Even mild Covid is linked to brain damage, scans show

The new British research is the first to reveal striking differences in areas of the brain based on scans taken before and after a coronavirus infection.

Authors: Benjamin Ryan Posted July 2022, From NBX News

During at least the first few months following a coronavirus infection, even mild cases of Covid-19 are associated with subtle tissue damage and accelerated losses in brain regions tied to the sense of smell, as well as a small loss in the brain’s overall volume, a new British study finds. Having mild Covid is also associated with a cognitive function deficit.

These are the striking findings of the new study led by University of Oxford investigators, one that leading Covid researchers consider particularly important because it is the first study of the disease’s potential impact on the brain that is based on brain scans taken both before and after participants contracted the coronavirus.

“This study design overcomes some of the major limitations of most brain-related studies of Covid-19 to date, which rely on analysis and interpretation at a single time point in people who had Covid-19,” said Dr. Serena S. Spudich, a neurologist at the Yale University School of Medicine, who was not involved in the research.

The research, which was published Monday in Nature, also stands out because the lion’s share of its participants apparently had mild Covid — by far, the most common outcome of coronavirus infections. Most of the brain-related studies in this field have focused on those with moderate to severe Covid.

Gwenaëlle Douaud, an associate professor at the Nuffield Department of Clinical Neurosciences at Oxford and the paper’s lead author, said that the excess loss of brain volume she and her colleagues observed in brain scans of hundreds of British individuals is equivalent to at least one extra year of normal aging.

“It is brain damage, but it is possible that it is reversible,” she said. “But it is still relatively scary because it was in mildly infected people.”

Douaud and her team relied on a rich data source: the United Kingdom Biobank. Before the Covid pandemic began, this mammoth database already had on hand tens of thousands of brain MRIs of people in Britain, along with responses to surveys about their diets and lifestyles and results from cognitive function tests.

The investigators focused on 401 people between 51 and 81 years old who had tested positive for Covid according to clinical data linked to the Biobank study. They were invited back for a second brain scan, which they received an average of about five months after contracting the coronavirus. Covid was apparently mild in the vast majority of these participants; only 15 of them were hospitalized with the disease.

The researchers compared these pairs of scans to those of a control group of 384 U.K. Biobank participants who had not tested positive for Covid and were matched according to the Covid-positive group’s rates of obesity, blood pressure, smoking and diabetes, as well as their socioeconomic status, age and sex.

Between the pairs of MRIs, which were separated by an average of about three years, the researchers observed a striking trend among those who had Covid: a greater loss of what’s known as gray matter in the brain, as well as a higher rate of abnormalities in the brain tissue. Gray matter, which appears gray on certain brain scans, is comprised of various cells, including neurons.

It would be normal for adults within the study’s age range to lose a small amount of brain tissue after three years of aging, the researchers note. But compared with the control group, those who had Covid experienced an additional 0.2 percent to 2 percent loss of brain tissue in regions which are mostly associated with the sense of smell — specifically, in the parahippocampal gyrus, the orbitofrontal cortex and the insula.

The overall brain volume in people with Covid declined by an extra 0.3 percent over those without the disease.

Older participants experienced all these excess brain-related declines more profoundly.

The study offers no indication whether a Covid vaccination would mitigate the risk of such changes. The participants tested positive for the disease between March 2020 and April 2021, before the vaccines were widely available in the U.K.

On cognitive function tests, those who had Covid demonstrated a slower ability to process information and had lower marks on what’s known as executive function, which is an umbrella measure of the brain’s ability to manage complex tasks. Again, these Covid-linked deficits were more pronounced among older individuals.

Dr. Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, said that these findings “have long-term implications, since we would be concerned about the possibility of similar cognitive dysfunction in a large population worldwide.”

“It needs to be determined if these patients could further deteriorate over a period of time,” he said.

The investigators had no access to data on any Covid-related symptoms the participants may have experienced. So they don’t know if the participants actually lost their sense of smell or have experienced long-term symptoms in the disease’s wake. Some likely had asymptomatic cases.

