Serological Evidence of Likely Reactivation Recurrent or Reinfection in Sars Cov2 Infection

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Okoror, Samuel A. Osanyinlusi, Pascal Hodogbe, Musah Mohammed, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6456552/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The ongoing COVID-19 pandemic continues to display varying dynamics in transmission, clinical manifestation, and recovery rates. In August 2020 asymptomatic male adult who was on transit reported to health authorities as been positive to COVID-19. He was evacuated to quarantine center, another test confirmed him positive, and his blood samples were obtained. Vital signs remain normal throughout isolation with no visible symptom, and he tested negative after 14 days. While still in quarantine facility, returned for another test 5 days after and he remained negative, 3 days after another sample was taken which came up positive. A confirmatory test was carried out the next day remained positive. He had low neutrophil, elevated S-ferritin level, and carbonate as well as IgG and IgM measuring a four-fold rise in titer. The reduction in neutrophil could be a reason for reactivation of the virus since the immune system may not have completely cleared the infection but the generality of the immune system was not compromised as indicated by high level of ferritin a sign of inflammatory response due to infection by the virus. It is recommended that a follow up of COVID-19 survivors may be necessary, though there is no evidence that they are transmitting the virus. Africa with paucity of research needs to document as much as possible new pathophysiological presentation of covid-19 to assist clinicians and scientists alike in making appropriate decisions. Ferritin Neutrophils Case report Hematological Endocrinological Figures Figure 1 Introduction The ongoing COVID-19 pandemics continues to exhibit varied dynamics in terms of new waves of transmissions, clinical manifestations, and recovery rates even as a couple of countries have begun vaccination while others are at the point of vaccine roll out. According to the Johns Hopkins Coronavirus resource center, as of 21st September 2020, there are 31,079,041 global cases with 960,992 deaths due to COVID-19. Africa has recorded 1,407,680 cases with 33,951 deaths and 1,153,967 recoveries as of 20th September 2020 [ 1 ]. COVID-19 is caused by the SARS-CoV-2, a positively-sense, single stranded RNA virus in the family of Coronaviridae that also contains similar viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Human coronaviruses specifically cause disease of the upper and lower respiratory tracts and elicit various symptoms including fever, persistent cough, sneezing as well as difficulty in breathing etc. The virus is believed to be hosted by bats or pangolins [ 2 , 3 ]. Recovery from COVID-19 is hinged upon the development of a strong innate and adaptive immunity to the virus. This comprises CD4 + and CD8 + T cells responses as well as development of neutralizing antibodies. However certain patients still suffer from hyperactive immune responses majorly characterized by excessive cytokine storm, and thus requires anti-inflammatory treatment with corticosteroids [ 4 , 5 ]. The length of protective immunity to COVID-19 is currently unknown, and data from similar seasonal Coronaviruses including- HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 suggest a non-lasting immunity [ 6 ]. During the ongoing pandemic, there have been a few reports of positive RT-PCR tests for recovered COVID-19 patients including the one from China [ 7 ], highlighting the need for proper follow-up and monitoring of recovered patients. Patient’s Information and Observation In August 2020, an adult male who was on transit on board a chartered flight in a neighboring country, and while in his designated hotel, he received information about his Covid-19 RT-PCR result from his country of origin. He had travelled after carrying out antibody testing (lateral flow immunochromatological assay (sensitivity=90%; specificity 84%) which came up non-reactive to both IgG and IgM (Golden Biotechnology, CA USA) and samples for RT-PCR collected with a promise that results will be transmitted to him in due course. Patient’s consent The patient gave his consent to be evaluated and managed for covid-19 as well as agreed to the publication of the case report as an important contribution to the pathophysiology of covid-19. Clinical findings At the point of boarding the aircraft his temperature remained at 36.3°C. On getting to the country of transit the temperature remained constant and he was escorted to the designated hotel where he checked in. Two days after checking in he received his RT-PCR (Life river SARS CoV-2 RT-PCR kit, Shangai China) result of been positive at CT of 36.5 (Day 3) and an evacuation was immediately organized to a quarantine center. During examination he reported not having close contact with anyone during his trip and that social distancing was maintained while inside the aircraft. Contact tracing activities were mobilized. It was reported that none of those in the aircraft with him had any symptoms of covid-19 after 14 days follow up. All method used in this case followed relevant guidelines and regulations. Therapeutic intervention Though he displayed no visible symptom he was put on a dose of azithromycin and zinc tablets coupled