Tag: viral reservoir

Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination

Abstract:

Background and study aims Gut infection is common during acute COVID-19, and persistent SARS-CoV-2 gut infection has been reported months after the initial infection, potentially linked to long-COVID syndrome. This study tested the incidence of persistent gut infection in patients with a history of COVID-19 undergoing endoscopic examination.

Patients and methods Endoscopic biopsies were prospectively collected from patients with previous COVID-19 infection undergoing upper or lower gastrointestinal endoscopy (UGE or LGE). Immunohistochemistry was used to detect the presence of persistent SARS-CoV-2 nucleocapsid proteins.

Results A total of 166 UGEs and 83 LGE were analyzed. No significant differences were observed between patients with positive and negative immunostaining regarding the number of previous COVID-19 infections, time since the last infection, symptoms, or vaccination status. The incidence of positive immunostaining was significantly higher in UGE biopsies than in LGE biopsies (37.34% vs. 16.87%, P =0.002). Smokers showed a significantly higher incidence of positive immunostaining in the overall cohort and UGE and LGE subgroups ( P <0.001). Diabetic patients exhibited a significantly higher incidence in the overall cohort ( P =0.002) and UGE subgroup ( P =0.022), with a similar trend observed in the LGE subgroup ( P =0.055).

Conclusions Gut mucosal tissues can act as a long-term reservoir for SARS-CoV-2, retaining viral particles for months following the primary COVID-19 infection. Smokers and individuals with diabetes may be at an increased risk of persistent viral gut infection. These findings provide insights into the dynamics of SARS-CoV-2 infection in the gut and have implications for further research.

Source: Hany M, Sheta E, Talha A, Anwar M, Selima M, Gaballah M, Zidan A, Ibrahim M, Agayby ASS, Abouelnasr AA, Samir M, Torensma B. Incidence of persistent SARS-CoV-2 gut infection in patients with a history of COVID-19: Insights from endoscopic examination. Endosc Int Open. 2024 Jan 5;12(1):E11-E22. doi: 10.1055/a-2180-9872. PMID: 38188925; PMCID: PMC10769582. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769582/ (Full text)

 

Long COVID: A Molecular, Cellular and Histopathology Overview

Abstract:

Long COVID has been studied as different sequelae that some individuals can develop after the acute phase of the disease. Persistent symptoms such as dry cough, fatigue, and dyspnea can remain after six months of COVID-19 cure. Others such as lung fibrosis, kidney injury, and thrombotic risk also are observed. Here, a deep review of each human organ and system infected by the virus was performed aiming to show how molecules expression and cell signaling can induce the organism cure or injuries and, subsequently sequelae. The review also suggests the importance of public health surveillance for these cases including a more comprehensive analysis of molecular biology tools that can clarify and assist in the prognosis, treatment, and preventive methods for potentially more serious disorders in post-COVID-19 patients.

Source: da Silva Barros, B. , de Oliveira Cruz, L. , de Sousa, G. , Souza-Silva, G. , de Lima, M. , Oliveira, E. , Silva, A. , Macêdo, L. , Leal, L. , Marcos, B. , Elsztein, C. , Invenção, M. , de Freitas, A. and Moutinho-Melo, C. (2023) Long COVID: A Molecular, Cellular and Histopathology Overview. Journal of Biosciences and Medicines, 11, 90-113. doi: 10.4236/jbm.2023.119009. https://www.scirp.org/journal/paperinformation.aspx?paperid=127523 (Full text)

SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)

Abstract:

Millions of people are suffering from Long COVID or post-acute sequelae of COVID-19 (PASC). Several biological factors have emerged as potential drivers of PASC pathology. Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection. Instead, replicating virus and/or viral RNA-potentially capable of being translated to produce viral proteins-persist in tissue as a ‘reservoir’. This reservoir could modulate host immune responses or release viral proteins into the circulation.

Here we review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. Mechanisms by which a SARS-CoV-2 reservoir may contribute to PASC pathology, including coagulation, microbiome and neuroimmune abnormalities, are delineated. We identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated.

Source: Proal AD, VanElzakker MB, Aleman S, Bach K, Boribong BP, Buggert M, Cherry S, Chertow DS, Davies HE, Dupont CL, Deeks SG, Eimer W, Ely EW, Fasano A, Freire M, Geng LN, Griffin DE, Henrich TJ, Iwasaki A, Izquierdo-Garcia D, Locci M, Mehandru S, Painter MM, Peluso MJ, Pretorius E, Price DA, Putrino D, Scheuermann RH, Tan GS, Tanzi RE, VanBrocklin HF, Yonker LM, Wherry EJ. SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC). Nat Immunol. 2023 Sep 4. doi: 10.1038/s41590-023-01601-2. Epub ahead of print. PMID: 37667052. https://www.nature.com/articles/s41590-023-01601-2 (Full text)

Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery

Abstract:

Background: Lingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in gut tissue might be a source of infection during bariatric surgery. This study aimed to confirm the presence of SARS-CoV-2 nucleocapsid in gastric and gallbladder tissues removed during bariatric surgery in individuals previously infected with coronavirus disease 2019 (COVID-19) who had negative polymerase chain reaction results prior to the surgery.

