Study reports SARS-CoV-2 persists in tissues of patients with long-term COVID

In a recent study published on Research Square*, researchers investigated whether residual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and ribonucleic acid (RNA) are present in tissue samples from patients with coronavirus disease long 2019 (COVID-19) (LC) beyond the recovery phase of COVID-19[FEMININE[FEMININE

Study: Persistence of residual SARS-CoV-2 viral antigen and RNA in tissues of patients with long-term COVID-19. Image Credit: ANDREI_SITURN/Shutterstock


SARS-CoV-2 is a single-stranded RNA virus comprising four structural proteins such as Nucleocapsid (NP), Membrane (M), Spike (S) and Envelop (E) proteins as well as several non-structural and accessory proteins, among which NP is of primary diagnostic importance.

The nucleocapsid forms complexes with viral genomic RNA which interacts with viral membrane proteins during virion assembly and plays a critical role in improving the transcription efficiency of the virus. The nucleocapsid contains NP antigens that can be detected by various serological diagnostic techniques based on the binding of viral NP antigen to host anti-NP antibodies, such as immunohistochemistry (IHC). Immunolabelling techniques such as IHC involve the use of chromogenic enzymes and special dyes with or without fluorescence to detect the presence of a particular antigen in a tissue sample.

The positive-sense single-stranded genomic RNA present in the molecular structure of SARS-CoV-2 requires the presence of negative-sense or replicative RNA. This RNA is used as a template to synthesize new copies of RNA, essential for viral replication. When the virus count is high enough, the clinical manifestations of COVID-19 begin to occur in the human body.

According to the World Health Organization (WHO), LC is a medical condition in which symptoms of COVID-19 such as fever, brain fog, fatigue, muscle aches and shortness of breath persist in the patient at beyond the acute period of the disease and cannot be attributed to any other diagnosis.

Residual copies of genomic viral RNA contribute to continued viral replication in the host nucleus, which could lead to reactivation of the immune system and reinfection in the presence of high numbers of virus. Asymptomatic COVID-19 patients with residual viral cells are also at risk of viral transmission to others. Residual viral antigens, if present, could lead to false positive results and decrease the accuracy of existing diagnostic procedures. Accurate and rapid diagnosis of these viral cells and residual antigens could lead to a decrease in the risk of reinfection and the chance of false positive results, respectively.

Previous studies have established that residual SARS-CoV-2 RNA and antigens are present in stool and gastrointestinal (GI) specimens from recovering LC patients. However, information on the detection of viable viral cells in human organ tissues is scarce.

About the study

The present study assessed whether residual viral antigens and viral RNA were present in post-convalescent tissues obtained from the skin, breast and appendix of two LC patients, approximately six months and 18 months later. the diagnosis of COVID-19. IHC analysis was used to detect SARS-CoV-2 NP, while RNAscope was used to detect the presence of positive-sense and negative-sense residual RNA.

To validate the study results and rule out the possibility of positive tissue staining due to infections other than COVID-19, labeled anti-SARS-CoV-2-NP antibodies were tested against the NP antigen in gastrointestinal tissues obtained in 2019 from another set of LC patients. Gastrointestinal tissues are the site of major viral shedding and high expression of host viral spike protein-binding angiotensin-converting enzyme 2 (hACE2) receptor (S ).


Residual virus was detected in the appendix and tumor-adjacent region of breast tissue by IHC. However, no viral antigens were identified in the tumor. The skin did not absorb the ICH stain, possibly due to the high cell turnover rate of the skin cells.

Negative-sense RNA (template or intermediate replicative) and positive-sense RNA (viral genomics) were detected in breast and appendix tissues using RNAscope, indicating constant viral replication.


Study results demonstrated that SARS-CoV-2 antigens and particles persist in human tissues for more than a year after diagnosis of COVID-19. These residual cells should be diagnosed and eradicated at the earliest to speed full host recovery, reduce the chances of reinfection, and increase the accuracy of diagnostic procedures.

Future studies with larger sample sizes incorporating different populations around the world are needed to validate and standardize the study results. Further research will also help determine the reason for the absence of residual SARS-CoV-2 antigens and RNA in breast tumors and skin cells and determine whether the gastrointestinal tract is a true reservoir of SARS. -CoV-2.

*Important Notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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