15 April 2021 Episode 130 Long COVID, testing and (of course) vaccines

Thu, 04/15/2021 - 19:02

Dear colleagues,

Quite some time ago, I found a good review in Nat Med on the “post-acute COVIS-19 syndrome”.  The vaccine news always took priority, but this time, I will briefly discuss this paper and related ones first and then, inevitably, update on some good and some bad vaccine news….



Ep 130-1: the review is quite didactic with nice tables and figures that are easy to read (and I added some underlining to enhance diagonal reading).  As could be expected, “long COVID” is a multisystemic disease, just like the acute phase, with dominant pulmonary (dyspnea), cardiovascular (chest pain, palpitations) and thrombo-embolic features.  A variety of so called “neuropsychiatric symptoms such as fatigue, headache, lack of concentration, loss of taste and smell, anxiety and depression etc.    Some people also experience hair loss, rash, but more importantly impaired kidney function, diabetes, hyper- and hypothyroidism etc.

With regard to pathophysiology: direct viral infection, inflammation, fibrosis are always mentioned and  the management is symptomatic and supportive.

Ep 130-2: is a discussion on research needed to clarify the real prevalence: the importance of a control group and the recognition of the syndrome is important for the patients.

Ep 130-3: An example of such a well-controlled study on sequelae post-EBOLA: joint pain and headache > memory loss, uveitis and muscle pain > urinary frequency.  However, as can be seen in Table 2 p. 930, many other originally suspected symptoms could not be linked to post-EBOLA, because they were also common in the controls.  In view of the older population that is hit by COVID, some of the suspected signs may have to be dropped as well…

Ep 130-4: The other, often neglected, side of “long COVID” is how the protracted  pandemic affects the frontline health care workers and scientists: many experience increasing fatigue, even exhaustion and doubts about recognition….


Importance of viral load, British variant and rapid antigen tests

Ep 130-5: A very nice preprint.  You have to see the self-explanatory figures pp 9-13. A very large population study on transmission.  The conclusions:

  • Confirmation that SGTF (B1.117 or British variant) increases SARS-CoV-2 transmission
  • Importance of viral load for SARS-CoV-2 infectivity is consistent across ages, ethnicities, and different types of contact events.
  • Most individuals have Ct values compatible with onward transmission.
  • Rapid antigen test (LFD) can detect most individuals who are potential transmission sources.

→ This supports wider use of LFDs as rapid and regular screens to detect infectiousness in populations at high risk of acquisition, including recent contacts of cases.

→ Prospective studies to demonstrate whether targeted isolation and/or contact tracing, together with wider use of LFDs in combination with vaccination are effective in preventing ongoing SARS-CoV-2 transmission.


Good and bad news on vaccines

Ep 130-6: A short paper in NEJM shows rather reassuring persistence of antibodies, including those which neutralize live virus (presumably Wuhan strain), for 6 months after two doses of Moderna mRNA , with rather small differences according to age.  The decrease is similar to the convalescent subjects (after natural infection).  It is not clear however, whether the 9 subjects in the oldest age group (> 71 years) also included people over 80 or 90 years old.    

Ep 130-7 a medRxiv preprint on spike-specific antibody levels after mRNA vaccination (> 95 % Moderna) in very old people (mean 85 yrs).  These are just ELISA results, so no info on neutralizing capacity.  A small proportion of the individuals have very low levels.  A longitudinal analysis shows that some people lose their antibodies rather quickly, especially the men, those with advanced age or on steroid medication.  

Ep 130-8 a Washington Post paper on breakthrough infections in the US.  At first view, nothing to worry about: 100-200 breakthroughs per million vaccinated people and mostly mild infections.  But no information on age of the subjects or sequencing for potential variants.   

Ep 130-9 The final Madhi NEJM paper on the rather catastrophically low efficacy of two doses of Astra-Zeneca against mild-to-moderate disease by B1.351 (“South-African variant).  

Ep 130-10 in medRxiv studies a small cohort of subjects who received the Sputnik V vaccine (recombinant SARS-CoV-2 Spike in Adenovirus-26, followed by Spike-Ad5).  The main readout is the neutralizing capacity of the serum against different variants in a sensitive pseudo)virus test. As has been seen with other vaccines, here also the neutralizing activity against wild-type and B1.1.7 (British variant) is similarly high, but there is a strong (6-10 X) drop of neut against B1.351 (South-African variant), while the E484K mutation alone provides only limited resistance to neut.   

Ep 130-11 a NEJM short paper, showing similar results, this time comparing plasma from convalescent patients, Moderna (mRNA) and Novavax (Spike protein) vaccine recipients: as compared to wild-type (with D614G) in a pseudovirus test neut activity was 2-3 lower against the B1.429 (Californian variant) and about 10 times lower against the B1.351 (South-African variant).

Ep 130-12 A a Cell Host Microb study, also with convalescent and Moderna vaccinated individuals in the US: they find a lower reduction of neut capacity (5X) against B1.351 as compared to B1 variant.

Ep 130-12 B: Very similar data for the Pfizer vaccinees.

Ep 130-13: 3 papers on the rare side effects of Astra-Zeneca and J§J. Since Sputnik’s first dose is also Ad26 (like J§J), most likely the same problem.

Ep 130-14: A perspective on the lessons learned from HIV treatment for roll-out of COVID-vaccines in  Africa.

Best wishes,