with vitamin C as recommended for the management of covid-19. Timeline The patient was kept under isolation at one of the isolation centers where his vital signs (temperature, pulse and blood pressure) were observed thrice daily. He remained in isolation for 14 days in accordance with WHO Covid-19 regulations. He displayed no visible symptoms throughout the isolation period. Diagnosis While in the quarantine center nasal and throat swabs were taken and again tested 4 days from the first test and results came out positive with a CT value of 36.5 (Realstar SARS-CoV-2 RT-PCR kit. Altona Diagnostic Germany). Blood samples were also taken by trained phlebotomists who maintained strict Infection Prevention Control protocols during the sample collection. Chemistry pathology analysis, heamatological analysis and endocronological were done with the blood samples. IgG and IgM were assayed using ELISA technique and the titre for both antibodies recorded (ABCAM USA; sensitivity=99.6%). A second blood sample was collected at the collection of the last RT-PCR samples for the second analysis, and another blood sample collected at the time of the 3 rd RT-PCR sample collection for a repeat analysis as earlier done. Follow up and Outcome Clinician and patient assessed outcome His vital signs throughout the period of quarantine remained normal, his average temperature was 35.8°C, his pulse rate averaged 66 bpm, blood pressure averaged 120/80 mmHg which were observed at least 3 times daily (Table 1). Diagnostic follow up After 14 days of quarantine, he was tested again using both nasopharyngeal and oropharyngeal samples and the result reported negative using the same RT-PCR kits, and he was discharged base of WHO guidelines. However, there was a four-fold rise in titer in both IgG and IgM antibody (Fig. 1), which occurred between the first and the second antibody testing (ELISA using the same ELISA kits previously used) while there was no significant difference (ρ=.000000001) the second and the third antibody titer (Fig. 1), all other parameters remain the same with only a slight change (daily RT-PCR and ELISA test results for IgM and IgG are shown in table 2), the neutrophil continue to be depleted. Five days after he tested negative to COVID-19 RT-PCR using oropharyngeal swab and 3 days later he came up positive using oropharyngeal swab with a CT value of 36.15 and nasopharyngeal 34.88. Blood sampling results here also remain constant for all parameters with neutrophil drip into neutropenia. IgG and IgM remained constant. The laboratory thinking that it made a mistake, the following day took both oropharyngeal and nasopharyngeal samples and was run in triplicates and they both reported positive using the same RT-PCR kit and same thermocycler earlier used (Biorad CFX 96). Oropharyngeal sample had an average of 36.92 while nasopharyngeal was 30.00 and control was 25.32. Report on Blood samples Chemistry pathology analysis, heamatological analysis and endocronological analysis were carried out on the blood samples (Table 1). Discussion Antibody test kits for COVID-19 are widely available in African markets and are a cheap and affordable alternative to the overly sensitive RT-PCR for the quick diagnosis of COVID-19. A couple of studies has shown excellent IgG and IgM responses to COVID-19 within 20 days of onset of clinical symptoms which suggest a point-of-care antibody testing may be helpful [8]. However, other studies are still skeptical of the accuracy of COVID-19 serological testing and wide usage [9] which also depends on when sampling was done. Some studies have it that neither IgM nor IgG is produced at the early stage of infection and there is possibility that the patient is in the early stage of infection and has not yet displayed symptoms or detectable IgM and/or IgG. A non-reactive COVID-19 antibody test result for the current case study may mean the kits used are not sensitive enough or might be due to a low antibody titer below the detection capacity of the kits but could be detected with RT-PCR. One of the preliminary factors responsible for recovered or RT-PCR negative cases testing positive few days afterwards is misdiagnosis/wrong diagnosis, which could be avoided by running each test at least twice and in triplicates as was done in this case study. Misdiagnosis is not likely in the current case study as all tests were done twice and in triplicates. Five days after discharge of the patient, there was a follow up and samples were taken, which twice tested positive for COVID-19 by RT-PCR. Also, on day eight after discharge, another sample was taken which tested positive as observed on day five. Scientific rationale to support reactivation of SARS-CoV-2 in the patient. There is no available data supporting reactivation for human coronaviruses as of this time, although this may be possible for COVID-19 since it shows some disparity most especially its ease of spread as well as clinical manifestations compared to other coronaviruses like SARS-CoV-1 and MERS-CoV [5]. From the time of sample collection of the second to the last sampling is not enough time for a reinfection and coupled with the fact that the patient was still in isolation though infection from isolation cannot be ruled out. Available data from different sources report various subset of immune cells responses to COVID-19 including the T cells [10] and B cells [8], however immune patterns in most COVID-19 