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COVID-19 clinical and laboratory diagnosis overview

COVID-19 clinical and laboratory diagnosis overview Background: COVID-19 was identified in Wuhan, China, in December 2019, and rapidly spread worldwide, being declared global pandemic on the 11th of March 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. Main body: The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019- nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results; therefore, additional serologic tests are needed. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics. Conclusion: The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. Diagnosis depends mainly on PCR testing and serological tests. However, even in the context of negative lab test results and clinical suspicion of COVID-19 infection, clinical decision should be based on clinical suspicion. Keywords: COVID-19, Serology, RT-PCR, Lab, Clinical 1 Background and many human CoVs most probably have originated The 2019 novel corona virus (2019-nCoV)/SARS-CoV-2 from bats [2, 3]. sequence was first identified in January 2020 from The disease caused by 2019-nCoV/SARS-CoV-2 was bronchoalveolar lavage (BAL) samples of five patients in named as coronavirus disease 2019 (COVID-19) by the Wuhan, China, presenting with unusual respiratory World Health Organization (WHO) [4]. On 30 January symptoms; fever, cough, and dyspnea accompanied by 2020, COVID-19 was declared by the WHO as a public complications of acute respiratory distress syndrome health emergency of international concern (PHEIC) [5]. with diffuse lung opacities and consolidation detected in In 2005, the WHO gained the power to declare an inter- chest radiography. Next generation sequencing results national emergency [6], since then, international emer- revealed an unknown β-CoV strain with 79.0% nucleo- gency was declared five times: H1N1 swine flu in 2009, tide identity with the sequence of SARS-CoV, 51.8% the Ebola outbreak in West Africa in 2013, the polio identity with the sequence of MERS-CoV and 87.7% nu- outbreak in 2014, the Zika outbreak in 2016, and Ebola cleotide identity with bat SARS-like CoV ZC45 [1]. outbreak in the Democratic Republic of Congo in 2019 Therefore, it was announced that the 2019-nCoV is of [6]. However, none of these previous emergencies has bat origin. In fact, bats are the key reservoir of CoVs, led to a worldwide pandemic [7]. Because of the rapid increase in numbers of COVID-19 cases and uncon- trolled worldwide spread, it was declared by the WHO a * Correspondence: rania.zayed@kasralainy.edu.eg pandemic on 11th of March 2020 [8]. As of July 16, Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt 2020, the virus has infected 13,378,853 total confirmed Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 2 of 5 cases with 580,045 deaths [9]. COVID-19 pandemic was Available RT-PCR testing targets two genes in the associated with strict measures to contain the situation virus genome: the E and RdRP genes. The E assay is spe- where many countries closed their borders associated cific for all SARS-CoV-related viruses, while the RdRP with partial lockdown of most daily activities and social assay only detects the COVID-19 virus, the recommen- distancing. The incubation period of COVID-19 is dation for laboratory confirmation of cases is to detect believed to be as long as 14 days, with potential asymp- two different genetic targets: E followed by RdRP [26]. tomatic transmission [10, 11]. COVID-19 is highly con- However, in areas where COVID-19 virus is widely tagious and has higher transmissibility (R0, 1.4–5.5) than spread, positive RT-PCR test result requires detection of both SARS-CoV (R0, 2–5) and MERS-CoV (R0, < 1) at least one target gene, with priority to the E gene being [12], although the mortality rate is lower 3.4% for more sensitive [26]. It should be well clear that one or COVID-19, compared to 10% for SARS-CoV and 34% more negative results do not rule out the possibility of for MERS-CoV [13–15]. COVID-19 virus infection, as false negative result in an infected individual may be caused by several factors: (1) 2 COVID-19 diagnosis poor quality of the specimen; (2) timing of specimen col- 2.1 Clinical presentation lection, late or very early in the infection; (3) inappropri- The China National Health Commission proposed ate specimen handling and/or and shipping; and (4) guidelines for initial diagnosis and disease severity triage technical error in the test. It is recommended that if a into mild, severe, and critical categories. Around 70 