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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 261-264
Coronavirus Disease-19 and Re-infection: Unknown of the Unknown

New Jersey Kidney Care; Division of Nephrology, CarePoint Health Hospitals; Division of Nephrology, Jersey City Medical Center, NJ, USA

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Date of Web Publication16-Jun-2021


Coronavirus disease has caused seven million infections worldwide, of which, 3.1 million individuals have recovered. Though, most individuals develop antibodies, whether these antibodies result in clinical improvement/immunity from future infection is not known. It is also not known about durability of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No human re-infection with SARS-CoV-2 has been confirmed to date, although a few case reports have mentioned patients who have tested positive again after recovery from the initial illness. Whether these cases represent a state of carrier or re-infection or reactivation, is not known. Nevertheless, the possibility of re-infection remains a matter of concern and yet another question about SARS-CoV-2 which is still unanswered.

How to cite this article:
Goel N, Jain D, Haddad DB. Coronavirus Disease-19 and Re-infection: Unknown of the Unknown. Saudi J Kidney Dis Transpl 2021;32:261-4

How to cite this URL:
Goel N, Jain D, Haddad DB. Coronavirus Disease-19 and Re-infection: Unknown of the Unknown. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2023 Jan 29];32:261-4. Available from: https://www.sjkdt.org/text.asp?2021/32/1/261/318536

   Introduction Top

Coronavirus disease (COVID-19) has been a global nightmare for public health since its initial case diagnosed in December 2019.[1] Declared a pandemic, it is caused by severe acute respiratory syndrome-related corona-viruses-2 (SARS-CoV-2). As per the world health organization, virus primarily spreads among humans via respiratory droplets and contact routes with the possibility of airborne transmission in health care settings.[2] Diagnosis can be made based upon clinical symptoms, serological testing, and computerized tomographic (CT) imaging of the chest. As of now, COVID-19 has caused seven million infections and 404,360 deaths, of these 3.1 million indi-viduals have recovered.[1] However, it is not known, whether these recovered people are immune from further COVID-19 infection and if so, for how long. There are only very few reports whereby patients were found to be tested positive again after the recovery from the initial illness. Whether these cases represent a state of carrier or re-infection by virus, is unclear.[3],[4] As per Kirkcaldy et al, evidence of re-infection will require culture-based documentation of a new infection following clearance of the preceding infection or evidence of re-infection with a molecularly distinct form of the same virus, and no human re-infections with SARS-CoV-2 has been confirmed till date.[5] We are reporting a case of re-infection in a dialysis patient who had recovered from SARS-CoV-2 infection.

   Case Report Top

The patient is a 59-year-old Caucasian male with a history of end-stage renal disease on maintenance hemodialysis (in-center) three times a week via arteriovenous fistula. His other co-morbidities include type II diabetes mellitus, hypertension, coronary artery disease, systolic heart failure, and peripheral vascular disease. Initially, he developed symptoms of cough and fever which required hospitalization on April 9, 2020, with concerns for COVID-19 pneumonia. His nasopharyngeal swab for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) (Quest Diagnostics) tested positive on the day of admission. Results for influenza and para-influenza viruses were negative. Blood cultures were also negative for any growth. Other laboratory parameters included leukopenia: 2.3 × 109/L (normal range: 4.5–11 × 109/L), elevated inflammatory markers as interleukin-6 level: 77 pg/mL (normal range: <5 pg/mL), erythrocyte sedimentation rate (ESR): 21 mm/h (normal range: 0–15 mm/h), C-reactive protein: 40.5 mg/L (normal range: 0.0–9.9 mg/L) and procalcitonin level of 0.76 ng/mL (normal range: 0.19–0.49 ng/mL). The CT scan of the chest showed multi-focal interstitial and ground glass patchy opacities in both lungs. The patient was treated with systemic antibiotics as ceftriaxone and doxycycline along with hydroxychloroquine. His initial hospital course was also significant for altered mental status which was likely due to sepsis and resolved spontaneously. He required oxygen supplementation via nasal cannula only during the first few days of hospitalization. The patient clinically improved and discharged to a skilled nursing facility (SNF) on April 17, 2020.

