Difference between revisions of "Template:COVID-19 Testing, Reporting, and Information Management in the Laboratory/Overview of COVID-19 and its challenges/Challenges of managing the disease in the human population"

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[[File:Fig1 Li JofPharmAnal2020 10-2.jpg|right|thumb|650px|The graphical abstract from [https://doi.org/10.1016/j.jpha.2020.03.001 Li ''et al.'' 2020], showing general features of SARS-CoV-2, current knowledge of molecular immune pathogenesis, and diagnosis methods of COVID-19 based on present understanding of SARS-CoV and MERS-CoV viral infections]]COVID-19 has presented numerous societal challenges, from supply line interruptions and economic sagging to overwhelmed healthcare systems and civil disorder. However, these are largely the social, economic, and political ripple effects of a disease that has brought with it a set of inherent attributes that make it more difficult to manage in human populations than say the flu.  
[[File:Fig1 Li JofPharmAnal2020 10-2.jpg|right|thumb|650px|The graphical abstract from [https://doi.org/10.1016/j.jpha.2020.03.001 Li ''et al.'' 2020], showing general features of SARS-CoV-2, current knowledge of molecular immune pathogenesis, and diagnosis methods of COVID-19 based on present understanding of SARS-CoV and MERS-CoV viral infections]]COVID-19 has presented numerous societal challenges, from supply line interruptions and economic sagging to overwhelmed healthcare systems and civil disorder. However, these are largely the social, economic, and political ripple effects of a disease that has brought with it a set of inherent attributes that make it more difficult to manage in human populations than say the flu.  


However, COVID-19 is not the flu, and it is indeed worse in its effects than the flu, contrary to many people's perceptions. Yes, COVID-19 and the flu have some symptom overlap. Yes, COVID-19 and the flu have some transmission type overlap. But from there it diverges. COVID-19 is different in that it is more prone to be transmitted to others during the presymptomatic phase. The disease may also be transmittable in other ways, such as an airborne route, though research is ongoing.<ref name="AchenbachStudies20">{{cite web |url=https://www.washingtonpost.com/health/2020/04/29/studies-leave-question-airborne-coronavirus-transmission-unanswered/ |title=Studies leave question of ‘airborne’ coronavirus transmission unanswered |author=Achenach, J.; Johnson, C.Y. |work=The Washington Post |date=29 April 2020 |accessdate=01 May 2020}}</ref> Hospitalization rates are higher, perhaps up to 10 times higher than the flu, and hospital stays are longer with COVID-19. People are dying more often from COVID-19 too, up to 10 times more often than people stricken with the flu. And of course, whereas people have been acquiring the flu vaccine yearly, limiting the percentage of the population that becomes ill, there is yet no vaccine for COVID-19, meaning everyone is susceptible.<ref name="HuangHow20">{{cite web |url=https://www.npr.org/sections/goatsandsoda/2020/03/20/815408287/how-the-novel-coronavirus-and-the-flu-are-alike-and-different |title=How The Novel Coronavirus And The Flu Are Alike ... And Different |author=Huang, P. |work=NPR: Goats and Soda |date=20 March 2020 |accessdate=01 April 2020}}</ref><ref name="ResnickWhy20">{{cite web |url=https://www.vox.com/science-and-health/2020/3/18/21184992/coronavirus-covid-19-flu-comparison-chart |title=Why Covid-19 is worse than the flu, in one chart |author=Resnick, B.; Animashaun, C. |work=Vox |date=18 March 2020 |accessdate=01 April 2020}}</ref><ref name="KumarCOVID20">{{cite web |url=https://abcnews.go.com/Health/covid-19-compared-flu-experts-wrong/story?id=69779116 |title=COVID-19 has been compared to the flu. Experts say that's wrong |author=Kumar, V. |work=ABC News |date=27 March 2020 |accessdate=01 April 2020}}</ref>
However, COVID-19 is not the flu, and it is indeed worse in its effects than the flu, contrary to many people's perceptions. Yes, COVID-19 and the flu have some symptom overlap. Yes, COVID-19 and the flu have some transmission type overlap. But from there it diverges. COVID-19 is different in that it is more prone to be transmitted to others during the presymptomatic phase. And the body of evidence has grown since April<ref name="AchenbachStudies20">{{cite web |url=https://www.washingtonpost.com/health/2020/04/29/studies-leave-question-airborne-coronavirus-transmission-unanswered/ |title=Studies leave question of ‘airborne’ coronavirus transmission unanswered |author=Achenach, J.; Johnson, C.Y. |work=The Washington Post |date=29 April 2020 |accessdate=01 May 2020}}</ref> that SARS-CoV-2 is transmittable in other ways, such as an airborne route.<ref name="VanBeusekomGlobal20">{{cite web |url=https://www.cidrap.umn.edu/news-perspective/2020/07/global-experts-ignoring-airborne-covid-spread-risky |title=Global experts: Ignoring airborne COVID spread risky |author=Van Beusekom, M. |work=Center for Infectious Disease Research and Policy |publisher=University of Minnesota |date=06 July 2020 |accessdate=07 July 2020}}</ref><ref name="DucharmeTheWHO20">{{cite web |url=https://time.com/5863220/airborne-coronavirus-transmission/ |title=The WHO Says Airborne Coronavirus Transmission Isn't a Big Risk. Scientists Are Pushing Back |author=Ducharme, J. |work=Time |date=07 July 2020 |accessdate=07 July 2020}}</ref> Hospitalization rates are higher, perhaps up to 10 times higher than the flu, and hospital stays are longer with COVID-19. People are dying more often from COVID-19 too, up to 10 times more often than people stricken with the flu. And of course, whereas people have been acquiring the flu vaccine yearly, limiting the percentage of the population that becomes ill, there is yet no vaccine for COVID-19, meaning everyone is susceptible.<ref name="HuangHow20">{{cite web |url=https://www.npr.org/sections/goatsandsoda/2020/03/20/815408287/how-the-novel-coronavirus-and-the-flu-are-alike-and-different |title=How The Novel Coronavirus And The Flu Are Alike ... And Different |author=Huang, P. |work=NPR: Goats and Soda |date=20 March 2020 |accessdate=01 April 2020}}</ref><ref name="ResnickWhy20">{{cite web |url=https://www.vox.com/science-and-health/2020/3/18/21184992/coronavirus-covid-19-flu-comparison-chart |title=Why Covid-19 is worse than the flu, in one chart |author=Resnick, B.; Animashaun, C. |work=Vox |date=18 March 2020 |accessdate=01 April 2020}}</ref><ref name="KumarCOVID20">{{cite web |url=https://abcnews.go.com/Health/covid-19-compared-flu-experts-wrong/story?id=69779116 |title=COVID-19 has been compared to the flu. Experts say that's wrong |author=Kumar, V. |work=ABC News |date=27 March 2020 |accessdate=01 April 2020}}</ref>