cohorts, and the efficiency of responses to the virus point towards a suboptimum range, that might permit a continued persistence of the virus and reactivation in some patients [11]. Results from IgG and IgM has shown a four-fold rise in titer from the first and second sampling, it remains constant in the third blood sampling showing that no new infection was initiated as that would have triggered an increase titer of IgM which is a pointer to recent infection. In the absence of recent infection what could cause a possible RT-PCR positive results will likely be a reactivation of an earlier infection or recurrent infection of which time interval in this case study cannot be referred to as recurrent. The current case has a low neutrophil blood concentration during the period and the neutrophils concentration continued to reduce further in the course of entire infection which goes to show that the infection is own going without been noticed which could only be explained by a likelihood of reactivation (Table 3) and may be reflective of the entire lymphocyte pool and could set a stage for a possible virus reactivation. Viruses generally encode numerous mechanisms to evade or modulate immune responses thereby paving way for persistent infections, even-though this is still not clear with COVID-19 [5]. Higher ferritin levels have been associated with elevated immune responses and exacerbate the prognosis of COVID-19 patients via cytokine storm [12]. However, the case study had a bit elevated ferritin levels (Table 3) that made it looks unlikely his immune system is compromised but is a sign of inflammatory reactions likely to be responsible for muscle pains in COVID-19 patients. The fact that all other granulocytes remain normal rules out the fact that here may have been a problem with immune generating cells. The high level of carbonate in the blood is also indicative of the infection in the lungs which remain stable throughout the period tested also confirming that no new infection was observed but a likely reactivation of the infection that was already in the system which made it have a reduced severity. Reactivation in the patient may have occurred due to continuous virus shedding by the patient since the time interval of RT-PCR positivity is not enough to report new external infection. Any form of re-infection will be within the patient himself and hence cannot be termed reinfection but reactivation of earlier infection. Though we suggest a reactivation of the virus, a proper confirmation with genomic sequencing would have further confirmed our suggestion which is limitation in the analysis of this case. Limitations The main limitation of this case is that there was no immediate access to genomic sequencing of the several samples collected from this case which would have pointed to the difference between the genomes of the different samples collected which would have guided and confirmed our conclusions. Lesson learned. It is important to include a follow-up of recovered COVID-19 cases in the current guidelines for discharge of patients. Also, more studies are needed to show whether reactivation of COVID-19 is possible from recovered patients. Patient’s perspective The patient observed that the covid-19 response team responded swiftly and the treatment and follow up at the isolation center was adequate. All recommendations towards handling of covid-19 patients were well followed. Monitoring was well carried out. Declarations Author contributions LEO: conceived and supervised the project up till writing and review process. SAO: Partly wrote the paper and gathered all literature PH, MM and EA: All carried out the laboratory work, supervised sample collection from the start to the end of the project in transit country. EIO, EAT, and AD conducted the initial sampling and diagnosis, which included laboratory testing. Conflict of interest We declare no conflict of interest. Funding information Not applicable Clinical trial number: Not applicable Ethical Approval This Case Report was approved by the ethical review board of Irrua Specialist Teaching Hospital, Irrua Edo State, Nigeria. Informed Consent to Participate: Informed consent to participate in this report was obtained from the patient. Informed Consent to publish: Consent to publish was obtained from the patient before submitting this report for publication. Acknowledgement We thank all the staffs of the isolation center who in one way or the other contributed to this work. References Africa CDC- Coronavirus Disease 2019 (COVID-19) Latest updates on the COVID-19 crisis (from Africa CDC). https://africacdc.org/covid-19/ Cui, J., Li, F. & Shi, Z. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17, 181–192. https://doi.org/10.1038/s41579-018-0118-9 Valencia D N. Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2. Cureus 2020. 12(3): e7386. doi:10.7759/cureus.7386 Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020; 20(5):269-270. doi:10.1038/s41577-020-0308-3 Vabret Nicolas, Graham J. Britton, Conor Gruber et al. Immunology of COVID-19: Current State of the Science . Immunity 2020; 52(6), 910-941. https://doi.org/10.1016/j.immuni.2020.05.002 Edridge, A.W.D., Kaczorowska, J., Hoste, A.C.R. et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med (2020). https://doi.org/10.1038/s41591-020-1083-1 Lan Lan, Dan Xu, Guangming Ye, et al., Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA,2020. 