Covid for Doctors

THE SEMMELWEIS REFLEX

https://en.m.wikipedia.org/wiki/Semmelweis_reflex

WILL AUSTRALIA CHOOSE TO PREVENT COVID DEATHS?

Video by John Snow Project. February 2023.

DEATHS FROM ROAD FATALITIES VS COVID INFECTIONS

https://www.abs.gov.au/articles/covid-19-mortality-australia-deaths-registered-until-31-january-2024

https://datahub.roadsafety.gov.au/progress-reporting/monthly-road-deaths#:~:text=Key%20statistics,last%20year%20(119%20deaths).

https://www.bitre.gov.au/sites/default/files/documents/rda_sep2024.pdf

COVID-19: HOW SARS-COV-2 BINDS

Video by Sensu. July 2021.

ACUTE COVID

Lamers MM, Haagmans BL. SARS-CoV-2 pathogenesis. Nat Rev Microbiol. (2022) 20:270-284.

Zhu Y, Sharma L, Chang D. Pathophysiology and clinical management of coronavirus disease (COVID-19): a mini-review. Front Immunol. (2023) 14:1116131.

ACE2 RECEPTORS

Bourgonje AR, Abdulle AE, Timens W et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. (2020) 251(3):228-248.

Hikmet F, Méar L, Edvinsson Å et al. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. (2020) 16(7):e9610.

Salamanna F, Maglio M, Landini MP et al. Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2. Front Med. (2021) 7:594495.

MECHANISMS FOR OTHER COMMON VIRUSES

Volpe S, Irish J, Palumbo S et al. Viral infections and chronic rhinosinusitis. J Allergy Clin Immunol. (2023) 152(4):819-826.

DEATHS FROM INFLUENZA VS COVID

https://www.abs.gov.au/articles/deaths-due-covid-19-influenza-and-rsv-australia-2022-november-2024

https://www.actuaries.digital/2024/12/17/mortality-in-first-eight-months-of-2024-2-higher-than-predicted/

LONG COVID

Chu L, Bishof K, Dumes AA et al. The 2024 National Academies of Sciences, Engineering, and Medicine Long COVID Definition: What Clinicians Need to Know. J Gen Intern Med. (2025)

Ely EW, Brown LM, Fineberg HV. Long Covid Defined. N Engl J Med. (2024) 391(18):1746-1753.

Ewing AG, Joffe D, Blitshteyn S et al. Long COVID clinical evaluation, research and impact on society: a global expert consensus. Ann Clin Microbiol Antimicrob. (2025) 24(1):27.

Ewing AG, Salamon S, Pretorius E et al. Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology. Med Rev. (2024) 5(1):66-75.

Ma Y, Deng J, Liu Q et al. Long-Term Consequences of Asymptomatic SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. (2023) 16;20(2):1613.

O'Mahoney LL, Routen A, Gillies C et al. The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies. Nat Commun. (2025) 16:4249.

LONG COVID MECHANISMS

Immunology of Long COVID. Yale School of Medicine, updated 17 September 2024.

Davis HE, McCorkell L, Vogel JM et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. (2023) 21:133-146.

Durstenfeld MS, Weiman S, Holtzman M et al. Long COVID and post-acute sequelae of SARS-CoV-2 pathogenesis and treatment: A Keystone Symposia report. Ann N Y Acad Sci. (2024) 1535:31-41.

Iwasaki A, Putrino D. Why we need a deeper understanding of the pathophysiology of long COVID. Lancet Infect Dis. (2023) 23(4):393-395.

Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. (2022) 479(4):537-559.

Kruger A, Joffe D, Lloyd-Jones G et al. Vascular pathogenesis in acute and long covid: current insights and therapeutic outlook. Semin Thromb Hemost. (2024) 51(3):256-271.

Pretorius E, Venter C, Laubscher GJ et al. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol. (2022) 21(1):148.

ASYMPTOMATIC ORGAN DAMAGE

Proal AD, VanElzakker MB, Aleman S et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat Immunol. (2023) 24:1616-1627.

Samanci B, Ay U, Gezegen H et al. Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection. Cortex. (2025) 187:98-110.

Xie Y, Al-Aly Z. Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. (2022) 10(5):311-321.

Xu E, Xie Y, Al-Aly Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol. (2023) 11(2):120-128.