Other aspects of the disease that make this difficult to manage include:
Other aspects of the disease that make this difficult to manage include:
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* ''Median incubation period'': According to research published in ''Annals of Internal Medicine'', the median (i.e., the central tendency, which is less skewed than average<ref name="NRCSMedian">{{cite web |url=https://www.wcc.nrcs.usda.gov/normals/median_average.htm |title=Median vs. Average to Describe Normal |author=National Water and Climate Center |publisher=U.S. Department of Agriculture |accessdate=01 April 2020}}</ref>) incubation period is 5.1 days, with 97.5% of symptomatic carriers showing symptoms within 11.5 days. The authors found this to be compatible with U.S. government recommendations of monitored 14-day self-quarantines if individuals were at risk of exposure.<ref name="LauerTheInc20">{{cite journal |title=The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application |journal=Annals of Internal Medicine |author=Lauer, S.A.; Grantz, K.H.; Bi, Q. et al. |year=2020 |doi=10.7326/M20-0504 |pmid=32150748 |pmc=PMC7081172}}</ref> However, many people continue to not take self-quarantines and other forms of social distancing seriously<ref name="PinskerWhatDo20">{{cite web |url=https://www.theatlantic.com/family/archive/2020/03/convince-family-take-coronavirus-seriously/608356/ |title=What Do You Tell Someone Who Still Won’t Stay Home? |author=Pinsker, J. |work=The Atlantic |date=19 March 2020 |accessdate=01 April 2020}}</ref><ref name="KeatingWhenThe20">{{cite web |url=https://www.buzzfeednews.com/article/shannonkeating/coronavirus-social-distancing-self-isolation-quarantine |title=When The People You Love Can’t Accept That They Need To Stay Home |author=Keating, S. |work=BuzzFeed News |date=17 March 2020 |accessdate=01 April 2020}}</ref><ref name="JacksonPolice20">{{cite web |url=https://www.cnn.com/2020/03/31/us/violating-coronavirus-orders-trnd/index.html |title=Police are arresting and fining people for violating social distancing orders |author=Jackson, A. |work=CNN |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="WFLA8Hawaii20">{{cite web |url=https://www.wfla.com/community/health/coronavirus/hawaii-police-arrest-visiting-tampa-man-for-violating-14-day-quarantine/ |title=Hawaii police arrest visiting Tampa man for violating 14-day quarantine order |author=WFLA 8 On Your Side Staff |work=WFLA News Channel 8 |date=31 March 2020 |accessdate=01 April 2020}}</ref>, and presymptomatic (and asymptomatic) carriers are thus more prone to spreading the virus.<ref name="MandavilliInfected20">{{cite web |url=https://www.nytimes.com/2020/03/31/health/coronavirus-asymptomatic-transmission.html |title=Infected but Feeling Fine: The Unwitting Coronavirus Spreaders |author=Mandavilli, A. |work=The New York Times |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="MockAsymptom20">{{cite web |url=https://www.discovermagazine.com/health/asymptomatic-carriers-are-fueling-the-covid-19-pandemic-heres-why-you-dont |title=Asymptomatic Carriers Are Fueling the COVID-19 Pandemic. Here’s Why You Don’t Have to Feel Sick to Spread the Disease |author=Mock, J. |work=Discover |date=26 March 2020 |accessdate=01 April 2020}}</ref>
* ''Median incubation period'': According to research published in ''Annals of Internal Medicine'', the median (i.e., the central tendency, which is less skewed than average<ref name="NRCSMedian">{{cite web |url=https://www.wcc.nrcs.usda.gov/normals/median_average.htm |title=Median vs. Average to Describe Normal |author=National Water and Climate Center |publisher=U.S. Department of Agriculture |accessdate=01 April 2020}}</ref>) incubation period is 5.1 days, with 97.5% of symptomatic carriers showing symptoms within 11.5 days. The authors found this to be compatible with U.S. government recommendations of monitored 14-day self-quarantines if individuals were at risk of exposure.<ref name="LauerTheInc20">{{cite journal |title=The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application |journal=Annals of Internal Medicine |author=Lauer, S.A.; Grantz, K.H.; Bi, Q. et al. |year=2020 |doi=10.7326/M20-0504 |pmid=32150748 |pmc=PMC7081172}}</ref> However, many people continue to not take self-quarantines and other forms of social distancing seriously<ref name="PinskerWhatDo20">{{cite web |url=https://www.theatlantic.com/family/archive/2020/03/convince-family-take-coronavirus-seriously/608356/ |title=What Do You Tell Someone Who Still Won’t Stay Home? |author=Pinsker, J. |work=The Atlantic |date=19 March 2020 |accessdate=01 April 2020}}</ref><ref name="KeatingWhenThe20">{{cite web |url=https://www.buzzfeednews.com/article/shannonkeating/coronavirus-social-distancing-self-isolation-quarantine |title=When The People You Love Can’t Accept That They Need To Stay Home |author=Keating, S. |work=BuzzFeed News |date=17 March 2020 |accessdate=01 April 2020}}</ref><ref name="JacksonPolice20">{{cite web |url=https://www.cnn.com/2020/03/31/us/violating-coronavirus-orders-trnd/index.html |title=Police are arresting and fining people for violating social distancing orders |author=Jackson, A. |work=CNN |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="WFLA8Hawaii20">{{cite web |url=https://www.wfla.com/community/health/coronavirus/hawaii-police-arrest-visiting-tampa-man-for-violating-14-day-quarantine/ |title=Hawaii police arrest visiting Tampa man for violating 14-day quarantine order |author=WFLA 8 On Your Side Staff |work=WFLA News Channel 8 |date=31 March 2020 |accessdate=01 April 2020}}</ref>, and presymptomatic (and asymptomatic) carriers are thus more prone to spreading the virus.<ref name="MandavilliInfected20">{{cite web |url=https://www.nytimes.com/2020/03/31/health/coronavirus-asymptomatic-transmission.html |title=Infected but Feeling Fine: The Unwitting Coronavirus Spreaders |author=Mandavilli, A. |work=The New York Times |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="MockAsymptom20">{{cite web |url=https://www.discovermagazine.com/health/asymptomatic-carriers-are-fueling-the-covid-19-pandemic-heres-why-you-dont |title=Asymptomatic Carriers Are Fueling the COVID-19 Pandemic. Here’s Why You Don’t Have to Feel Sick to Spread the Disease |author=Mock, J. |work=Discover |date=26 March 2020 |accessdate=01 April 2020}}</ref>


