Covid-19
Covid-19
- Public Description
- Infections and Diseases
- Disease Factors
- Infection Locations
- Immune Response and Symptoms
- Clinical Pictures
- Disease Stages
- Virion Shedding
- Prevention and Treatment
- Recovery and Long Lasting Effects
- Fatality Rate
- References
- Appendix
Public Description
Respiratory SARS-CoV-2 infections causing uneasiness are the disease Covid-19. Covid-19 has different clinical pictures and symptoms. The appearances vary since SARS-CoV-2 can infect different parts of the respiratory tract (except the vocal folds) and also other parts of the body (though the clinical significance of these infections quite unclear as of 12.11.21). The locations infected in turn determine the symptoms. Therefore any kind of respiratory symptoms - except a hoarse voice - can indicate Covid-19. With symptoms avoiding crowded indoor spaces is important. Many of the symptoms are not specific to Covid-19, they may have other causes than SARS-CoV-2 such as having a (respiratory) infection with different virus or a bacterium, having eaten/drunken something harmful (e.g. rotten or too much alcohol) or just not having had enough sleep. In doubt a Covid-19 test can help. A positive results means avoiding foreign indoor spaces. A negative result is no free pass however, a single negative test does not exclude an infection.
Infections and Diseases
Disease
A disease is a biological disorder of structure or function in an organism causing inconvenience and/or unwanted effects.
Literally disease means without-ease (dis=without, separated from).
Disease: YES or NO
- Chemical/biochemical damages such as dehydration, a poisoning or physical damage such as a fracture or an injury are not diseases themselves but chemical/physical damage can result from a disease.
- Longer lasting biological damage or out of biological homeostasis is usually considered a disease. Life form interactions at the cellular level can cause biological imbalance.
- A disease is can be (and often is) caused by life form interactions at the cellular level (e.g. pathogens infecting a host).
- Metabolic disorder
- Yes: Being out of balance due to lack of vitamins (e.g. scurvy caused by a shortage of vitamin C) is also considered a disease.
- No: Short term disturbances of the homeostasis e.g. by shortage of water is usually not considered a disease despite dis-ease is caused.
There are many different causes of diseases:
- other life forms interactions with the metabolism, called infections. As life from interactions are dynamic, the disease is dynamic and an immune response is induced/involved.
On this page, the immune system is defined as a system which regulates life form interactions to keep homeostasis (Concepts of Immunology).
- immune disease in which the immune system overreacts to substances without need (notes on the immune system in the Immune System chapter)
- shortage of necessary biological substances e.g. vitamins.
Infection
When microorganisms induce metabolism changes on a host organism, the host is infected by the microorganisms. [in work and in consideration whether this is a suitable definition]
Examples:
- outside of cells but inside multicellular organisms
- most bacteria
- fungi
- inside cells
- some bacteria
- all viruses
Virus diseases are caused by virus infections:
Virus Infection
A virus infects an organism by infecting cells of the organism. A virus infects a cell by entering it and changing the cells metabolism. More about viruses and how they live in the chapter Introduction to Viruses.
If a virus infection causes lack of ease, one has a virus disease:
Virus Disease
A virus disease is a virus infection of an organism causing adverse effects.
Adverse effects result either directly through tissue damage caused by viruses or more frequent to keep the core parts of the body virus free (to prevent future cell/tissue damage) a strong immune response is induced causing effects on its own.
The definition of a virus disease is not strict: Adverse effects or tissue damage are often small and no lack of ease is caused. For most viruses very mild infections are not considered diseases.
For the SARS-CoV-2 virus, usually any infection is Covid even when asymptomatic:
Covid-19
Covid-19 stands for COronaVIrus Disease 2019.
On this page, Covid-19 is used when there is a disease. An asymptomatic SARS-CoV-2 infection is denoted as such. [rework in work as of October 21]
From early 2020 on, all SARS-CoV-2 infections are called Covid-19. Thus Covid-19 is not used to denote a disease but it is used to denote an infection with the SARS-CoV-2 coronavirus.
In colloquial language, “Covid-19” is often used synonymously with detecting parts of SARS-CoV-2 viruses in the upper respiratory tract, often tested by nasopharyngeal sampling and PCR testing. However the situation is not that simple:
- Not all persons infected with SARS-CoV-2 have a detectable amount of viruses in the nose since SARS-CoV-2 can infect the lower respiratory tract only. Especially people with a sensible immune system may experience symptoms without having a detectable viral load in the upper respiratory tract. But it is also possible to have severe Covid-19 without having detectable viruses by nose swabs [citation in work].
