Kox, Henk L.M. (2021): Relative Infectuousness of Asymptomatic and Symptomatic COVID-19 Infections - Analytical time table.
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Abstract
The question on the relative infectuousness of asymptomatic and symptomatic infections of COVID-19 is surrounded by contradictory clinical findings and confusion. This article undertakes a critical review of the available clinical literature on this topic, from the perspective of individual infection cycles and from the perpective of epidemiologic dynamics. Using the available results from the clinical and virological lietrature, we analyse how they fit in the time table of individual infection cycles, separately for the symptomatic and asymptomatic infection mode. The time table is based on a Susceptible-Infected-Resolve (SIR) mainframe, but the Infection compartment is sub-divided in 5 clinical stages for the symptomatic infection mode and 3 clinical stages for the asymptomatic infection mode. From the perpective of epidemiologic dynamics, the only period that matters is the time interval that infectives shed viable virus material, which is capable of self-replication in another host. The duration of this period can only be assessed by subjecting the positive RT-PCR tests samples to viral culture to isolate virus material that is able to self-replicate. Doing this on a daily basis reveals the time profile of effective infectuousness, separately for symptomatics and asymptomatics. For mild to moderate symptomatic cases we calculate that this period is 14 days on average, while for asymptomatic cases it is 9 days. Most of the replication-competent virus material is emitted during the first 4 days of this period, with few differences between symptomatics and asymptomatics. Because they shed virus over a longer interval, symptomatic infectives are likely to constitute the largest source of secondary infections. However, asymptomatic infectives have the largest average daily infectivity, because they shed most infective virus load during a short period. If the contact network of susceptibles has a sufficiently high share of asymptomatics in their early infection stage, the asymptomatic persons become the dominant source of secondary infections.
Item Type: | MPRA Paper |
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Original Title: | Relative Infectuousness of Asymptomatic and Symptomatic COVID-19 Infections - Analytical time table |
Language: | English |
Keywords: | COVID-19, public health policy, relative infectuousness, asymptomatic infections |
Subjects: | I - Health, Education, and Welfare > I0 - General > I00 - General I - Health, Education, and Welfare > I1 - Health > I10 - General I - Health, Education, and Welfare > I1 - Health > I12 - Health Behavior I - Health, Education, and Welfare > I1 - Health > I18 - Government Policy ; Regulation ; Public Health |
Item ID: | 108778 |
Depositing User: | Henk L.M. Kox |
Date Deposited: | 15 Jul 2021 04:17 |
Last Modified: | 15 Jul 2021 04:17 |
References: | [1] Adam, D., P. Weng, Y. Wong, E. Lau, T. Tsang, et al. (2020), Clustering and superspreading potential of SARS-CoV-2 infections in Hong Kong, Nature Medicine, 26 (September), 1714-1719. [2] Avanzato V., M. Matson, S. Seifert, R. Pryce, et al. (2020), Case study: Prolonged infectious SARS-CoV- 2 shedding from an asymptomatic immunocompromised individual with cancer, Cell, 183 (7), 1901–1912. [3] Backer, J., D. Klinkenberg, and J. Wallinga(2020), Incubation period of 2019 novel coronavirus (2019- nCoV) infections among travellers from Wuhan, China, 20–28 January 2020, Euro Surveillance, 25 (5), 1-6 [4] Beale S, A. Hayward, L. Shallcross, R. Aldridge and E. Fragaszy (2020), A rapid review and meta- analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections in community settings, Wellcome Open Res 2020 (Nov), 5:266 (https://doi.org/10.12688/wellcomeopenres.16387.1). [5] Bullard, J., K. Dust, D. Funk, et al. (2020), Predicting infectious severe acute respiratory syndrome coronavirus 2 from diagnostic samples, Clinical Infectious Diseases, 71 (10, Nov.). 