Winter Diseases: Why the Cold Makes Us Sick

By Jeremy Aguinaldo
November 23, 2015

Pneumonia_x_rayI knew since yesterday that I was going to come down with something. My eyes felt warm and the back of my throat had that annoying constant itch. I currently have a headache. My nose is congested, red, and sore. I have been constantly sneezing and blowing into tissues that it started to peel the skin around the nostrils. Most likely I have a cold. I anticipate the occasional scratching pain that radiates to my ears. It got to the point where I keep the trash bin next to me and will occasionally spit directly into it, rather than painfully swallow.

An old colleague asked me many years ago, “Why do we get sick when it gets cold?” I have thought about it a lot since then. I was always told that it was due to crowding when the temperature gets low. People naturally prefer to stay indoors and congregate in warm areas when it gets cooler outside, allowing the spread of infection to be accomplished. We spread these germs in our homes, at work, gyms, at school, in buses, subways; pretty much anywhere that is within coughing distance. Those suffering from Winter Depression (Seasonal Affective Disorder) can also be susceptible to illness. I know that there are multiple factors that play a role on why we get sick. I also know it is impossible to include every single physiological mechanism that leads to illness or explain every single pathogen that causes disease. Therefore, I would only focus on the most common pathogens as well as a broad and general physiological overview related to the winter season.

Common Cold:

RhinovirusThe rhinovirus is the most common cause of the “common cold” although many other viruses can also cause cold-like symptoms. It is a naked positive RNA virus and is spread by aerosols and fomites, and can infect through the nose, eyes, and mouth, as it is stable for hours on surfaces. It is sensitive to temperature and ideally replicates several degrees below the normal body temperature, 36.5 – 37.5 °C (97.7 – 99.5°F) and infects the upper respiratory tract. The virus binds to ICAM-1, a receptor that mediates cell-to-cell adhesion for epithelial cells. When infection occurs, additional ICAM-1 receptors are expressed due to inflammatory process, which facilitates the spread. Because of multiple serotypes of the virus, it makes vaccine ineffective and impossible (Murray, Rosenthal, & Pfaller, 2012).

There is no treatment for a cold except for symptomatic therapies such as resting and consuming plenty of fluid. Over-the-counter medication such as antihistamine-decongestant is recommended for symptomatic relief. Antibiotics will not be helpful since they do not work against viruses. Taking antibiotics unnecessarily will make it difficult in the future to fight other bacterial infections and increases the chances of antibiotic resistance (Common Colds: Protect Yourself and Others, 2015).

Flu:

Influenza virusGenerally, the term “Flu” is given to any upper respiratory illness with additional features such as headache, body aches, and chills. Flu can be caused by different types of bacteria or viruses; and the most common pathogen is the Influenza virus (Murray, Rosenthal, & Pfaller, 2012).

The Influenza virus is a member of the orthomyxovirus family with type A, B, and C; with type A usually associated with major outbreaks. It is usually spread by aerosols and fomites for a short period of time. After the virus infects the epithelial cells of the respiratory tract, the damaged cells die and impair the ciliary mucus escalator, which weakens the clearance of pathogens in the respiratory tract. This exposes the host to additional risk of infection.

A 2007 study with guinea pigs showed that the influenza virus is stable under cool temperatures at 5°C (41°F) with low humidity. The study showed the virus rapidly spreads to other guinea pigs but decreases in infectivity when both the temperature and humidity rose to 35°C (95°F) and 80%, respectively (Lowen, Mubareka, Steel, & Palese, 2007).

Patients with flu may present with joint/muscle pain, cough, fever, headache and sore throat, nausea, vomiting, or diarrhea. For diagnosis, a nasopharyngeal swab or wash within 48 hours since the onset of symptoms is required in order to rapidly detect the antigen associated with influenza. Treatment is also dependent on the time. Less than 48 hours of symptoms, treatment includes neurominidase inhibitors such as Oseltamivir and Zanamivir. These drugs shorten the duration of symptoms and can treat both Influenza A and B. After eight hours, treatment is focused on the symptoms only: analgesics, rest, antipyretics, and hydration (Influenza (Flu), 2015).

The best way to prevent seasonal flu is to get vaccinated each year.

