Late Complications of COVID-19

Abstract

Context: Studies of lungs in patients with COVID-19 have focused on early findings. Objective: To systematically study histopathologic, imaging features and presence of SARSCoV-2 RNA in lung tissue from patients in later stages of COVID-19. Design: Autopsies, explants, surgical lung biopsies; and transbronchial, cryo, and needle biopsies were studied from patients with COVID-19, whose onset of symptoms/confirmed diagnosis was more than 28 days before the procedure. Available images were reviewed. Reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for SARS-CoV-2 RNA was performed on lung tissue. Results: Forty-four specimens (43 patients, median age 59.3 years, 26 [60.5%] male) showed features of acute lung injury (ALI) in 39 (88.6%), predominantly organizing pneumonia (OP) and diffuse alveolar damage (DAD), up to 298 days after onset of COVID-19. Fibrotic changes were found in 33 specimens (75%), most commonly fibrotic DAD (N=22) and cicatricial OP (N=12). Time between acquiring COVID-19 and specimen was shorter in patients with diffuse ALI (median 61.5 days) compared to patients with focal (140 days) or no ALI (130 days) (P=.009). Sixteen (of 20, 80%) SARS-CoV-2 RT-ddPCR tests were positive, up to 174 days after COVID-19 onset. Time between COVID-19 onset and most recent CT in patients with consolidation on imaging was shorter (median 43.0 days) versus patients without consolidation (87.5 days; P=.02). Reticulations were associated with longer time after COVID-19 onset to CT (median 82 days vs 23.5 days, P=.006). Conclusions: ALI and SARS-CoV-2 RNA can be detected in patients with COVID-19 for many months. ALI may evolve into fibrotic interstitial lung disease.

SARS-CoV-2 RNA detection in Formalin-Fixed Paraffin-Embedded (FFPE) tissue by droplet digital PCR (ddPCR)

“…Initially, common indications for clinical testing included evaluating brain or lung tissue, often in the setting of autopsy. Over time, fewer tests were ordered for these indications, and instead testing was used to evaluate lung tissue that showed morphologic features or sequela of an acute or acute on chronic lung injury [24] , skin rashes, gastrointestinal tract ulceration and/or inflammation, and other findings in the setting of current or recent COVID-19. In addition, testing has been used in the transplant setting to test organs from COVID-positive donors, as well as the donated organ after transplant in the setting of recipients with SARS-CoV-2 infection to better understand a patient’s clinical course and to distinguish organ damage from SARS-CoV-2 from damage due to rejection.…”

Vascular/epithelial changes as late sequelae after recovery from SARS‐COV‐2 infection: an in‐vivo comparative study

“…There are a few studies concerning late complications in COVID-19 survivors, mainly coming from explants or autopsy, and rare cases from in-vivo sampling. [10][11][12] Evidence suggests that in at least a subset of patients the disease may progress to fibrosing interstitial lung disease with different features, sometimes associated with thromboembolic vascular sequelae. [12][13][14][15] Moreover, the persistent presence of SARS-CoV-2 genome in the tissue of patients with a previous COVID-19 pneumonia remains a debated topic.…”

“…[10][11][12] Evidence suggests that in at least a subset of patients the disease may progress to fibrosing interstitial lung disease with different features, sometimes associated with thromboembolic vascular sequelae. [12][13][14][15] Moreover, the persistent presence of SARS-CoV-2 genome in the tissue of patients with a previous COVID-19 pneumonia remains a debated topic. 12,15 These considerations are crucial for more appropriate management of frail individuals such as cancer patients with a previous SARS-CoV-2 infection.…”

“…[12][13][14][15] Moreover, the persistent presence of SARS-CoV-2 genome in the tissue of patients with a previous COVID-19 pneumonia remains a debated topic. 12,15 These considerations are crucial for more appropriate management of frail individuals such as cancer patients with a previous SARS-CoV-2 infection.…”

SARS-CoV-2-Infektion und interstitielle Lungenerkrankungen – Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin

“…Auch bleibt selbst bei positiver SARS-CoV-2-RT-PCR aus der histologischen Probe letztlich offen, ob es damit infektionsfähige SARS-CoV-2-Viren vorliegen und die interstitiellen pulmonalen Veränderungen in Gänze durch diese bedingt sind.Bei asymptomatischen Patienten mit leerer Infektanamnese ist es unwahrscheinlich, dass interstitielle Lungenveränderungen durch eine COVID-19-Pneumonie bedingt sind. Hier scheint die negative SARS-CoV-2-RT-PCR aus dem nasopharyngealen Abstrich verlässlich zu sein, eine zusätzliche BAL führt zu keiner Diagnoseänderung und ist damit i.d.R, nicht indiziert[27,28].…”