* ''Presymptomatic and asymptomatic virus shedding'': As mentioned in the previous point, carriers can be contagious during the presymptomatic phase of the disease, even while remaining symptom-free.<ref name="MandavilliInfected20" /><ref name="MockAsymptom20" /><ref name="YuenSARS20">{{cite journal |title=SARS-CoV-2 and COVID-19: The most important research questions |journal=Cell & Bioscience |author=Yuen, K.-S.; Fung, S.-Y.; Chan, C.-P.; Jin, D.-Y. |volume=10 |at=40 |year=2020 |doi=10.1186/s13578-020-00404-4 |pmid=32190290 |pmc=PMC7074995}}</ref><ref name="DiamondAsympt20">{{cite web |url=https://www.infectioncontroltoday.com/covid-19/asymptomatic-carriers-covid-19-make-it-tough-target |title=Asymptomatic Carriers of COVID-19 Make It Tough to Target |author=Diamond, F. |work=Infection Control Today |date=17 March 2020 |accessdate=01 April 2020}}</ref> This contagion is a result of what's called [[viral shedding]], when the virus moves from cell to cell following successful reproduction. When the virus is in this state, it can be actively found in a carrier's body fluids, excrement, and other sources. Depending on the virus, the virus can then be introduced to another person via those sources. In the case of COVID-19, the route of transmission is still being studied<ref name="JordanEnviron20">{{cite web |url=https://news.stanford.edu/2020/03/26/understanding-spread-covid-19/ |title=Environmental engineers at Stanford discuss how to identify factors affecting COVID-19 transmission |author=Jordan, R. |work=Stanford News |date=26 March 2020 |accessdate=01 April 2020}}</ref><ref name="GreenfieldboyceWHO20">{{cite web |url=https://www.npr.org/2020/03/28/823292062/who-reviews-available-evidence-on-coronavirus-transmission-through-air |title=WHO Reviews 'Current' Evidence On Coronavirus Transmission Through Air |author=Greenfieldboyce, N. |work=NPR |date=28 March 2020 |accessdate=01 April 2020}}</ref>, though water droplets (from sneezes, cough, talking, etc.) and potentially even aerosolized water droplets (water droplets from the body that have become fine spray or suspension in the air) are likely sources.<ref name="GreenfieldboyceWHO20" /> This initial uncertainty of transmission routes, along with mixed messages early on about masks and their effectiveness for COVID-19<ref name="GreenfieldboyceWHO20" /><ref name="CSTEditorialIgnore31">{{cite web |url=https://chicago.suntimes.com/2020/3/31/21200144/coronavirus-covid-19-masks-wear-cdc-pritzker-trump-public-health-virus-face-cough-sneeze |title=Ignore the mixed messages and wear that mask |author=Chicago Sun Times Editorial Board |work=Chicago Sun Times |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="MulhollandToMask20">{{cite web |url=http://www.rfi.fr/en/international/20200329-to-mask-or-not-to-mask-mixed-messages-in-a-time-of-coronavirus-crisis-france-covid-19-spread-droplets |title=To mask or not to mask: mixed messages in a time of crisis |author=Mulholland, J. |work=RFI |date=29 March 2020 |accessdate=01 April 2020}}</ref>, makes social distancing an even stronger necessity to limit community transmission of the disease.
* ''Presymptomatic and asymptomatic virus shedding'': As mentioned in the previous point, carriers can be contagious during the presymptomatic phase of the disease, even while remaining symptom-free.<ref name="MandavilliInfected20" /><ref name="MockAsymptom20" /><ref name="YuenSARS20">{{cite journal |title=SARS-CoV-2 and COVID-19: The most important research questions |journal=Cell & Bioscience |author=Yuen, K.-S.; Fung, S.-Y.; Chan, C.-P.; Jin, D.-Y. |volume=10 |at=40 |year=2020 |doi=10.1186/s13578-020-00404-4 |pmid=32190290 |pmc=PMC7074995}}</ref><ref name="DiamondAsympt20">{{cite web |url=https://www.infectioncontroltoday.com/covid-19/asymptomatic-carriers-covid-19-make-it-tough-target |title=Asymptomatic Carriers of COVID-19 Make It Tough to Target |author=Diamond, F. |work=Infection Control Today |date=17 March 2020 |accessdate=01 April 2020}}</ref> (Rough estimates appear to indicate that anywhere between 25 to 45 percent of infected people may go without any recognizable symptoms after infection occurs.<ref name="LovelaceJrDrAnthony20">{{cite web |url=https://www.cnbc.com/2020/06/10/dr-anthony-fauci-says-whos-remark-on-asymptomatic-coronavirus-spread-was-not-correct.html |title=Dr. Anthony Fauci says WHO’s remark on asymptomatic coronavirus spread ‘was not correct’ |author=Lovelace Jr., B. |work=CNBC |date=10 June 2020 |accessdate=07 July 2020}}</ref>) This contagion is a result of what's called [[viral shedding]], when the virus moves from cell to cell following successful reproduction. When the virus is in this state, it can be actively found in a carrier's body fluids, excrement, and other sources. Depending on the virus, the virus can then be introduced to another person via those sources. In the case of COVID-19, the route of transmission is still being studied<ref name="JordanEnviron20">{{cite web |url=https://news.stanford.edu/2020/03/26/understanding-spread-covid-19/ |title=Environmental engineers at Stanford discuss how to identify factors affecting COVID-19 transmission |author=Jordan, R. |work=Stanford News |date=26 March 2020 |accessdate=01 April 2020}}</ref><ref name="GreenfieldboyceWHO20">{{cite web |url=https://www.npr.org/2020/03/28/823292062/who-reviews-available-evidence-on-coronavirus-transmission-through-air |title=WHO Reviews 'Current' Evidence On Coronavirus Transmission Through Air |author=Greenfieldboyce, N. |work=NPR |date=28 March 2020 |accessdate=01 April 2020}}</ref>, though water droplets (from sneezes, cough, talking, etc.) and potentially even aerosolized water droplets (water droplets from the body that have become fine spray or suspension in the air) are likely sources.<ref name="GreenfieldboyceWHO20" /> This initial uncertainty of transmission routes, along with mixed messages early on about masks and their effectiveness for COVID-19<ref name="GreenfieldboyceWHO20" /><ref name="CSTEditorialIgnore31">{{cite web |url=https://chicago.suntimes.com/2020/3/31/21200144/coronavirus-covid-19-masks-wear-cdc-pritzker-trump-public-health-virus-face-cough-sneeze |title=Ignore the mixed messages and wear that mask |author=Chicago Sun Times Editorial Board |work=Chicago Sun Times |date=31 March 2020 |accessdate=01 April 2020}}</ref><ref name="MulhollandToMask20">{{cite web |url=http://www.rfi.fr/en/international/20200329-to-mask-or-not-to-mask-mixed-messages-in-a-time-of-coronavirus-crisis-france-covid-19-spread-droplets |title=To mask or not to mask: mixed messages in a time of crisis |author=Mulholland, J. |work=RFI |date=29 March 2020 |accessdate=01 April 2020}}</ref>, makes social distancing an even stronger necessity to limit community transmission of the disease.


