RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies

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.

Evidence of SARS-CoV-2 Antibodies and RNA on Autopsy Cases in the Pre-Pandemic Period in Milan (Italy)

“…However, the viremia is transient and infrequent, especially in paucisymptomatic or asymptomatic cases of COVID-19 (Andersson et al, 2020 ; Owusu et al, 2021 ). On the contrary, a recent work demonstrated that SARS-CoV-2 RNA could persist for longer periods in the lung (Caniego-Casas et al, 2022 ).…”

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…Many non-retroviral, single-stranded RNA viruses, including the Ebola virus [ 34 ], measles virus [ 35 , 36 ], Zika virus [ 37 ], and SARS-CoV-2 [ 38 , 39 ], can establish viral reservoirs within a population, employing different mechanisms to increase viral persistence in hosts that can lead to chronic disease or relapses of acute infection [ 40 ]. The Ebola virus is a negative, single-stranded RNA virus [ 41 ] capable of extended viral persistence in semen [ 42 ].…”

Persistent but dysfunctional mucosal SARS-CoV-2-specific IgA and low lung IL-1β associate with COVID-19 fatal outcome: A cross-sectional analysis

“…When the presence of SARS-CoV-2 in BAL was correlated to patient clinical data, the mean time from the onset of symptoms to sampling was shorter for virus-containing BAL (22 ± 4.4 mean days) compared to virus-free BAL (38 ± 3 mean days, p = 0.003, unpaired Mann–Whitney test, Figure 1C ). Although they partially overlapped due to the heterogeneous dynamic of viral persistence ( 33 , 34 ), the two groups appeared thus to be statistically significantly different when stratified by time from onset of symptoms. We therefore associated the presence of the virus in BAL with the phase of the disease ( 35 ).…”