SARS-CoV-2 RNA in Plasma Samples of COVID-19 Affected Individuals: a Cross-sectional Proof-of-concept Study

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2021 Feb 18

PMID 33596855

Citations 22

Authors

Luna Colagrossi

Maria Antonello

Silvia Renica

Marco Merli

Elisa Matarazzo

Giovanna Travi

Marta Vecchi

Jacopo Colombo

Antonio Muscatello

Giacomo Grasselli

Silvia Nerini Molteni

Vittorio Scaravilli

Emanuele Cattaneo

Diana Fanti

Chiara Vismara

Alessandra Bandera

Andrea Gori

Massimo Puoti

Valeria Cento

Claudia Alteri

Carlo Federico Perno

Affiliations

Soon will be listed here.

Abstract

Background: Recent studies showed that plasma SARS-CoV-2 RNA seems to be associated with worse COVID-19 outcome. However, whether specific population can be at higher risk of viremia are to date unexplored.

Methods: This cross-sectional proof-of-concept study included 41 SARS-CoV-2-positive adult individuals (six affected by haematological malignancies) hospitalized at two major hospital in Milan, for those demographic, clinical and laboratory data were available. SARS-CoV-2 load was quantified by ddPCR in paired plasma and respiratory samples. To assess significant differences between patients with and patients without viremia, Fisher exact test and Wilcoxon test were used for categorical and continuous variables, respectively.

Results: Plasma SARS-CoV-2 RNA was found in 8 patients (19.5%), with a median (IQR) value of 694 (209-1023) copies/mL. Viremic patients were characterized by an higher mortality rate (50.0% vs 9.1%; p = 0.018) respect to patients without viremia. Viremic patients were more frequently affected by haematological malignancies (62.5% vs. 3.0%; p < 0.001), and had higher viral load in respiratory samples (9,404,000 [586,060-10,000,000] vs 1560 [312-25,160] copies/mL; p = 0.002).

Conclusions: Even if based on a small sample population, this proof-of-concept study poses the basis for an early identification of patients at higher risk of SARS-CoV-2 viremia, and therefore likely to develop severe COVID-19, and supports the need of a quantitative viral load determination in blood and respiratory samples of haematologic patients with COVID-19 in order to predict prognosis and consequently to help their further management.

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References

Martin-Moro F, Marquet J, Piris M, Michael B, Saez A, Corona M . Survival study of hospitalised patients with concurrent COVID-19 and haematological malignancies. Br J Haematol. 2020; 190(1):e16-e20. PMC: 7267398. DOI: 10.1111/bjh.16801. View

Hagman K, Hedenstierna M, Gille-Johnson P, Hammas B, Grabbe M, Dillner J . Severe Acute Respiratory Syndrome Coronavirus 2 RNA in Serum as Predictor of Severe Outcome in Coronavirus Disease 2019: A Retrospective Cohort Study. Clin Infect Dis. 2020; 73(9):e2995-e3001. PMC: 7499508. DOI: 10.1093/cid/ciaa1285. View

Shi J, Li Y, Zhou X, Zhang Q, Ye X, Wu Z . Lactate dehydrogenase and susceptibility to deterioration of mild COVID-19 patients: a multicenter nested case-control study. BMC Med. 2020; 18(1):168. PMC: 7268591. DOI: 10.1186/s12916-020-01633-7. View

Chen W, Lan Y, Yuan X, Deng X, Li Y, Cai X . Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity. Emerg Microbes Infect. 2020; 9(1):469-473. PMC: 7054964. DOI: 10.1080/22221751.2020.1732837. View

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-1062. PMC: 7270627. DOI: 10.1016/S0140-6736(20)30566-3. View

Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y . Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019. Clin Infect Dis. 2020; 71(8):1937-1942. PMC: 7184354. DOI: 10.1093/cid/ciaa449. View

Nakajima Y, Ogai A, Furukawa K, Arai R, Anan R, Nakano Y . Prolonged viral shedding of SARS-CoV-2 in an immunocompromised patient. J Infect Chemother. 2020; 27(2):387-389. PMC: 7836222. DOI: 10.1016/j.jiac.2020.12.001. View

Peng L, Liu J, Xu W, Luo Q, Chen D, Lei Z . SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. J Med Virol. 2020; 92(9):1676-1680. PMC: 7264521. DOI: 10.1002/jmv.25936. View

Lamure S, Dulery R, Di Blasi R, Chauchet A, Laureana C, Deau-Fischer B . Determinants of outcome in Covid-19 hospitalized patients with lymphoma: A retrospective multicentric cohort study. EClinicalMedicine. 2020; 27:100549. PMC: 7550257. DOI: 10.1016/j.eclinm.2020.100549. View

10.

Veyer D, Kerneis S, Poulet G, Wack M, Robillard N, Taly V . Highly Sensitive Quantification of Plasma Severe Acute Respiratory Syndrome Coronavirus 2 RNA Sheds Light on its Potential Clinical Value. Clin Infect Dis. 2020; 73(9):e2890-e2897. PMC: 7454373. DOI: 10.1093/cid/ciaa1196. View

11.

Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q . Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020; 369:m1443. PMC: 7190077. DOI: 10.1136/bmj.m1443. View

12.

Gu L, Qu J, Sun B, Yu X, Li H, Cao B . Sustained Viremia and High Viral Load in Respiratory Tract Secretions Are Predictors for Death in Immunocompetent Adults with Adenovirus Pneumonia. PLoS One. 2016; 11(8):e0160777. PMC: 4988761. DOI: 10.1371/journal.pone.0160777. View

13.

Di Cristanziano V, Meyer-Schwickerath C, Eberhardt K, Rybniker J, Heger E, Knops E . Detection of SARS-CoV-2 viremia before onset of COVID-19 symptoms in an allo-transplanted patient with acute leukemia. Bone Marrow Transplant. 2020; 56(3):716-719. DOI: 10.1038/s41409-020-01059-y. View

14.

Campbell A, Chien J, Kuypers J, Englund J, Wald A, Guthrie K . Respiratory virus pneumonia after hematopoietic cell transplantation (HCT): associations between viral load in bronchoalveolar lavage samples, viral RNA detection in serum samples, and clinical outcomes of HCT. J Infect Dis. 2010; 201(9):1404-13. PMC: 2853730. DOI: 10.1086/651662. View

15.

Eberhardt K, Meyer-Schwickerath C, Heger E, Knops E, Lehmann C, Rybniker J . RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients. Viruses. 2020; 12(9). PMC: 7551174. DOI: 10.3390/v12091045. View

16.

Hogan C, Stevens B, Sahoo M, Huang C, Garamani N, Gombar S . High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease. Clin Infect Dis. 2020; 72(9):e291-e295. PMC: 7543277. DOI: 10.1093/cid/ciaa1054. View

17.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. PMC: 7159299. DOI: 10.1016/S0140-6736(20)30183-5. View

18.

Karatas A, Inkaya A, Demiroglu H, Aksu S, Haziyev T, Cinar O . Prolonged viral shedding in a lymphoma patient with COVID-19 infection receiving convalescent plasma. Transfus Apher Sci. 2020; 59(5):102871. PMC: 7333597. DOI: 10.1016/j.transci.2020.102871. View

19.

Wang W, Xu Y, Gao R, Lu R, Han K, Wu G . Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA. 2020; 323(18):1843-1844. PMC: 7066521. DOI: 10.1001/jama.2020.3786. View

20.

Zhang W, Du R, Li B, Zheng X, Yang X, Hu B . Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020; 9(1):386-389. PMC: 7048229. DOI: 10.1080/22221751.2020.1729071. View