Mucosal Immunity

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at air-liquid interface (ALI).

 

HCoV-229E, HCoV-NL63 and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33°C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally-directed IFNs as potential therapeutics.

 

Preprint in bioRxiv (Dec.19, 2023):

https://doi.org/10.1101/2023.12.18.571720 

Via Juan Lama

The results of 3 new studies reveal unknown ways until now that COVID-19 spreads, leading scientists to urge the use of face coverings in public. Research from various parts of the world considered three separate factors in each study: low humidity, public restrooms and airborne dust. The implications from all three of these studies? Mask up!

 

Low Humidity

A study just published in Transboundary and Emerging Diseases confirms an earlier study conducted in the Greater Sydney, Australia area during the early stages of the pandemic that reported a link between low humidity and community spread of COVID-19. The new research led by Dr. Michael Ward in the Sydney School of Veterinary Science adds to the growing body of evidence that low humidity is a key factor in the spread of the Coronavirus. The scientists estimated that for a 1% decrease in relative humidity, COVID-19 cases increase by 7 to 8%. The same link was not found in other weather patterns such as rainfall, temperature or wind. According to Ward, dry air favors the spread of the virus: “”When the humidity is lower, the air is drier and it makes the aerosols smaller,” he said, adding that aerosols are smaller than droplets. “When you sneeze and cough those smaller infectious aerosols can stay suspended in the air for longer. That increases the exposure for other people. When the air is humid and the aerosols are larger and heavier, they fall and hit surfaces quicker.” These findings add to a growing body of research that recommends wearing a mask.

 

Public Restrooms

A second study conducted by Chinese researchers from Yangzhou University reported that flushing a public restroom toilet or urinal can release clouds of virus-laden aerosols that can be inhaled, posing a serious public health challenge. The scientists simulated and tracked virus-laden particle movements when toilets and urinals were flushed. They discovered that flushing involves an interaction between gas and liquid, resulting in a large spread of aerosol particles. The disturbing results revealed that the trajectory of the particles ejected from flushing showed that more than 57% of the particles traveled away from the urinal. The researchers further point out that when men use urinals in a public restroom, these tiny particles can reach their thigh within 5.5 seconds when compared to the toilet flush, which takes 35 seconds to reach slightly higher. “From our work, it can be inferred that urnial flushing indeed promotes the spread of bacteria and viruses,” said Xiang-Dong Liu, one of the study’s authors. “Wearing a mask should be mandatory within public restrooms during the pandemic, and anti-diffusion improvements are urgently needed to prevent the spread of COVID-19.”

 

Airborne Dust

A third study from the University of California, Davis and the Icahn School of Medicine at Mt. Sinai reported that influenza viruses can spread through the air on dust, fibers and other microscopic particles. Until now, scientists assumed airborne transmission occurred mainly due to respiratory droplets by coughing, sneezing or talking. The scientists examined whether tiny, non-respiratory particles could carry influenza between guinea pigs. Using an automated particle sizer to count airborne particles, they found that uninfected guinea pigs give off spikes of up to 1,000 particles per second as they move around the cage. Particles given off by the animals’ breathing were at a constant but lower rate. Immune guinea pigs with influenza virus painted on their fur could transmit the virus through the air to other, susceptible guinea pigs, showing that the virus did not have to come directly from the respiratory tract to be infectious. Next the researchers tested whether microscopic fibers from an inanimate object could carry infectious viruses. They treated paper facial tissues with influenza virus, let them dry out and then crumpled them in front of the automated particle sizer. Crumpling the tissues released up to 900 particles per second in a size range that could be inhaled. They were also able to infect cells from these particles released from the virus-contaminated paper tissues. According to the researchers, the surprising findings that dust can spread viruses have obvious implications for Coronavirus transmission and use of masks for protection. Plus, they said, it opens up an entire new field of investigation on how outbreaks are interpreted.

 

Original studies available in these sites:

https://doi.org/10.1063/5.0021450

https://doi.org/10.1038/s41467-020-17888-w

https://doi.org/10.1111/tbed.13766

Via Juan Lama

Despite signs of infection—including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules—the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae.

 

Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission. 

 

Published in Nature Medicine (March 25, 2021):

https://doi.org/10.1038/s41591-021-01296-8 

Via Juan Lama

The lungs are ground zero for COVID-19, but blood clots may play a surprisingly big role in severe illness. On rounds in a 20-bed intensive care unit (ICU) one recent day, physician Joshua Denson assessed two patients with seizures, many with respiratory failure and others whose kidneys were on a dangerous downhill slide. Days earlier, his rounds had been interrupted as his team tried, and failed, to resuscitate a young woman whose heart had stopped. All shared one thing, says Denson, a pulmonary and critical care physician at the Tulane University School of Medicine. “They are all COVID positive.”

 

As the number of confirmed cases of COVID-19 surges past 2.2 million globally and deaths surpass 150,000, clinicians and pathologists are struggling to understand the damage wrought by the coronavirus as it tears through the body. They are realizing that although the lungs are ground zero, its reach can extend to many organs including the heart and blood vessels, kidneys, gut, and brain.  “[The disease] can attack almost anything in the body with devastating consequences,” says cardiologist Harlan Krumholz of Yale University and Yale-New Haven Hospital, who is leading multiple efforts to gather clinical data on COVID-19. “Its ferocity is breathtaking and humbling.” 

 

Understanding the rampage could help the doctors on the front lines treat the fraction of infected people who become desperately and sometimes mysteriously ill. Does a dangerous, newly observed tendency to blood clotting transform some mild cases into life-threatening emergencies? Is an overzealous immune response behind the worst cases, suggesting treatment with immune-suppressing drugs could help? What explains the startlingly low blood oxygen that some physicians are reporting in patients who nonetheless are not gasping for breath? “Taking a systems approach may be beneficial as we start thinking about therapies,” says Nilam Mangalmurti, a pulmonary intensivist at the Hospital of the University of Pennsylvania (HUP)....

Via Juan Lama