The patient was arranged to receive maintenance dialysis as outpatient in an isolation hemodialysis unit designated for COVID-19 infected patients. His follow-up nasopharyngeal swab remained positive for SARS-CoV-2 (BioReference Laboratories, Inc.) when checked again on May 7, 2020. He finally returned to his original dialysis unit after two consecutive nasopharyngeal swabs were resulted negative, done on May 21, 2020, and May 28, 2020, using real-time RT-PCR (BioReference laboratories, Inc.), deeming him free of infection.

On June 7, 2020, the patient was referred back to the hospital from SNF with symptoms of cough, shortness of breath, and bilateral leg swelling for one week. He was re-admitted to hospital with findings of large right sided pleural effusion, partially loculated with compressive consolidation. There were minimal scattered opacities within the right upper lobe and scattered throughout the left hemithorax. His laboratory data again showed leukopenia: 3.5 × 109/L, ESR: 15 mm/h, C-reactive protein: 21.7 mg/L and procalcitonin level of 0.27 ng/mL. As per the Infection Disease Society of America (IDSA) recommendations, all patients admitted to hospital are being tested for SARS-CoV-2.[6] His nasopharyngeal swab surprisingly came back positive for SARS-CoV-2 as checked using BioFire Respiratory panel 2.1, a multiplexed nucleic acid test. Rest of the viral serologies including other coronavirus strains (OC43, 229E, NL63) were negative. SARS-CoV-2 IgG antibody was detected positive using immunometric technique (VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack Assay). Patient is presently being treated in hospital for fluid overload with pneumonia concerning for healthcare associated infection versus COVID-19 re-infection.

The authors obtained all appropriate consent forms from the patient for the publication of the case report.

   Discussion Top

In our patient, initially presentation in April fits with characteristics of COVID-19 illness. He remained confirmed positive for the virus for at least 29 days (till May 7, 2020). Further negative testing on 42nd day (May 21) and 49th day (May 28) likely reflect his recovery from the COVID-19. Prolonged shedding of SARS-CoV-2 has been reported with median of 53.5 days (IQR 47.75–60.5),[7] which we observed in our patient as well. However, it can cloud the ability to differentiate among carrier states versus re-infection versus reactivation of virus. Since our patient tested positive again after two consecutive negative tests, it raises the concern of re-infection. Moreover, he was at increased risk of infection owing to the potential for re-exposure to SARS-CoV-2 in health care settings such as dialysis units and SNF.

IDSA recommends collecting nasopharyngeal, or mid-turbinate or nasal swabs for SARS-CoV-2 RNA testing using nucleic acid amplification test (NAAT).[6] It is also recommended to test all asymptomatic individuals who are being hospitalized. Real-time RT-PCR, RT-PCR and reverse transcription loop-mediated isothermal amplification are some of the diagnostic techniques presently being utilized for COVID-19 testing.[8] In our patient, initial test done on April 9 was a NAAT, a qualitative multi-target molecular diagnostics test. Follow up positive test and the two consecutive negative tests in the month of May were done using same techniques as real time RT-PCR and same laboratory. Last test done on June 7 utilized multiplexed nucleic acid test to detect SARS-CoV-2 RNA. Whether a difference in viral testing technique resulted in to variable false positive or false negative results is possible but less likely for the following reasons. We had two consecutive negative tests, a week apart, which decreased the chances of false negative results. Moreover, the patient was mostly asymptomatic at the time. During the latest hospitalization episode, test was positive only for SARS-CoV-2 but negative for other corona virus strains which argues against the likely-hood of a false positive result. [Table 1] summarizes the sensitivity and specificity of serologic tests used in diagnosing COVID-19 infection.
Table 1: Sensitivity and specificity of COVID-19 serologic tests.[9]