That said, the loss of smell was particularly prevalent among those infected with the coronavirus during the first two major waves of the pandemic. And when particular regions of the brain go unused, they are inclined to atrophy. Nevertheless, the study’s authors don’t know whether the coronavirus caused a loss of smell through a nonbrain-based mechanism and this, in turn, prompted the brain damage, or if possibly the brain damage caused the loss of smell.

How long do Covid brain changes last?

A study published in Cell in February found that a coronavirus infection of various cells in the nasal cavity gives rise to inflammation that inhibits the functioning of smell-receptor proteins on nerve cells, leading to smell loss.

Long COVID symptoms lasted a median of 15 months, Northwestern study finds

Authors: Lisa Schencker, Chicago Tribune May 24, 2022

People with long COVID-19 who visited a Northwestern Medicine clinic were still experiencing symptoms such as headaches, dizziness, fatigue and brain fog for a median of 15 months after first falling ill, despite never needing hospitalization, according to a new Northwestern study.

The study looked at 52 patients who were seen at Northwestern’s Neuro COVID-19 clinic between May 2020 and November 2020, who initially had mild COVID-19 symptoms. Study senior author Dr. Igor Koralnik said the study is the first to look, over such a long time period, at neurological symptoms in people who didn’t need to be hospitalized for COVID-19.

The study was published Tuesday in peer-reviewed journal Annals of Clinical and Translational Neurology.

“It’s important because … long COVID is not going to be going away,” said Koralnik, who is chief of Neuro-infectious Diseases and Global Neurology at Northwestern Medicine and oversees the Neuro COVID-19 Clinic.

Researchers believe long COVID may affect up to 30% of people who get COVID-19, which means an estimated 24 million people in the U.S. may be experiencing lingering symptoms, according to the American Academy of Physical Medicine and Rehabilitation, though some studies have found that being vaccinated may reduce a person’s risk of developing long COVID if they catch COVID-19.

“This is something people need to know about because it impacts a very large population in the U.S.,” Koralnik said.

In the study, there was no significant change in the frequency of patients experiencing symptoms including brain fog, numbness/tingling, headache, dizziness, blurred vision, tinnitus and fatigue, between their first appointments and when they completed questionnaires six to nine months later.

Loss of taste and smell decreased over time, but heart rate and blood pressure variation and gastrointestinal symptoms increased at follow-up.

The average age of the participants was 43, and nearly two-thirds were women. More than two-thirds were vaccinated, but they were vaccinated after they began experiencing COVID-19 symptoms because the vaccines were not yet available when they first got sick. The vaccines did not seem to worsen or improve their cognitive function or fatigue, according to the study.

For the study, researchers reached out to the first 100 non-hospitalized patients who visited the Northwestern clinic, and the 52 studied were those who completed follow-up questionnaires. Those patients had varying experiences with long COVID, with some mainly experiencing loss of taste and/or smell, while others, like Emily Caffee, struggled with a debilitating litany of symptoms.

Caffee said she likely got COVID-19 at the very beginning of the pandemic while traveling for a rowing competition. She had body aches, fatigue, shortness of breath, chest pain and foggy thinking. Though she felt ill, she wasn’t so sick that she had to be hospitalized.

After her initial bout with COVID-19, she returned to her then-job as a physical therapist for Northwestern, but her symptoms soon worsened, to the point that she took a three-month-long medical leave from work, starting in May 2020.

She was plagued by crushing fatigue, brain fog, heart palpitations, vision issues, pain in her legs and neck and unrelenting anxiety — what she called her “buffet of misery.”

“I couldn’t stand for five minutes without getting so dizzy and nauseous I needed to lay down for an hour,” said Caffee, 36, of Wheaton. “If I knew I had to take a shower or follow a recipe or walk downstairs to get the mail, that was it, that was all I could do all day.”

In August 2020, she returned to work, slowly ramping up her hours. By September 2020, when she saw Koralnik, she was feeling about 50% better, she said. Koralnik told her to continue doing what she was doing, slowly resuming her activities, she said.

The feedback was validating, considering that she had previously been told her problems were related to anxiety. She never tested positive for COVID-19, as testing wasn’t yet widespread when she got sick.