LONG COVID PREVALENCE

Long COVID in Australia - a review of the literature. Australian Institute of Health and Welfare, 16 December 2022.

Lopez-Leon S, Wegman-Ostrosky T, Ayuzo del Valle NC et al. Long-COVID in children and adolescents: a systematic review and meta-analyses. Sci Rep. (2022) 12:9950.

COVID AND THE BRAIN

Douaud G, Lee S, Alfaro-Amagro F et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. (2022) 604:697-707.

Hampshire A, Azor A, Atchinson C et al. Cognition and Memory after Covid-19 in a Large Community Sample. N Engl J Med. (2024) 390:806-18.

AEROSOL PHYSICS

Duval D, Palmer JC, Tudge I et al. Long distance airborne transmission of SARS-CoV-2: rapid systematic review. BMJ. (2022) 377:e068743.

Greenhalgh T, Jimenez JL, Prather KA et al. Ten scientific reasons in support of airborne transmission of SARS-CoV-2. Lancet. (2021) 397:1603-1605.

Jimenez JL, Marr LC, Randall K et al. What were the historical reasons for the resistance to recognizing airborne transmission during the COVID-19 pandemic? Indoor Air. (2022) 32:8:e13070.

Nikuri P, Maalouf A, Geneid A et al. Aerosol transmission and exposure in non-invasive ventilation. Sci Rep. (2025) 15:14058.

Randall K, Ewing ET, Marr L et al. How Did We Get Here: What Are Droplets and Aerosols and How Far Do They Go? A Historical Perspective on the Transmission of Respiratory Infectious Diseases (2021). Available at SSRN.

Tang JW, Marr LC, Li Y et al. COVID-19 has redefined aerosol transmission. BMJ. (2021) 373:n913.

Wang CC, Prather KA, Sznitman J et al. Airborne transmission of respiratory viruses. Science. (2021) 373. eabd9149.

INFECTIVITY

Differentiation between asymptomatic and pre-symptomatic transmission, and the period of time persistent positive cases are infectious. National Health and Medical Research Council, 14 July 2020.

Boucau J, Marino C, Regan J et al. Duration of shedding of culturable virus in SARS-CoV-2 Omicron (BA.1) infection. N Engl J Med. (2022) 387:275-277.

HOSPITAL ACQUIRED INFECTION

Healthcare- associated infection in Victoria, surveillance report 2021-22. Victorian Healthcare Associated Infection Surveillance Coordinating Centre, July 2023.

MITIGATION STRATEGIES

MASKS

Greenhalgh T, MacIntyre CR, Baker MG et al. Masks and respirators for prevention of respiratory infections: a state of the science review. Clin Microbiol Rev. (2024) 37:e00124-23.

VENTILATION

Morawska L, Allen J, Bahnfleth W et al. Mandating indoor air quality for public buildings. Science. (2024) 383:1418-1420.

CO2 MONITORS

Iwamura N, Tsutsumi K. SARS-CoV-2 airborne infection probability estimated by using indoor carbon dioxide. Environ Sci Pollut Res. (2023) 30:79227-79240.

AIR PURIFIERS

What is a HEPA filter? Environmental Protection Agency, updated 4 September 2024.

Frydas IS, Kermenidou K, Karypidou M et al. SARS-CoV-2 airborne detection within different departments of a COVID-19 hospital building and evaluation of air cleaners in air viral load reduction. J Aerosol Sci. (2025) 187:106587.

Morris AC, Sharrocks K, Bousfield R et al. The Removal of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Other Microbial Bioaerosols by Air Filtration on Coronavirus Disease 2019 (COVID-19) Surge Units. Clin Infect Dis. (2022) 75(1):e97-e101.

AUSTRALIAN VACCINATION GUIDELINES

COVID-19 vaccine advice and recommendations. Australian Government Department of Health, Disability and Ageing, updated 20 November 2024.

