Analysis of seemingly recovered COVID-19 patients indicates that SARS-CoV-2 infection can persist significantly longer than suggested by PCR-negative tests

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can persistently progress into a deadly condition even after clinical resolution of the acute infection suggested by polymerase chain reaction (PCR) negative test results.

Study: Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19. Image Credit: Jarun Ontakrai/Shutterstock
Study: Persistent SARS-CoV-2 infection in patients seemingly recovered from COVID-19. Image Credit: Jarun Ontakrai/Shutterstock

In a study published in The Journal of Pathology, scientists have described the infection dynamics and clinical features of PCR-negative patients who eventually died due to the worsening of COVID-19.  

Background

COVID-19 is a highly heterogeneous disease, with clinical features ranging from mild or asymptomatic to fatal infections. Fatal SARS-CoV-2 infections are characterized by severe lung damage, micro- and macrovascular thrombosis, and persistent infection of pneumocytes and endothelial cells.

A considerable proportion of COVID-19 patients remain symptomatic for several months, even after the clinical resolution of acute infection. This condition is medically termed as long COVID. Some patients with persistent PCR-negative test results exhibit signs of disease progression and eventually die.

In the current study, scientists have conducted post-mortem analyses of a group of COVID-19 patients who eventually died due to progressive worsening of clinical conditions, despite having SARS-CoV-2-negative tests for up to 300 days post-acute infection.

Study design

The post-mortem analyses were conducted on a total of 27 COVID-19 patients. Three remained PCR-negative for more than nine months, and the rest were PCR-negative for 11-300 consecutive days. In most of the patients, death occurred due to pneumonia.

The lung tissue samples collected from these patients were subjected to histopathological and immunohistochemistry analyses. The RNA samples extracted from the tissues were analyzed by PCR to detect viral RNA.

Lung pathology

The post-mortem analysis of lung tissue samples revealed that about 81% of patients had interstitial pneumonia. In 48% of patients, pneumonia was severe and caused death. The most prominent characteristics of pneumonia in these patients were severe alveolar damage, immune cell infiltration, and extensive fibrotic substitution.

Micro- and macrovasculature thrombosis was noted in 67% of patients. This is the most common feature in acute SARS-CoV-2 infection. Other clinical features observed in tested samples included vasculitis, squamous metaplasia of the respiratory epithelium, cytological abnormalities and syncytia, and bronchial cartilage dystrophy.  

Overall, these observations indicate that pathological changes noted in these patients are not significantly different from that observed in patients with acute infection. In other words, despite persistently not having detectable SARS-CoV-2 RNA in respiratory samples for a long period, these patients represent clinical features similar to acute infection with detectable viral RNA.

Persistence of viral infection

The study further explored whether an undetectable but persisting viral infection is responsible for pathological changes observed in deceased patients. Immunohistochemistry analysis was carried out using anti-spike and anti-nucleocapsid antibodies to detect the presence of SARS-CoV-2-infected cells in the lung.

The immunohistochemistry findings revealed a complete absence of virus-infected cells in the respiratory epithelium. This justifies the PCR findings of the persistent absence of detectable viral RNA in nasopharyngeal samples.

Interestingly, about 70% of the patients exhibited detectable virus-infected cells in specific lung regions. Specifically, the presence of SARS-CoV-2 infection was detected in chondrocytes, para-bronchial cells, syncytial cells, and to some extent, in pericyte endothelial cells.

Study significance

The study describes pathological lung features of COVID-19 patients who died due to progressively worsening disease, despite having persistent virus-negative PCR results for a long period. The pathological lung features of these deceased patients are similar to that observed in a patient with acute SARS-CoV-2 infection.

Interestingly, virus-infected cells have been detected in specific lung regions of these patients, including the para-bronchial glands and bronchial cartilage. As mentioned by the scientists, the long-term presence of specific virus-infected cells could cause pathological lung changes by maintaining a pro-inflammatory, immunoreactive, and pro-thrombogenic status. Further studies are required to establish the relationship between persistently infected cells and the development of long-COVID.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.

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Comments

  1. Beth Sanchez Beth Sanchez United States says:

    How many of the 27 patients were vaccinated? Aren’t we worried about Antibody dependent enhancement caused by the vaccine?

  2. Donna Rega Donna Rega United States says:

    Does this apply to vaccinated people as well...

  3. Brett McIver Brett McIver New Zealand says:

    Were the patients pre jab or post jab? I notice that's not mentioned in the article? Why? Is it possible the virus remnant found in those unusual lung places was from the jab? Or was it from the actual infection?

  4. Stephanie Last Stephanie Last United States says:

    Ok you were one step closer, how many had the mRNA shot?  What was it about them that was different from people who get rid of COVID? Was it blood type or something?

  5. Didi MD Didi MD United States says:

    I'm a 59 yr old female that was diagnosed with and in critical care for Covid-19 in March 2021. I had a very serious case, and looking to participate in any studies that may assist in determining the long haul effects. I am still on oxygen while sleeping, my oxygen dips into the 70s and rarely averages in low 90s for a 24 hr period. I also have some other lingering symptoms. Finally, however, after 20 months the brain fog lifted. The brain fog was very difficult to get through. I lost all of my hair which it still not mentioned in any articles I read, but there are thousands that have experienced this effect, my taste and smell is still off. Please contact me if you would like further information, thank you.

    • David Jacobs David Jacobs United States says:

      Please send via email to [email protected]

      Sorry to hear of you struggles.  Please help us understand better.

    • Peter Flitcroft Peter Flitcroft United Kingdom says:

      I to got Covid 19 and spent 10 days in an ICU. Having seen the scans by rights I shouldn't come out of there alive. Consultant wanted me on a ventilator when my O2 sats were dropping fast. I asked whats the alternative? palative care was the reply. I demanded my B12 injection which I get monthly and was overdue and was given it same day. Within 24 hours my sats had improved significantly and 5 days later I was back on a normal ward. i was discharged a week after that. The following B12 injection was done at the GP's surgery and my sats went from 91 to 95 overnight. If they had put me on a ventilator the nitrous Oxide gas they use would have depleted my already low B12 levels further and I would undoubtedly have died. A lucky escape. I have developed symptoms of 'Long Covid' but having taken to self injection of B12 they have markedly improved since starting SI weekly.

    • Rachal Young Rachal Young United States says:

      I'm a 55yo female who 1st tested 1-8-23. I remained positive for 17 days & although I've tested negative, am feeling just as many if not more symptoms now including now on oxygen at night,  but the brain fog is the one I'm most concerned with. Some days I can't even complete a simple thought like "I'm hungry. I need to eat." I've found myself in middle of kitchen floor not even being able to open a can of corn! This scares me beyond words. I wish there were more studies on brain fog because I honestly feel like I'm losing my mind but my Dr doesn't seem to be concerned with this at all.

  6. Chris McDonald Chris McDonald United States says:

    Did the study also include the vaccination status of the individuals? If so, how many of the patients were vaccinated vs non vaccinated that died?

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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