to negative result is obtained from a patient with a high 80% of patients are mild, and 20 to 30% are severe or index of suspicion for COVID-19 virus infection, par- critical [16] (Table 1). ticularly when only upper respiratory tract specimens Clinical diagnosis requires epidemic exposure, in were collected, additional specimens should be collected addition to two clinical findings of the following: fever, and tested preferably from the lower respiratory tract radiographic features, normal or lowered white blood [27]. Rectal swab can be used in suspicious patients and cells, or reduced lymphocyte count [16]. close contacts with confirmed cases, who test negative for COVID-19 in throat swab as some patients were 2.2 Real-time-PCR found to have viral RNA in their feces starting from 1 The current diagnostic test for COVID-19 is RT-PCR day after infection and for up to 12 days [28]. assay [17]. It would not be possible to do PCR test to all suspected individuals, so the Centers for Disease Control 2.3 Serological tests and Prevention (CDC) released guidance for priorities Serological testing detects antigens and antibodies di- for COVID-19 PCR testing [18] (Table 2). rected against the virus. SARS-CoV2 belongs to the The recommended specimen for testing is lower re- same family of β-coronaviruses as those caused SARS spiratory tract specimen: sputum and/or endotracheal and MERS outbreaks; it is expected to have similar anti- aspirate or bronchoalveolar. If not possible or in asymp- body generation process [29] where there is a lag period tomatic contacts, upper respiratory tract specimen, of 14-28 days after the onset of illness till the antibodies nasopharyngeal and oropharyngeal swab, or wash in am- appears in patients’ serum [30]. In some people with bulatory patients is collected, with preference of com- COVID-19 disease confirmed by RT-PCR, weak, late, or bined nasopharyngeal swab and oropharyngeal swab absent antibody responses have been reported [31, 32]. collection [19]. The strength of antibody response is dependent on mul- High viral loads in both upper and lower respiratory tiple factors as age, nutritional status, disease severity, tract are detected 5-6 days of the onset of symptoms and certain medications or infections that may suppress [20–23]. Lower respiratory tract specimens yield highest the immune system [31–33]. viral loads for the diagnosis of COVID-19 [24]. As for In March 2020, the FDA issued a policy that allows upper respiratory tract specimens higher sensitivity of developers of certain serological tests to begin to market nasopharyngeal swabs (63%) was detected compared to or use their tests once appropriate evaluation to ensure oropharyngeal swabs (32%) [25]. test validation is performed. The FDA issued this policy Table 1 COVID-19 severity triage Mild Severe Critical � Fever � Need to meet one of the following criteria: � Need to meet one of the following criteria: � Respiratory symptoms � Respiratory distress, RR ≥ 30/min � Respiratory failure needing mechanical oxygenation � Pneumonia on chest � Resting blood oxygen saturation ≤ 93% � Shock radiography � Arterial blood oxygen partial pressure (PaO2)/FiO2 ≤ � Development of other organ failures, requiring intensive 300 mmHg care unit care Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 3 of 5 Table 2 Priorities for PCR testing of suspected COVID-19 patients according to CDC guidelines [18] Priority 1 � Hospitalized patients Ensure optimal care options for all hospitalized patients, lessen the risk of � Symptomatic healthcare workers nosocomial infections, and maintain the integrity of the healthcare system Priority 2 � Patients in long-term care facilities with symptoms Ensure that those who are at highest risk of complication of infection are rapidly � Patients 65 years of age and older with symptoms identified and appropriately triaged � Patients with underlying conditions with symptoms � First responders with symptoms Priority 3 � Critical infrastructure workers with symptoms As resources allow, test individuals in the surrounding community of rapidly � Individuals who do not meet any of the above categories increasing hospital cases to decrease community spread, and ensure health of with symptoms essential workers � Healthcare workers and first responders � Individuals with mild symptoms in communities experiencing high 2019-nCoV hospitalizations Non-priority � Individuals without symptoms to allow early patient access to certain serological tests. provides complimentary diagnostic tool in RT-PCR test— Until 17 July 2020, thirty