tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2026 Nov 3;123(44):e2604414123.
doi: 10.1073/pnas.2604414123. Epub 2026 Oct 27.
Hamed Nilforoshan # 1 , Julia Reisler # 1 , Erfan Jahanparast # 2 , Michael Moor 1 3 , Steven N Goodman 4 , Stefan Wager 5 , Jure Leskovec 1
Affiliations Expand
COVID-19 has been reported to cause multisystem effects lasting years [Z. Al-Aly, E. Topol, Science 383, 830-832 (2024)]. These findings are primarily based on cohort studies comparing test-positive COVID-19 patients to controls without known COVID-19 infection, tested or untested [M. Cai, Y. Xie, E. J. Topol, Z. Al-Aly, Nat. Med. 30, 1564-1573 (2024)]. However, such comparisons can be biased by the reasons people were tested. Using 14.4 billion insurance claims from 244.7 million US patients, we find that most long-term effects attributed to COVID-19 by unrestricted control designs likely reflect bias due to selective testing of individuals with non-COVID conditions, causing long-term effects of those conditions to be misattributed to COVID-19. We removed this bias by analyzing only tested individuals, comparing test-positive to test-negative patients. Across 614 clinical outcomes followed over 2 y, the test-based design resulted in 83.5% fewer symptoms being attributable to COVID-19 between 30 to 119 d after infection (43 attributable symptoms vs. 262 for the unrestricted control design), a 98.2% reduction at 120 to 359 d (5 vs. 286), and a 100% reduction at 360 to 719 d (0 vs. 369). The unrestricted control design also attributed unrelated outcomes (e.g., firearm injuries) to COVID-19 at a high rate, whereas the testing-based design did not. The test-based control design may modestly underestimate some effects. This study does not indicate that symptoms beyond one year are not genuine but that their attributability to COVID-19 is uncertain.
Keywords: causal inference; epidemiology; long COVID.
. 2026 Nov 3;123(44):e2604414123.
doi: 10.1073/pnas.2604414123. Epub 2026 Oct 27.
Revised estimates of types and duration of long COVID symptoms based on claims records from 245 million US patients
Hamed Nilforoshan # 1 , Julia Reisler # 1 , Erfan Jahanparast # 2 , Michael Moor 1 3 , Steven N Goodman 4 , Stefan Wager 5 , Jure Leskovec 1
Affiliations Expand
- PMID: 42945239
- DOI: 10.1073/pnas.2604414123
Abstract
COVID-19 has been reported to cause multisystem effects lasting years [Z. Al-Aly, E. Topol, Science 383, 830-832 (2024)]. These findings are primarily based on cohort studies comparing test-positive COVID-19 patients to controls without known COVID-19 infection, tested or untested [M. Cai, Y. Xie, E. J. Topol, Z. Al-Aly, Nat. Med. 30, 1564-1573 (2024)]. However, such comparisons can be biased by the reasons people were tested. Using 14.4 billion insurance claims from 244.7 million US patients, we find that most long-term effects attributed to COVID-19 by unrestricted control designs likely reflect bias due to selective testing of individuals with non-COVID conditions, causing long-term effects of those conditions to be misattributed to COVID-19. We removed this bias by analyzing only tested individuals, comparing test-positive to test-negative patients. Across 614 clinical outcomes followed over 2 y, the test-based design resulted in 83.5% fewer symptoms being attributable to COVID-19 between 30 to 119 d after infection (43 attributable symptoms vs. 262 for the unrestricted control design), a 98.2% reduction at 120 to 359 d (5 vs. 286), and a 100% reduction at 360 to 719 d (0 vs. 369). The unrestricted control design also attributed unrelated outcomes (e.g., firearm injuries) to COVID-19 at a high rate, whereas the testing-based design did not. The test-based control design may modestly underestimate some effects. This study does not indicate that symptoms beyond one year are not genuine but that their attributability to COVID-19 is uncertain.
Keywords: causal inference; epidemiology; long COVID.