Covid 10/26/20 | COVID 19 Information Page

Covid19mathblog.com

A great overview of what we know about covid-19 – SARS-CoV-2 – https://www.bmj.com/content/371/bmj.m3862

A very good point as discussed numerous time is the PCR test – what are you trying to test for – existence at some point or infectiousness?

“In the respiratory tract, peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness, with subsequent decline thereafter indicating the highest infectiousness potential just before or within the first five days of symptom onset”

“Reverse transcription polymerase chain reaction (RT-PCR) tests can detect viral SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days; however, detection of viral RNA does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness”

“Symptomatic and pre-symptomatic transmission (1-2 days before symptom onset), is likely to play a greater role in the spread of SARS-CoV-2 than asymptomatic transmission”

“SARS-CoV-2 is an enveloped β-coronavirus, with a genetic sequence very similar to SARS-CoV-1 (80%) and bat coronavirus RaTG13 (96.2%).2 The viral envelope is coated by spike (S) glycoprotein, envelope (E), and membrane (M) proteins"

“(1) The virus binds to ACE 2 as the host target cell receptor in synergy with the host’s transmembrane serine protease 2 (cell surface protein), which is principally expressed in the airway epithelial cells and vascular endothelial cells. This leads to membrane fusion and releases the viral genome into the host cytoplasm (2). Stages (3-7) show the remaining steps of viral replication, leading to viral assembly, maturation, and virus release”

“Coronaviruses have the capacity for proofreading during replication, and therefore mutation rates are lower than in other RNA viruses. As SARS-CoV-2 has spread globally it has, like other viruses, accumulated some mutations in the viral genome, which contains geographic signatures”

“The G614 variant in the S protein has been postulated to increase infectivity and transmissibility of the virus.3 Higher viral loads were reported in clinical samples with virus containing G614 than previously circulating variant D614, although no association was made with severity of illness as measured by hospitalisation outcomes.3 These findings have yet to be confirmed with regards to natural infection.”

“SARS-CoV-2 has a higher reproductive number (R0) than SARS-CoV-1, indicating much more efficient spread.”

“SARS-CoV-2 has structural differences in its surface proteins that enable stronger binding to the ACE 2 receptor4 and greater efficiency at invading host cells.1 SARS-CoV-2 also has greater affinity (or bonding) for the upper respiratory tract and conjunctiva,5 thus can infect the upper respiratory tract and conduct airways more easily”

“peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness with subsequent decline thereafter, which indicates the highest infectiousness potential just before or within the first five days of symptom onset (fig 2).7 In contrast, in SARS-CoV-1 the highest viral loads were detected in the upper respiratory tract in the second week of illness, which explains its minimal contagiousness in the first week after symptom onset, enabling early case detection in the community.”

“Quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology can detect viral SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days (maximum 83 days) after symptom onset.7 However, detection of viral RNA by qRT-PCR does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness”

“While asymptomatic individuals (those with no symptoms throughout the infection) can transmit the infection, their relative degree of infectiousness seems to be limited.91011 People with mild symptoms (paucisymptomatic) and those whose symptom have not yet appeared still carry large amounts of virus in the upper respiratory tract, which might contribute to the easy and rapid spread of SARS-CoV-2.7 Symptomatic and pre-symptomatic transmission (one to two days before symptom onset) is likely to play a greater role in the spread of SARS-CoV-2.1012 A combination of preventive measures, such as physical distancing and testing, tracing, and self-isolation, continue to be needed.”

WE NEED TO SEPARATE CASES BY ASYMPTOMATIC vs non – this is ridiculous the testing output we need more information. The next article I describe the CT numbers – these need to come associated with the test results to – also noted before.