- Detectable SARS-2 parts (either RNA by PCR or proteins by antigens test) can result from a past infection and thus not equivalent to an ongoing infection and shedding infectious virions.
More in the chapter Diagnosis and Infections Locations.
The following terms describe the symptom stage of a person.
Symptomatic
A person experiencing/notifying/showing symptoms of a disease is called symptomatic.
Asymptomatic
A person not experiencing/notifying/showing symptoms while having an infection is called asymptomatic.
Presymptomatic
Even those developing symptoms are asymptomatic in the early phase of a disease. This asymptomatic stage is called presymptomatic.
Disease Factors
A virus disease is an interplay of host factors including the host immune system, the behavior of the virus and of environmental factors.
- Host Factors relevant for the tropism of Covid-19 are
- Cells susceptible to infection and capable of producing viruses (not all cells are susceptible e.g. red blood cells are not susceptible to virus infections ).
- Host immune response.
- Capabilities and Behavior of the Virus Viruses growth differently under different environmental factors called tropism (-> Tropism of viruses. E.g. SARS-2 virions can initiate cell entry only for cells containing a matching receptor. To infect a tissue several conditions must be met as described in coronavirus behavior.
- Environmental Factors
- the travel of virions between hosts and thus the mode of the initial infection. E.g. in dry air exhaled droplets dry out and these are more likely to be deposited deep in the lungs.
- Environmental factors can influence the host factors as well as the virus tropism and thus indirectly the course of the disease. E.g.:
- Very dry air can weaken the immune system of the mucous membrane in the respiratory tract.
- Dirty air can weaken defence mechanisms against viruses e.g. ciliated cells are damaged and thereby the clearance of particles in the respiratory tract is reduced.
Infection Locations
SARS-CoV-2 infects different tissues in humans. The effects from the virus infection such as tissue damage and symptoms are often local to the infected locations.
Different topics related to the infection locations are described in the sections:
- The chapter Diagnosis and Viral Load describes in which body fluids and tissues how many virions are observed. This indicates an infected tissues close by.
- The Immune Response and Symptoms section gives an overview of the different symptoms induced by the infection location.
- In the coronavirus chapter, the section tissue tropism describes how and which tissues are infected by coronaviruses and SARS-2 especially.
- The experimental chapter Coronavirus Disease Pattering describes that coronavirus infections at different locations can be experienced/observed as different diseases.
Immune Response and Symptoms
[in work]
Causes of Symptoms
The symptoms of a virus disease are caused:
- Direct symptoms through cell damage. Only in severe cases.
- Indirect symptoms through the induced immune response(Sketching of the Immune System.
Symptoms at different Locations
A similar section is in the chapter Disease Pattering, a merge is planned.
Infection symptoms depend on the infected locations. SARS-CoV-2 infects different Locations. Typical symptoms for the different locations are:
- Upper Respiratory Tract => Symptoms are similar to other respiratory diseases: a sore throat, coughing and a runny nose. Loss of smell or taste.
- Throat => Coughing, the body wants to get rid of the viruses in the respiratory tract, virions cleared to the intestine can cause diarrhea.
- Trachea => Coughing
- Central Lungs i.e. bronchi => Strange feeling in the chest like something sticky being inside (dry mucus loaded with viruses).
- Deep Lungs i.e. in the alveoli => The lungs can get inflamed. Strange feeling in the chest. Shortness of breath. Early on virions are released into the blood.
- Blood i.e. viraemia => This feels like it is starting from within. Symptoms can be chills (because the body is increasing the temperature to fight the viruses) or just strange feeling, similar to a weak poisoning when having eaten something rotten or drunken too much. Feeling tired, energy-less.
- Intestine => Diarrhea can both start early and later on and often outlasts the respiratory infection by days or even weeks.
Individual Immune System Adequateness
The immune system preparedness to new viruses vary and some clear the viruses faster and earlier. E.g. younger people tend to have an immune system which better and faster learns new pathogens and the the innate immune is stronger (the acquired immunity has the learn new pathogens by definition, so it needs to be learnable and the immune system needs backups to handle unknown pathogens since each pathogen is new on the first encounter) which can handle and control new pathogens quickly. Essentially SARS-CoV-2 is as new to them as any other pathogens. With increasing age to immune system becomes less adaptable (e.g. the number of naive T cells decrease) and relies much more on acquired immunity, in this case the immune response is often delayed and/or not adequate [citations coming].