323(15)/ doi:10.1001/jama.2020.2783 Long, Q., Liu, B., Deng, H. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 26, 845–848 (2020). https://doi.org/10.1038/s41591-020-0897-1 Bastos Mayara Lisboa, Gamuchirai Tavaziva, Syed Kunal Abidi, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ 2020; 370:m2516 http://dx.doi.org/10.1136 bmj.m2516 Chen, Z., John Wherry, E. T cell responses in patients with COVID-19. Nat Rev Immunol 20, 529–536 (2020). https://doi.org/10.1038/s41577-020-0402-6 Mathew Divij, Josephine R. Giles, Amy E. Baxter, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020. 369, eabc8511. DOI: 10.1126/science.abc8511 Vargas-Vargas M, Cortés-Rojo C. Ferritin levels and COVID-19. Rev Panam Salud Publica. 2020 Jun 1; 44:e72. doi: 10.26633/RPSP.2020.72. Tables Table 1: Daily average vital signs of patient who tested positive to positive to SARS-CoV-2 while on transit Day Temperature ( °C) Pulse (BPM) Blood Pressure (mmHg) Blood Oxygen (%) 4 35.5 66 98 110/80 5 35.3 66 98 110/80 6 36.0 65 97 120/80 7 36.2 66 94 120/100 8 35.5 67 96 110/80 9 35.3 68 99 120/80 10 35.7 65 98 135/100 11 36.0 66 96 120/100 12 35.2 66 99 110/80 13 35.3 66 99 120/80 Table 2: Results of Daily Diagnosis using RT-PCR, ELISA and Blood RDT (IgG and IgM) of the patient who tested positive to SARS-CoV-2 while on transit. Day RT-PCR (CT- value) ELISA Antibody titer Blood RDT IgM IgG 1 36.5 (Nasopharyngeal and Oropharyngeal) N/A N/A Both IgM and IgG, Not reactive 4 36.5 (Nasopharyngeal and Oropharyngeal) 1:320 1:40 N/A 14 43.6 (Nasopharyngeal and Oropharyngeal) 1:640 1:80 N/A 17 36.15 (Oropharyngeal) (Nasopharyngeal=34.88) 1:640 1:160 N/A 18 36.92 (Nasopharyngeal =30.00) N/A N/A N/A Table 3: Biochemical, heamatological and endocronological parameters of the patient testing positive to SARS-CoV-2 while on transit Blood test performed Initial Results Final Results Reference Biochemistry (Renal) Total CO 2 (Bicarbornate) 29.31 mmol/L 27.21 22-29 (Liver function test) S-Bilirubin 21 mmol/L 21 3.42-20.5 S-g-glutamyl transferase 136 Im/L 104 <55 S-LDL-cholesterol 3.1 mmol/L 3 <3 Endocrinology S-Ferritin 451 ng/ml 449 23.9-336.2 Heamatology Neutrophils 25.6% (1.18x10 9 /L) 0.18X10 9 2.0-7.5x10 9 /L Lymphocytes 61.2% (2.82x10 9 ) 69.7% (2.4x10 9 ) 20-40% WBC 4.6 x 10 9 3.4 x 10 9 4.0-12.0 Additional Declarations No competing interests reported. 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According to the Johns Hopkins Coronavirus resource center, as of 21st September 2020, there are 31,079,041 global cases with 960,992 deaths due to COVID-19. Africa has recorded 1,407,680 cases with 33,951 deaths and 1,153,967 recoveries as of 20th September 2020 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCOVID-19 is caused by the SARS-CoV-2, a positively-sense, single stranded RNA virus in the family of \u003cem\u003eCoronaviridae\u003c/em\u003e that also contains similar viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Human coronaviruses specifically cause disease of the upper and lower respiratory tracts and elicit various symptoms including fever, persistent cough, sneezing as well as difficulty in breathing etc. The virus is believed to be hosted by bats or pangolins [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecovery from COVID-19 is hinged upon the development of a strong innate and adaptive immunity to the virus. This comprises CD4\u0026thinsp;+\u0026thinsp;and CD8\u0026thinsp;+\u0026thinsp;T cells responses as well as development of neutralizing antibodies. However certain patients still suffer from hyperactive immune responses majorly characterized by excessive cytokine storm, and thus requires anti-inflammatory treatment with corticosteroids [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe length of protective immunity to COVID-19 is currently unknown, and data from similar seasonal Coronaviruses including- HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1 suggest a non-lasting immunity [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. During the ongoing pandemic, there have been a few reports of positive RT-PCR tests for recovered COVID-19 patients including the one from China [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], highlighting the need for proper follow-up and monitoring of recovered patients.\u003c/p\u003e"},{"header":"Patient’s Information and Observation","content":"\u003cp\u003eIn August 2020, an adult male who was on transit on board a chartered flight in a neighboring country, and while in his designated hotel, he received information about his Covid-19 RT-PCR result from his country of origin. He had travelled after carrying out antibody testing (lateral flow immunochromatological assay (sensitivity=90%; specificity 84%) which came up non-reactive to both IgG and IgM (Golden Biotechnology, CA USA) and samples for RT-PCR collected with a promise that results will be transmitted to him in due course.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient gave his consent to be evaluated and managed for covid-19 as well as agreed to the publication of the case report as an important contribution to the pathophysiology of covid-19.