17 Sept Antibody testing, IFR, tracing ageing

1. The place of rapid serological tests in diagnosis in LMIC (Peeling et al).  Whereas molecular tests are the gold standard and rapid antigen tests are gaining sensitivity (as explained in the previous episode), they are not yet widely available at affordable cost.  Measuring IgM or IgG antibodies using rapid tests could be an alternative, but what about sensitivity and specificity? 

• Sensitivity: The mean time for seroconversion is 9–11 days after onset of symptoms for total antibody, 10–12 days for IgM, and 12–14 days for IgG. So clearly, you can have false negative results, which, if possible, should be checked with a second sample about 10 days later.
• With regard to specificity it is advised to rather measure antibodies for the receptor binding site of the spike, since nucleocapsid Ab show more cross-reactivity with common Coronaviruses.

When recommended:

• Community setting strategy in Peru:
  • A positive result for IgM in symptomatic patients fulfilling the COVID-19 case definition is strongly suggestive of SARS-CoV-2 infection. This approach is probably most effective in individuals 5–10 days after symptom onset.
  • All contacts are also tested with the rapid serology test. Anyone who tests negative in the antibody test has a swab collected for molecular testing.
• Testing all contacts of confirmed cases at population level (e.g. Singapore): similar approach

• Serology approach is particularly important in the early stages when there are only sporadic or clusters of cases, or for countries coming down from the peak to continue to reduce the extent of infection in the community. Only individuals who test negative should have a throat swab collected for molecular testing, which will reduce the strain on laboratories doing these tests.
• In general, antibody tests can be used to establish the true extent of an outbreak, map its geographical distribution, and identify hotspots and populations that are particularly at risk.

Not recommended:

• Not for population surveys, if the prevalence of infection is 1%, , a test with 98% specificity will identify two false-positive results for every true positive. 
• Patients at an early stage in the disease course, or asymptomatic or paucisymptomatic patients, might have low antibody concentrations that could give false negative results
• Not as a criterium to allow HCW return to work or patients to be discharged: antibodies may be positive, while infectious virus is still being shed.

2. A very interesting modeling on the impact of digital contact tracing by Pollman et al.  They show that this is not the magic bullet that will exempt us from following “difficult” measures, such as social distancing, unless the whole population applies it and the risk is that still up to 15 % of the population has to go into quarantine!    

3. More detailed news on superspreading in carnival in Gangelt provides a good idea of the consequences of a superspreading event in “first wave”:

• Despite a shutdown 11 days after the event, Fig 1 p. 23 shows that the curve of observed infection reached its peak only 1 month after the event. 
• A seroprevalence study indicated that 15 % of the population got infected, which is 5 times more than those that were diagnosed by calling medical attention themselves.
• Being infected during the carnival was associated with more symptoms than later infection (which suggest that a higher inoculum causes more severe disease).
• Household studies showed that a second person (partner with intimate contact?)  had a 43 % chance  of infection, the second and third was 35% and in a 4 household only 18 % for 2nd, 3rd and 4th.  Remarkably, households with at least one child (< 18) had higher infection risks.
• Co-morbidities were not associated with higher rate of infection or symptoms.
• Only 7 people died, thus infection fatality was only 0.34 %    

4. A very nice review comparing the different flu epidemics in the 20th century with SARS-COV-1 and -2, with many ready-to-use Tables for presentations.

5. A review on how ageing aggravates COVID-19.   One of the known mechanisms is “inflamm-ageing”: a lowering of the specific (T and B-mediated) immune responses because of high “background inflammation”. Logically, to enhance vaccine efficacy, you should suppress this inflammation.  A paper that goes into that direction shows that suppression of the p38MAP can increase the specific cutaneous response to varicella-zoster.