SIR AUSTIN BRADFORD HILL

https://en.wikipedia.org/wiki/Austin_Bradford_Hill

https://en.wikipedia.org/wiki/Bradford_Hill_criteria

STRENGTH OF ASSOCIATION

Cai M, Xie Y, Topol EJ, et al. Three-year outcomes of post-acute sequelae of COVID-19. Nat Med. (2024) 30, 1564–1573. DOI: 10.1038/s41591-024-02987-8 Published 30 May 2024 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ Figure 2 cropped and adapted from original

Tzang C, Sheng H, Kuo VF, et al. Association between COVID-19 and New-Onset Autoimmune Diseases: Updated Systematic Review and Meta-Analysis of 97 Million Individuals. Clin Rev Allergy Immunol. (2025) 68:111. DOI: 10.1007/s12016-025-09124-4 Published 26 December 2025 Figure 2 (highlighted) reproduced with permission of SNCSC (Springer Nature). Licence Ref: RP2026016. Transaction/Licence No: 6195620452977, electronic reuse. License issued 6 February 2026

TEMPORALITY

Douaud G, Lee S, Alfaro-Almagro F, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. (2022) 604, 697–707. DOI: 10.1038/s41586-022-04569-5 Published 7 March 2022 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ Table 1 adapted from original

Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. (2022) 28, 583–590. DOI: 10.1038/s41591-022-01689-3 Published 7 February 2022 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ Figure 2 and Extended Data Figure 4 adapted from original

CONSISTENCY

Gross RS, Carmilani M, Stockwell MS. Long COVID in Young Children, School-Aged Children, and Teens. JAMA Pediatr. (2025) 179(7):809. DOI: 10.1001/jamapediatrics.2025.1415 Published 27 May 2025 Permission: AMA/CCC License 6195721045401 25 January 2026

Gross RS, Thaweethai T, Kleinman LC, et al. Characterizing Long COVID in Children and Adolescents. JAMA. (2024) 332(14):1174–1188. DOI: 10.1001/jama.2024.12747 Published 21 August 2024

Gross RS, Thaweethai T, Salisbury AL, et al. Characterizing Long COVID Symptoms During Early Childhood. JAMA Pediatr. (2025) 179(7):781–792. DOI: 10.1001/jamapediatrics.2025.1066 Published 27 May 2025

Zhang B, Thacker D, Zhou T, et al. Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records. Nat Commun. (2025) 16:3445. DOI: 10.1038/s41467-025-56284-0 Published 11 April 2025 Open Access (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

Anderer S. COVID-19 in Pregnancy Linked With Risk of Neurodevelopmental Disorders in Early Childhood. JAMA. (2026) DOI: 10.1001/jama.2025.23090 Published 2 January 2026

Shook LL, Castro V, Ibanez-Pintor L, et al. Neurodevelopmental Outcomes of 3-Year-Old Children Exposed to Maternal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Utero. Obstet Gynecol. (2026) 147(1):11–20. DOI: 10.1097/AOG.0000000000006112 Published 30 October 2025

SPECIFICITY

Manganotti P, Iscra K, Furlanis G, et al. Mapping brain changes in post-COVID-19 cognitive decline via FDG PET hypometabolism and EEG slowing. Sci Rep. (2025) 15:23141. DOI: 10.1038/s41598-025-04815-6 Published 2 July 2025 Open Access (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

Samanci B, Ay U, Gezegen H, et al. Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection. Cortex. (2025) 187:98–110. DOI: 10.1016/j.cortex.2025.04.004 Published 2 May 2025

COHERENCE

Che W, Guo S, Wang Y, et al. SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations. J Adv Res. (2025) ISSN 2090-1232. DOI: 10.1016/j.jare.2025.05.013 Published 10 May 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ Graphical abstract reproduced from original (unchanged)

Bruno RM, Badhwar S, Abid L, et al. Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study. Eur Heart J. (2025) 46(39):3905–3918. DOI: 10.1093/eurheartj/ehaf430 Published 17 August 2025 Open Access (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/

Secades D, Dufner Krieger S, Hidalgo Ramos RA, et al. (July 24, 2025) Incidence of Deep Vein Thrombosis in Patients With COVID-19: A Systematic Review. Cureus. (2025) 17(7):e88697. DOI: 10.7759/cureus.88697 Published 24 July 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOSE-RESPONSE

Babalola TK, Clouston SAP, Sekendiz Z, et al. SARS-COV-2 re-infection and incidence of post-acute sequelae of COVID-19 (PASC) among essential workers in New York: a retrospective cohort study. Lancet Reg Health Am. (2025) 42:100984. DOI: 10.1016/j.lana.2024.100984 Published 8 January 2025 Open Access (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