Pharyngitis (Strep Throat)

Streptococcus pyogenes Strept ThroatStreptococci bacteria are gram-positive facultative anaerobic organisms. Pharyngitis, also known as Strep Throat, is caused by Group A Streptococcus pyogenes and infects the throat and tonsils, but viruses can also cause infection of the pharynx (Murray, Rosenthal, & Pfaller, 2012). It is spread through aerosols by coughing or sneezing and also through eating contaminated food. Infection through contact with open sores on the skin is also possible. The bacterial capsule S. pyogenesis plays a role in the initial colonization of the mucosal surfaces of the throat or on the skin at lower temperatures compared to normal body temperature. The capsule also has an anti-phagocytic function during inflammation, preventing the bacteria from being consumed by white blood cells.

Pharyngitis presents with pain on swallowing, enlarged lymph node in the neck, exudates in the pharynx, fever, without cough or hoarseness. The best initial test is with the “rapid strep test” to help differentiate between bacterial and viral cause. Bacterial pharyngitis often resolves after a few days; however antibiotics should be used to prevent complication such as rheumatic fever and post streptococcal glomerulonephritis. The best antibiotic for bacterial pharyngitis is penicillin or amoxicillin. Those allergic to penicillin can be treated with cephalosporin (Is it Strep Throat?, 2015)

Pneumonia

Streptococcus pneumoniaPneumonia is due to infection of the lungs and the alveoli (air sacs) and can be caused by bacteria, virus, or fungi; but is most commonly caused by the bacteria Streptococcus pneumonia in all age groups, particularly in the young and elders (Murray, Rosenthal, & Pfaller, 2012). S. pneumoniae is spread by contact with saliva and mucus. Pneumonia usually occurs after a viral infection damaging the upper respiratory tract. During pneumonia, alveoli are filed with pus and fluid which leads to consolidation of the lung which causes a reduced gas exchange with oxygen intake as well as making breathing difficult. Symptoms include productive and persistent cough, fever, chest pain, and shortness of breath. Coughing up blood or deep red-colored mucus can be seen as the disease progress. Complications include middle ear infections and meningitis (Pneumococcal Disease, 2015).

Pneumonia_x_ray2Atypical Pneumonia have a slightly different manifestations compared to pneumonia caused by S. pneumoniae. The symptoms are slightly milder with less amounts of sputum, a mild fever, and no consolidation in the lungs. Bacteria that can cause atypical pneumonia include Mycoplasma pneumoniae, Chlamydophila pneunomiae, and Legionella pneumophila. Other names for Atypical Pneumonia include “Walking Pneumonia” (due to its mild characteristics and able to walk-in to a clinic) and “Community-Acquired Pneumonia” (Mycoplasma pneumoniae Infection, 2014).

The best initial test for all respiratory infections is a chest X-ray, however it cannot determine a specific etiology. Sputum gram stain and culture are the best ways to first try to determine a specific microbial etiology, but Atypical pneumonia organisms are not visible on gram stain and not culturable on standard blood agar. Leukocytosis (elevated white blood cell count) is often present, but a nonspecific marker of infection. Tests for severe disease with unclear etiology or those not responding to treatments include: thoracentesis, analyzing the empyema, and bronchoscopy (Pneumonia, 2015).

Almost all infectious diseases are initially treated empirically, meaning without a specific etiology. The most important step in the initial management of pneumonia is determining the severity of the disease. Patients who were previously healthy in the past three months while not taking any antibiotics and presents with only mild symptoms are given macrolides (Azithromycin or Clarithromycin) or doxycycline. Patients suffering with comorbidities and taking antibiotics in the past three months are given respiratory fluroquinolones (Levofloxacin or Moxifloxacin). Majority of pneumonia cases can be treated safely as outpatients with oral antibiotics, with severe 20% of disease that needs to be hospitalized.

There are several vaccines that prevent infection by bacteria or viruses that may cause pneumonia in the United States. These include: Pneumococcal, Influenza, Haemophilus influenza type b (Hib), Measles, Pertussis (whooping cough), and Varicella (chickenpox).

Cold feet make you sick

DSC06714All living things are constantly exposed to viruses. Majority of these viruses are harmless, with only a small number actually causing infection. Even those that do cause infection, there is a small number from that proportion that actually causes disease. Therefore, when certain viruses that cause the common cold are circulating in a community, there will be a certain proportion of those who are subclinically infected and will appear asymptomatic.