* ''Understanding of high viral loads and infectious doses'': Respiratory diseases such as influenza, SARS, and MERS see a correlation between the infectious dose amount and the severity of disease symptoms, meaning the higher the infectious dose, the worse the symptoms.<ref name="GeddesDoesA20">{{cite web |url=https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/ |title=Does a high viral load or infectious dose make covid-19 worse? |author=Geddes, L. |work=New Scientist |date=27 March 2020 |accessdate=01 April 2020}}</ref> Similarly, viral load—a quantification of viral genomic fragments—also tends to correlate with clinical symptoms.<ref name="HijanoClinical19">{{cite journal |title=Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR |journal=PLoS One |author=Hijano, D.R.; Brazelton de Cardenas, J.; Maron, G. et al. |volume=14 |issue=9 |at=e0220908 |year=2019 |doi=10.1371/journal.pone.0220908 |pmid=31479459 |pmc=PMC6720028}}</ref>  However, we are still in the investigative stages of determining if that similarly holds true to COVID-19.<ref name="GeddesDoesA20" /><ref name="LiuViral20">{{cite journal |title=Viral dynamics in mild and severe cases of COVID-19 |journal=The Lancet Infectious Diseases |author=Liu, Y.; Yan, L.-M.; Wan, L. et al. |year=2020 |doi=10.1016/S1473-3099(20)30232-2 |pmid=32199493}}</ref><ref name="JoyntUnder20">{{cite journal |title=Understanding COVID-19: what does viral RNA load really mean? |journal=The Lancet Infectious Diseases |author=Joynt, G.M.; Wu, W.K.K. |year=2020 |doi=10.1016/S1473-3099(20)30237-1}}</ref> Early research seem to indicate, for example, there is little difference between the viral load of those with mild or no COVID-19 symptoms and those with more severe symptoms.<ref name="GeddesDoesA20" /> More research must be performed to better understand how the viral load infectious dose plays a role in transmission. Given these unknowns, social distancing, wearing masks, and other means of minimizing exposure remain the best defense against the disease.<ref name="GeddesDoesA20" />
* ''Understanding of high viral loads and infectious doses'': Respiratory diseases such as influenza, SARS, and MERS see a correlation between the infectious dose amount and the severity of disease symptoms, meaning the higher the infectious dose, the worse the symptoms.<ref name="GeddesDoesA20">{{cite web |url=https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/ |title=Does a high viral load or infectious dose make covid-19 worse? |author=Geddes, L. |work=New Scientist |date=27 March 2020 |accessdate=01 April 2020}}</ref> Similarly, viral load—a quantification of viral genomic fragments—also tends to correlate with clinical symptoms.<ref name="HijanoClinical19">{{cite journal |title=Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR |journal=PLoS One |author=Hijano, D.R.; Brazelton de Cardenas, J.; Maron, G. et al. |volume=14 |issue=9 |at=e0220908 |year=2019 |doi=10.1371/journal.pone.0220908 |pmid=31479459 |pmc=PMC6720028}}</ref>  However, we are still in the investigative stages of determining if that similarly holds true to COVID-19.<ref name="GeddesDoesA20" /><ref name="LiuViral20">{{cite journal |title=Viral dynamics in mild and severe cases of COVID-19 |journal=The Lancet Infectious Diseases |author=Liu, Y.; Yan, L.-M.; Wan, L. et al. |year=2020 |doi=10.1016/S1473-3099(20)30232-2 |pmid=32199493}}</ref><ref name="JoyntUnder20">{{cite journal |title=Understanding COVID-19: what does viral RNA load really mean? |journal=The Lancet Infectious Diseases |author=Joynt, G.M.; Wu, W.K.K. |year=2020 |doi=10.1016/S1473-3099(20)30237-1}}</ref> Early research seem to indicate, for example, there is little difference between the viral load of those with mild or no COVID-19 symptoms and those with more severe symptoms.<ref name="GeddesDoesA20" /> More research must be performed to better understand how the viral load infectious dose plays a role in transmission. Given these unknowns, social distancing, wearing masks, and other means of minimizing exposure remain the best defense against the disease.<ref name="GeddesDoesA20" />


* ''Cardiovascular issues'': Coronaviruses and their accompanying respiratory infections are known to complicate issues of the cardiovascular system, which in turn may "increase the incidence and severity" of infectious diseases such as SARS and COVID-19.<ref name="MadjidPotent20">{{cite journal |title=Potential Effects of Coronaviruses on the Cardiovascular System |journal=JAMA Cardiology |author=Madjid, M.; Safavi-Naeini, P.; Solomon, S.D. |year=2020 |doi=10.1001/jamacardio.2020.1286 |pmid=32219363}}</ref><ref name="XiongCorona20">{{cite journal |title=Coronaviruses and the cardiovascular system: acute and long-term implications |journal=European Heart Journal |author=Xiong, T.-Y.; Redwood, S.; Prendergast, B.; Chen, M. |at=ehaa231 |year=2020 |doi=10.1093/eurheartj/ehaa231 |pmid=32186331}}</ref><ref name="DrigginCardio20">{{cite journal |title=Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic |journal=Journal of the American College of Cardiology |author=Driggin, E.; Madhavan, M.V.; Bikdeli, B. et al. |year=2020 |doi=10.1016/j.jacc.2020.03.031 |pmid=32201335}}</ref> While the exact cardiac effect COVID-19 has on patients is still unknown, suspicion is those with "hypertension, diabetes, and diagnosed cardiovascular disease" may be more prone to having cardiovascular complications from the disease.<ref name="OttoCardiac20">{{cite web |url=https://www.the-hospitalist.org/hospitalist/article/219645/coronavirus-updates/cardiac-symptoms-can-be-first-sign-covid-19 |title=Cardiac symptoms can be first sign of COVID-19 |author=Otto, M.A. |work=The Hospitalist |date=26 March 2020 |accessdate=01 April 2020}}</ref><ref name="ClerkinCorona20">{{cite journal |title=Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease |journal=Circulation |author=Clerkin, K.J.; Fried, J.A.; Raikhelkar, J. et al. |year=2020 |doi=10.1161/CIRCULATIONAHA.120.046941 |pmid=32200663}}</ref> Current thinking is SARS-CoV-2 either attacks heart tissues, causing myocardial dysfunction, or inevitably causes heart failure through a "cytokine storm,"<ref name="MadjidPotent20" /><ref name="XiongCorona20" /><ref name="OttoCardiac20" /><ref name="ClerkinCorona20" /><ref name="MehtaCOVID20">{{cite journal |title=COVID-19: Consider cytokine storm syndromes and immunosuppression |journal=The Lancet |author=Mehta, P.; McAuley, D.F.; Brown, M. et al. |volume=395 |issue=10229 |pages=P1033–34 |year=2020 |doi=10.1016/S0140-6736(20)30628-0 |pmid=32192578}}</ref><ref name="MandavilliTheCoronaCyto20">{{cite web |url=https://www.nytimes.com/2020/04/01/health/coronavirus-cytokine-storm-immune-system.html |title=The Coronavirus Patients Betrayed by Their Own Immune Systems |author=Mandavilli, A. |work=The New York Times |date=01 April 2020 |accessdate=01 April 2020}}</ref>, an overproduction of signaling molecules that promote inflammation by white blood cells (leukocytes).