Updates on laboratory investigations in coronavirus disease 2019 (COVID-19)

Main Article Content

Giuseppe Lippi
Brandon M. Henry
Fabian Sanchis-Gomar
Camilla Mattiuzzi


Coronavirus; COVID-19; Laboratory Medicine; Laboratory Test


The coronavirus disease 2019 (COVID-19) pandemic is still spreading worldwide, affecting several million people. Unlike the previous two coronavirus outbreaks, COVID-19 has caused several thousand deaths for respiratory and multiple organ failure. As specifically concerns this latest infectious pathology, laboratory medicine can provide a substantial contribution to diagnosing an acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through molecular testing, establishing the presence and extent of an immune response against the virus, mostly through serological testing. However, it can also help to predict the risk of unfavorable disease progression by measuring some conventional laboratory tests and, last but not least, can provide reliable therapeutic guidance. This article is hence aimed at offering recent updates on the important role and value of laboratory investigations in COVID-19, also providing information on some hot topics such as virus RNA detection in different biological samples, causes of recurrent positivity of reverse-transcription polymerase chain reaction (RT-PCR), potential strategies for enhancing the throughput of molecular testing (i.e., pre-test probability assessment, sample pooling, use of rapid tests), as well as pragmatic indications for enhancing the quality and value of serological testing and laboratory-based monitoring.



Download data is not yet available.


