29 March Duration of infectiousness and upcoming serological tests

Mon, 03/30/2020 - 18:48

People asked me about the duration of infectiousness

  1. Well, there is a paper in the Chinese Medical Journal on 66 recovering patients that provides a first answer: after the appearance of  first symptoms, pharyngeal swabs remain positive for an average of 9.5 (6-11) days, but, remarkably feces remains positive for a significantly longer time: 11 (9-16) days.  Levels in urine and blood are much lower and more inconsistent. Remarkably also, the authors say that feces can be positive, in swab negative cases.

My discussion: The values are median and interquartiles.  So the “rule of thumb” of staying home for 14 days after the first symptoms, seems rather OK. Based on this study, you could argue for a few days more, if you want 100% safety. However, a qualitative test was used and the method is not well described.    

  1. A very recent paper (23 March) in Lancet Infect Dis from Hongkong sheds a slightly different light on the question.  In this case, only 23 patients were included, subdivided in mild and severe cases.  The PCR (an serology) tests are “home brewed”, but described in detail and results are expressed quantitatively.  These authors also introduce a novel, more elegant way to collect samples: the “posterior oropharyngeal saliva specimen”, explained as “ … patients were asked to produce an early morning saliva sample from the posterior oropharynx (ie, coughed up by clearing the throat) before toothbrushing and breakfast,… “ (p.2). Peak viral load varied from less than 100 to over 108 copies per ml and it clearly increased with age (but not with severity or comorbidity see Fig 3 p. 6).  Obviously, VL declined with time (Fig 2), but interestingly, VL remained measurable after more than 20 days in saliva in 50 % of severe and 23 % of mild cases (and to a lesser percentage also in blood and rectal swab -Table p. 5).

My discussion: This a study with few in-hospital patients and therefore certainly not representative for mild cases that just stay home.  The techniques used by these authors seem rather sensitive and it is not clear whether low levels of less than 100 copies that you find in saliva of some milder cases after 3 weeks still provides a risk for transmission. 

Conclusion: The jury is still out about duration of infectiousness: 14 days is the minimum for safety, but even 3 weeks could still carry a small risk …..

I add also two interesting papers on serology:

  1. Li Gou in CID investigated the early antibody responses against the Nucleoprotein in PCR-confirmed and in “probable” Wuhan patients.  The latter were “suspected to be infected with SARS-CoV-2 based on clinical manifestation, chest radiography imaging and epidemiology but no virus was detected by deep sequencing or a qPCR assay”.

Two interesting observations:

  • Their test shows low cross-reactivity from sera from patients with antibodies against the “common cold” CoV, but extensive cross-reactivity from the “old” SARS-CoV  (Fig 1 p.25). 
  • IgM seropositivity could aid to ascertain the diagnosis in PCR (-) cases. See Fig 4 p. 28.
  1.  Zhengtu Li et al. propose an elegant rapid test for IgM and IgG against receptor binding domain (RBD) of the spike protein (see Fig 1 p. 14).  Using serum from confirmed COVID patients and healthy controls, they obtain a sensitivity of 88 % and a specificity of 90 % (Table 1 p. 15). Interestingly, in a small sub-study (7 positive samples), they provide evidence that besides serum, also plasma or fingerprick blood can be used.   

Best wishes,

Guido Vanham