<ref name="TisoncikInto12">{{cite journal |title=Into the eye of the cytokine storm |journal=Microbiology and Molecular Biology Reviews |author=Tisoncik, J.R.; Korth, M.J.; Simmons, C.P. et al. |volume=76 |issue=1 |pages=16–32 |year=2012 |doi=10.1128/MMBR.05015-11 |pmid=22390970 |pmc=PMC3294426}}</ref> What's scary is that like the 1918 Spanish flu, SARS, and other epidemics, some otherwise healthy patients' immune responses are entirely overreactive, leading to acute respiratory distress syndrome (ARDS) or heart failure.<ref name="MandavilliTheCoronaCyto20" /><ref name="BasilioANew20">{{cite web |url=https://www.mdlinx.com/internal-medicine/article/6590 |title=A new potential risk of COVID-19: Sudden cardiac death |author=Basilio, P. |work=MDLinx |date=26 March 2020 |accessdate=01 April 2020}}</ref> Additionally, as the disease has progressed, medical professionals have noted two additional cardiovascular issues. First, an atypical amount of blood clotting has shown up in some infected patients, which may or may not be related to overreactive immune systems and underlying health conditions.<ref name="RettnerMyster20">{{cite web |url=https://www.livescience.com/coronavirus-blood-clots.html |title=Mysterious blood clots in COVID-19 patients have doctors alarmed |author=Rettner, R. |work=LiveScience |date=23 April 2020 |accessdate=28 April 2020}}</ref> Second, what is being called pediatric multisystem inflammatory syndrome (PMIS) is beginning to show up in children after the infection has passed, characterized by inflamed blood vessels and toxic shock syndrome.<ref name="MoyerWhatWe20">{{cite web |url=https://www.nytimes.com/2020/05/19/parenting/pmis-coronavirus-children.html |title=What We Know About the Covid-Related Syndrome Affecting Children |work=The New York Times |author=Moyer, M.W. |date=19 May 2020 |accessdate=19 May 2020}}</ref><ref name="FischerWhatTo20">{{cite web |url=https://www.healthline.com/health-news/what-to-know-pmis-syndrome-linked-to-covid-19-affects-children |title=What to Know About PMIS, the COVID-19-Linked Syndrome Affecting Children |work=Healthline |author=Fischer, K. |date=18 May 2020 |accessdate=19 May 2020}}</ref> These uncertainties only add to the level of difficulty of properly treating COVID-19.
* ''Cardiovascular issues'': Coronaviruses and their accompanying respiratory infections are known to complicate issues of the cardiovascular system, which in turn may "increase the incidence and severity" of infectious diseases such as SARS and COVID-19.<ref name="MadjidPotent20">{{cite journal |title=Potential Effects of Coronaviruses on the Cardiovascular System |journal=JAMA Cardiology |author=Madjid, M.; Safavi-Naeini, P.; Solomon, S.D. |year=2020 |doi=10.1001/jamacardio.2020.1286 |pmid=32219363}}</ref><ref name="XiongCorona20">{{cite journal |title=Coronaviruses and the cardiovascular system: acute and long-term implications |journal=European Heart Journal |author=Xiong, T.-Y.; Redwood, S.; Prendergast, B.; Chen, M. |at=ehaa231 |year=2020 |doi=10.1093/eurheartj/ehaa231 |pmid=32186331}}</ref><ref name="DrigginCardio20">{{cite journal |title=Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic |journal=Journal of the American College of Cardiology |author=Driggin, E.; Madhavan, M.V.; Bikdeli, B. et al. |year=2020 |doi=10.1016/j.jacc.2020.03.031 |pmid=32201335}}</ref> While the exact cardiac effect COVID-19 has on patients is still unknown, suspicion is those with "hypertension, diabetes, and diagnosed cardiovascular disease" may be more prone to having cardiovascular complications from the disease.<ref name="OttoCardiac20">{{cite web |url=https://www.the-hospitalist.org/hospitalist/article/219645/coronavirus-updates/cardiac-symptoms-can-be-first-sign-covid-19 |title=Cardiac symptoms can be first sign of COVID-19 |author=Otto, M.A. |work=The Hospitalist |date=26 March 2020 |accessdate=01 April 2020}}</ref><ref name="ClerkinCorona20">{{cite journal |title=Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease |journal=Circulation |author=Clerkin, K.J.; Fried, J.A.; Raikhelkar, J. et al. |year=2020 |doi=10.1161/CIRCULATIONAHA.120.046941 |pmid=32200663}}</ref> Current thinking is SARS-CoV-2 either attacks heart tissues, causing myocardial dysfunction, or inevitably causes heart failure through a "cytokine storm,"<ref name="MadjidPotent20" /><ref name="XiongCorona20" /><ref name="OttoCardiac20" /><ref name="ClerkinCorona20" /><ref name="MehtaCOVID20">{{cite journal |title=COVID-19: Consider cytokine storm syndromes and immunosuppression |journal=The Lancet |author=Mehta, P.; McAuley, D.F.; Brown, M. et al. |volume=395 |issue=10229 |pages=P1033–34 |year=2020 |doi=10.1016/S0140-6736(20)30628-0 |pmid=32192578}}</ref><ref name="MandavilliTheCoronaCyto20">{{cite web |url=https://www.nytimes.com/2020/04/01/health/coronavirus-cytokine-storm-immune-system.html |title=The Coronavirus Patients Betrayed by Their Own Immune Systems |author=Mandavilli, A. |work=The New York Times |date=01 April 2020 |accessdate=01 April 2020}}</ref>, an overproduction of signaling molecules that promote inflammation by white blood cells (leukocytes).<ref name="TisoncikInto12">{{cite journal |title=Into the eye of the cytokine storm |journal=Microbiology and Molecular Biology Reviews |author=Tisoncik, J.R.; Korth, M.J.; Simmons, C.P. et al. |volume=76 |issue=1 |pages=16–32 |year=2012 |doi=10.1128/MMBR.05015-11 |pmid=22390970 |pmc=PMC3294426}}</ref> What's scary is that like the 1918 Spanish flu, SARS, and other epidemics, some otherwise healthy patients' immune responses are entirely overreactive, leading to acute respiratory distress syndrome (ARDS) or heart failure.