Metrics Loading ...
Abstract 32 | PDF Downloads 5


1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1):157-160.
2. Coronaviridae Study Group of the International Committee on Taxonomy of V. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020; 5:536-544.
3. Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med. 2020; 8(7):497.
4. Lippi G, Lavie CJ, Henry BM, Sanchis-Gomar F. Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)? Clin Chem Lab Med. 2020; doi: 10.1515/cclm-2020-0727.
5. Lippi G, Mattiuzzi C, Bovo C, Plebani M. Current laboratory diagnostics of coronavirus disease 2019 (COVID-19). Acta Biomed. 2020; 91(2):137-145.
6. Lippi G, Plebani M. A modern and pragmatic definition of Laboratory Medicine. Clin Chem Lab Med. 2020; 58(8):1171.
7. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med. 2020; 58(7):1063-1069.
8. Bohn MK, Lippi G, Horvath A, Sethi S, Koch D, Ferrari M, et al. Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence. Clin Chem Lab Med. 2020; 58:1037-1052.
9. World Health Organization. Laboratory testing for coronavirus disease 2019 (‎COVID-19)‎ in suspected human cases: interim guidance, 2 March 2020, 2020: Geneva.
10. Magleby R, Westblade LF, Trzebucki A, Simon MS, Rajan M, Park J, et al. Impact of SARS-CoV-2 Viral Load on Risk of Intubation and Mortality Among Hospitalized Patients with Coronavirus Disease 2019. Clin Infect Dis. 2020; doi: 10.1093/cid/ciaa851.
11. Clementi N, Ferrarese R, Tonelli M, Amato V, Racca S, Locatelli M, et al. Lower nasopharyngeal viral load during the latest phase of COVID-19 pandemic in a Northern Italy University Hospital. Clin Chem Lab Med. 2020; doi: 10.1515/cclm-2020-0815.
12. Scohy A, Anantharajah A, Bodeus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol. 2020; 129:104455.
13. Blairon L, Wilmet A, Beukinga I, Tre-Hardy M. Implementation of rapid SARS-CoV-2 antigenic testing in a laboratory without access to molecular methods: Experiences of a general hospital. J Clin Virol. 2020; 129:104472.
14. Mak GC, Cheng PK, Lau SS, Wong KK, Lau CS, Lam ET, et al. Evaluation of rapid antigen test for detection of SARS-CoV-2 virus. J Clin Virol. 2020; 129:104500.
15. Plebani M, Lippi G. Molecular diagnostics at the times of SARS-CoV-2 outbreak. Diagnosis (Berl). 2020; doi: 10.1515/dx-2020-0050.
16. Lippi G, Simundic AM, Plebani M. Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19). Clin Chem Lab Med. 2020; 58(7):1070-1076.
17. Zhang JJ, Cao YY, Dong X, Wang BC, Liao MY, Lin J, et al. Distinct characteristics of COVID-19 patients with initial rRT-PCR-positive and rRT-PCR-negative results for SARS-CoV-2. Allergy. 2020; doi. 10.1111/all.14316.
18. Mohammadi A, Esmaeilzadeh E, Li Y, Bosch RJ, Li J. SARS-CoV-2 Detection in Different Respiratory Sites: A Systematic Review and Meta-Analysis. medRxiv. 2020; 2020.05.14.20102038.
19. Andersson M, Arancibia - Carcamo CV, Auckland K, Baillie JK, Barnes E, Beneke T, et al. SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus. medRxiv. 2020; 2020.05.21.20105486.
20. Wong MC, Huang J, Lai C, Ng R, Chan FKL, Chan PKS. Detection of SARS-CoV-2 RNA in fecal specimens of patients with confirmed COVID-19: A meta-analysis. J Infect. 2020; doi: 10.1016/j.jinf.2020.06.012.
21. Chan VW, Chiu PK, Yee CH, Yuan Y, Ng CF, Teoh JY. A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions. World J Urol. 2020; doi: 10.1007/s00345-020-03246-4.
22. Walsh KA, Jordan K, Clyne B, Rohde D, Drummond L, Byrne P, et al. SARS-CoV-2 Detection, Viral Load and Infectivity over the Course of an Infection: SARS-CoV-2 Detection, Viral Load and Infectivity. J Infect. 2020; doi: 10.1016/j.jinf.2020.06.067.
23. Ye G, Pan Z, Pan Y, Deng Q, Chen L, Li J, et al. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect. 2020; 80(5):e14-e17.
24. Cento V, Colagrossi L, Nava A, Lamberti A, Senatore S, Travi G, et al. Persistent positivity and fluctuations of SARS-CoV-2 RNA in clinically-recovered COVID-19 patients. J Infect. 2020; doi: 10.1016/j.jinf.2020.06.024.
25. Xiao AT, Tong YX, Zhang S. False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence. J Med Virol. 2020; doi: 10.1002/jmv.25855.
26. Yuan J, Kou S, Liang Y, Zeng J, Pan Y, Liu L. PCR Assays Turned Positive in 25 Discharged COVID-19 Patients. Clin Infect Dis. 2020; doi: 10.1093/cid/ciaa398.
27. Huang J, Zheng L, Li Z, Hao S, Ye F, Chen J, et al. Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications. medRxiv. 2020; 2020.05.06.20089573.
28. Kurstjens S, van der Horst A, Herpers R, Geerits MWL, Kluiters-de Hingh YCM, Gottgens EL, et al. Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing. Clin Chem Lab Med. 2020; doi: 10.1515/cclm-2020-0593.
29. Qin L, Yang Y, Cao Q, Cheng Z, Wang X, Sun Q, et al. A predictive model and scoring system combining clinical and CT characteristics for the diagnosis of COVID-19. Eur Radiol. 2020; doi: 10.1007/s00330-020-07022-1.