“Just hearing from them, from a physician … that what I was going through was real and not just anxiety was key for me,” she said.

Caffee, who now works at PT Solutions in Bloomingdale, said she now feels about 95% back to normal. “This took over two years of my life that I feel was just suffering in so many ways, but I consider myself lucky I’ve come through it without any major complications.”

Like Caffee, about half of the patients in the study never tested positive for COVID-19. But Koralnik said it was important to include them because, like Caffee, many likely had COVID-19, based on their symptoms, before testing was readily available.

“Those patients have experienced a lot of rejection and stigma, and those people are often women in their 40s,” Koralnik said. “There are millions of those people who couldn’t get tested in 2020 yet they continued to have long COVID symptoms.”

Koralnik acknowledges that the study has its limitations. The study is based on just 52 patients, but Koralnik said researchers felt it was important to share what they’ve learned so far, rather than wait longer to study a larger group of people. Also, because the study consists of people who visited the Northwestern clinic and chose to participate in the study, it’s not representative of all people with long COVID who didn’t require hospitalization. About 90% of the study participants were white.

Still, Koralnik said Northwestern has had an open-door policy for its clinic, meaning patients did not need to be referred by other doctors or show proof of insurance. The clinic also has seen people from across the country, by performing both in-person appointments and telehealth visits.

The findings in the new study follow up on a Northwestern study published in March 2021 that found that 85% of people with long COVID-19, who did not require hospitalization, experienced four or more neurological symptoms that impacted their quality of life, and, in some cases, their cognitive abilities.

“This study is the first of its kind that was started in a difficult circumstance, in the lockdown in Chicago, and provides very unique and important data on this population of patients,” Koralnik said. “We hope it’s going to help clinicians take care of those patients and further studies are going to be done.”

Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae


  • Longitudinal multiomics associate PASC with autoantibodies, viremia and comorbidities
  • Reactivation of latent viruses during initial infection may contribute to PASC
  • Subclinical autoantibodies negatively correlate with anti-SARS-CoV-2 antibodies
  • Gastrointestinal PASC uniquely present with post-acute expansion of cytotoxic T cells


Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Article Info

Publication History

Accepted: January 19, 2022Received in revised form: December 14, 2021Received: September 29, 2021

Click on Link Below for Complete Study:


Acute inflammatory demyelinating polyneuropathy or Guillain-Barré syndrome associated with COVID-19: a case report

Journal of Medical Case Reports volume 15, Article number: 219 (2021) 



Coronavirus disease 2019 (COVID-19) is a global pandemic. The disease, typically characterized by bilateral pulmonary infiltrates and profound elevation of inflammatory markers, can range in severity from mild or asymptomatic illness to a lethal cytokine storm and respiratory failure. A number of recognized complications of COVID-19 infection are described in the literature. Common neurological complications include headache and anosmia. Guillain-Barré syndrome (GBS) is an uncommon complication described in isolated case reports. However, a causal relationship has yet to be established. This case report adds to the growing body of evidence that GBS is a potential COVID-19 complication.

Case presentation

A 70-year-old Caucasian woman with recently diagnosed COVID-19 infection presented to the emergency department with 4 days of gradually worsening ascending lower extremity weakness. Exam revealed bilateral lower extremity weakness, mute reflexes, and sensory loss. Soon after starting intravenous administration of immunoglobulin (IVIG), the patient developed respiratory distress, eventually requiring intubation. She remained intubated for the duration of her IVIG treatment. After five rounds of treatment, the patient was successfully extubated and transferred to acute rehab. Following 4 weeks of intense physical therapy, she was able to walk with assistance on room air.


At the present time, this is one of the few reports of acute inflammatory demyelinating polyneuropathy (AIDP) or GBS associated with COVID-19 in the United States. It is unclear whether a causal relationship exists given the nature of the syndrome. However, in light of the growing number of reported cases, physicians should be aware of this possible complication when evaluating COVID-19 patients.

For More Information: https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-021-02831-4

Prevalence of anosmia and ageusia symptoms among long-term effects of COVID-19.