2663–2666. [6] Brauer, F., C. Castillo-Chavez (2010), Mathematical models in population biology and epidemiology, Second edition, Springer, New York. [7] Buitrago-Garcia, D., D. Egli-Gany, M. Counotte, S. Hossmann, H. Imeri, A. Ipekci, G. Salanti, and N. Low (2020), Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis, PLOS Medicine, 17(9): e1003346.(https://doi. org/10.1371/journal.pmed.1003346). [8] Byambasuren, O., M. Cardona et all. (2020), Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis, Off. Journal Assoc. Med. Microbiology and Infectuous Diseases Canada, 5 (4, Dec.), 223–234 (https://doi.org/10.3138/jammi-2020-0030). [9] Casey, M. , J. Griffin, C. McAloon, A. Byrne, et al. (2020), Pre-symptomatic transmission of SARS- CoV-2 infection: a secondary analysis using published data, MedRxiv, June, (https://doi.org/10.1101/2020.05.08.20094870). [10] CDC (2020-21), COVID-19 Pandemic Planning Scenarios: Updates April 2020, September 2020, and March 2021, Center for Disease Control and Prevention (USA). [11] Cereda, D., M. Tirani, F. Rovida, et al. (2020), The early phase of the COVID-19 outbreak in Lombardy, Italy, March 20, 2020 [https://arxiv.org/abs/2003.09320). [12] Cevik, M., M. Tate, O. Lloyd, A. Maraolo, J. Schafers, and A. Ho (2021), SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis, The Lancet / Microbe, 2 (Jan), e13-e22. [13] Chau N, L. Thanh, D. Thanh et all. (2020), The natural history and transmission potential of asymptomatic SARS-CoV-2 infection, Clinical Infectuous Diseases, 71 (10, Nov.), 2679–2687 (doi: 10.1093/cid/ciaa711). [14] Chau, N., V. Lam, N. Dung, et al. (2020), The natural history and transmission potential of asymptomatic SARS-CoV-2 infection, Clinical Infectious Diseases, 71 (15 Nov.), 2679-2687. [15] Chen X., B. Zhu, W. Hong, et al. (2020), Associations of clinical characteristics and treatment regimens with the duration of viral RNA shedding in patients with COVID-19, International Journal of Infectious Diseases, 98 (Sept.), 252–60. [16] Chen Y., P. Li, Y. Ding, M. Liu, L. Liu, B. Yi, et al. (2021), Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/ pre- symptomatic COVID-19 patients, Journal of Infection and Public Health, May. (PMCID: PMC8154191). [17] Contreras, S., J. Birron-Lattes, H. Villavicencio, et al. (2020), Statistically-based methodology for revealing real contagion trends and correcting delay-induced errors in the assessment of COVID- 19 pandemic, Chaos, Solitons and Fractals, 139 (2020) 110087. [18] Daley D. and J. Gani (1999), Epidemic Modelling: An Introduction, C.U.P. , Cambridge. [19] Davies, N., P. Klepac, Y. Liu, K. Prem, M. Jit, et all. (2020), Age-dependent effects in the transmission and control of COVID-19 epidemics, Nature Medicine, 26 (Aug), 1205-1211. [20] Fernandez-Villaverde, J. and C.I. Jones (2020), Estimating and simulating a SIRD model of COVID- 19 for many countries, states, and cities, NBER WP #27128, NBER, Cambridge (MA). [21] Fried, M., J. Crawford, A. Mospan, S. Watkins, et al. (2021), Patient Characteristics and outcomes of 11,721 Patients with COVID-19 hospitalized across the United States, Clinical Infectuous Diseases, 72 (10, May), e558-e565. [22] Guan, W., Z. Ni, Y. Hu, W. Liang et al. (2020), Clinical Characteristics of Coronavirus Disease 2019 in China, New England Journal of Medicine, 382, 1708-1720 [23] Gudbjartsson, D., A. Helgason, H. Jonsson, O. Magnusson, et al. (2020), Spread of SARS-CoV-2 in the Icelandic population, New England Journal of Medicine, 382 (June), 2302-2315. [24] He, X., E. Lau, P. Wu, X. Deng , J. Wang, et al. (2020), Temporal dynamics in viral shedding and transmissibility of COVID-19, Nature Medicine, 26 (May), 672–675. [25] Hasanoglu, I., G. Korukluogu, D. Asilturk, Y. Cosgun et al. (2021), Higher viral loads in asymptomatic COVID-19 patients might be the invisible part of the iceberg, Infection, 49 (1), 117- 126. [26] He, J., Y. Guo, R. Mao, and J. Zhang (2021), Proportion of asymptomatic coronavirus disease 2019: A systematic review and meta-analysis, Journal of Medical Virology, 93 (2, Febr), 820-830 (doi: 10.1002/jmv.26326). [27] Jefferson