SARS-CoV-2 replication persists in the lungs for weeks after symptoms develop in severe COVID-19

*Important Notices: medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

In a recent study posted on medrex sib* preprint server, Researchers are observing persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the lungs of severe coronavirus disease (COVID-19) patients in 2019.

study: SARS-CoV-2 viral replication persists in human lungs for weeks after symptomatic severe COVID-19 onset and is associated with diminished lung immunity and variant-specific clinical sequelae. Image Credit: Jaroslav Moravcik / Shutterstock

Persistence of SARS-CoV-2 during severe COVID-19

COVID-19 is a major contributor to global mortality. Despite recent research advances, the pathogenesis of severe his COVID-19 regarding viral dynamics is still poorly understood.

Postmortem studies have reported persistent virus in tissues by immunohistochemistry or polymerase chain reaction (PCR) assays. The SARS-CoV-2 detected in these assays may not be replication competent, which can only be determined by viral culture.

In addition, several studies have shown that shedding of replicating virus from the upper respiratory tract persists for up to 8 days after the onset of symptoms. Nevertheless, information on the persistence of replicating virus in the lower respiratory tract is scarce, especially among her severely ill COVID-19 patients requiring mechanical ventilation.

About research

In this study, researchers determined whether SARS-CoV-2 replication in severe COVID-19 persists in the lower respiratory tract for more than 10 days, independent of viral persistence in the upper respiratory tract. increase.

To this end, researchers determined the duration and frequency of replication-competent virus in the lungs. Lung samples were obtained by needle biopsy within 2 hours after death from her 42 patients ventilated between beta and delta.

Investigation result

Culturable virus was detected within 4 weeks of symptom onset in 38% of patients. In contrast, culturable virus was detected in a control cohort of outpatient subjects. Nasopharyngeal swab It was not the sample collected on day 12, but not the sample collected on day 19 after onset. Notably, multiple organs were positive for SARS-CoV-2 by PCR of offspring from the delta cohort that were positive for culturable virus.

Clinical features were similar between culture-positive and culture-negative groups. Cycle threshold (Ct) values ​​of nasopharyngeal swab samples at admission and death were not associated with positive cultures.

Only culture-positive Delta cohort subjects had a shorter interval between symptom onset and death, more secondary bacterial infections, and a higher rate of comorbid bronchopneumonia than culture-negative individuals.

Immunohistochemical staining showed differentiation cluster 4 positive (CD4⁺) macrophages and T cells, CD8⁺ T cells in the stroma and alveoli of culture-positive subjects compared to culture-negative subjects in the delta cohort. Immunohistochemical analysis was not performed on the offspring of the beta cohort.

Similarly, attenuated CD4⁺ and CD8⁺ T helper type 1 (T_H.1) Cellular responses were observed in cells from dissected lung tissue of progeny from the delta cohort.

The researchers also performed transcriptional analysis of lungs and identified 630 up-regulated and 885 down-regulated genes between culture-positive and -negative individuals.

The upregulated genes were involved in pathways related to proinflammatory responses, whereas the downregulated genes were mainly related to homeostasis. After adjusting for multiple factors, 11 upregulated and 5 downregulated genes were identified in culture-positive individuals.the pattern of T cells Fatigue was not evident.

Finally, the team evaluated whether differentially expressed genes could be biomarkers to distinguish between culture-positive individuals and culture-negative subjects. By logistic regression, gremlin-1 (i am GO1) and fibroblast growth factor binding protein 1 (FGFBP1) with high sensitivity and specificity.

Conclusion

Taken together, the results of this study demonstrate the simultaneous occurrence of viremia and hyperinflammation during weeks 3 and 4 of COVID-19, inconsistent with the notion that these stages occur sequentially. I’m here. Proinflammatory and antiviral responses were overrepresented in culture-positive deceased.

The researchers did not observe an attenuated type 1 interferon (IFN) response. Typical histologic features of severe COVID-19, such as microvascular thrombosis and diffuse alveolar damage, were comparable between culture-positive and culture-negative groups and these occurred at early stages of disease suggests that

Notably, culture-negative decedents showed higher pulmonary cell infiltration than culture-positive subjects. These results are relevant for her patients with severe COVID-19 and acute respiratory distress syndrome (ARDS) and may not apply to patients with mild disease. Nevertheless, only patients with beta-dominant and delta-dominant phases were considered. Therefore, these findings do not necessarily apply to infections by SARS-CoV-2 Omicron and its variants.

A control cohort of subjects with ARDS of other etiologies was also lacking. Overall, the findings of this study have potential implications for the use of antiviral drugs in critically ill patients.

Nonetheless, there remains an urgent need to identify better biomarkers for phenotypes and patient subsets that may benefit from the concurrent use of antiviral and anti-inflammatory therapies.

*Important Notices: medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.