<ref name="MandavilliTheCoronaCyto20" /><ref name="BasilioANew20">{{cite web |url=https://www.mdlinx.com/internal-medicine/article/6590 |title=A new potential risk of COVID-19: Sudden cardiac death |author=Basilio, P. |work=MDLinx |date=26 March 2020 |accessdate=01 April 2020}}</ref> Additionally, as the disease has progressed, medical professionals have noted two additional cardiovascular issues. First, an atypical amount of blood clotting has shown up in some infected patients, which may or may not be related to overreactive immune systems and underlying health conditions.<ref name="RettnerMyster20">{{cite web |url=https://www.livescience.com/coronavirus-blood-clots.html |title=Mysterious blood clots in COVID-19 patients have doctors alarmed |author=Rettner, R. |work=LiveScience |date=23 April 2020 |accessdate=28 April 2020}}</ref> Second, what is being called pediatric multisystem inflammatory syndrome (PMIS) is beginning to show up in children after the infection has passed, characterized by inflamed blood vessels and toxic shock syndrome.<ref name="MoyerWhatWe20">{{cite web |url=https://www.nytimes.com/2020/05/19/parenting/pmis-coronavirus-children.html |title=What We Know About the Covid-Related Syndrome Affecting Children |work=The New York Times |author=Moyer, M.W. |date=19 May 2020 |accessdate=19 May 2020}}</ref><ref name="FischerWhatTo20">{{cite web |url=https://www.healthline.com/health-news/what-to-know-pmis-syndrome-linked-to-covid-19-affects-children |title=What to Know About PMIS, the COVID-19-Linked Syndrome Affecting Children |work=Healthline |author=Fischer, K. |date=18 May 2020 |accessdate=19 May 2020}}</ref> While research is ongoing to determine whether these seemingly hyperactive cardiovascular responses are directly linked to the virus<ref name="MannePlatelet20">{cite journal |title=Platelet Gene Expression and Function in COVID-19 Patients |journal=Blood |author=Manne, B.K.; Denorme, F.; Middleton, E.A. et al. |at=blood.2020007214 |year=2020 |doi=10.1182/blood.2020007214}}</ref> or if virus-independent immunopathology is responsible<ref name="DorwardTissue20">{{cite journal |title=Tissue-specific tolerance in fatal Covid-19 |journal=medRxiv |author=Dorward, D.A.; Russell, C.D.; Um, I.H. et al. |year=2020 |doi=10.1101/2020.07.02.20145003}}</ref>, these uncertainties only emphasize the level of difficulty of properly treating COVID-19.

Revision as of 23:45, 7 July 2020

1.3 Challenges of managing the disease in the human population

The graphical abstract from Li et al. 2020, showing general features of SARS-CoV-2, current knowledge of molecular immune pathogenesis, and diagnosis methods of COVID-19 based on present understanding of SARS-CoV and MERS-CoV viral infections

COVID-19 has presented numerous societal challenges, from supply line interruptions and economic sagging to overwhelmed healthcare systems and civil disorder. However, these are largely the social, economic, and political ripple effects of a disease that has brought with it a set of inherent attributes that make it more difficult to manage in human populations than say the flu.

However, COVID-19 is not the flu, and it is indeed worse in its effects than the flu, contrary to many people's perceptions. Yes, COVID-19 and the flu have some symptom overlap. Yes, COVID-19 and the flu have some transmission type overlap. But from there it diverges. COVID-19 is different in that it is more prone to be transmitted to others during the presymptomatic phase. And the body of evidence has grown since April[1] that SARS-CoV-2 is transmittable in other ways, such as an airborne route.[2][3] Hospitalization rates are higher, perhaps up to 10 times higher than the flu, and hospital stays are longer with COVID-19. People are dying more often from COVID-19 too, up to 10 times more often than people stricken with the flu. And of course, whereas people have been acquiring the flu vaccine yearly, limiting the percentage of the population that becomes ill, there is yet no vaccine for COVID-19, meaning everyone is susceptible.[4][5][6]

Other aspects of the disease that make this difficult to manage include:

  • Median incubation period: According to research published in Annals of Internal Medicine, the median (i.e., the central tendency, which is less skewed than average[7]) incubation period is 5.1 days, with 97.5% of symptomatic carriers showing symptoms within 11.5 days. The authors found this to be compatible with U.S. government recommendations of monitored 14-day self-quarantines if individuals were at risk of exposure.[8] However, many people continue to not take self-quarantines and other forms of social distancing seriously[9][10][11][12], and presymptomatic (and asymptomatic) carriers are thus more prone to spreading the virus.[13][14]
  • Presymptomatic and asymptomatic virus shedding: As mentioned in the previous point, carriers can be contagious during the presymptomatic phase of the disease, even while remaining symptom-free.[13][14][15][16] (Rough estimates appear to indicate that anywhere between 25 to 45 percent of infected people may go without any recognizable symptoms after infection occurs.[17]) This contagion is a result of what's called viral shedding, when the virus moves from cell to cell following successful reproduction. When the virus is in this state, it can be actively found in a carrier's body fluids, excrement, and other sources. Depending on the virus, the virus can then be introduced to another person via those sources. In the case of COVID-19, the route of transmission is still being studied[18][19], though water droplets (from sneezes, cough, talking, etc.) and potentially even aerosolized water droplets (water droplets from the body that have become fine spray or suspension in the air) are likely sources.[19] This initial uncertainty of transmission routes, along with mixed messages early on about masks and their effectiveness for COVID-19[19][20][21], makes social distancing an even stronger necessity to limit community transmission of the disease.