T., E. Spencer, L. Brassey, C. Heneghan (2020), Viral cultures for COVID-19 infectious potential assessment — a systematic review, Clinical Infectuous Diseases, (December 3) (epub ahead of print). [28] Johansson, M., T. Quandelacy, S. Kada, P. Prasad, et al. (2021), SARS-CoV-2 Transmission From People Without COVID-19 Symptoms, JAMA Network Open, 4 (1, January), e2035057. [29] Kawasuji, H., Y. Takegoshi, M. Kaneda, A. Ueno, Y. Myajima, et al. (2020), Transmissibility of COVID-19 depends on the viral load around onset in adult and symptomatic patients, Plos One, Dec. 9 2020, (https://doi.org/10.1371/journal.pone.0243597). [30] Koh, W., L. Naing, M. Rosledzana, M. Alikhan, L. Chaw, M. Griffith, R. Pastore and J. Wong (2020), What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate and associated risk factors, Plos One, Oct. 8 2020 (https://doi.org/10.371/journal.pone. 0240205). [31] Kox, H. (2021), A discrete-time model for quantifying the impact of asymptomatic COVID-19 infections, KVL Discussion Paper No. 2021-05, KVL Policy Research, Hertogenbosch. [32] Kristiansen, M., B. Heimustovu, S. á Borg, et al. (2021), Epidemiology and clinical course of first wave coronavirus disease cases, Faroe Islands, Emerging Infectuous Diseases, 27 (3, March), 749– 758. [33] Kucharski, A., T. Russell,C. Diamond, Y. Liu, et al. (2020), Early dynamics of transmission and control of COVID-19: A mathematical modelling study, The Lancet Infection, 20 (May), 553-558. [34] Lauer, S., K. Grantz, Q. Bi, F. Jones, et al. (2020), The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application, Annals of Internal Medicine, 172 (9, May 5), 577-582. [35] Lavezzo, E., E. Franchin, C. Ciavarell, et all. (2020), Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature 584 (August), 425-429 (plus online Annex). [36] Leclerc, Q., N. Fuller, L. Knight, et al. (2020), What settings have been linked to SARS-CoV-2 transmission clusters? , Wellcome Open Research, 5, 83 (doi:10.12688/wellcomeopenres.15889.1.) [37] Lee Y., C. Hong, D. Kim, T. Lee , and J Lee (2020), Clinical course of asymptomatic and mildly symptomatic patients with coronavirus disease admitted to community treatment center in the Republic of Korea, JAMA Internal Medicine, 180, 1447-1452. [38] Lewis, N., L. Duca, P. Marcenac, E. Dietrich, et al. (2021), Characteristics and timing of initial virus shedding in Severe Acute Respiratory Syndrome Coronavirus 2, Utah, USA, Emerging Infectuous Diseases, 27 (2, Febr.), 352-359. [39] Li, J., D. Huang, B. Zou, H. Yang, et al. (2020), Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes, Journal of Medical Virology, August. [40] Li. Q., P. Wu, X. Wang et all. (2020), Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia, The New England Journal of Medicine, 382 (13, March 26), 1199-1207. [41] Liu, Z., R. Chu, L. Gong, B. Su, and J. Wu (2020), The assessment of transmission efficiency and latent infection period in asymptomatic carriers of SARS-CoV-2 infection, International Journal of Infectious Diseases, 99, 325–327. [42] Liu, Y., L. Yan, L. Wan,T. Xiang, et al. (2020), Viral dynamics in mild and severe cases of COVID- 19, Lancet Infectuous Diseases, 20 (6, June), 656–657. [43] Lloyd, A. (2001), Destabilisation of epidemic models with the inclusion of realistic distributions of infectuous period, Proceedings of the Royal Society London (Proc. R. Soc.Lond), B 268, 985-993. [44] Ma, S., J. Zhang, M. Zeng, Q. Jun, et al. (2020), Epidemiological Parameters of COVID-19: Case Series Study, Journal of Medical Internet Research, 22 (10, October), e19994 (doi: 10.2196/19994). [45] McAloon, C., A. Collins, K. Hunt, A. Barber, A. Byrne, et al. (2020), Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research, BMJ Open, 10 (8), e039652 (doi: 10.1136/bmjopen-2020-039652). [46] McEvoy, S, C. McAloon, A. Colllins, K. Hunt, F. Butler, et al. (2021), Relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: a rapid scoping review, BMJ Open, 11, e042354. [doi:10.1136/ bmjopen-2020-042354]. [47] Melsew, Y., A. Adekunle, A. Cheng, E. McBryde, et al. (2020), Heterogeneous infectiousness in mathematical models of tuberculosis: A systematic review, Epidemics, 30, 100374. [48] Moghadas, S., M. Kirkpatrick, P. Sah, A. Pandey, A. Shoukat. B. Singer, and A. Galvani (2020), The implications of silent transmission for the control of COVID-19 outbreaks, PNAS (Proceedings of the National Academy of Sciences), 117 (30, July), 17513-17515. 