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the point of boarding the aircraft his temperature remained at 36.3\u0026deg;C. On getting to the country of transit the temperature remained constant and he was escorted to the designated hotel where he checked in. Two days after checking in he received his RT-PCR (Life river SARS CoV-2 RT-PCR kit, Shangai China) result of been positive at CT of 36.5 (Day 3) and an evacuation was immediately organized to a quarantine center. During examination he reported not having close contact with anyone during his trip and that social distancing was maintained while inside the aircraft. Contact tracing activities were mobilized. It was reported that none of those in the aircraft with him had any symptoms of covid-19 after 14 days follow up. All method used in this case followed relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Though he displayed no visible symptom he was put on a dose of azithromycin and zinc tablets coupled with vitamin C as recommended for the management of covid-19.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTimeline\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient was kept under isolation at one of the isolation centers where his vital signs (temperature, pulse and blood pressure) were observed thrice daily. He remained in isolation for 14 days in accordance with WHO Covid-19 regulations. He displayed no visible symptoms throughout the isolation period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhile in the quarantine center nasal and throat swabs were taken and again tested 4 days from the first test and results came out positive with a CT value of 36.5 (Realstar SARS-CoV-2 RT-PCR kit. Altona Diagnostic Germany). Blood samples were also taken by trained phlebotomists who maintained strict Infection Prevention Control protocols during the sample collection. Chemistry pathology analysis, heamatological analysis and endocronological were done with the blood samples. IgG and IgM were assayed using ELISA technique and the titre for both antibodies recorded (ABCAM USA; sensitivity=99.6%). A second blood sample was collected at the collection of the last RT-PCR samples for the second analysis, and another blood sample collected at the time of the 3\u003csup\u003erd\u003c/sup\u003e RT-PCR sample collection for a repeat analysis as earlier done.\u003c/p\u003e"},{"header":"Follow up and Outcome","content":"\u003cp\u003e\u003cstrong\u003eClinician and patient assessed outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHis vital signs throughout the period of quarantine remained normal, his average temperature was 35.8\u0026deg;C, his pulse rate averaged 66 bpm, blood pressure averaged 120/80 mmHg which were observed at least 3 times daily (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic follow up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter 14 days of quarantine, he was tested again using both nasopharyngeal and oropharyngeal samples and the result reported negative using the same RT-PCR kits, and he was discharged base of WHO guidelines. However, there was a four-fold rise in titer in both IgG and IgM antibody (Fig. 1), which occurred between the first and the second antibody testing (ELISA using the same ELISA kits previously used) while there was no significant difference (\u0026rho;=.000000001) the second and the third antibody titer (Fig. 1), all other parameters remain the same with only a slight change (daily RT-PCR and ELISA test results for IgM and IgG are shown in table 2), the neutrophil continue to be depleted. Five days after he tested negative to COVID-19 RT-PCR using oropharyngeal swab and 3 days later he came up positive using oropharyngeal swab with a CT value of 36.15 and nasopharyngeal 34.88. Blood sampling results here also remain constant for all parameters with neutrophil drip into neutropenia. IgG and IgM remained constant. The laboratory thinking that it made a mistake, the following day took both oropharyngeal and nasopharyngeal samples and was run in triplicates and they both reported positive using the same RT-PCR kit and same thermocycler earlier used (Biorad CFX 96). Oropharyngeal sample had an average of 36.92 while nasopharyngeal was 30.00 and control was 25.32.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReport on Blood samples\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChemistry pathology analysis, heamatological analysis and endocronological analysis were carried out on the blood samples (Table 1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAntibody test kits for COVID-19 are widely available in African markets and are a cheap and affordable alternative to the overly sensitive RT-PCR for the quick diagnosis of COVID-19. A couple of studies has shown excellent IgG and IgM responses to COVID-19 within 20 days of onset of clinical symptoms which suggest a point-of-care antibody testing may be helpful [8]. However, other studies are still skeptical of the accuracy of COVID-19 serological testing and wide usage [9] which also depends on when sampling was done. Some studies have it that neither IgM nor IgG is produced at the early stage of infection and there is possibility that the patient is in the early stage of infection and has not yet displayed symptoms or detectable IgM and/or IgG. A non-reactive COVID-19 antibody test result for the current case study may mean the kits used are not sensitive enough or might be due to a low antibody titer below the detection capacity of the kits but could be detected with RT-PCR. One of the preliminary factors responsible for recovered or RT-PCR negative cases testing positive few days afterwards is misdiagnosis/wrong diagnosis, which could be avoided by running each test at least twice and in triplicates as was done in this case study. Misdiagnosis is not likely in the current case study as all tests were done twice and in triplicates. Five days after discharge of the patient, there was a follow up and samples were taken, which twice tested positive for COVID-19 by RT-PCR. Also, on day eight after discharge, another sample was taken which tested positive as observed on day five.