfund.com/p/ending-respiratory-infections (accessed 2026-06-25).

The Intercept essay argues that common acute respiratory infections impose a large hidden burden not only through the acute illness but through downstream chronic and acute disease sequelae. It cites several striking epidemiological associations between an index respiratory infection and a later (or acute-triggered) disease:

Index infection Downstream disease Reported effect size (blog) Primary source used here Verified effect size
Early-life rhinovirus wheezing Childhood asthma (by age 6) ~9.8× Jackson et al. 2008, AJRCCM (PMID:18565953) OR 9.8 ✓
Influenza Acute myocardial infarction (first 7 days) ~6.1× Kwong et al. 2018, NEJM (PMID:29365305) IRR 6.05 (3.86–9.50) ✓
RSV Heart failure ~1.3× Verschoor et al. 2025, JAGS (PMID:40696870) adj. HR 1.48–3.74 (blog figure not corroborated; real effect larger)
Severe influenza (w/ pneumonia) Alzheimer's / dementia ~4.5–5× (dem); ~2.6–4.1× (AD) Levine 2023, Neuron (PMID:36669485); Sipilä 2021, Lancet ID (PMID:34166620) qualitative only; numeric HRs in source tables, unverified from abstract → CANDIDATE

What was curated into dismech

Per the chosen scope ("enhance existing disorders"), the two best-evidenced links that map onto existing dismech entries were added as pathophysiology nodes with verified primary-literature evidence (exact-quote snippets validated against the cached abstracts):

  1. kb/disorders/Influenza.yaml — new node "Triggering of Acute Myocardial Infarction", placed downstream of the existing "Endothelial Dysfunction and Thromboinflammation" node via an INDIRECT_KNOWN_INTERMEDIATES causal edge (inflammation → coronary plaque instability → platelet activation / atherothrombotic occlusion). Evidence: Kwong et al. NEJM 2018 self-controlled case series, incidence ratio 6.05 (95% CI 3.86–9.50) for acute MI in the 7-day risk interval, no excess after day 7 (PMID:29365305).

  2. kb/disorders/Asthma.yaml — new node "Early-Life Rhinovirus Wheezing Illness and Asthma Inception", with a downstream edge into the existing "Type 2 Immune Response / Th2 Signaling" node. Evidence: Jackson et al. AJRCCM 2008 COAST birth cohort, rhinovirus wheezing in the first 3 years associated with ~9.8× odds of asthma at age 6 (PMID:18565953).

Endpoint disorders + directional trajectory entries (second pass)

To represent the directional disease-to-disease edges in the trajectory/comorbidity layer (kb/comorbidities/, the home of dismech "trajectories"), three missing endpoint Disease entries were created, then four com_*.yaml A_BEFORE_B trajectory entries:

New endpoint disorders (kb/disorders/), each validated (schema/term/reference): - Myocardial_Infarction.yaml — generic type 1 (atherothrombotic) acute MI (MONDO:0005068). Evidence: Bentzon 2014 Circ Res (PMID:24902970, plaque rupture → coronary thrombosis), Reed 2017 Lancet (PMID:27502078). - Rhinovirus_Infection.yaml — human rhinovirus infection (MONDO:0005709 common cold as closest term; rhinovirus-specific preferred_term). Evidence: Jacobs 2013 CMR (PMID:23297263). - Respiratory_Syncytial_Virus_Infection.yaml — RSV infection (MONDO:0001577). Evidence: Griffiths 2017 CMR (PMID:27903593), Falsey 2005 NEJM (PMID:15858184), Verschoor 2025 JAGS (PMID:40696870).

New trajectory entries (kb/comorbidities/, all A_BEFORE_B): - com_Influenza__Myocardial_Infarction.yaml — IRR 6.05 (CI 3.86–9.50), Kwong 2018 (PMID:29365305). CURATED. - com_Rhinovirus_Infection__Asthma.yaml — OR 9.8, Jackson 2008 (PMID:18565953). CURATED. - com_Respiratory_Syncytial_Virus_Infection__Heart_Failure.yaml — adjusted HR range 1.48–3.74, Verschoor 2025 (PMID:40696870). CURATED. Note: the blog's "~1.3×" HF figure could not be corroborated; the verified primary source reports a larger effect, so the entry is curated to the verified HR range, not the blog number. - com_Influenza__Alzheimer_Disease.yaml — CANDIDATE. The blog's 4.5–5× (dementia) / 2.6–4.1× (Alzheimer's) magnitudes most plausibly trace to per-disease HRs in Levine 2023 Neuron (PMID:36669485) but live in that paper's tables, not verifiable from the abstract, so they are NOT asserted as quantitative signals. Only the verifiable qualitative statement ("Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied") is curated, plus Sipilä 2021 Lancet ID (PMID:34166620) as adjacent (any-infection→dementia) context. Flagged for follow-up to extract the influenza-specific AD hazard ratio from full text.

The within-disease pathophysiology nodes (first pass) and these trajectory entries are complementary: the nodes model mechanism inside the index disease; the com_* entries model the directional epidemiological edge with quantitative association_signals.