18 [49] Mollan, K., J. Eron, T. Krajewski, W, Painter, et al. (2021), SARS-CoV-2 infectious virus, viral RNA in nasopharyngeal swabs, and serostatus of symptomatic COVID-19 outpatients in the United States, medRxiv preprint, June, (doi: https://doi.org/10.1101/2021.05.28.21258011). [50] Ng, S., P. Kaur, C. Kremer, W. Tan et al. (2020), Estimating Transmission Parameters for COVID- 19 Clusters by Using Symptom Onset Data, Singapore, January–April 2020, Emerging Infectuous Diseases, 27 (2), 582-585. [51] Ng, O., K. Marimuthu, V. Koh, J. Pang, K. Linn, et al. (2021), SARS-CoV-2 seroprevalence and transmission risk factors among high-risk close contacts: A retrospective cohort study, The Lancet/Infection, 21 (March), 333-343. [52] Noh, J., J. Yoon, H. Seong, et al. (2020), Asymptomatic infection and atypical manifestations of COVID-19: Comparison of viral shedding duration, Journal of Infection, 81 (5, Nov.), 816-846. [53] Oran, D., and E. Topol (2021), The proportion of SARS-CoV-2 Infections that are asymptomatic: A systematic review, American College of Physicians, Annals of Internal Medicine, Jan.21 (doi:10.7326/M20-6976). [54] Owusu, D., M. Pomeroy, N. Lewis, A. Wadhwa, A, Yousaf, et al. (2021), Persistent SARS-CoV-2 RNA shedding without evidence of infectiousness: A cohort study of individuals with COVID-19, The Journal of Infectious Diseases, 27 Febr. 2021, 1-10 (DOI: 10.1093/infdis/jiab107). [55] Pan, D., S. Sze, A. Abraham, C. Williams, et al. (2021), Rapid tests for quantification of infectuousness are urgently needed in patients with COVID-19, The Lancet Microbe, (May 12), (epub ahead of print). [56] Park, S., Y. Kim, S. Yi, S. Lee, B. Na, et al. (2020), Coronavirus disease outbreak in call center, South Korea, Emerging Infectious Diseases, 26 (8), 1666-1670. [57] Pollán, M., B. Perez-Gomez, R. Pastor-Barriuso, et al. (2020), Prevalence of SARS-Cov-2 in Spain (ENE-COVID): A nationwide, population-based seroepidemiological study, Lancet, 396, 535-544. (doi: 10.1016/S0140-6736(20)31483-5). [58] Pollock, A. and J. Lancaster (2020), Asymptomatic transmission of COVID-19, The BMJ, #371 (Dec.), m4851 (http://dx.doi.org/10.1136/bmj.m4851). [59] Pung, R., C. Chiew, B. Young, S. Chin, et al. (2020), Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures, The Lancet, 395 (10229, March), 1039-1046. [60] Qui, X., A. Nergiz, A. Maraolo, I. Bogoch, N. Low and M. Cevik (2021), Defining the role of asymptomatic and pre-symptomatic SARS-CoV-2 transmission, Clinical Microbiology and Infection, pre-publication (https//www.doi.org/10.1016/j.cmi.2021.01.011). [61] Ra, S., J. Lim, G. Kim, M. Kim, et al. (2021), Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection, BMJ Thorax, 76, 61-63. [62] Rambo, A., L. Goncalves, A. Gonzales, et al. (2021), Impact of super-spreaders on COVID-19: systematic review, Sao Paulo Medical Journal, 139 (2, March-April), 163-169 (doi: 10.1590/1516- 3180.2020.0618.R1.10122020). [40] Ravindra, K., V. Malik, B. Padhi, S. Goel, and S. Gupta (2020), Consideration for the asymptomatic transmission of COVID-19: Systematic review and meta-analysis, medRxiv (DOI: 10.1101/2020.10.06.20207597). [64] RIVM (2021), Epidemiologische situatie van SARS-CoV-2 in Nederland, Rijksinstituut voor Volksgezondheid en Milieu (RIVM), 16 februari 2021, 47-49. [65] Rodrigues-Grande, C., J. Adan-Jimenez, P. Catalan, L. Alcala, et al. (2021), Inference of active viral replication in cases with sustained positive Reverse Transcription-PCR Results for SARS-CoV-2, Journal of Clinical Microbiology, 59 (2, Febr.), e02277-20. [66] Sanche S., Y. Lin, C. Xu, E. Romero-Severson, N. Hengartner, R. Ke (2020), High contagiousness and rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2, Emerging Infectuous Diseases, 26 (7), 1470-1477. [67] Singanayagam, A., M. Patel, A. Charlett, et