serology/antibody tests and negative patients presenting late or in detecting past infec- two antigen diagnostic tests for SARS-CoV-2 were is- tion when done 15 days or more after the onset of symp- sued an Emergency Use Authorization (EUA) intended toms [38]. for use by clinical laboratories [34]. Criteria for EUA A study by Carmen et al. evaluated six different were as follows: (1) The SARS-CoV-2 can cause a ser- commercial enzyme immunoassays (EIA) platforms ious or life-threatening disease or condition, including and eight points of care tests (POCT) with the same severe respiratory illness, to humans infected by this serum panel to identify the sensitivity of the available virus; (2) based on the totality of scientific evidence assay in COVID-19 diagnosis over time ranging from available to FDA, it is reasonable to believe that the as early as 3 days post symptoms onset to > 45 days product may be effective in diagnosing COVID-19, and post symptoms onset. Their conclusion was that ser- that the known and potential benefits of the product ology assays should not be used for the diagnosis of when used for diagnosing COVID-19 outweigh its acute infections [39]. known and potential risks; and (3) there is no adequate, The American Society for Microbiology (ASM) [40], approved, and available alternative to the emergency use the WHO [41], the Centers for Disease Control and Pre- of the product [35]. vention [42], and the Public Health Agency of Canada It is recommended to use combined IgG and IgM anti- [43] also published similar recommendations against body testing for more accurate results [29]. The average using serology testing for diagnosis of acute infection. time for seroconversion in reported studies is 12 days, while positive RT-PCR is detected 5-6 days from the on- 3 Conclusion set of symptoms, making antibody testing still inferior to COVID-19 available diagnostics puts the health author- RT-PCR in COVID-19 diagnosis but more likely used ities in challenging situation as diagnosis based on clin- when RT-PCR is not available or accessible [36]. ical symptoms alone is inaccurate, in addition to the Also, cross-reactivity of other respiratory viruses with presence of asymptomatic carriers and long incubation SARS-CoV-2 is reported and may influence serology test period of the virus. False negative RT-PCR results in in- results, especially in patients recently exposed to respira- fected patients adds to the challenge, necessitating the tory infections [37]. need for a rapid and sensitive technique to be available A systematic review including 55 publications analyzing in most laboratories for swift detection of COVID-19 in 8526 SARS-CoV-2 patients’ samples from Asia (n =38), order to limit spread and properly treat infected individ- Europe (n =15), USA (n =1), andChina (n = 1), con- uals. Available diagnostic tests alone are not enough to cluded that results for IgG, IgM, IgA, total antibodies, and provide guaranteed diagnosis of COVID-19. Clinical sus- IgG/IgM, all showed low sensitivity during the first week picion of COVID-19 should be thoroughly taken in con- from onset of symptoms (less than 30.1%), rose in the sec- sideration even with negative test results to allow timely ond week and reached their highest values in the third management of COVID-19, contain and limit the dam- week. The combination of IgG/IgM had a sensitivity of age of current outbreak. 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI To monitor disease progression, it is recommended to 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) combine both serial viral load monitoring and antibody for 15 to 21 days. Therefore, antibody testing is not rec- response, as viral load was found to be inversely related ommended as primary tool in COVID-19 diagnosis but to serum antibody response [22]. Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 4 of 5 Detection of antibody responses to COVID-19 in the 5. 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Consent for publication Accessed 28 Apr 2020. Not applicable. 19. World Health Organization. Laboratory testing for coronavirus disease (COVID-19) in suspected human cases: interim guidance. WHO/COVID-19/ Competing interests laboratory/2020.5. Geneva: WHO; 2020. Available from: https://www.who.int/ The authors declare that they have no competing interests. publications-detail/laboratory-testing-for-2019-novel-coronavirus-in- suspectedhuman-cases-20200117. Accessed 28 Apr 2020. Author details 20. Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo clinical samples. Lancet Infect Dis. 2020;24:30113–4. University, Cairo, Egypt. Department of Endemic Medicine and 21. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Hepatogastroentrology, Faculty of Medicine, Cairo University, Cairo, Egypt. load in upper respiratory specimens of infected patients. N Engl J Med. 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COVID-19 clinical and laboratory diagnosis overview

