Abstract
The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9–108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.
Highlights
IntroductionCOVID-19 is described as a disease with a biphasic course and three stages (early infection, pulmonary, and hyperinflammatory stage) (Siddiqi and Mehra, 2020)
COVID-19 is described as a disease with a biphasic course and three stages (Siddiqi and Mehra, 2020)
The autopsies corresponded to patients with severe respiratory disease and were requested by the medical staff according to clinical interest and represented about 3% of all COVID-19 deaths during this period
Summary
COVID-19 is described as a disease with a biphasic course and three stages (early infection, pulmonary, and hyperinflammatory stage) (Siddiqi and Mehra, 2020). In those patients with mild or moderate COVID-19 disease, the viral load decreases; in critical patients, high viral loads have been quantified up to 2 weeks using real-time RT-PCR, and detected by immunohistochemistry (IHC) and in situ hybridization (ISH; Schaefer et al, 2020). Several studies showed that viral RNA could be detected using RT-PCR for periods longer than 2 months (Avanzato et al, 2020; Reuken et al, 2021), but the presence of viral RNA and protein was difficult to demonstrate using ISH and IHC, respectively, after 2 weeks (Evert et al, 2021). Most autopsy studies have been performed in patients with
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