Clinical Pictures
- Lung anomalies in the case for moderate and damage for severe Covid are typical and thus can be used to diagnose moderate or severe Covid as described in the chapter Diagnosis and Viral Load).
- Endothelial tissue damage in the case of severe Covid (Varga et al).
- Severe
Disease Stages
[in work]
Virion Shedding
Being infected does not imply one sheds infectious virions. The viral shedding depends on where the infection is and physiology of the respiratory tract. The virions need to be breath or coughed out. How many small particulates persons exhale is highly individual and tends to increase with age, male sex and BMI (described on in the section particle source on the transmission page.
Prevention and Treatment
in work and incomplete
Movement
Movement is import for optimal functioning of the immune system. A good working immune system in turn is important regarding the prevention, the treatment and recovering of/from Covid-19. Moderate movement (e.g. a walk or home stretching. For home sports ventilation of the room before and afterwards is important) is recommended even when infected, while exercise is only recommended when fit and healthy.
Recommended articles regarding movement and exercise are:
- Should, and how can, exercise be done during a coronavirus outbreak? An interview with Dr. Jeffrey A. Woods. by Zhu
- COVID-19: A pandemic that threatens physical and mental health by promoting physical inactivity by Ali and Kunugi
The articles are found on a chapter dedicated to the benefits of movements regarding Covid: Movement Chapter. In the Movement chapter possible mechanisms and epidemiological evidences are discussed.
Quarantine Rules contradict a Healthy Recovery
The strict quarantine and isolation rules contradict a healthy recovery and therefore this rules should be relaxed.
In some regions if tested positive a walk outdoors is only allowed for people in house with a garden. Though the detection rate of mild cases is usually very low, so many will have no formal restrictions.
Movement can be associated with deep breathing which is aerosol generating. Therefore when possibly infected and with people to protect in the same flat, it is important to be in a separate room and ventilate the room even after stretching and light exercise. Regarding aerosol transmission outdoors is still way safer.
Local Temperature and Humidity Modulation
Local temperature and humidity modulation such as sauna or steam inhalation are promising prevention and steam inhalation also an early treatment method since:
- coronaviruses are susceptible to environment changes especially high temperatures.
- set the immune system into an alert state to provoke an early reaction.
- coronaviruses live on the surface of the respiratory tract which is well reachable from the outside.
Further discussed in the separate chapter Local Temperature and Humidity Modulation.
Recovery and Long Lasting Effects
Over 90 % of people are adverse effects free a couple of weeks after a SARS-CoV-2 infection. Regarding athletes, countless have been diagnosed with Covid-19: Many of them competed in professional sports just a few weeks later and - to my knowledge - long-term adverse effects haven’t been observed for any athlete even though even the slight performance losses would be observed. Athletes often have good fitness, do regular exercise and eat healthily . A healthy lifestyle including movement helps everybody to be in good health.
Nevertheless for some people a healthy life-style is not enough and some experience long lasting effects.
Literature Recovery
- A recommended read is Long COVID: A Primer for Family Physicians by Greenhalgh and Knight
- More detailed reads are Management of post-acute covid-19 in primary care by Greenhalgh et al and The Stanford Hall consensus statement for post-COVID-19 rehabilitation by Barker-Davies et al
Long Lasting Effects
Sometime long lasting symptoms such as fatigue and decreased physical fitness can occur, called long Covid/long-haulers. Tissues damage which needs some time to repair can be a cause (Marshall). Another cause for long covid can be that immune system overshoots. To prevent the latter careful and at most moderate movement in the diseased phased and with carefully increased intensities after the disease in the recovery phase.
Fatality Rate
Infection Fatality Rate
The infection fatality rate/death rate denotes the ratio of the people who die from the infection to all people overcoming the infection.
ifr = #(deaths)/#(all infected)
Fatality rate on this page is used synonymously to infection fatality rate.