Authors: Moraschini V1Reis D1Sacco R2Calasans-Maia MD3

COVID‐19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that currently presents the greatest, most challenging health concern worldwide. Since the first reports of the disease in December 2019, clinicians and scientists have endeavored to understand the main symptoms, risk factors, and prognosis of the disease (Wynants et al., 2020). Although a significant portion of the infected population remains asymptomatic, many COVID‐19‐infected individuals develop symptoms that vary from mild to severe (Stasi et al., 2020).

Some patients may experience long‐term effects of COVID‐19, which persist for two or more weeks after the onset of the disease (Tenforde et al., 2020). Loss of taste (ageusia) and smell (anosmia) are symptoms that have drawn substantial attention from researchers because of their high prevalence in the early stages of the disease (Eliezer et al., 2020; Gane et al., 2020). However, recent studies have observed persistent dysgeusia and anosmia following recovery from COVID‐19 infection (Andrews et al., 2020; Garrigues et al., 2020; Panda et al., 2020).

The aim of this study was to estimate the prevalence of dysgeusia and anosmia in studies that assessed the long‐term effects of COVID‐19. Four databases (PubMed/MEDLINE, EMBASE, Scopus, and Lilacs) were searched for articles without any restrictions regarding language, and the inclusion criteria were based on the PECO strategy (Morgan et al., 2018). This review included studies that analyzed the prevalence of persistent symptoms (>30 days) of anosmia and dysgeusia in patients who had COVID‐19. There were no language restrictions. Two independent review authors (V.M. and M.D.C.M.) conducted the search‐and‐screening process, commencing with the analysis of titles and abstracts. Next, full papers were selected for careful reading and matched with the eligibility criteria for subsequent data extraction. The search strategy is described in Table S1.

Regarding the quality of the analyzed studies and risk of bias, one study was classified as low quality (Andrews et al., 2020), two as satisfactory (Garrigues et al., 2020; Horvath et al., 2020), and five as of high quality (Carfì et al., 2020; Carvalho‐Schneider et al., 2020; Chopra et al., 2020; Galván‐Tejada et al., 2020; Panda et al., 2020). The analyses can be viewed in Table S2.

The two review authors (V.M. and M.D.C.M.) independently performed risk‐of‐bias and study quality analyses. The Newcastle–Ottawa Scale (Lo et al., 2014) was used in the analysis of non‐randomized studies. For data analysis, the effects reported in one simple arm were estimated by dividing the number of patients with each symptom by the total number of patients with COVID‐19 in the sample and then by multiplying by 100 to estimate the percentage. The prevalence with 95% confidence intervals (CIs) was presented using the software Comprehensive Meta‐Analysis (BioStat).

A total of eight observational studies were selected for this study. Six cohort studies (Andrews et al., 2020; Carfì et al., 2020; Carvalho‐Schneider et al., 2020; Chopra et al., 2020; Horvath et al., 2020; Panda et al., 2020), one cross‐sectional study (Garrigues et al., 2020), and one case–control study (Galván‐Tejada et al., 2020) were included in this study (Figure S1). The studies analyzed 1,483 patients (773 male and 710 female) with a mean age of 48.3 ± 11.2. All patients were diagnosed with COVID‐19 through reverse transcription polymerase chain reaction (RT‐PCR) and exhibited mild, moderate, or severe symptoms. The mean overall follow‐up time was 60.7 days. The main data for each study are shown in Table ​Table11.

For More Information: https://europepmc.org/article/PMC/PMC8242542

Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis

Authors: Marion Renaud, MD1Claire Thibault, MD1Floriane Le Normand, MD1et al


Since the pandemic was declared in early 2020, COVID-19–related anosmia quickly emerged as a telltale sign of infection.1,2 However, the time course and reversibility of COVID-19–related olfactory disorders, which may persist and negatively affect patients’ lives, require further study. To clarify the clinical course and prognosis, we followed a cohort of patients with COVID-19–related anosmia for 1 year and performed repeated olfactory function evaluations for a subset of patients.Methods

This cohort study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Participants provided written informed consent. The study was approved by the ethics committee of the University Hospitals of Strasbourg.