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScientific rationale to support reactivation of SARS-CoV-2 in the patient.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no available data supporting reactivation for human coronaviruses as of this time, although this may be possible for COVID-19 since it shows some disparity most especially its ease of spread as well as clinical manifestations compared to other coronaviruses like SARS-CoV-1 and MERS-CoV [5]. From the time of sample collection of the second to the last sampling is not enough time for a reinfection and coupled with the fact that the patient was still in isolation though infection from isolation cannot be ruled out. Available data from different sources report various subset of immune cells responses to COVID-19 including the T cells [10] and B cells [8], however immune patterns in most COVID-19 cohorts, and the efficiency of responses to the virus point towards a suboptimum range, that might permit a continued persistence of the virus and reactivation in some patients [11]. Results from IgG and IgM has shown a four-fold rise in titer from the first and second sampling, it remains constant in the third blood sampling showing that no new infection was initiated as that would have triggered an increase titer of IgM which is a pointer to recent infection. In the absence of recent infection what could cause a possible RT-PCR positive results will likely be a reactivation of an earlier infection or recurrent infection of which time interval in this case study cannot be referred to as recurrent. The current case has a low neutrophil blood concentration during the period and the neutrophils concentration continued to reduce further in the course of entire infection which goes to show that the infection is own going without been noticed which could only be explained by a likelihood of reactivation (Table 3) and may be reflective of the entire lymphocyte pool and could set a stage for a possible virus reactivation. Viruses generally encode numerous mechanisms to evade or modulate immune responses thereby paving way for persistent infections, even-though this is still not clear with COVID-19 [5]. Higher ferritin levels have been associated with elevated immune responses and exacerbate the prognosis of COVID-19 patients via cytokine storm [12]. However, the case study had a bit elevated ferritin levels (Table 3) that made it looks unlikely his immune system is compromised but is a sign of inflammatory reactions likely to be responsible for muscle pains in COVID-19 patients. The fact that all other granulocytes remain normal rules out the fact that here may have been a problem with immune generating cells. The high level of carbonate in the blood is also indicative of the infection in the lungs which remain stable throughout the period tested also confirming that no new infection was observed but a likely reactivation of the infection that was already in the system which made it have a reduced severity. Reactivation in the patient may have occurred due to continuous virus shedding by the patient since the time interval of RT-PCR positivity is not enough to report new external infection. Any form of re-infection will be within the patient himself and hence cannot be termed reinfection but reactivation of earlier infection. Though we suggest a reactivation of the virus, a proper confirmation with genomic sequencing would have further confirmed our suggestion which is limitation in the analysis of this case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe main limitation of this case is that there was no immediate access to genomic sequencing of the several samples collected from this case which would have pointed to the difference between the genomes of the different samples collected which would have guided and confirmed our conclusions. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLesson learned.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is important to include a follow-up of recovered COVID-19 cases in the current guidelines for discharge of patients. Also, more studies are needed to show whether reactivation of COVID-19 is possible from recovered patients. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s perspective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient observed that the covid-19 response team responded swiftly and the treatment and follow up at the isolation center was adequate. All recommendations towards handling of covid-19 patients were well followed. Monitoring was well carried out. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLEO: conceived and supervised the project up till writing and review process.\u003c/p\u003e\n\u003cp\u003eSAO: Partly wrote the paper and gathered all literature\u003c/p\u003e\n\u003cp\u003ePH, MM and EA: All carried out the laboratory work, supervised sample collection from the start to the end of the project in transit country.