A study have shown chilling of the feet in cold water (12°C) had caused intense vasoconstriction of both the systemic cutaneous and upper airway blood vessels (Eccles & Johnson, 2005). This would lead to decreased number of immune cells that play a role in fighting bacteria/viruses and limits them access to sites of infection. Despite the small sample size of the study, it demonstrated that chilling of the feet is associated with the onset of common cold-like symptoms. Disease occurs from an asymptomatic viral infected patient that was initially considered subclinical and will later result in actual sickness due to their suppressed immune defenses.

The sniffles

DSC06715Rhinorrhea (runny nose) is when the nasal cavity is filled with significant amount of mucus produced by glands. The nasal cavities must be constantly coated with mucus in order to maintain the constant warm air entering into the body. The mucus membranes must work harder during the cold and dry season due to the mucus lining drying out. Due to the high concentration of blood vessels in the nasal cavity, changes in these blood vessels contribute to nasal congestion. With the blood vessels in the nasal cavity dilated, the cavity can fill up with mucus. This gives the nose that familiar red appearance. Excess fluid usually spills out externally through the nostrils and gives us the characteristic “sniffles.”

The nasal mucosa blood flow (NMBF) plays a probable role to cold temperature (M., J., & N., 1991). When a person is exposed to cool temperature, there is a cutaneous vasoconstriction throughout the body to reduce the loss of body-heat. The nasal cavity paradoxically dilates the blood vessels, which warms ups inspired air. To avoid damage to the lungs and to provide adequate gas exchange, inspired air must be warmer than 30°C. A stuffy or congested nose occurs when the tissue lining becomes swollen due to the inflamed blood vessels.

A study demonstrated that decrease NBMF in cold environments results in cooling of the nasal airway, which affects the nasal defenses against infection and increases susceptibility to viral infections (Lu, Chu, & Wang, 2010).

Decrease in Mucociliary Escalator Function

DSC06717The “mucociliary escalator” is a defense mechanism that involves the action of cilia and directs the flow of mucus from bronchioles, to the bronchi and trachea, and then to the pharynx. Foreign particulate matter trapped in the mucus is filtered and removed from the respiratory tract. The mucus provides a thick layer, preventing pathogens access to the sensitive epithelial layer below. Goblet cells secretes the main component of mucus. The process is similar to a constant flowing river of molasses that carries debris down a stream, and the viscous quality prevents anything to reach and settle at the bottom.

Animal studies have shown that repeated cooling and drying of the airways results in loss of ciliated epithelium, and damage to the structure of the airway’s walls. This disrupts the production and function of the mucociliary escalator. Experiments with exposure to cold air reduce the mucus velocity and greatly decrease the clearance of the pathogens (MS., B., & AN., 2003).

Immune system responds to cold stress

DSC06716Cold exposure is a broad concept that includes multiple levels of physiological effects, depending of the degree of cooling (vasoconstriction, secretion of hormones, release of chemokines, etc.) Drop in core body temperature causes leukocytopenia, suppression of chemotactic migration of leukocytes, suppress phagocytosis, and reduces the release of cytokines. Insulin resistance and hyperglycemia has also been found in exposure to cold stress. A study determined that cold exposure may influence cytokine production by upregulating IL-1 and IL-6, which mediates an inflammatory response such as fevers (Gagnon, et al., 2014).

Peripheral White Blood Cells (WBCs), cells important in fighting against dangerous pathogens, has an optimum rate of between 33 and 41°C but will be less functional outside of this range.

The Seasons and Genetics

DSC06718Every cell contains genes that specialize in a specific function. These genes are DNA that helps to determine the order of amino acids that will later be made into proteins. Some functions of these proteins are required for normal function of the cell, while others are not expressed and simply turned off. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine that induces proteins that expresses various inflammatory activities. Studies have shown that MIP-1 alpha is required for a normal inflammatory response against Influenza and other viruses (Macrophage inflammatory protein-1 alpha activates basophils and mast cells, 1992).

A new study has shown that human genes changes with the seasons, which includes its immune functions (Dopico, et al., 2015). During the winter season, the immune system primes up inflammatory responses, resulting in people who are susceptible to inflammatory effects to suffer from an amplified reaction. It has been proposed that in seasons when infectious pathogens are most prevalent in circulation, the human body promotes a pro-inflammatory mode to help fight the disease. Despite the response to fight off the infection, it does worsen the effects related to inflammation.