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With these findings and observations, we believe this is likely a COVID-19 re-infection and as such the first case reported from the United States of America. We do not think that this latest hospitalization can be solely attributed to COVID-19. Although, the patient is placed in an isolation room as per hospital policy, it is not known whether he is still infectious with SARS-CoV-2 and if can spread it to health care workers or other patients. In an analysis of 285 re-positive cases from South Korea, investigators found only three newly confirmed cases among their contacts (n = 790), which was attributed to their contact with religious group or confirmed cases in their family and not to the re-positive cases. In all 285 cases, neutralizing antibody in serum was detected. In addition, viral cell culture testing of 108 cases was also negative.[10] These findings are probably reassuring for SARS-CoV-2 re-infection benign nature, even if it occurs. Most individuals develop IgM and IgG antibodies within days to weeks after COVID-19 symptoms onset. Whether these antibodies results in clinical improvement or future protection is not known. It is also not known about the effectiveness of IgG against SARS-CoV-2.[5] Our patient had developed IgG against SARS-CoV-2 which was confirmed with a qualitative test. Apparently, it did not prevent him from getting re-infection with COVID-19 but may have helped reduce the severity of second the viral illness. Hence, there are many unanswered questions about possibility and severity of COVID-19 reinfection, durability of antibody response and its ability to protect from subsequent reinfections.

   Conclusions Top

There is much to be learned about SARS-CoV-2 and its long-term outcomes. Millions of people have recovered from it. If they developed neutralizing antibodies against the virus, whether it will protect them from further infection is not known. It is also not known, for how long this protective immunity will last. Re-infection does not seem to be common but possible based upon sporadic case reports including our case. In conclusion, there seems to be a lot of unknown about the unknown SARS-CoV-2.

   Financial Disclosure Top

Dr. Narender Goel and Dr Danny Haddad has served on nephrology advisory board meeting for Horizon Therapeutics.

Conflict of interest: None declared.

   References Top

John Hopkins Corona Resource Center. Available from: https://coronavirus.jhu.edu/. [Last accessed on 2020 Jun 08].  Back to cited text no. 1
World Health Organization. Available from: https://www.who.int/. [Last accessed on 2020 May 26]. Available from: https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations. [Last accessed on 2020 Jun 08].  Back to cited text no. 2
Wang H, Li Y, Wang F, Du H, Lu X. Rehospitalization of a recovered coronavirus disease 19 (COVID-19) child with positive nucleic acid detection. Pediatr Infect Dis J 2020;39:e69-70.  Back to cited text no. 3
Lan L, Xu D, Ye G, et al. Positive RT-PCR test results in patients recovered from COVID-19. JAMA 2020;323:1502-3.  Back to cited text no. 4
Kirkcaldy RD, King BA, Brooks JT. COVID-19 and Postinfection immunity: Limited evidence, many remaining questions. JAMA 2020;323:2245-6.  Back to cited text no. 5
Hanson KE, Caliendo AM, Arias CA, et al. The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular diagnostic testing. Clin Infect Dis 2020;ciaa760.  Back to cited text no. 6
Li N, Wang X, Lv T. Prolonged SARS-CoV-2 RNA shedding: Not a rare phenomenon. J Med Virol 2020;92:2286-7.  Back to cited text no. 7
Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents 2020; 55:105955.  Back to cited text no. 8
FDA In vitro Diagnostics EUAs. U.S Food and Drug Administration, June 9, 2020. Available from: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd. [Last accessed on 2020 Jun 09].  Back to cited text no. 9
Findings from Investigation and Analysis of Re-Positive Cases. Korea Center for Disease Control and Prevention; May 19, 2020. Available from: https://www.cdc.go.kr/board/ board.es?mid=a30402000000&bid=0030. [Last accessed on 2020 Jun 08].  Back to cited text no. 10

Correspondence Address:
Narender Goel
Division of Nephrology, Jersey City Medical Center, NJ
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.318536

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