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Abstract

Background: COVID-19 was identified in Wuhan, China, in December 2019, and rapidly spread worldwide, being declared global pandemic on the 11th of March 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. Main body: The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019- nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results; therefore, additional serologic tests are needed. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics. Conclusion: The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. Diagnosis depends mainly on PCR testing and serological tests. However, even in the context of negative lab test results and clinical suspicion of COVID-19 infection, clinical decision should be based on clinical suspicion. Keywords: COVID-19, Serology, RT-PCR, Lab, Clinical 1 Background and many human CoVs most probably have originated The 2019 novel corona virus (2019-nCoV)/SARS-CoV-2 from bats [2, 3]. sequence was first identified in January 2020 from The disease caused by 2019-nCoV/SARS-CoV-2 was bronchoalveolar lavage (BAL) samples of five patients in named as coronavirus disease 2019 (COVID-19) by the Wuhan, China, presenting with unusual respiratory World Health Organization (WHO) [4]. On 30 January symptoms; fever, cough, and dyspnea accompanied by 2020, COVID-19 was declared by the WHO as a public complications of acute respiratory distress syndrome health emergency of international concern (PHEIC) [5]. with diffuse lung opacities and consolidation detected in In 2005, the WHO gained the power to declare an inter- chest radiography. Next generation sequencing results national emergency [6], since then, international emer- revealed an unknown β-CoV strain with 79.0% nucleo- gency was declared five times: H1N1 swine flu in 2009, tide identity with the sequence of SARS-CoV, 51.8% the Ebola outbreak in West Africa in 2013, the polio identity with the sequence of MERS-CoV and 87.7% nu- outbreak in 2014, the Zika outbreak in 2016, and Ebola cleotide identity with bat SARS-like CoV ZC45 [1]. outbreak in the Democratic Republic of Congo in 2019 Therefore, it was announced that the 2019-nCoV is of [6]. However, none of these previous emergencies has bat origin. In fact, bats are the key reservoir of CoVs, led to a worldwide pandemic [7]. Because of the rapid increase in numbers of COVID-19 cases and uncon- trolled worldwide spread, it was declared by the WHO a * Correspondence: rania.zayed@kasralainy.edu.eg pandemic on 11th of March 2020 [8]. As of July 16, Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt 2020, the virus has infected 13,378,853 total confirmed Full list of author information is available at the end of the article © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 2 of 5 cases with 580,045 deaths [9]. COVID-19 pandemic was Available RT-PCR testing targets two genes in the associated with strict measures to contain the situation virus genome: the E and RdRP genes. The E assay is spe- where many countries closed their borders associated cific for all SARS-CoV-related viruses, while the RdRP with partial lockdown of most daily activities and social assay only detects the COVID-19 virus, the recommen- distancing. The incubation period of COVID-19 is dation for laboratory confirmation of cases is to detect believed to be as long as 14 days, with potential asymp- two different genetic targets: E followed by RdRP [26]. tomatic transmission [10, 11]. COVID-19 is highly con- However, in areas where COVID-19 virus is widely tagious and has higher transmissibility (R0, 1.4–5.5) than spread, positive RT-PCR test result requires detection of both SARS-CoV (R0, 2–5) and MERS-CoV (R0, < 1) at least one target gene, with priority to the E gene being [12], although the mortality rate is lower 3.4% for more sensitive [26]. It should be well clear that one or COVID-19, compared to 10% for SARS-CoV and 34% more negative results do not rule out the possibility of for MERS-CoV [13–15]. COVID-19 virus infection, as false negative result in an infected individual may be caused by several factors: (1) 2 COVID-19 diagnosis poor quality of the specimen; (2) timing of specimen