30. Jehi L, Ji X, Milinovich A, Erzurum S, Rubin B, Gordon S, et al. Individualizing Risk Prediction for Positive COVID-19 Testing: Results from 11,672 Patients. Chest. 2020; doi: 10.1016/j.chest.2020.05.580.
31. Fukumoto T, Iwasaki S, Fujisawa S, Hayasaka K, Sato K, Oguri S, et al. Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification. Int J Infect Dis. 2020; doi: 10.1016/j.ijid.2020.06.074.
32. Pilcher CD, Westreich D, Hudgens MG. Group Testing for Sars-Cov-2 to Enable Rapid Scale-Up of Testing and Real-Time Surveillance of Incidence. J Infect Dis. 2020; doi: 10.1093/infdis/jiaa378.
33. Cherif A, Grobe N, Wang X, Kotanko P. Simulation of Pool Testing to Identify Patients With Coronavirus Disease 2019 Under Conditions of Limited Test Availability. JAMA Netw Open. 2020; 3(6):e2013075.
34. Ben-Ami R, Klochendler A, Seidel M, Sido T, Gurel-Gurevich O, Yassour M, et al. Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection. Clin Microbiol Infect. 2020; doi: 10.1016/j.cmi.2020.06.009.
35. Yelin I, Aharony N, Shaer Tamar E, Argoetti A, Messer E, Berenbaum D, et al. Evaluation of COVID-19 RT-qPCR test in multi-sample pools. Clin Infect Dis. 2020; doi: 10.1093/cid/ciaa531.
36. European Centre for Disease Prevention and Control. Methodology for estimating point prevalence of SARSCoV-2 infection by pooled RT-PCR testing. Stockholm: ECDC; 2020.
37. Nalbantoglu OU. Group testing performance evaluation for SARS-CoV-2 massive scale screening and testing. BMC Med Res Methodol. 2020; 20(1):176.
38. Xu X, Sun J, Nie S, Li H, Kong Y, Liang M, et al. Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China. Nat Med. 2020; doi: 10.1038/s41591-020-0949-6.
39. Liu ZL, Liu Y, Wan LG, Xiang TX, Le AP, Liu P, et al. Antibody profiles in mild and severe cases of COVID-19. Clin Chem. 2020; doi: 10.1093/clinchem/hvaa137.
40. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020; 6:CD013652.
41. Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ. 2020; 370:m2516.
42. Tollanes MC, Bakken Kran AM, Abildsnes E, Jenum PA, Breivik AC, Sandberg S. Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2. Clin Chem Lab Med. 2020; doi: 10.1515/cclm-2020-0628.
43. Li H, Pan J, Su Y, Wang B, Ge J. SARS-CoV-2 lgM/lgG antibody detection confirms the infection after three negative nucleic acid detection. J Cell Mol Med. 2020; doi: 10.1111/jcmm.15275.
44. Benoit J, Benoit S, Lippi G, Henry BM. False negative RT-PCR or false positive serological testing in SARS-CoV-2 diagnostics? Navigating between Scylla and Charybdis to prevent misclassification bias in COVID-19 clinical investigations. Diagnosis (Berl). 2020;
45. Inoue K, Ohira Y, Takeshita H. The risk of the collapse of public health centres under the current system to prevent the spread of COVID-19. Int Marit Health. 2020; 71(2):149.
46. Wurmb T, Scholtes K, Kolibay F, Schorscher N, Ertl G, Ernestus RI, et al. Hospital preparedness for mass critical care during SARS-CoV-2 pandemic. Crit Care. 2020; 24(1):386.
47. Armstrong RA, Kane AD, Cook TM. Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies. Anaesthesia. 2020; doi: 10.1111/anae.15201.
48. Lippi G, Sanchis-Gomar F, Henry BM. COVID-19: unravelling the clinical progression of nature’s virtually perfect biological weapon. Ann Transl Med. 2020; 8(11):693.
49. Lauretani F, Ravazzoni G, Roberti MF, Longobucco Y, Adorni E, Grossi M, et al. Assessment and treatment of older individuals with COVID 19 multi-system disease: Clinical and ethical implications. Acta Biomed. 2020; 91(2):150-168.
50. Jang JG, Hur J, Hong KS, Lee W, Ahn JH. Prognostic Accuracy of the SIRS, qSOFA, and NEWS for Early Detection of Clinical Deterioration in SARS-CoV-2 Infected Patients. J Korean Med Sci. 2020; 35(25):e234.
51. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020; 58(7):1131-1134.
52. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020; 58:1021-1028.
53. Zaninotto M, Mion MM, Cosma C, Rinaldi D, Plebani M. Presepsin in risk stratification of SARS-CoV-2 patients. Clin Chim Acta. 2020; 507:161-163.
54. Yan L, Zhang H-T, Goncalves J, Xiao Y, Wang M, Guo Y, et al. An interpretable mortality prediction model for COVID-19 patients. Nat Mach Intell. 2020; 2(5):283-288.
55. Dong Y, Zhou H, Li M, Zhang Z, Guo W, Yu T, et al. A novel simple scoring model for predicting severity of patients with SARS-CoV-2 infection. Transbound Emerg Dis. 2020; doi: 10.1111/tbed.13651.
56. Favaloro EJ, Lippi G. Recommendations for Minimal Laboratory Testing Panels in Patients with COVID-19: Potential for Prognostic Monitoring. Semin Thromb Hemost. 2020; 46(3):379-382.
57. Lippi G, Mattiuzzi C. Diagnostic and clinical significance of "atypical" symptoms in coronavirus disease 2019. Pol Arch Intern Med. 2020; 130(6):478-480.
58. Harahwa TA, Lai Yau TH, Lim-Cooke MS, Al-Haddi S, Zeinah M, Harky A. The optimal diagnostic methods for COVID-19. Diagnosis (Berl). 2020; doi: 10.1515/dx-2020-0058.