Thread by @jeffgilchrist

[Part 2 of 2] COVID-19: Why respiratory viruses surge in winter

In part 1 we looked at the seasonality of respiratory viruses in the human population and the effect of environmental factors on stability and transmission of respiratory viruses (

https://twitter.com/jeffgilchrist/status/1454443918981009408

). 🧵1/

We continue with part 2 focusing on the effect of environmental factors on the host airway antiviral defense ( annualreviews.org/doi/10.1146/an… ). 2/

The mucosal surface of the respiratory tract is continuously exposed to inhaled environmental air that contains pollutants and pathogens but there are multiple defense systems that prevent infection. 3/

Seasonal fluctuations of temperature and humidity of the inhaled air have been shown to directly affect the airway mucosal surface defense as seen in the image. 4/

Epithelial cells ( askabiologist.asu.edu/epithelial-cel… ) lining the airway surface make up an efficient mechanical barrier and provide mucociliary clearance (MCC, en.wikipedia.org/wiki/Mucocilia…) while mucus provides chemical barriers at the mucosal surface with its antimicrobial properties. 5/

Incoming viruses must first find epithelial cells to invade the host. Mucus layers can effectively trap the virus before it can enter host cells (see image). 6/

Under low temperature and humidity, mucous transport becomes less efficient and immobilizes the cilia (vibrating hair like structure) which are pressed down by the reduced height of the periciliary layer below the mucus. 7/

Inhaling cold dry air causes impairment of MCC which found that movement begins to decline below 20C and is no longer observed below 5C. Mucociliary speed decreased progressively when relative humidity (RH) of breathing air was reduced from 70% to 20%. 8/

This provides more opportunity for viruses to access and invade epithelial cells. Multiple innate immune sensors recognize virus-associated molecular patterns which signal the immune system to react. 9/

Recent studies have shown that season-dependent environmental factors such as temperature and humidity can affect this antiviral innate immunity against respiratory virus infections. 10/

Human rhinoviruses, a major source of the common cold, cause illness mostly in winter. These viruses are known to replicate much better at 33C which is found in the cooler nasal cavity than the core body temperature found in lower airways (37C). 11/

At 33C, rhinoviruses triggered only low levels of immune response from infected epithelial cells, while at 37C had robust antiviral response from the body. Keeping the nose warm during the winter might boost antiviral innate resistance to the common cold virus. 12/

The story that we were told as kids that you will catch a cold if you don't wear a jacket outside to stay warm, is actually partially true and you have an increased chance of getting infected if you let your nose get cold/dry. 13/

Seasonal epidemics of influenza virus-related mortality are preceded by a drop in absolute humidity (AH) levels during the winter season in the USA. Low outdoor AH leads to low indoor RH. Mice were infected by influenza at 10%-20% RH more rapidly than 50% RH. 14/

MCC was severely impaired at low humidity which also impaired airway tissue repair mechanisms. Exposure to dry air also impairs global interferon immune response in airway epithelial cells and also cell types found throughout the lung. 15/

The figure shows possible mechanisms of increased host susceptibility to virus infections in winter. 16/

Looking at innate defense mechanisms, it appears that short daylight (8h) vs long daylight (16h) contributes to the impairment of the innate immune responses in winter. Adaptive immunity however provides highly specific and long-lived protection against infectious agents. 17/

The initiation of this adaptive immunity begins when a pathogen stimulates immune T cells to become activated, expand, and differentiate into effector T cells that can mediate antiviral responses at the site of infection. 18/

Studies have found that the surrounding temperature of the host (30C vs 22C) can affect adaptive immune responses in general so vaccines given at an optimal temperature might induce better immunity. 19/

High ambient heat (summer heat wave) weakens virus-specific adaptive immunity following influenza infection in mice. Impaired immune response in heat-exposed mice was partially restored by glucose suggesting a role for diet and microbiome in heat-mediated immune impairment. 20/

According to the CDC all 6 recent influenza pandemics occurring in the Northern Hemisphere (1957-2009) were in the spring to summer time. The role of abnormal temperature fluctuations in pandemics will become even more relevant with the increasing effects of climate change. 21/

Low humidity during influenza infection in mice has been shown to increase mortality, weight loss, and pulmonary viral burden. Severe tissue damage after infection was observed in the lung tissue of dry air-exposed mice. 22/

The authors speculate that low humidity and temperature environments would promote viability of COVID-19 virus and provide robust access to the deep lung tissue and rapid transmission between infected individuals. 23/

A study in the USA found that humidifying preschool classrooms during January to March to 45% RH resulted in a significant reduction in the total number of influenza virus found in the air and on objects compared to control classrooms ( journals.plos.org/plosone/articl… ). 24/

The researchers even tested the virus samples to see if they were infectious (and not just viral fragments). They found that 81% of samples taken from the control classrooms contained infectious influenza while only 19% of the humidified rooms did. 25/

While their study was not testing for causation, they noted that there were 2.3x as many influenza like illness (IFI) cases in the control rooms compared to the humidified rooms. 26/

Imagine if policy makers recognized respiratory virus transmission was airborne and they combined better ventilation, air cleaners to remove particles in rooms, and humidity and temperature control to help inactivate viruses...27/

...reduce the chance of the virus staying in the air longer, and optimize the conditions for the human body to prevent infection and fight off infection all at the same time. 28/

These kinds of improvements in schools and workplaces do not just benefit people during this COVID-19 pandemic but for respiratory viruses all year long, every year going forward. 29/