Methods: Gastric and gallbladder specimens from 80 patients who underwent bariatric surgery between November 2021 and May 2022 and had a history of COVID-19 infection with gastrointestinal symptoms were examined for the presence of lingering SARS-CoV-2 nucleocapsid proteins using immunohistochemistry.

Results: Gastric specimens from 26 (32.5%) patients and 4 (100%) cholecystectomy specimens showed positive cytoplasmic staining for the anti-SARS-CoV-2 nucleocapsid protein in surface mucosal epithelial cells. The mean age was 37.8 ± 10.3 years. The average body mass index was 44.2 ± 7.0 kg/m2; most of the patients were females (71.3%). The positive staining group was significantly younger than the negative staining group (p = 0.007). The full-dose vaccination rate was 58.8%, with a median of 91 days after the last vaccine dose. A positive serological anti-spike IgG response was observed in 99% of the patients. The median time between initial COVID-19 infection and surgery was 274 and 380 days in the positive and negative staining groups, respectively (p = 0.371).

Conclusion: Gastric and gallbladder tissues can retain SARS-CoV-2 particles for a long time after COVID-19 infection, handling stomach specimens from patients during an operation must be done with care, as we usually do, but now with the knowledge that in 1/3 of patients they can be present. Performing LSG on post-COVID patients did not seem to increase perioperative morbidity.

Source: Hany, M., Zidan, A., Gaballa, M. et al. Lingering SARS-CoV-2 in Gastric and Gallbladder Tissues of Patients with Previous COVID-19 Infection Undergoing Bariatric Surgery. OBES SURG (2022). https://doi.org/10.1007/s11695-022-06338-9  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9628579/ (Full text)

SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy

Abstract:

Background: In utero transmission of SARS coronavirus 2 (SARS-CoV-2) has not been fully investigated. We investigated whether newborns of mothers with COVID-19 during pregnancy might harbor SARS-CoV-2 in the gastrointestinal tract.

Methods: This cohort study investigated stool from 14 newborns born at 25-41 weeks admitted at delivery to our urban academic hospital whose mothers had COVID-19 during pregnancy. Eleven mothers had COVID-19 resolved more than 10 weeks before delivery. Newborn stool was evaluated for SARS-CoV-2 RNA, Spike protein, and induction of inflammatory cytokines interleukin-6 (IL-6) and interferon-γ (IFN-γ) in macrophages.

Results: Despite negative SARS CoV-2 nasal PCRs from all newborns, viral RNAs and Spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life and increased over time in 6. Stool homogenates from all 14 newborns elicited elevated inflammatory IL-6 and IFN-γ from macrophages. Most newborns were clinically well except for one death from gestational autoimmune liver disease and another who developed necrotizing enterocolitis.

Conclusions: These findings suggest in utero transmission of SARS-CoV-2 and possible persistent intestinal viral reservoirs in the newborns. Further investigation is required to understand the mechanisms and their clinical implications.

Impact: SARS-CoV-2 RNAs or Spike protein was detected in the stool of 11 out of 14 preterm newborns born to mothers with resolved COVID-19 weeks prior to delivery despite negative newborn nasal PCR swabs. These novel findings suggest risk of in utero SARS-CoV-2 transmission to the fetal intestine during gestation. The presence of SARS-CoV-2 RNAs and Spike protein in the intestines of newborns may potentially impact the development of the gut microbiome and the immune system; the long-term health impact on the preterm infants should be further investigated.

Source: Jin JC, Ananthanarayanan A, Brown JA, Rager SL, Bram Y, Sanidad KZ, Amir M, Baergen RN, Stuhlmann H, Schwartz RE, Perlman JM, Zeng MY. SARS CoV-2 detected in neonatal stool remote from maternal COVID-19 during pregnancy. Pediatr Res. 2022 Aug 19. doi: 10.1038/s41390-022-02266-7. Epub ahead of print. PMID: 35986143. https://www.nature.com/articles/s41390-022-02266-7 (Full text)

SARS-CoV-2 infection and persistence throughout the human body and brain

Abstract:

COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14.
We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection.
Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.
Source: Daniel Chertow, Sydney Stein, Sabrina Ramelli et al. SARS-CoV-2 infection and persistence throughout the human body and brain, 20 December 2021, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1139035/v1] https://www.researchsquare.com/article/rs-1139035/v1 https://www.nature.com/articles/s41586-022-05542-y (Full text)

Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae

Abstract:

The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers. Strikingly, we detect SARS-CoV-2 spike antigen in a majority of PASC patients up to 12 months post-diagnosis, suggesting the presence of an active persistent SARS-CoV-2 viral reservoir. Furthermore, temporal antigen profiles for many patients show the presence of spike at multiple time points over several months, highlighting the potential utility of the SARS-CoV-2 full spike protein as a biomarker for PASC

Source: Zoe Swank, Yasmeen Senussi, Galit Alter, David R. Walt. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. medRxiv 2022.06.14.22276401; doi: https://doi.org/10.1101/2022.06.14.22276401 https://www.medrxiv.org/content/10.1101/2022.06.14.22276401v1 (Full text available as PDF file)