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SUMMARY OF SARS-CoV/SARS-CoV-2 AND COVID-19 FINDINGS
SUMMARY OF SARS-CoV/SARS-CoV-2 AND COVID-19 FINDINGS
SECTION I: Overview
Current COVID-19 tracking services:
Johns Hopkins
New York Times (NYT)
Worldometer
Evaluation of current therapies:
Chloroquine: Showing the most promise
Hydroxychloroquine: Effective, but many side effects including prolonged QTC interval possibly dangerous in patients with hypertension and low ejection fractions.
Remdesivir: Currently undergoing trials
Tocilizumab: Currently undergoing trials
Convalescent Plasma: determined to be a promising treatment, however the supply of plasma as the ratio of cured individuals to sick patients is extremely low. Convalescent plasma therapy is a labor-intensive therapy, and in a time of pandemic, may not be the most economically viable treatment available. This type of therapy is widely known to be effective.
Note: All dates on all linked articles are in ISO YYYY-MM-DD format. All articles are to be sorted by oldest-first and formatted with the title in italics, date in bold with parentheses, and URL in brackets.[/SPOILER]
SECTION II: Pathology
Section II-A: Transmission & Strains
There is a lot of conflicting information on R0 values for COVID-19. In one epidemiological study, the disease was estimated to have a peak R0, the reproduction value, of around 6.6, which means 1 person infects that many other people, on average. One Belgian scientist said it was between 4.7 to 7. In various other locations and studies, the R0 was calculated at around 2 to 3, largely because of differences in population density and public transport use. In other words, the R0 has been variously calculated as being somewhere between 2 and 7. In some locales, the R0 may vary depending on human behavior. There are also super-spreader incidents where one person can infect dozens of others:
The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated (2020-02-11) [https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1]
Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) (2020-02-16 to 2020-02-24) [https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf]
Open letter to the Minister of Public Health: "Coronavirus, you have to know how to listen to fear" (2020-02-28 ) [https://www.rtbf.be/info/opinions/detail_lettre-ouverte-a-la-ministre-de-la-sante-publique-coronavirus-il-faut-savoir-ecouter-la-peur?id=10443799]
The median incubation period is around 5 days, but rare outliers of 24+ days have been seen:
Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population-level observational study (2020-02-20) [https://www.thelancet.com/journals/landig/article/PIIS2589-7500(20)30026-1/fulltext]
The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application (2020-03-10) [https://annals.org/aim/fullarticle/2762808/incubation-period-coronavirus-disease-2019-covid-19-from-publicly-reported]
SARS-CoV-2 is apparently airborne and can linger in aerosols for a very long time. One study in China indicated that the virus could travel as far as 4.5 meters/15 feet, rendering the CDC’s 6-foot gap provision insufficient:
China confirms aerosol spread of Covid-19, frontline medical workers need to wear right masks (2020-02-24) [https://www.msn.com/en-sg/news/world/china-confirms-aerosol-spread-of-covid-19-frontline-medical-workers-need-to-wear-right-masks/ar-BB10ljdt?ocid=ems.msn.dl.RosetteNebula]
Transmission routes of 2019-nCoV and controls in dental practice (2020-03-03) [https://www.nature.com/articles/s41368-020-0075-9]
Coronavirus can travel twice as far as official ‘safe distance’ and stay in air for 30 minutes, Chinese study finds (2020-03-09) [https://www.scmp.com/news/china/science/article/3074351/coronavirus-can-travel-twice-far-official-safe-distance-and-stay]
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 (2020-03-17) [https://www.nejm.org/doi/full/10.1056/NEJMc2004973]
Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings (2020-03-19) [https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html]
SARS-CoV-2 RNA was detectable on the Diamond Princess for 17 days. However, these could be non-viable fragments of virions:
CDC says coronavirus RNA found in Princess Cruise ship cabins up to 17 days after passengers left (2020-03-23) [https://www.cnbc.com/2020/03/23/cdc-coronavirus-survived-in-princess-cruise-cabins-up-to-17-days-after-passengers-left.html]
Expert reaction to CDC report on COVID-19 outbreaks on cruise ships, which includes that SARS-CoV-2 RNA was identified on surfaces in cabins up to 17 days after they were vacated (2020-03-24) [https://www.sciencemediacentre.org/expert-reaction-to-cdc-report-on-covid-19-outbreaks-on-cruise-ships-which-includes-that-sars-cov-2-rna-was-identified-on-surfaces-in-cabins-up-to-17-days-after-they-were-vacated/]
SARS-CoV is known to have spread by the oral-fecal route and through airborne sewage particulate matter, and SARS-CoV-2 is likely no different in that regard. SARS causes enteric symptoms and contaminates sewers and makes them hazardous:
Pathogen cross-transmission via building sanitary plumbing systems in a full scale pilot test-rig (2017-02-10) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302810/]
COVID-19: Gastrointestinal manifestations and potential fecal-oral transmission (2020-02-26) [https://www.gastrojournal.org/article/S0016-5085(20)30281-X/pdf]
Gastrointestinal Symptoms Could Be New Focus for Coronavirus Diagnosis (2020-03-09) [https://www.contagionlive.com/news/gastrointestinal-symptoms-could-be-new-focus-for-coronavirus-diagnosis-]
Guidance for Kansas Drinking Water and Wastewater (2020-03-12) [http://www.kdheks.gov/coronavirus/toolkit/COVID-19_Water_and_Wastewater_Guidance.pdf]
Stomach Ache And Diarrhea May Be Among The First Signs Of COVID-19 Coronavirus (2020-03-20) [https://www.forbes.com/sites/robertglatter/2020/03/20/stomach-ache-and-diarrhea-may-be-some-of-the-first-signs-of-covid-19-coronavirus/]
SARS-CoV-2 is capable of asymptomatic transmission and it is practically impossible to stop the spread by contact tracing and minor quarantines. There are a multitude of asymptomatic carriers walking around:
Asymptomatic cases in a family cluster with SARS-CoV-2 infection (2020-02-19) [https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30114-6/fulltext]
Potential Transmission of SARS-CoV-2 from an Asymptomatic Carrier (2020-02-24) [https://www.jwatch.org/na50998/2020/02/24/potential-transmission-sars-cov-2-asymptomatic-carrier]
Potential Presymptomatic Transmission of SARS-CoV-2, Zhejiang Province, China, 2020 (2020-03-09) [https://wwwnc.cdc.gov/eid/article/26/5/20-0198_article]
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients (2020-03-19) [https://www.nejm.org/doi/full/10.1056/NEJMc2001737]
SARS-CoV-2 can enter the eye through the ocular surface. Any protective mask must be full-face. Half-face masks are insufficient. Conjunctivitis can be a sign of infection:
2019-nCoV transmission through the ocular surface must not be ignored (2020-02-06) [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30313-5/fulltext]
Coronavirus Eye Safety (2020-03-10) [https://www.aao.org/eye-health/tips-prevention/coronavirus-covid19-eye-infection-pinkeye]
There is conflicting evidence that the virus may be a possible recombinant chimera:
Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event (2020-01-29) [https://www.sciencedirect.com/science/article/pii/S1567134820300447]
Coronavirus Could Be a 'Chimera' of Two Different Viruses, Genome Analysis Suggests (2020-03-24) [https://www.sciencealert.com/genome-analysis-of-the-coronavirus-suggests-two-viruses-may-have-combined]
There are now two recognized strains of the disease. The L strain is more infectious and severe than the ancestral S strain:
On the origin and continuing evolution of SARS-CoV-2 (2020-03-03) [https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463]
Coronavirus: aggressive ‘L type’ strain affecting 70 per cent of cases (2020-03-06) [https://www.sciencefocus.com/news/coronavirus-aggressive-l-type-strain-affecting-70-per-cent-of-cases/]
How fast can the coronavirus mutate? (2020-03-09) [https://www.livescience.com/coronavirus-mutations.html]
SARS-CoV and SARS-CoV-2 are around 80% genetically similar and may have a few shared pathological factors:
Severe acute respiratory syndrome coronavirus 2 isolate 2019-nCoV WHU01, complete genome (2020-01-02) [https://www.ncbi.nlm.nih.gov/nuccore/MN988668]