In April 2020, we published a study1 about a cohort of patients with polymerase chain reaction–proven COVID-19 with acute smell loss (lasting >7 days). Over the course of 1 year, at 4-month intervals, patients were asked to complete a survey, and their olfactory function was assessed by psychophysical testing (the threshold and identification tests; Sniffin’ Sticks Test; Burghardt).3 Hyposmic or anosmic patients were followed until objective olfactory recovery (normal results were defined as those at or above the 10th percentile). Data analysis was performed from June 2020 to March 2021.Results

We evaluated 97 patients (67 women [69.1%]; mean [SD] age, 38.8 [11.5] years) with acute smell loss beyond 7 days. Of these patients, 51 (52.6%) underwent both subjective and objective olfactory test, and 46 (47.4%) underwent subjective assessment alone (Figure). After subjective assessment at 4 months, 23 of 51 patients (45.1%) reported full recovery of olfaction, 27 of 51 patients (52.9%) reported partial recovery, and 1 of 51 patients (2.0%) reported no recovery. On psychophysical testing, 43 of 51 patients (84.3%) were objectively normosmic, including 19 of 27 (70.0%) who self-evaluated as only partially recovered (all patients who self-reported normal return of smell were corroborated with objective testing) (Table). The remaining 8 patients (15.7%) with persistent subjective or objective loss of smell were followed up at 8 months, and an additional 6 patients became normosmic on objective testing. At 8 months, objective olfactory assessment confirmed full recovery in 49 of 51 patients (96.1%). Two patients remained hyposmic at 1 year, with persistent abnormalities (1 with abnormal olfactory threshold and 1 with parosmia causing abnormal identification). Among those who underwent subjective assessment alone, 13 of 46 patients (28.2%) reported satisfactory recovery at 4 months (7 with total and 6 with partial recovery), and the remaining 33 patients (71.7%) did so by 12 months (32 with total and 14 with partial recovery).

For More Information: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781319

Anosmia and dysgeusia in SARS-CoV-2 infection: incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms – a systematic review and meta-analysis

Authors: Endang Mutiawati, Conceptualization, Data Curation, Resources, Validation, Writing – Original Draft Preparation, Writing – Review & Editing,a,1,2Marhami Fahriani, Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing,3Sukamto S. Mamada, Data Curation, Investigation, Validation, Writing – Review & Editing,4Jonny Karunia Fajar, Conceptualization, Formal Analysis, Investigation, Methodology, Writing – Review & Editing,3,5Andri Frediansyah, Data Curation, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing,6Helnida Anggun Maliga, Data Curation, Investigation, Validation, Writing – Review & Editing,7Muhammad Ilmawan, Data Curation, Investigation, Validation, Writing – Review & Editing,7Talha Bin Emran, Validation, Writing – Review & Editing,8Youdiil Ophinni, Investigation, Validation, Writing – Review & Editing,9Ichsan Ichsan, Validation, Writing – Review & Editing,3,10Nasrul Musadir, Validation, Writing – Review & Editing,1,2Ali A. Rabaan, Validation, Writing – Review & Editing,11Kuldeep Dhama, Supervision, Validation, Writing – Review & Editing,12Syahrul Syahrul, Supervision, Validation, Writing – Review & Editing,1,2Firzan Nainu, Data Curation, Investigation, Supervision, Validation, Writing – Review & Editing,4 and Harapan aPreparation, Writing – Review & Editing3,10,13


Background: The present study aimed to determine the global prevalence of anosmia and dysgeusia in coronavirus disease 2019 (COVID-19) patients and to assess their association with severity and mortality of COVID-19. Moreover, this study aimed to discuss the possible pathobiological mechanisms of anosmia and dysgeusia in COVID-19.

Methods: Available articles from PubMed, Scopus, Web of Science, and preprint databases (MedRxiv, BioRxiv, and Researchsquare) were searched on November 10th, 2020. Data on the characteristics of the study (anosmia, dysgeusia, and COVID-19) were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Newcastle–Ottawa scale was used to assess research quality. Moreover, the pooled prevalence of anosmia and dysgeusia were calculated, and the association between anosmia and dysgeusia in presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed using the Z test.