The fatality rate depends on the definition of a SARS-CoV-2 infection and a death cause by SARS-CoV-2. Both are not straight forward to define:
- Counting overall Cases: SARS-CoV-2 infections and diseases are described in the section Diseases and Infections. Acute Covid-19 is usually diagnosed by PCR tests and past infections by detecting antibodies with serology. These methods don’t agree in all cases: One can have a positive PCR test but no antibody in the blood or an antibody response in the blood without a negative PCR test in the nose (especially if measured only at a single time point) (Diagnosis and Viral Load).
- Counting Deaths: For many Covid associated deaths Covid is the main death cause. But for some cases the patients have other severe illnesses and to finally single out a death cause is difficult. Hard to estimate is also how many life years Covid takes.
Once agreed upon a uniform way to measure the fatality rate, the rate still varies considerably due to different populations structures (e.g. age, overall health, …), medical systems, environmental factors and living conditions such as climate and air pollution. These determinants are insightful to analyse for prevention and treatment.
Case Fatality Rate
The case fatality rate denotes the deaths divided by the official case counts:
cfr = #deaths/#(official cases)
Comparing Case and Infection Fatality
The official Covid-19 case counts are in most countries fare to low and thus the cfr fare to high.
The resulting mismatch between cfr and ifr can be used to estimate the detection rate = #(case count)/#(all infected) = [#(deaths)/#(all infected)] / [#(deaths)/#(cases count)] = ifr / cfr
(more in the section Validate Estimates in the Monitoring chapter).
Estimates
[in work]
- John Ioannidis infers the death rate from seroprevalence data across the world. Results:
- 0.27% is the median COVID-19 infection fatality rate (0.23% if corrected for the number of antibody types tested (immunoglobin, IgG, IgM, IgA))
- 0.09% infection-fatality-rate in locations with COVID-19 population-mortality-rates less than the global average (< 118 deaths/million)
- 0.20% infection-fatality-rate in locations with 118–500 COVID-19 deaths/million people
- 0.57% infection-fatality-rate in locations with > 500 COVID-19 deaths/million people
- 0.05% infection-fatality-rate corrected median for people younger than 70 years
References
Fatality
Ioannidis
Ioannidis J. The infection fatality rate of COVID-19 inferred from seroprevalence data. accessed version published on 14.10.2020: https://www.who.int/bulletin/online_first/BLT.20.265892.pdf
References Long Term Effects
Marshall
Michael Marshall, COVID-19’S LASTING MISERY, Nature Medicine
References Rehabilitation
Greenhalgh Nov2020
Long COVID: A Primer for Family Physicians Trisha Greenhalgh, Matthew Knight
Background
- “Among nonhospitalized patients with COVID-19, two-thirds are symptom-free by 14 days after symptom onset, and 90% are symptom-free by 21 days[2],[3]. The rest of patients experience persistent—or relapsing and remitting—symptoms, including cough, breathlessness, fatigue, fever, sore throat, nonspecific chest pains (lung burn), cognitive blunting (brain fog), anxiety, depression, skin rashes, and diarrhea. [4],[5]”
Treatment Recommendations
- “A social history may reveal relevant issues, such as isolation, economic hardship, pressure to return to work, bereavement, or loss of personal routines (e.g., shopping, church), which can impact patients’ well-being.”
- “Those with persistent cough and breathlessness may benefit from simple breathing exercises (slow, diaphragmatic breathing with a 1:2 inspiration to expiration ratio several times per day).”