  • Understanding of high viral loads and infectious doses: Respiratory diseases such as influenza, SARS, and MERS see a correlation between the infectious dose amount and the severity of disease symptoms, meaning the higher the infectious dose, the worse the symptoms.[22] Similarly, viral load—a quantification of viral genomic fragments—also tends to correlate with clinical symptoms.[23] However, we are still in the investigative stages of determining if that similarly holds true to COVID-19.[22][24][25] Early research seem to indicate, for example, there is little difference between the viral load of those with mild or no COVID-19 symptoms and those with more severe symptoms.[22] More research must be performed to better understand how the viral load infectious dose plays a role in transmission. Given these unknowns, social distancing, wearing masks, and other means of minimizing exposure remain the best defense against the disease.[22]
  • Cardiovascular issues: Coronaviruses and their accompanying respiratory infections are known to complicate issues of the cardiovascular system, which in turn may "increase the incidence and severity" of infectious diseases such as SARS and COVID-19.[26][27][28] While the exact cardiac effect COVID-19 has on patients is still unknown, suspicion is those with "hypertension, diabetes, and diagnosed cardiovascular disease" may be more prone to having cardiovascular complications from the disease.[29][30] Current thinking is SARS-CoV-2 either attacks heart tissues, causing myocardial dysfunction, or inevitably causes heart failure through a "cytokine storm,"[26][27][29][30][31][32], an overproduction of signaling molecules that promote inflammation by white blood cells (leukocytes).[33] What's scary is that like the 1918 Spanish flu, SARS, and other epidemics, some otherwise healthy patients' immune responses are entirely overreactive, leading to acute respiratory distress syndrome (ARDS) or heart failure.[32][34] Additionally, as the disease has progressed, medical professionals have noted two additional cardiovascular issues. First, an atypical amount of blood clotting has shown up in some infected patients, which may or may not be related to overreactive immune systems and underlying health conditions.[35] Second, what is being called pediatric multisystem inflammatory syndrome (PMIS) is beginning to show up in children after the infection has passed, characterized by inflamed blood vessels and toxic shock syndrome.[36][37] While research is ongoing to determine whether these seemingly hyperactive cardiovascular responses are directly linked to the virus[38] or if virus-independent immunopathology is responsible[39], these uncertainties only emphasize the level of difficulty of properly treating COVID-19.
  1. ↑ Achenach, J.; Johnson, C.Y. (29 April 2020). "Studies leave question of ‘airborne’ coronavirus transmission unanswered". The Washington Post. https://www.washingtonpost.com/health/2020/04/29/studies-leave-question-airborne-coronavirus-transmission-unanswered/. Retrieved 01 May 2020. 
  2. ↑ Van Beusekom, M. (6 July 2020). "Global experts: Ignoring airborne COVID spread risky". Center for Infectious Disease Research and Policy. University of Minnesota. https://www.cidrap.umn.edu/news-perspective/2020/07/global-experts-ignoring-airborne-covid-spread-risky. Retrieved 07 July 2020. 
  3. ↑ Ducharme, J. (7 July 2020). "The WHO Says Airborne Coronavirus Transmission Isn't a Big Risk. Scientists Are Pushing Back". Time. https://time.com/5863220/airborne-coronavirus-transmission/. Retrieved 07 July 2020. 
  4. ↑ Huang, P. (20 March 2020). "How The Novel Coronavirus And The Flu Are Alike ... And Different". NPR: Goats and Soda. https://www.npr.org/sections/goatsandsoda/2020/03/20/815408287/how-the-novel-coronavirus-and-the-flu-are-alike-and-different. Retrieved 01 April 2020. 
  5. ↑ Resnick, B.; Animashaun, C. (18 March 2020). "Why Covid-19 is worse than the flu, in one chart". Vox. https://www.vox.com/science-and-health/2020/3/18/21184992/coronavirus-covid-19-flu-comparison-chart. Retrieved 01 April 2020. 
  6. ↑ Kumar, V. (27 March 2020). "COVID-19 has been compared to the flu. Experts say that's wrong". ABC News. https://abcnews.go.com/Health/covid-19-compared-flu-experts-wrong/story?id=69779116. Retrieved 01 April 2020. 
  7. ↑ National Water and Climate Center. "Median vs. Average to Describe Normal". U.S. Department of Agriculture. https://www.wcc.nrcs.usda.gov/normals/median_average.htm. Retrieved 01 April 2020. 
  8. ↑ Lauer, S.A.; Grantz, K.H.; Bi, Q. et al. (2020). "The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application". Annals of Internal Medicine. doi:10.7326/M20-0504. PMC PMC7081172. PMID 32150748. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081172. 
  9. ↑ Pinsker, J. (19 March 2020). "What Do You Tell Someone Who Still Won’t Stay Home?". The Atlantic. https://www.theatlantic.com/family/archive/2020/03/convince-family-take-coronavirus-seriously/608356/. Retrieved 01 April 2020. 
  10. ↑ Keating, S. (17 March 2020). "When The People You Love Can’t Accept That They Need To Stay Home". BuzzFeed News. https://www.buzzfeednews.com/article/shannonkeating/coronavirus-social-distancing-self-isolation-quarantine. Retrieved 01 April 2020. 
  11. ↑ Jackson, A. (31 March 2020). "Police are arresting and fining people for violating social distancing orders". CNN. https://www.cnn.com/2020/03/31/us/violating-coronavirus-orders-trnd/index.html. Retrieved 01 April 2020. 
  12. ↑ WFLA 8 On Your Side Staff (31 March 2020). "Hawaii police arrest visiting Tampa man for violating 14-day quarantine order". WFLA News Channel 8. https://www.wfla.com/community/health/coronavirus/hawaii-police-arrest-visiting-tampa-man-for-violating-14-day-quarantine/. Retrieved 01 April 2020. 
  13. ↑ 13.0 13.1 Mandavilli, A. (31 March 2020). "Infected but Feeling Fine: The Unwitting Coronavirus Spreaders". The New York Times. https://www.nytimes.com/2020/03/31/health/coronavirus-asymptomatic-transmission.html. Retrieved 01 April 2020. 
  14. ↑ 14.0 14.1 Mock, J. (26 March 2020). "Asymptomatic Carriers Are Fueling the COVID-19 Pandemic. Here’s Why You Don’t Have to Feel Sick to Spread the Disease". Discover. https://www.discovermagazine.com/health/asymptomatic-carriers-are-fueling-the-covid-19-pandemic-heres-why-you-dont. Retrieved 01 April 2020. 
  15. ↑ Yuen, K.-S.; Fung, S.-Y.; Chan, C.-P.; Jin, D.-Y. (2020). "SARS-CoV-2 and COVID-19: The most important research questions". Cell & Bioscience 10: 40. doi:10.1186/s13578-020-00404-4. PMC PMC7074995. PMID 32190290. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074995. 
  16. ↑ Diamond, F. (17 March 2020). "Asymptomatic Carriers of COVID-19 Make It Tough to Target". Infection Control Today. https://www.infectioncontroltoday.com/covid-19/asymptomatic-carriers-covid-19-make-it-tough-target. Retrieved 01 April 2020. 