al. (2020), Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020, Eurosurveillance, 25 (32, Aug.). [68] Siordia, J. (2020), Epidemiology and clinical features of COVID-19: a review of current literature, Journal of Clinical Virology, 127, (June), 104357 (Online 20 April 20, https://doi.org/10.1016/j.jcv.2020.104357). [69] Strahlin, K., E. Wahlström, S. Walther, A. Bennet-Bark, et al. (2021), Mortality trends among hospitalised COVID-19 patients in Sweden: A nationwide observational cohort study, The Lancet Regional Health - Europe, 4 (May). (https://doi.org/10.1016/j.lanepe.2021.100054). [70] Subramanian, R., Q. He and M. Pascual (2021), Quantifying asymptomatic infection and transmission of COVID-19 in New York City using observed cases, serology, and testing capacity, PNAS (Proceedings of the National Academy of Sciences), 118 (9, Feb.) (https://doi.org/10.1073/pnas.2019716118). [71] Tindale, L., J. Stockdale, M. Coombe, E. Garlock, W. Lau, M. Saraswat, L. Zhang, D. Chen, J. Wallinga, and, C. Colijn (2020), Evidence for transmission of COVID-19 prior to symptom onset, Elife, 2020 (Jun), (DOI: https://doi.org/10.7554/eLife.57149). [72] Trauer, J., P. Dodd, M. Gomes, G. Gomez, R. Houben , et al. (2019), The importance of heterogeneity to the epidemiology of tuberculosis, Clinical Infectious Diseases, 69 (1 July), 159- 166. [73] Uhm, J., J. Ahn, J. Hyun, Y. Sohn, et al. (2020), Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19, International Journal of Infectuous Diseases, 99, 279-285. [74] Verity, R., L. Okell, I. Dorigatti, P. Winskill, et al. (2020), Estimates of the severity of coronavirus disease 2019: A model-based analysis, The Lancet Infection, 20 (June), 669-677. [75] Walsh, K., S. Spillane, L. Comber, K. Cardwell, et al. (2020), The duration of infectiousness of individuals infected with SARS-CoV-2, Journal of Infection, 81 (Dec.), 847–856. [76] Ward, H., G. Cooke,C. Atchinson, et al. (2020), Declining prevalence of antibody positivity to SARS- Cov-2: A community study of 365,000 adults. medRxiv, posted online October 2020 (doi:10.1101/2020. 10.26.20219725). [77] Wölfel R., V. Corman, W. Guggemos, et al. (2020), Virological assessment of hospitalized patients with COVID-2019, Nature, 581, 465-469. [78] Xu, X., et al. (2020), Reconstruction of transmission pairs for novel coronavirus disease 2019 (COVID-19) in mainland China: estimation of super-spreading events, serial interval and hazard of infection, Clinical Infectuous Diseases, 71 (12, December), 3163–3167. [79] Yu, C., M. Zhou, Y. Liu, C. Ou, et al. (2020) Characteristics of asymptomatic COVID-19 infection and progression: A multicenter, retrospective study, Virulence, 11 (1), 1006-1014. [80] Zhang, Y., Y. Li, L. Wang, M. Li, X. Zhou (2021), Evaluating transmission heterogeneity and super- spreading event of COVID-19 in a metropolis of China, International Journal of Environmental Research and Public Health, 17( 10), 3705; (https://doi.org/10.3390/ijerph17103705). [81] Zhou, R., F. Li, F. Chen, H. Liu, et al. (2020), Viral dynamics in asymptomatic patients with COVID- 19, International Journal of Infectious Diseases, 96, 288–290. [82] Zhou, F., T. Yu, R. Du, G. Fan, Y. Liu, et al. (2020), Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, The Lancet, 395, 1054-1062. [83] Zou L., F. Ruan, M. Huang, L. Liang, et al. (2020), SARS-CoV-2 viral load in upper respiratory specimens of infected patients, New England Journal of Medicine, 382 (12, March), 1177–1179. [84] Cheng, H., S. Jian, D. Liu, T. Ng, W.Hung, et al. (2020), Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset, JAMA Internal Medicine, 180 (9), 1156–1163. [85] Hu, Y., J. Sun, Z. Dai, H. Deng, et al. (2020) , Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis, Journal of Clinical Virology, 127 ( June), 104371. |
URI: | https://mpra.ub.uni-muenchen.de/id/eprint/108778 |
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Relative Infectuousness of Asymptomatic and Symptomatic COVID-19 Infections - Analytical time table. (deposited 04 Jul 2021 14:33)
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