Prevention – How to Stay Safe

During the cold season, it is important to protect yourself as well as others. Vaccinations is very important in prevention against several diseases, specifically against the Flu. It usually takes two weeks after a Flu Vaccine to gain its benefits. By protecting oneself, it will also aid in protecting those around you who are more vulnerable to serious illnesses such as the elderly, children, and those with chronic health conditions. For those who do get sick, vaccinations also may make illnesses milder. I should also make a point that you are still at risk for getting a cold right after you receive a flu shot. This usually leads to confusion of being infected with influenza from the vaccine. It also important to point out that it does not mean everyone who gets a flu shot is protected from the flu virus. How well the vaccine works can range from the characteristic of the person being vaccinated such as their age and health, as well as the season of which strain of the flu virus is spreading in the community. Please review from a reliable source on the most common side effects from each vaccine.

Good hygiene is important in prevention of illness. To reduce the risk of getting infected, one should wash their hands often with soap and water for 20 seconds. This simple task is especially important in children. Alcohol-based hand sanitizer is also an alternative if soap and water is not available. To avoid viruses and other pathogens that live on the hands, refrain from touching your eyes, nose, and mouth with unwashed hands.

It is also highly recommended to stay away from those who are sick, since the common cold and other pathogens can be spread through close contact with others. If you are sick, cough/sneeze directly into a tissue and dispose of it, or cough/sneeze directly into your sleeve, covering the nose and mouth with the region of the elbow (Vampire Sneeze).

Final Thoughts:

Once again, I need to repeat that this article does not cover every reason why we get sick when it gets cold. This only covers a broad review base on recent data. Because of so many factors, it is important to stay vigilant in staying healthy. This season, I wish everyone to stay safe and warm.

References

Common Colds: Protect Yourself and Others. (2015, October 6). Retrieved from CDC: http://www.cdc.gov/Features/Rhinoviruses/index.html

Dopico, X. C., Evangelou, M., Ferreira, R. C., Guo, H., Pekalski, M. L., Smyth, D. J., & Cooper, N. (2015). Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nature Communications, 12;6:700.

Eccles, R., & Johnson, C. (2005). Acute cooling of the feet and onset of common cold symptoms. Family Practice, 22, 608-613.

Gagnon, D. D., Gagnon, S. S., Rintamaki, H., Tormakangas, T., Puukka, K., & Herzig, K.-H. (2014). The Effects of Cold Exposure on Leukocytes, Hormones and Cytokines during Acute Exercise in Humans. PLoS ONE, 9(10), e110774.

Influenza (Flu). (2015, October 30). Retrieved from CDC: http://www.cdc.gov/flu/index.htm

Is it Strep Throat? (2015, October 19). Retrieved from CDC: http://www.cdc.gov/Features/StrepThroat/index.html

Lowen, A. C., Mubareka, S., Steel, J., & Palese, P. (2007). Influenza Virus Transmission Is Dependent on Relative Humidity and Temperature. PLoS Pathogens, 3(10), e151.

Lu, D.-W., Chu, Y.-H., & Wang, H.-W. (2010). Ambient cold air Decreased nasal mucosa blood flow measured by laser Doppler flowmeter. Rhinology, 48, 160-162.

M., P., J., M., & N., T. (1991). The effect of ice packs upon nasal mucosal blood flow. Rhinology, 111(6), 1122-1125.

Macrophage inflammatory protein-1 alpha activates basophils and mast cells. (1992). The Journal of Experimental Medicine, 176(3), 781-786.

MS., D., B., S., & AN., F. (2003). Repeated peripheral airway hyperpnea causes inflammation and remodeling in dogs. Medical Science Sports Exercise, 35(4), 608-616.

Murray, R. P., Rosenthal, S. K., & Pfaller, A. M. (2012). Medical Microbiology. Saunders.

Mycoplasma pneumoniae Infection. (2014, February 7). Retrieved from CDC: http://www.cdc.gov/pneumonia/atypical/mycoplasma/index.html

Pneumococcal Disease. (2015, June 10). Retrieved from CDC: http://www.cdc.gov/pneumococcal/index.html

Pneumonia. (2015, February 25). Retrieved from CDC: http://www.cdc.gov/pneumonia/index.html

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