Viral Persistence
Research now strongly suggests that many cases of Long Covid are driven by ongoing persistence of SARS-CoV-2 in viral reservoirs in the human body.
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No research has yet shown that the human body ever fully clears the SARS-CoV-2 virus after acute Covid-19 infection. This is very difficult to establish.
Many viruses establish chronic infection in the human body. Common examples include EBV, CMV, HIV, Hepatitis B, Hepatitis C, chickenpox, ebola and enteroviruses. The list also includes coronaviruses like SARS-CoV-2.
To investigate the ongoing presence of SARS-CoV-2 in patients with Long Covid, researchers must look in the body’s tissues, rather than only in blood.
Selection of locations in the human body where SARS-CoV-2 was found in autopsy patients long after acute infection. Source: NIH, December 2021
Key Research Studies
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Lancet review of evidence for the persistence of SARS-CoV-2 as a driver of Long Covid, "Association of SARS-CoV-2 infection and persistence with long COVID".
University of British Columbia, May 2023
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Comprehensive review of research, "Viral persistence, reactivation, and mechanisms of long COVID".
NIH RECOVER Mechanistic Pathways Task Force, April 2023
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Autopsies of 44 patients in the US with prior confirmed cases of SARS-CoV-2 showed viral infection dispersed extensively throughout the body.
NIH, December 2021
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Description goes hereSpike protein found circulating in the blood of long haulers, but not controls, 12 months post diagnosis.
Harvard, June 2022
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4% of patients with COVID-19 shed fecal viral RNA 10 months after diagnosis. Presence of fecal SARS-CoV-2 RNA is associated with gastrointestinal symptoms.
Stanford, April 2022
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SARS-CoV-2 persistent infection documented for 15 months in a single individual, involving extensive ongoing viral mutation mirroring mutations in the population at large.
University of Wisconsin-Madison, April 2022
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Positive impact of Paxlovid in Long Covid patient.
Stanford, March 2022
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Positive effect of Paxlovid on Long Covid: a case series
UCSF, May 2022
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Distinguishing features of Long Covid identified through immune profiling
Yale, August 2022
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SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy.
Cornell, August 2022
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Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2
UCSF, February 2023
Detection of SARS-CoV-2 RNA in Biopsies & Fluids
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Persistent SARS-CoV-2 infection found in patients seemingly recovered from COVID-19
University of Trieste, January 2023
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Viable SARS-CoV-2 Omicron sub-variants isolated from autopsy tissues
Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina, May 2023
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Viral persistence found in the lungs over a year after infection
Cornell, November 2022
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Ongoing loss of smell is associated with detectable viral particles
Institut Pasteur, May 2021
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Active viral replication of SARS-CoV2 demonstrated in the lung 3 months after onset of the disease
Hospital Universitario Ramón y Cajal, Spain, January 2022
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Successful virus isolation confirmed up to 128 days post infection. Complete SARS-CoV-2 genome integrity was demonstrated, suggesting the presence of replication-competent viruses.
Universidade Federal do Rio de Janeiro, November 2021
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Virus found replicating in testes nearly a month after death - testes found to be viral reservoir for SARS-CoV-2 replication.
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Viral persistence confirmed by autopsies, and found in the lungs and windpipe.
University Hospital of Zurich, February 2022
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SARS-CoV-2 RNA found in the cerebrospinal fluid of a patient with Long Covid.
Faculty Hospital Nové Zámky, Nové Zámky, Slovakia, October 2021
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Prolonged SARS-CoV-2 positivity found in immunocompetent patients.
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil, November 2021
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SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms.
Hospital General Universitario Gregorio Marañon, Spain, March 2022
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SARS-CoV-2 identified in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain.
Hospital Universitari Mútua Terrassa, Spain, August 2021
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Sniffer dogs identify viral persistence in 23/45 Long Covid patients, and 0/180 healthy controls.
Assistance Publique Hôpitaux de Paris, January 2022
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SARS-CoV-2 RNA detected in the lungs of patients with COVID-19 for many months
Mayo Clinic Rochester, March 2022
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SARS-CoV-2 RNA in the gut mucosa ~7 months after mild acute COVID-19 in 32 of 46 patients with IBD. Viral nucleocapsid protein persisted in 24 of 46 patients in gut epithelium and CD8+ T cells. Expression of SARS-CoV-2 antigens was not detectable in stool and viral antigen persistence was unrelated to severity of acute COVID-19.
Medical University of Innsbruck, Austria, 2022
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Demonstrat[ing] the presence of the COVID-19 virus in the penis long after the initial infection in humans.
University of Miami, May 2021
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Neural cells infected by SARS-CoV-2 shed shedding spike and nucleocapsid proteins; levels are significantly higher in Long Covid and higher in Long Covid with neuropsych problems.
UCSF, March 2022
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SARS-CoV-2 RNA detection in plasma, stool, and urine.
Hospital General Universitario Gregorio Marañon, Spain, March 2022
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Persistent presence of spike protein and viral RNA in the circulation of Individuals with Long Covid
University of Kansas, August 2022
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Persistent SARS-CoV-2 found in the saphenous veins of an asymptomatic patient
Kansai Medical University, Osaka, Japan, June 2022
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Lingering SARS-CoV-2 in gastric and gallbladder tissues of patients with previous COVID-19 infection
Alexandria University, Egypt, November 2022
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Viral compartmentalization in different tissue sites, and viral reservoir.
Harvard, February 2023
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High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients
Universidade Federal de Minas Gerais, Brazil, February 2023
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Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with Long Covid
Martin Luther University, Halle-Wittenberg, Germany, September 2022
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SARS-CoV-2 RNA found in the corneal epithelium
Johns Hopkins, March 2021
Immunology
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Immune abnormalities consistent with persistence of SARS-CoV-2 in the gut mucosa.
Inserm, Université Paris Cité, University of Minho, March 2023
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600 person Swiss study showed long haulers typically failed to produce certain antibodies during acute infection.
University Hospital Zurich, January 2022
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Long haulers more likely to have reactivated EBV at time of acute infection (i.e. increased immune burden / weakened immune response).
Fred Hutchinson Cancer Research Center, Seattle, January 2022
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Memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.
Rockefeller University, January 2021
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MHC-I downregulation in cells infected with SARS-CoV-2: MHC-I downregulation is frequently associated with viruses that cause persistent infection.
Rockefeller University, May 2022
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Intestinal mucosal abnormalities shed light on ‘viral persistence’ of long COVID-19.
Mount Sinai, May 2022
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Pulmonary Long Covid is in part driven by inflammatory cytokines produced by activated virus-specific T cells, which are likely maintained by persistent virus.
University of Colorado, May 2022
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Serum Level of anti-nucleocapsid, but not anti-spike antibody, is associated with improvement of Long COVID symptoms.
University of Pecs, Hungary, December 2021
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Evasion mechanisms: SARS-CoV-2 non-structural protein 1 (Nsp1) mediates the downregulation of NKG2D ligands and transfection with Nsp1 alone is sufficient to confer resistance to NK cell killing.
Stanford, June 2022
Further Reading
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Similarities between SARS-CoV-2 and feline coronaviruses, which persist chronically.
University of Milan, September 2020
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Persistent infections contribute to Long Covid.
April 2021
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Role of antivirals in treating chronic feline coronavirus infections.
October 2021
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Primer on persistent RNA viruses.
Johns Hopkins, April 2017
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Treatment of chronic SARS-CoV-2 infection in immunocompromised patients with antivirals.
University College London, May 2023