Virologists Find Coronavirus Is 80% The Same as SARS, Which May Help Us Neutralise It (2020-02-04) [https://www.sciencealert.com/genetic-analysis-shows-wuhan-coronavirus-is-similar-to-sars]
What We Know Today about Coronavirus SARS-CoV-2 and Where Do We Go from Here (2020-02-19) [https://www.genengnews.com/insights/what-we-know-today-about-coronavirus-sars-cov-2-and-where-do-we-go-from-here/]
Section II-B: Cellular Entry
The virus binds to ACE2 receptors in human cells. ACE2 receptors are found in many vital organs and reproductive tissues in the human body. Lungs, heart, kidneys, brain. SARS-CoV-2 infection may also have negative effects on male fertility. ACE2 receptors are found in the seminiferous ducts of the testis:
Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis (2004-05-07) [https://onlinelibrary.wiley.com/doi/full/10.1002/path.1570]
ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia (2020-11-10) https://jvi.asm.org/content/79/23/14614
Angiotensin converting enzyme 2 in the brain (2008-11-05) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667944/]
ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection (2020-02-13) [https://www.medrxiv.org/content/10.1101/2020.02.12.20022418v1]
scRNA-seq Profiling of Human Testes Reveals the Presence of ACE2 Receptor, a Target for SARS-CoV-2 Infection, in Spermatogonia, Leydig and Sertoli Cells (2020-02-18 ) [https://www.preprints.org/manuscript/202002.0299/v1]
The Cardiac Implications of Novel Coronavirus (2020-02-20) [https://www.dicardiology.com/article/cardiac-implications-novel-coronavirus]
ACE2 Is the SARS-CoV-2 Receptor Required for Cell Entry (2020-03-18 ) [https://www.jwatch.org/na51115/2020/03/18/ace2-sars-cov-2-receptor-required-cell-entry]
When the virus binds to ACE2 receptors, it blocks off the ACE2 receptors and leaves excess circulating Angiotensin II (normally, Ang II uses ACE2 to convert into Ang 1-7, a MasR agonist). This goes on to cause inflammation and possibly even hypertension and/or electrolyte imbalance:
Renin–angiotensin system in human coronavirus pathogenesis (2010-03-01) [https://www.futuremedicine.com/doi/10.2217/fvl.10.4]
Pathology and Pathogenesis of Severe Acute Respiratory Syndrome (2010-12-16) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1829448/]
Response to the emerging novel coronavirus outbreak (2020-01-31) [https://www.bmj.com/content/368/bmj.m406/rr-15]
Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target (2020-03-03) [https://link.springer.com/article/10.1007/s00134-020-05985-9]
SARS-CoV has been shown to be capable of Dengue-like antibody-dependent enhancement, tricking the immune system into aiding the virus. It is unknown whether or not SARS-CoV-2 can do the same:
Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS (2011-01-10) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019510/]
Molecular Mechanism for Antibody-Dependent Enhancement (2019-12-11) [https://www.msi.umn.edu/~lifang/flpapers/fang_li_mers_ade_jvi_2019.pdf]
Is COVID-19 receiving ADE from other coronaviruses? (2020-02-13) https://www.sciencedirect.com/science/article/pii/S1286457920300344?via%3Dihub
Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (ADE) (2020-03-08 ) [https://www.preprints.org/manuscript/202003.0138/v1]
SARS-CoV-2 has a furin cleavage site on the spike glycoprotein that may greatly enhance cell-to-cell fusion and infectiousness:
Furin cleavage site in the SARS-CoV-2 coronavirus glycoprotein (2020-02-13) [http://www.virology.ws/2020/02/13/furin-cleavage-site-in-the-sars-cov-2-coronavirus-glycoprotein/]
The Proximal Origin of SARS-CoV-2 (2020-02-16) http://virological.org/t/the-proximal-origin-of-sars-cov-2/398
Coronavirus far more likely than Sars to bond to human cells due to HIV-like mutation, scientists say (2020-02-27) [https://www.scmp.com/news/china/society/article/3052495/coronavirus-far-more-likely-sars-bond-human-cells-scientists-say]
Why does SARS-CoV-2 spread so easily? (2020-03-17) [https://www.medicalnewstoday.com/articles/why-does-sars-cov-2-spread-so-easily]
Angiotensin blockers (ARBs), like Losartan and Telmisartan may have unwanted side effects, like increasing the number of host cell receptors that the virus can use. Generally, patients treated with ARBs have higher concentrations of ACE2 receptors on pulmonary, etc. Epithelial cells, increasing the efficacy of host cell binding. Some conflicting information indicates that they may also block the effects of the virus, leaving open the possibility of their use in therapy. Whether or not ARBs are safe to use on COVID-19 patients remains a matter of some dispute:
Response to the emerging novel coronavirus outbreak (2020-01-31) [https://www.bmj.com/content/368/bmj.m406/rr-2]
Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia (2020-02-16) [https://www.ncbi.nlm.nih.gov/pubmed/32061198]
Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? (2020-03-11) [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext]
ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19, paper suggests (2020-03-23) [https://www.sciencedaily.com/releases/2020/03/200323101354.htm]
Section II-C: Pulmonary Signs
The primary pathology of note in COVID-19 is bilateral pneumonia with ground-glass lesions visible in CT scans:
Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study (2020-02-24) [https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30086-4/fulltext]
A Medical Worker Describes Terrifying Lung Failure From COVID-19 — Even in His Young Patients (2020-03-21) [https://www.propublica.org/article/a-medical-worker-describes--terrifying-lung-failure-from-covid19-even-in-his-young-patients]
SARS-CoV-2 can potentially cause irreversible lung fibrosis and chronic lung disease if not caught and treated with antivirals at an early stage. This has serious implications for treatment of recovered patients who subsequently get infected with a different strain; their weakened condition may increase mortality. One COVID-19 victim had such severe damage to their lungs, they needed to be treated with a double lung transplant:
Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19) (2020-02-26) [https://www.preprints.org/manuscript/202002.0407/v3/download]
Autopsies offer key clues for early stage COVID-19 patients (2020-02-29) [https://www.globaltimes.cn/content/1181121.shtml]
China's Zhejiang completes lung transplant for COVID-19 patient (2020-03-02) [http://www.xinhuanet.com/english/2020-03/02/c_138836428.htm]
Chinese doctors say coronavirus ‘like a combination of SARS and AIDS’, can cause irreversible lung damage (2020-03-05) [https://www.news.com.au/lifestyle/health/health-problems/chinese-doctors-say-coronavirus-like-a-combination-of-sars-and-aids-can-cause-irreversible-lung-damage/news-story/f58f19c5eeae99b845c54e2d2b9305ca]
Section II-D: Cardiovascular Signs
SARS-CoV-2 can potentially cause myocarditis leading to myoglobin accumulation in the blood, cardiomyopathy, and cardiac or renal failure. Some contradictory studies indicate heart tissue remains mostly normal under histopathological examination, while others indicate severe myocarditis:
Here’s What Happens to the Body After Contracting the Coronavirus (2020-02-20) [https://www.healthline.com/health-news/heres-what-happens-to-the-body-after-contracting-the-coronavirus#Liver-and-kidneys]
COVID-19 Clinical Guidance For the Cardiovascular Care Team (2020-03-06) [https://www.acc.org/~/media/665AFA1E710B4B3293138D14BE8D1213.pdf]
First Case of COVID-19 Infection with Fulminant Myocarditis Complication: Case Report and Insights (2020-03-10) [https://www.preprints.org/manuscript/202003.0180/v1]
SARS-CoV has been known to cause vasculitis of the organs, possibly by attacking blood vessels directly. It is unknown whether or not this also applies to SARS-CoV-2. Substantially more research is needed on this topic:
Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection (2007-10-12) [https://cmr.asm.org/content/20/4/660]
Section II-E: Neurological Signs
SARS-CoV (a relative of SARS-CoV-2) has been shown to cause neural death (surprisingly without encephalitis) in transgenic mouse models. Recent, concerning reports of anosmia in COVID-19 patients may perhaps indicate olfactory nerve infiltration or inflammation of the surrounding tissues; this needs investigation:
Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008-05-21) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493326/]
If you've lost your sense of smell or taste, you could be a 'hidden carrier' of the coronavirus (2020-03-22) [https://www.businessinsider.com/coronavirus-symptoms-loss-of-smell-taste-covid-19-anosmia-hyposmia-2020-3]