Results: Out of 32,142 COVID-19 patients from 107 studies, anosmia was reported in 12,038 patients with a prevalence of 38.2% (95% CI: 36.5%, 47.2%); whereas, dysgeusia was reported in 11,337 patients out of 30,901 COVID-19 patients from 101 studies, with prevalence of 36.6% (95% CI: 35.2%, 45.2%), worldwide. Furthermore, the prevalence of anosmia was 10.2-fold higher (OR: 10.21; 95% CI: 6.53, 15.96, p < 0.001) and that of dysgeusia was 8.6-fold higher (OR: 8.61; 95% CI: 5.26, 14.11, p < 0.001) in COVID-19 patients compared to those with other respiratory infections or COVID-19 like illness. To date, no study has assessed the association of anosmia and dysgeusia with severity and mortality of COVID-19.

Conclusion: Anosmia and dysgeusia are prevalent in COVID-19 patients compared to those with the other non-COVID-19 respiratory infections. Several possible mechanisms have been hypothesized; however, future studies are warranted to elucidate the definitive mechanisms of anosmia and dysgeusia in COVID-19.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993408/

Parosmia post COVID-19: an unpleasant manifestation of long COVID syndrome

As we begin to slowly unravel the mystery hidden behind the current pandemic, novel clinical manifestations are emerging ceaselessly following SARS-CoV-2. Olfactory dysfunction, which has become one of the sought-after clinical features of COVID-19, has been associated with less severe disease manifestation.1 Yet, the previously deemed ‘fortunate’ patients with olfactory dysfunction who successfully recovered from COVID-19 are now being afflicted by another sinister condition known as parosmia, which is found to be more debilitating than loss of smell. Parosmia or distortion of smell is currently regarded as one of the long COVID-19 syndrome or chronic COVID-19 syndrome. Carfi et al found that 87.4% of patients in their study who recovered from COVID-19 had at least one persistent symptom with loss of smell among them.2 However, recent reports have discovered that a number of patients with loss of smell or anosmia regained their smell, yet surprisingly this time, the smell was distorted. The magical aroma of coffee had turned into a nightmare as coffee began to smell pungent like gasoline and favorite dishes were turning to smell more like rotten food or garbage, which inadvertently affects taste as food becomes almost unpalatable. The word parosmia is taken from the Greek words: para and osme (smell) which is defined as a distortion of smell with the presence of odorant, whereas phantosmia is a condition when there is a distortion of smell with the absence of odorant. Anosmia, on the other hand, means complete loss of smell. As of the latest report, three hypotheses exist to explain the pathophysiology of olfactory dysfunction secondary to COVID-19, which include: (1) Mechanical obstruction ensuing the inflammation around the olfactory cleft, which prevents the odorants from binding with the olfactory receptors,3 (2) infection of the ACE-2 expressing supporting cell, mainly the sustentacular cell of the olfactory epithelium4 and (3) direct invasion of olfactory neurons by SARS-CoV-2, which impedes the olfaction transmission.5

For More Information: https://pmj.bmj.com/content/postgradmedj/early/2021/03/31/postgradmedj-2021-139855.full.pdf

Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms

Authors: Julien Brechbühl,Ana Catarina Lopes,Dean Wood,Sofiane Bouteiller,Aurélie de Vallière,Chantal Verdumo, and Marie-Christine Broillet


COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent’s nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.


The Corona Virus Disease 2019 (COVID-19) has federated worldwide scientific efforts for understanding the viral epidemiological mechanisms of the coronavirus 2 (SARS-CoV-2) that causes this severe acute respiratory syndrome. In humans, the viral syndrome is characterized by an increased mortality rate in aged and/or comorbidity patients associated with the upper respiratory infection symptoms, such as severe respiratory distress13. In addition to its major impact, COVID-19 is associated by its direct alteration of human olfaction and gustation, in absence of substantial nasal inflammation or coryzal signs, resulting to anosmia and ageusia in up to 77% of the patients47. While these sensory symptoms are well established and intensely affect everyday behaviors8,9, the precise related mechanisms remain elusive10.