“Target host receptors are found mainly in the human respiratory tract epithelium, including the oropharynx and upper airway. The conjunctiva and gastrointestinal tracts are also susceptible to infection and may serve as transmission portals.6”

“Most transmission occurs through close range contact (15 minutes face to face and within 2 m),13 and spread is especially efficient within households and through gatherings of family and friends.12 Household secondary attack rates (the proportion of susceptible individuals who become infected within a group of susceptible contacts with a primary case) ranges from 4% to 35%.12 Sleeping in the same room as, or being a spouse of an infected individual increases the risk of infection, but isolation of the infected person away from the family is related to lower risk of infection.12 Other activities identified as high risk include dining in close proximity with the infected person, sharing food, and taking part in group activities 12 The risk of infection substantially increases in enclosed environments compared with outdoor settings.12 Aerosol transmission can still factor during prolonged stay in crowded, poorly ventilated indoor settings (meaning transmission could occur at a distance >2 m).12141516”

“SARS-CoV-2 binds to ACE 2, the host target cell receptor”

“the distribution of ACE 2 receptors in different tissues may explain the sites of infection and patient symptoms. For example, the ACE 2 receptor is found on the epithelium of other organs such as the intestine and endothelial cells in the kidney and blood vessels, which may explain gastrointestinal symptoms and cardiovascular complications.21 Lymphocytic endotheliitis has been observed in postmortem pathology examination of the lung, heart, kidney, and liver as well as liver cell necrosis and myocardial infarction in patients who died of covid-19.122 These findings indicate that the virus directly affects many organs, as was seen in SARS-CoV-1 and influenzae.”

“the initial inflammatory response attracts virus-specific T cells to the site of infection, where the infected cells are eliminated before the virus spreads, leading to recovery in most people.23 In patients who develop severe disease, SARS-CoV-2 elicits an aberrant host immune response.”

“Cytokines normally mediate and regulate immunity, inflammation, and haematopoiesis; however, further exacerbation of immune reaction and accumulation of cytokines in other organs in some patients may cause extensive tissue damage, or a cytokine release syndrome (cytokine storm), resulting in capillary leak, thrombus formation, and organ dysfunction”

“Sex-related differences in immune response have been reported, revealing that men had higher plasma innate immune cytokines and chemokines at baseline than women.30 In contrast, women had notably more robust T cell activation than men, and among male participants T cell activation declined with age, which was sustained among female patients. These findings suggest that adaptive immune response may be important in defining the clinical outcome as older age and male sex is associated with increased risk of severe disease and mortality.”

“Covid-19 leads to an antibody response to a range of viral proteins, but the spike (S) protein and nucleocapsid are those most often used in serological diagnosis. Few antibodies are detectable in the first four days of illness, but patients progressively develop them, with most achieving a detectable response after four weeks.35 A wide range of virus-neutralising antibodies have been reported, and emerging evidence suggests that these may correlate with severity but wane over time”

PCR and cycles as discussed before are very important to understand – not much is discussed as it is quite nerdy and complicated but its important. PCR test are not black and white – investigated before https://covid19mathblog.com/2020/09/covid-9-28-20/

In this paper they discuss correlations between PCR Cycles Threshold and positive and infectiousness – https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1491/5912603

“Several works published recently and based on more

than 100 studies attempt to propose such cut off for Ct value and duration of eviction with a

consensus at approximately Ct > 30 and at least 10 days, respectively [2–5]. However, in an

article published in this journal, a group reported that patients could be not be contagious

above 25 Ct as the virus was not detected in culture above this Ct”

“It can be observed that at Ct=25, up to 70% of

patients remain positive in culture and that at Ct=30 this value drops to 20%. At Ct=35, the

value we used to report positive result for PCR, less than 3% of culture are negative. Our Ct

value of 35 initially based on the results obtained by RT-PCR on control negative samples in our laboratory and initial results of cultures [8] is validated by the present work and is in

correlation with what was proposed i.e. in Korea [9] or Taiwan [10]. We could observe that

subcultures, especially the first one, allow increasing percentage of viral isolation on high Ct

samples, confirming that these high Ct are mostly correlated with low viral loads. From our

cohort, we now need to try to understand and define the duration and frequency of live virus

shedding in patients on a case-by-case basis, in the rare cases where the PCR is positive

beyond 10 days, often at a Ct above 30. In any cases, these rare cases should not impact

public health decisions.”

Ct and the patient classification of asymptomatic or not will aid in interpreting the cases we are seeing. Labs need to start releasing this data. Ct decision does not seem to be universal. This could cause misinterpretation and worse yet hysteria when there does not need to be – at the very least transparency would help everyone understand what is going on.

Super low numbers worldwide even for a Sunday – US 340