- “Because the role of exercise in recovery is controversial,10 patients should be counseled to pace themselves carefully and cut back if symptoms worsen. Specific guidance has been published for athletes returning to sports participation.10,13-15”
- “Mental health and well-being may be greatly improved by reestablishing social connections, community and peer support, and attention to structural determinants (e.g., measures to mitigate poverty, fight discrimination, and achieve social justice).16,1”
Greenhalgh Aug2020
Management of post-acute covid-19 in primary care Trisha Greenhalgh, Matthew Knight, Christine A’Court, Maria Buxton, Laiba Husain BMJ 2020;370:m3026 https://dx.doi.org/10.1136/bmj.m3026 [in work]
Barker-Davies
The Stanford Hall consensus statement for post-COVID-19 rehabilitation Barker-Davies RM, O’Sullivan O, Senaratne KPP, et al. Br J Sports Med 2020;54:949–959. https://dx.doi.org/10.1136/ bjsports-2020-102596 [in work]
- “Beyond respiratory function a prospective cohort study of 171 SARS survivors demonstrated deficits in cardiorespiratory (6MWT) and musculoskeletal performance (handheld dynamometry for major muscle groups), as well as QoL compared with age-matched norms.25 A similar picture was reported following the 2009H1N1 influenza epidemic.26”
- “Early mobilisation has shown to be practical and safe in an ICU setting.17 “
- “Pulmonary rehabilitation (PR) has been advocated for several decades as a way to provide comprehensive care and improve the functional status of patients with respiratory diseases.27”
- “Exercise training (ET) is considered the foundation of PR and included in 76%–100% of programmes internationally.33–35”
Pathogenesis and Viral Loads Sars-Cov-1
Lau
Yu Lung Lau and JS Malik Peiris Pathogenesis of severe acute respiratory syndrome Current Opinion in Immunology 2005, 17:404–410 https://doi.org/10.1016/j.coi.2005.05.009
Peiris
J S M Peiris, Y Guan, K-Y Yuen Severe acute respiratory syndrom nature medicine, 30 November 2004 https://doi.org/10.1038/nm1143
Pathogenesis and Viral Loads Sars-Cov-2
Further references in the chapter Diagnosis and Viral Load
case-series-france
Francois-Xavier Lescure, Lila Bouadma, Bruno Lina, Sylvie van-der-Werf, Yazdan Yazdanpanah et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series Lancet Infect Dis 2020 PublishedOnline March 27, 2020 https://doi.org/10.1016/ S1473-3099(20)30200-0 See Online/Comment https://doi.org/10.1016/ S1473-3099(20)30237-1
To
Kelvin Kai-Wang To, Owen Tak-Yin Tsang, Wai-Shing Leung, Anthony Raymond Tam, Tak-Chiu Wu, David Christopher Lung, Cyril Chik-Yan Yip, Jian-Piao Cai, Jacky Man-Chun Chan, Thomas Shiu-Hong Chik, Daphne Pui-Ling Lau, Chris Yau-Chung Choi, Lin-Lei Chen, Wan-Mui Chan, Kwok-Hung Chan, Jonathan Daniel Ip, Anthony Chin-Ki Ng, Rosana Wing-Shan Poon, Cui-Ting Luo, Vincent Chi-Chung Cheng, Jasper Fuk-Woo Chan, Ivan Fan-Ngai Hung, Zhiwei Chen, Honglin Chen, Kwok-Yung Yuen Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study Lancet Infect Dis 2020 Published Online March 23, 2020 https://doi.org/10.1016/S1473-3099(20)30196-1 SeeOnline/Comment https://doi.org/10.1016/S1473-3099(20)30235-8
References Pathology
Varga
Endothelial cell infection and endotheliitis in COVID-19 Published Online April 17, 2020 https://doi.org/10.1016/ S0140-6736(20)30937-5
Appendix
Personal Covid Experience
I likely had Covid-19 myself around mid March 2020 when temperatures were freezing cold in my living place back then at 1400 meters altitude. The initial experience was very different from a common respiratory disease and so diagnosis was not obvious: 1) lack of respiratory symptoms - not a single cough if I recall correctly, 2) the supposed low prior probability according to the official prevalence and 3) I didn’t want to have it and so was satisfied with not experiencing known and obvious symptoms. It first felt like a minor food poisoning but no vomiting or the like. Just felt strange for about two days. Soon the initial symptoms faded and I felt fit again. I went for some cross country ski session which was more intense than planned since three quarters were through deep snow. The sport session went well by itself, but was bad for the disease progression. The following days some chills started and accompanied by a temperature increase, up to 36.x from my normal 35 degrees. But since I didn’t record the temperature systematically before, the temperature measurements of 36.x degrees were calming instead of ringing the bells. Later the temperatures further increased to 37.x and scratched 38 accompanied by a strange sticky feeling in the chest; at this point I started to consider Covid as likely. Counting everything up it likely was Covid-19. Noteworthy: The day before the first symptoms was long and rather stressful, so the immune system likely wasn’t in optimal state to control the viruses initially. The immune response was timely though: Less than twelve hours after the likely infection event (someone repeatedly coughing about 4 meters away in the same room and I was there for about 2 hours) the initial strange feeling started.
While light movement such as a short walk is recommended during mild to moderate Covid, intense exercise is strongly discouraged since it increases the risk for complications (movement chapter).