col- 2.1 Clinical presentation lection, late or very early in the infection; (3) inappropri- The China National Health Commission proposed ate specimen handling and/or and shipping; and (4) guidelines for initial diagnosis and disease severity triage technical error in the test. It is recommended that if a into mild, severe, and critical categories. Around 70 to negative result is obtained from a patient with a high 80% of patients are mild, and 20 to 30% are severe or index of suspicion for COVID-19 virus infection, par- critical [16] (Table 1). ticularly when only upper respiratory tract specimens Clinical diagnosis requires epidemic exposure, in were collected, additional specimens should be collected addition to two clinical findings of the following: fever, and tested preferably from the lower respiratory tract radiographic features, normal or lowered white blood [27]. Rectal swab can be used in suspicious patients and cells, or reduced lymphocyte count [16]. close contacts with confirmed cases, who test negative for COVID-19 in throat swab as some patients were 2.2 Real-time-PCR found to have viral RNA in their feces starting from 1 The current diagnostic test for COVID-19 is RT-PCR day after infection and for up to 12 days [28]. assay [17]. It would not be possible to do PCR test to all suspected individuals, so the Centers for Disease Control 2.3 Serological tests and Prevention (CDC) released guidance for priorities Serological testing detects antigens and antibodies di- for COVID-19 PCR testing [18] (Table 2). rected against the virus. SARS-CoV2 belongs to the The recommended specimen for testing is lower re- same family of β-coronaviruses as those caused SARS spiratory tract specimen: sputum and/or endotracheal and MERS outbreaks; it is expected to have similar anti- aspirate or bronchoalveolar. If not possible or in asymp- body generation process [29] where there is a lag period tomatic contacts, upper respiratory tract specimen, of 14-28 days after the onset of illness till the antibodies nasopharyngeal and oropharyngeal swab, or wash in am- appears in patients’ serum [30]. In some people with bulatory patients is collected, with preference of com- COVID-19 disease confirmed by RT-PCR, weak, late, or bined nasopharyngeal swab and oropharyngeal swab absent antibody responses have been reported [31, 32]. collection [19]. The strength of antibody response is dependent on mul- High viral loads in both upper and lower respiratory tiple factors as age, nutritional status, disease severity, tract are detected 5-6 days of the onset of symptoms and certain medications or infections that may suppress [20–23]. Lower respiratory tract specimens yield highest the immune system [31–33]. viral loads for the diagnosis of COVID-19 [24]. As for In March 2020, the FDA issued a policy that allows upper respiratory tract specimens higher sensitivity of developers of certain serological tests to begin to market nasopharyngeal swabs (63%) was detected compared to or use their tests once appropriate evaluation to ensure oropharyngeal swabs (32%) [25]. test validation is performed. The FDA issued this policy Table 1 COVID-19 severity triage Mild Severe Critical � Fever � Need to meet one of the following criteria: � Need to meet one of the following criteria: � Respiratory symptoms � Respiratory distress, RR ≥ 30/min � Respiratory failure needing mechanical oxygenation � Pneumonia on chest � Resting blood oxygen saturation ≤ 93% � Shock radiography � Arterial blood oxygen partial pressure (PaO2)/FiO2 ≤ � Development of other organ failures, requiring intensive 300 mmHg care unit care Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 3 of 5 Table 2 Priorities for PCR testing of suspected COVID-19 patients according to CDC guidelines [18] Priority 1 � Hospitalized patients Ensure optimal care options for all hospitalized patients, lessen the risk of � Symptomatic healthcare workers nosocomial infections, and maintain the integrity of the healthcare system Priority 2 � Patients in long-term care facilities with symptoms Ensure that those who are at highest risk of complication of infection are rapidly � Patients 65 years of age and older with symptoms identified and appropriately triaged � Patients with underlying conditions with symptoms � First responders with symptoms Priority 3 � Critical infrastructure workers with symptoms As resources allow, test individuals in the surrounding community of rapidly � Individuals who do not meet any of the above categories increasing hospital cases to decrease community spread, and ensure health