\u0026nbsp;EIO, EAT, and AD conducted the initial sampling and diagnosis, which included laboratory testing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflict of interest\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding information\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical trial number:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003cem\u003eApproval\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis Case Report was approved by the ethical review board of Irrua Specialist Teaching Hospital, Irrua Edo State, Nigeria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent to Participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent to participate in this report was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent to publish:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent to publish was obtained from the patient before submitting this report for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the staffs of the isolation center who in one way or the other contributed to this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAfrica CDC- Coronavirus Disease 2019 (COVID-19) Latest updates on the COVID-19 crisis (from Africa CDC). https://africacdc.org/covid-19/\u003c/li\u003e\n\u003cli\u003eCui, J., Li, F. \u0026amp; Shi, Z. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; \u003cstrong\u003e17, \u003c/strong\u003e181\u0026ndash;192. https://doi.org/10.1038/s41579-018-0118-9\u003c/li\u003e\n\u003cli\u003eValencia D N. Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2. Cureus 2020. 12(3): e7386. doi:10.7759/cureus.7386\u003c/li\u003e\n\u003cli\u003eCao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020; 20(5):269-270. doi:10.1038/s41577-020-0308-3\u003c/li\u003e\n\u003cli\u003eVabret Nicolas, Graham J. Britton, Conor Gruber et al. Immunology of COVID-19: Current State of the Science\u003cstrong\u003e. \u003c/strong\u003eImmunity 2020;\u003cem\u003e \u003c/em\u003e52(6), 910-941. https://doi.org/10.1016/j.immuni.2020.05.002 \u003c/li\u003e\n\u003cli\u003eEdridge, A.W.D., Kaczorowska, J., Hoste, A.C.R. et al. Seasonal coronavirus protective immunity is short-lasting. Nat Med (2020). https://doi.org/10.1038/s41591-020-1083-1\u003c/li\u003e\n\u003cli\u003eLan Lan, Dan Xu, Guangming Ye, et al., Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA,2020. 323(15)/ doi:10.1001/jama.2020.2783\u003c/li\u003e\n\u003cli\u003eLong, Q., Liu, B., Deng, H. \u003cem\u003eet al.\u003c/em\u003e Antibody responses to SARS-CoV-2 in patients with COVID-19. \u003cem\u003eNat Med\u003c/em\u003e \u003cstrong\u003e26, \u003c/strong\u003e845\u0026ndash;848 (2020). https://doi.org/10.1038/s41591-020-0897-1\u003c/li\u003e\n\u003cli\u003eBastos Mayara Lisboa, Gamuchirai Tavaziva, Syed Kunal Abidi, et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ 2020; 370:m2516 http://dx.doi.org/10.1136 bmj.m2516\u003c/li\u003e\n\u003cli\u003eChen, Z., John Wherry, E. T cell responses in patients with COVID-19. \u003cem\u003eNat Rev Immunol\u003c/em\u003e \u003cstrong\u003e20, \u003c/strong\u003e529\u0026ndash;536 (2020). https://doi.org/10.1038/s41577-020-0402-6\u003c/li\u003e\n\u003cli\u003eMathew Divij, Josephine R. Giles, Amy E. Baxter, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020. 369, eabc8511. DOI: 10.1126/science.abc8511\u003c/li\u003e\n\u003cli\u003eVargas-Vargas M, Cort\u0026eacute;s-Rojo C. Ferritin levels and COVID-19. Rev Panam Salud Publica. 2020 Jun 1; 44:e72. doi: 10.26633/RPSP.2020.72.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Daily average vital signs of patient who tested positive to positive to SARS-CoV-2 while on transit\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTemperature (\u003c/strong\u003e\u003cstrong\u003e\u0026deg;C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulse (BPM)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood Pressure (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood Oxygen (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e110/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e110/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e120/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e36.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e120/100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e110/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e120/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e135/100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e120/100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e110/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 19.5827%;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.9904%;\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.7432%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.3852%;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18.2986%;\"\u003e\n \u003cp\u003e120/80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Results of Daily Diagnosis using RT-PCR, ELISA and Blood RDT (IgG and IgM) of the patient who tested positive to SARS-CoV-2 while on transit.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRT-PCR (CT- value)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 231px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eELISA Antibody titer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood RDT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIgG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e36.5 (Nasopharyngeal and Oropharyngeal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eBoth IgM and IgG, Not reactive\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e36.5 (Nasopharyngeal and Oropharyngeal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e43.6 (Nasopharyngeal and Oropharyngeal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e36.15 (Oropharyngeal) \u0026nbsp;(Nasopharyngeal=34.