SARS-CoV was also found in the brains of infected patients in previous outbreaks:
New Study Shows SARS Can Infect Brain Tissue (2005-09-15) [https://www.sciencedaily.com/releases/2005/09/050915002938.htm]
Neurological manifestations in severe acute respiratory syndrome. (2005-10-29) [https://www.ncbi.nlm.nih.gov/pubmed/16252612]
Angiotensin converting enzyme 2 in the brain (2009-04-12) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667944/
Recent information seems to suggest that SARS-CoV-2 can cause neurological symptoms and cerebrovascular disease, leading to loss of autonomic functions of the brain and, in the worst case, lingering brain damage. The virus can apparently attack the medulla or even cause viral encephalitis, and some patients have had the virus found in their cerebrospinal fluid:
The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients (2020-02-24) [https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.25728]
Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study (2020-02-25) [https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1]
Beijing hospital confirms nervous system infections by novel coronavirus (2020-03-05) [http://www.xinhuanet.com/english/2020-03/05/c_138846529.htm]
Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms (2020-03-13) [https://pubs.acs.org/doi/10.1021/acschemneuro.0c00122]
Section II-F: Renal Signs
COVID-19 can cause acute kidney injury, and can be a serious threat to those with pre-existing kidney disease:
COVID-19: challenges for renal services (2020-03-11) [https://renal.org/covid-19/ra-resources-renal-professionals/covid-19-challenges-renal-services/]
Kidney disease is associated with in-hospital death of patients with COVID-19 (2020-03-16) [https://www.kidney-international.org/article/S0085-2538(20)30255-6/fulltext#sec1.3]
Section II-G: Hepatic Signs
Patients with severe COVID-19 were known to have notable changes to their liver function:
Liver injury in COVID-19: management and challenges (2020-03-04) [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30057-1/fulltext]
Section II-H: Gastrointestinal Signs
COVID-19 patients with digestive symptoms have worse clinical outcomes:
The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes (2020-01-31) [https://www.biorxiv.org/content/10.1101/2020.01.30.927806v1]
About Half of COVID-19 Cases Show Digestive Signs (2020-03-19) [https://www.webmd.com/lung/news/20200319/about-half-of-covid-cases-show-digestive-signs]
COVID-19 can also possibly cause massive co-infections of prevotella, a normally harmless gut bacteria, potentially even displaying bacteriophage-like synergistic behavior with prevotella. The researchers seemed to have low confidence in this result, but it may be something worth following up on to see if SARS-CoV-2 is capable of bacteriophage-like behavior in vitro. Bacteriophage-like behavior, if present, could make the virus into a persistent environmental contaminant, and would have serious implications vis a vis disposal of bodies of COVID-19 victims and treatment of wastewater. However, the idea of a virus that infects both prokaryotic and eukaryotic cells is very strange:
The 2019 Wuhan outbreak could be caused by the bacteria Prevotella, which is aided by the coronavirus - Prevotella is present (sometimes in hugea mounts) in patients from two studies in China and one in Hong Kong (2020-02-03) [https://osf.io/usztn/]
Sequencing data (N=3) shows Wuhan coronavirus integration in bacteria (Prevotella mostly). Sequencing artifact - or is the virus infecting both bacterial and human cells? (2020-02-04) [https://osf.io/ktngw/]
Section II-I: Immunological Signs
SARS-CoV and SARS-CoV-2 can both cause cytokine storms, where inflammatory agents released by the body's own immune system begin to over-accumulate and damage tissues that they were sent to protect:
Into the Eye of the Cytokine Storm (2012-03-05) [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294426/]
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China (2020-01-24) [https://www.thelancet.com/action/showPdf?pii=S0140-6736(20)30183-5]
Pathological findings of COVID-19 associated with acute respiratory distress syndrome (2020-02-18 ) [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30076-X/fulltext]