of with symptoms essential workers � Healthcare workers and first responders � Individuals with mild symptoms in communities experiencing high 2019-nCoV hospitalizations Non-priority � Individuals without symptoms to allow early patient access to certain serological tests. provides complimentary diagnostic tool in RT-PCR test— Until 17 July 2020, thirty serology/antibody tests and negative patients presenting late or in detecting past infec- two antigen diagnostic tests for SARS-CoV-2 were is- tion when done 15 days or more after the onset of symp- sued an Emergency Use Authorization (EUA) intended toms [38]. for use by clinical laboratories [34]. Criteria for EUA A study by Carmen et al. evaluated six different were as follows: (1) The SARS-CoV-2 can cause a ser- commercial enzyme immunoassays (EIA) platforms ious or life-threatening disease or condition, including and eight points of care tests (POCT) with the same severe respiratory illness, to humans infected by this serum panel to identify the sensitivity of the available virus; (2) based on the totality of scientific evidence assay in COVID-19 diagnosis over time ranging from available to FDA, it is reasonable to believe that the as early as 3 days post symptoms onset to > 45 days product may be effective in diagnosing COVID-19, and post symptoms onset. Their conclusion was that ser- that the known and potential benefits of the product ology assays should not be used for the diagnosis of when used for diagnosing COVID-19 outweigh its acute infections [39]. known and potential risks; and (3) there is no adequate, The American Society for Microbiology (ASM) [40], approved, and available alternative to the emergency use the WHO [41], the Centers for Disease Control and Pre- of the product [35]. vention [42], and the Public Health Agency of Canada It is recommended to use combined IgG and IgM anti- [43] also published similar recommendations against body testing for more accurate results [29]. The average using serology testing for diagnosis of acute infection. time for seroconversion in reported studies is 12 days, while positive RT-PCR is detected 5-6 days from the on- 3 Conclusion set of symptoms, making antibody testing still inferior to COVID-19 available diagnostics puts the health author- RT-PCR in COVID-19 diagnosis but more likely used ities in challenging situation as diagnosis based on clin- when RT-PCR is not available or accessible [36]. ical symptoms alone is inaccurate, in addition to the Also, cross-reactivity of other respiratory viruses with presence of asymptomatic carriers and long incubation SARS-CoV-2 is reported and may influence serology test period of the virus. False negative RT-PCR results in in- results, especially in patients recently exposed to respira- fected patients adds to the challenge, necessitating the tory infections [37]. need for a rapid and sensitive technique to be available A systematic review including 55 publications analyzing in most laboratories for swift detection of COVID-19 in 8526 SARS-CoV-2 patients’ samples from Asia (n =38), order to limit spread and properly treat infected individ- Europe (n =15), USA (n =1), andChina (n = 1), con- uals. Available diagnostic tests alone are not enough to cluded that results for IgG, IgM, IgA, total antibodies, and provide guaranteed diagnosis of COVID-19. Clinical sus- IgG/IgM, all showed low sensitivity during the first week picion of COVID-19 should be thoroughly taken in con- from onset of symptoms (less than 30.1%), rose in the sec- sideration even with negative test results to allow timely ond week and reached their highest values in the third management of COVID-19, contain and limit the dam- week. The combination of IgG/IgM had a sensitivity of age of current outbreak. 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI To monitor disease progression, it is recommended to 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) combine both serial viral load monitoring and antibody for 15 to 21 days. Therefore, antibody testing is not rec- response, as viral load was found to be inversely related ommended as primary tool in COVID-19 diagnosis but to serum antibody response [22]. Zayed et al. Journal of the Egyptian Public Health Association (2021) 96:25 Page 4 of 5 Detection of antibody responses to COVID-19 in the 5. 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Journal

Journal of the Egyptian Public Health AssociationSpringer Journals

Published: Aug 18, 2021

Keywords: COVID-19; Serology; RT-PCR; Lab; Clinical

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