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003e1:160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e36.92 (Nasopharyngeal =30.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 116px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Biochemical, heamatological and endocronological parameters of the patient testing positive to SARS-CoV-2 while on transit\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood test performed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial Results\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinal Results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eBiochemistry\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u0026nbsp;(Renal)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eTotal CO\u003csub\u003e2\u003c/sub\u003e (Bicarbornate)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e29.31 mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e27.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e22-29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cem\u003e(Liver function test)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eS-Bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e21\u0026nbsp;mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3.42-20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eS-g-glutamyl transferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e136 Im/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026lt;55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eS-LDL-cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e3.1 mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eEndocrinology\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eS-Ferritin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e451 ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e23.9-336.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHeamatology\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eNeutrophils\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e25.6% (1.18x10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e0.18X10\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e2.0-7.5x10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eLymphocytes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e61.2% (2.82x10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e69.7% (2.4x10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e20-40%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 167px;\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e4.6 x 10\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003e3.4 x 10\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 157px;\"\u003e\n \u003cp\u003e4.0-12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ferritin, Neutrophils, Case report, Hematological, Endocrinological","lastPublishedDoi":"10.21203/rs.3.rs-6456552/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6456552/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe ongoing COVID-19 pandemic continues to display varying dynamics in transmission, clinical manifestation, and recovery rates. In August 2020 asymptomatic male adult who was on transit reported to health authorities as been positive to COVID-19. He was evacuated to quarantine center, another test confirmed him positive, and his blood samples were obtained. Vital signs remain normal throughout isolation with no visible symptom, and he tested negative after 14 days. While still in quarantine facility, returned for another test 5 days after and he remained negative, 3 days after another sample was taken which came up positive. A confirmatory test was carried out the next day remained positive. He had low neutrophil, elevated S-ferritin level, and carbonate as well as IgG and IgM measuring a four-fold rise in titer. The reduction in neutrophil could be a reason for reactivation of the virus since the immune system may not have completely cleared the infection but the generality of the immune system was not compromised as indicated by high level of ferritin a sign of inflammatory response due to infection by the virus. It is recommended that a follow up of COVID-19 survivors may be necessary, though there is no evidence that they are transmitting the virus. Africa with paucity of research needs to document as much as possible new pathophysiological presentation of covid-19 to assist clinicians and scientists alike in making appropriate decisions.\u003c/p\u003e","manuscriptTitle":"Serological Evidence of Likely Reactivation Recurrent or Reinfection in Sars Cov2 Infection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 01:42:28","doi":"10.21203/rs.3.rs-6456552/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9d28dbfb-371d-4a57-b997-dfe5020371a5","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-22T01:42:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 01:42:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6456552","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6456552","identity":"rs-6456552","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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