Zhang B, Wu Q, Jhaveri R, et al. Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study. Lancet Infect Dis. (2025) DOI: 10.1016/S1473-3099(25)00476-100476-1) Published 30 September 2025

BIOLOGICAL PLAUSIBILITY

Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. (2020) 581, 215–220. DOI: 10.1038/s41586-020-2180-5 Published 30 March 2020 Springer Nature/CCC License No 6197010446967 Jan 25 2026 Figure 1c reproduced with permission (unchanged)

Proal AD, VanElzakker MB, Aleman S, et al. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat Immunol. (2023) 24, 1616–1627. DOI: 10.1038/s41590-023-01601-2 Published 4 September 2023

Thierry AR, Usher T, Sanchez C, et al. Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients. J Med Virol. (2025) 97: 1–14. DOI: 10.1002/jmv.70613 Published 2 October 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Jiang Z, Shan T, Li Y, et al. Persistent Attenuation of Lymphocyte Subsets After Mass SARS-CoV-2 Infection. Int J Infect Dis. (2025) 108287. DOI: 10.1016/j.ijid.2025.108287 Published 5 December 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

ANALOGY

Miller CM, Moen JK, Iwasaki A. The lingering shadow of epidemics: post-acute sequelae across history. Trends Immunol. (2026) DOI: 10.1016/j.it.2025.10.010 Published 4 December 2025

Løkke FB, Hansen KS, Dalgaard LS, et al. Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV - Lessons to learn in long COVID? Infect Dis Now. (2023) 53(8):104779. DOI: 10.1016/j.idnow.2023.104779 Published 9 September 2023

Li K, Wu Q, Li H, et al. Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study. Lancet eClinicalMedicine. (2023) Vol 58, 101884. DOI: 10.1016/j.eclinm.2023.101884 Published 27 February 2023

EXPERIMENT

Lee SJ, Kim E, Im JH, et al. Effect of Personal Protective Equipment on the Prevention of SARS-CoV-2 Infection in Healthcare Workers. J Korean Med Sci. (2025) 40(43):e276. DOI: 10.3346/jkms.2025.40.e276 Published 11 September 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

MacIntyre CR, Chughtai AA, Kunasekaran M, et al. The role of masks and respirators in preventing respiratory infections in healthcare and community settings. Br Med J. (2025) 388:e078573. DOI: 10.1136/bmj-2023-078573 Published 27 February 2025

Greenhalgh T, MacIntyre CR, Baker MG, et al. Masks and respirators for prevention of respiratory infections: a state of the science review. Clin Microbiol Rev. (2024) 37(2):e0012423. DOI: 10.1128/cmr.00124-23 Published 22 May 2024

Frydas IS, Kermenidou M, Karypidou M, et al. SARS-CoV-2 airborne detection within different departments of a COVID-19 hospital building and evaluation of air cleaners in air viral load reduction. J Aerosol Sci. (2025) Volume 187; 106587. DOI: 10.1016/j.jaerosci.2025.106587 Published 9 April 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Landry SA, Jamriska M, Menon VJ, et al. Ultraviolet radiation vs air filtration to mitigate virus laden aerosol in an occupied clinical room. J Hazard Mater. (2025) 487: 137211. DOI: 10.1016/j.jhazmat.2025.137211 Published 13 January 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Peine C, Stoliaroff-Pepin A, Reinacher U, et al. Effectiveness of COVID-19 vaccines against post-COVID-19 condition/long COVID: systematic review and meta-analysis. Clin Microbiol Infect. (2025) 31(12):1961–1971. DOI: 10.1016/j.cmi.2025.07.026 Published 1 August 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Sampri A, Shi W, Bolton T, et al. Vascular and inflammatory diseases after COVID-19 infection and vaccination in children and young people in England: a retrospective, population-based cohort study using linked electronic health records. Lancet Child Adolesc Health. (2025) 9(12): 837–847. DOI: 10.1016/S2352-4642(25)00247-000247-0) Published 4 November 2025 Open Access (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ Figure 3 adapted from original (arrows added)

Ioannidis JPA, Pezzulo AM, Cristiano A. Global Estimates of Lives and Life-Years Saved by COVID-19 Vaccination During 2020-2024. JAMA Health Forum. (2025) 6(7):e252223. DOI: 10.1001/jamahealthforum.2025.2223