The target cells of the virus share a molecular signature: the concomitant cellular expression of the angiotensin-converting enzyme 2 (ACE2) and of its facilitating transmembrane serine protease 2 (TMPRSS2), which plays a crucial role for the interaction of viral spike proteins with the host cell1113. Paradoxically, these entry sites seem to be lacking in sensory cells1418, while a direct SARS-CoV-2 contamination has been observed both in humans and rodents19,20, requesting further investigations to explain the sensory-associated symptoms2124. Therefore, the characterization of the animal model is necessary prior to its use to understand the causality underling the viral-induced sensory symptoms.

The use of mice is indeed limited for epidemiological studies due to their absence of hands, which, with aerosols, are the foremost passages of interindividual viral transmission25, as well as their published lack of SARS-CoV-2 ACE2-spike protein affinity26,27. Nevertheless, the ease of production of genetically modified mice and their scientific availability, as well as their well-studied and specialized chemosensory systems2830, make them a valuable ally for the development of potential prophylactic and protective treatments related to these sensory symptoms.

Thus, we aimed here at characterizing the potential viral entry sites across mouse sensory systems. We found SARS-CoV-2 entry cells to be of different origins depending on the sensory systems. In summary, the virus could target cells involved in tissue regulation such as the supporting cells of the olfactory receptor neurons and the regenerative basal cells but also, specifically, the chemosensory cells of both gustatory and olfactory systems. We finally revealed that the emergence of viral entry sites in sensory and basal cells only occurs with age, which could explain both, the observed COVID-19 long-lasting effects and the age-dependent sensory-symptomatology in human.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282876/

COVID-19-Associated Bronchiectasis and Its Impact on Prognosis

Authors: Aasir M. SulimanBassel W. BitarAmer A. FarooqiAnam M. ElarabiMohamed R. AboukamarAhmed S. Abdulhadi


Coronavirus disease 2019 (COVID-19), which initially emerged in Wuhan, China, has rapidly swept around the world, causing grave morbidity and mortality. It manifests with several symptoms, on a spectrum from asymptomatic to severe illness and death. Many typical imaging features of this disease are described, such as bilateral multi-lobar ground-glass opacities (GGO) or consolidations with a predominantly peripheral distribution. COVID-19-associated bronchiectasis is an atypical finding, and it is not a commonly described sequel of the disease. Here, we present a previously healthy middle-aged man who developed progressive bronchiectasis evident on serial chest CT scans with superimposed bacterial infection following COVID-19 pneumonia. The patient’s complicated hospital course of superimposed bacterial infection in the setting of presumed bronchiectasis secondary to COVID-19 is alleged to have contributed to his prolonged hospital stay, with difficulty in weaning off mechanical ventilation. Clinicians should have high suspicion and awareness of such a debilitating complication, as further follow-up and management might be warranted.


Beginning in December 2019, a series of pneumonia cases were reported in Wuhan City, Hubei Province, China. Further investigations revealed that it was a new type of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which was termed coronavirus disease 2019 (COVID-19). Symptoms are variable, nonspecific, and include dry cough, fever, fatigue, myalgia, dyspnea, anosmia, and ageusia [1]. The real-time reverse transcription-polymerase chain reaction (rRT-PCR) test is the current gold standard for confirming infection and is performed using nasal or pharyngeal swab specimens.

Computerized tomography of the thorax (CT thorax), as a routine imaging tool for pneumonia diagnosis, is of great importance in the early detection and treatment of patients affected by COVID-19. Chest CT may detect the early parenchymal abnormalities in the absence of positive rRT-PCR at initial presentation [2]. Since chest CT was introduced as a diagnostic tool for COVID-19 pneumonia, many typical features of this disease were described such as bilateral multi-lobar ground-glass opacification (GGO) with a prevalent peripheral or posterior distribution, mainly in the lower lobes; sometimes, consolidative opacities superimposed on GGOs could be found [3]. To our knowledge, bronchiectasis is not a classical finding in COVID-19 pneumonia, with a paucity of reporting on its development and progression during the disease course.

For More Information: https://www.cureus.com/articles/59350-covid-19-associated-bronchiectasis-and-its-impact-on-prognosis