  17. ↑ Lovelace Jr., B. (10 June 2020). "Dr. Anthony Fauci says WHO’s remark on asymptomatic coronavirus spread ‘was not correct’". CNBC. https://www.cnbc.com/2020/06/10/dr-anthony-fauci-says-whos-remark-on-asymptomatic-coronavirus-spread-was-not-correct.html. Retrieved 07 July 2020. 
  18. ↑ Jordan, R. (26 March 2020). "Environmental engineers at Stanford discuss how to identify factors affecting COVID-19 transmission". Stanford News. https://news.stanford.edu/2020/03/26/understanding-spread-covid-19/. Retrieved 01 April 2020. 
  19. ↑ 19.0 19.1 19.2 Greenfieldboyce, N. (28 March 2020). "WHO Reviews 'Current' Evidence On Coronavirus Transmission Through Air". NPR. https://www.npr.org/2020/03/28/823292062/who-reviews-available-evidence-on-coronavirus-transmission-through-air. Retrieved 01 April 2020. 
  20. ↑ Chicago Sun Times Editorial Board (31 March 2020). "Ignore the mixed messages and wear that mask". Chicago Sun Times. https://chicago.suntimes.com/2020/3/31/21200144/coronavirus-covid-19-masks-wear-cdc-pritzker-trump-public-health-virus-face-cough-sneeze. Retrieved 01 April 2020. 
  21. ↑ Mulholland, J. (29 March 2020). "To mask or not to mask: mixed messages in a time of crisis". RFI. http://www.rfi.fr/en/international/20200329-to-mask-or-not-to-mask-mixed-messages-in-a-time-of-coronavirus-crisis-france-covid-19-spread-droplets. Retrieved 01 April 2020. 
  22. ↑ 22.0 22.1 22.2 22.3 Geddes, L. (27 March 2020). "Does a high viral load or infectious dose make covid-19 worse?". New Scientist. https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/. Retrieved 01 April 2020. 
  23. ↑ Hijano, D.R.; Brazelton de Cardenas, J.; Maron, G. et al. (2019). "Clinical correlation of influenza and respiratory syncytial virus load measured by digital PCR". PLoS One 14 (9): e0220908. doi:10.1371/journal.pone.0220908. PMC PMC6720028. PMID 31479459. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720028. 
  24. ↑ Liu, Y.; Yan, L.-M.; Wan, L. et al. (2020). "Viral dynamics in mild and severe cases of COVID-19". The Lancet Infectious Diseases. doi:10.1016/S1473-3099(20)30232-2. PMID 32199493. 
  25. ↑ Joynt, G.M.; Wu, W.K.K. (2020). "Understanding COVID-19: what does viral RNA load really mean?". The Lancet Infectious Diseases. doi:10.1016/S1473-3099(20)30237-1. 
  26. ↑ 26.0 26.1 Madjid, M.; Safavi-Naeini, P.; Solomon, S.D. (2020). "Potential Effects of Coronaviruses on the Cardiovascular System". JAMA Cardiology. doi:10.1001/jamacardio.2020.1286. PMID 32219363. 
  27. ↑ 27.0 27.1 Xiong, T.-Y.; Redwood, S.; Prendergast, B.; Chen, M. (2020). "Coronaviruses and the cardiovascular system: acute and long-term implications". European Heart Journal: ehaa231. doi:10.1093/eurheartj/ehaa231. PMID 32186331. 
  28. ↑ Driggin, E.; Madhavan, M.V.; Bikdeli, B. et al. (2020). "Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic". Journal of the American College of Cardiology. doi:10.1016/j.jacc.2020.03.031. PMID 32201335. 
  29. ↑ 29.0 29.1 Otto, M.A. (26 March 2020). "Cardiac symptoms can be first sign of COVID-19". The Hospitalist. https://www.the-hospitalist.org/hospitalist/article/219645/coronavirus-updates/cardiac-symptoms-can-be-first-sign-covid-19. Retrieved 01 April 2020. 
  30. ↑ 30.0 30.1 Clerkin, K.J.; Fried, J.A.; Raikhelkar, J. et al. (2020). "Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease". Circulation. doi:10.1161/CIRCULATIONAHA.120.046941. PMID 32200663. 
  31. ↑ Mehta, P.; McAuley, D.F.; Brown, M. et al. (2020). "COVID-19: Consider cytokine storm syndromes and immunosuppression". The Lancet 395 (10229): P1033–34. doi:10.1016/S0140-6736(20)30628-0. PMID 32192578. 
  32. ↑ 32.0 32.1 Mandavilli, A. (1 April 2020). "The Coronavirus Patients Betrayed by Their Own Immune Systems". The New York Times. https://www.nytimes.com/2020/04/01/health/coronavirus-cytokine-storm-immune-system.html. Retrieved 01 April 2020. 
  33. ↑ Tisoncik, J.R.; Korth, M.J.; Simmons, C.P. et al. (2012). "Into the eye of the cytokine storm". Microbiology and Molecular Biology Reviews 76 (1): 16–32. doi:10.1128/MMBR.05015-11. PMC PMC3294426. PMID 22390970. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426. 
  34. ↑ Basilio, P. (26 March 2020). "A new potential risk of COVID-19: Sudden cardiac death". MDLinx. https://www.mdlinx.com/internal-medicine/article/6590. Retrieved 01 April 2020. 
  35. ↑ Rettner, R. (23 April 2020). "Mysterious blood clots in COVID-19 patients have doctors alarmed". LiveScience. https://www.livescience.com/coronavirus-blood-clots.html. Retrieved 28 April 2020. 
  36. ↑ Moyer, M.W. (19 May 2020). "What We Know About the Covid-Related Syndrome Affecting Children". The New York Times. https://www.nytimes.com/2020/05/19/parenting/pmis-coronavirus-children.html. Retrieved 19 May 2020. 
  37. ↑ Fischer, K. (18 May 2020). "What to Know About PMIS, the COVID-19-Linked Syndrome Affecting Children". Healthline. https://www.healthline.com/health-news/what-to-know-pmis-syndrome-linked-to-covid-19-affects-children. Retrieved 19 May 2020. 
  38. ↑ {cite journal |title=Platelet Gene Expression and Function in COVID-19 Patients |journal=Blood |author=Manne, B.K.; Denorme, F.; Middleton, E.A. et al. |at=blood.2020007214 |year=2020 |doi=10.1182/blood.2020007214}}
  39. ↑ Dorward, D.A.; Russell, C.D.; Um, I.H. et al. (2020). "Tissue-specific tolerance in fatal Covid-19". medRxiv. doi:10.1101/2020.07.02.20145003. 
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