Covid-19 Weekly Updates

Prof Salim Abdool Karim Weekly COVID-19 UPDATES

1. Overall, the number of cases and test positivity continue to decline. 
2. But the decline has slowed substantially (slides 1 & 2) in the last week. This may be related to increased spread during Christmas and holiday gatherings, noting that South Africa has had minimal restrictions in place throughout the omicron wave. For those not familiar with the South African approach, restrictions are titrated in relation to 2 factors jointly – level of viral transmission and pressure on the health services. Since health services have not been under strain during the omicron wave, restrictions were not increased (they were actually lowered, when the curfew was removed). If the slowing in decline is holiday-related, the decline can be expected to get back on the expected trajectory within the next week or so.
3. The mean viral load in the PCR test data from the NHLS has increased significantly during the omicron wave when compared to the past 3 waves. The Ct-number (Cycle threshold) for the many thousands of PCR tests being done is about 2-3 points lower (Slide 3), which translates into a roughly 10-fold increase in viral load. This is an important contributor to the increased transmissibility of omicron.
4. There are now at least 3 papers that show that omicron is much more efficient in infecting nasal epithelial cells (Wendy Barclay’s lab has 2 preprints on this) than lung cells. In addition, omicron has altered its cell entry mechanism to enable it to infect cells more easily (Thompson lab) – this is likely to decrease the infectious dose needed for infection (Slides 4 & 5).
5. The combination of infected people producing higher viral loads and uninfected people getting infected at a lower infectious dose are the most likely key factors driving the higher transmission rate of omicron. Incidentally, when I first saw omicron’s sequence in November a few days before it was publicly announced, I thought that it would be similar to or just slightly faster than Delta in transmission because of the mutations near the furin cleavage site. However, omicron does not use that mutation for its higher transmissibility. This change in viral pathogenesis could not have been predicted based on what we knew about the mutations.
6. This change in viral pathogenesis (and specifically its switching of cell entry mechanism), is probably why omicron is much less efficient in infecting lung cells – though this still needs to be shown empirically. These biological findings explain what we are seeing clinically in South Africa.
7. The clinical picture is now much clearer – omicron causes a higher proportion of asymptomatic infections, but because it spreads so much more easily, it infects a lot more people – hence, the overall number of cases is only slightly higher than in previous waves. Among those who are symptomatic, the admission rate is about 4 times lower than Delta, among those admitted the severity of disease is much lower (68% severe in Delta vs 27% severe in omicron) and case fatality rates are much lower.
8. The clinical picture of an infection that looks more like a flu (headache, fever, muscle pain, etc) than the past waves of SARS-CoV-2 (loss of smell/taste much lower with omicron) is likely due to a less virulent virus, vaccine immunity and past infection natural immunity, most likely in that order, with lower virulence and vaccination being particularly important. 
9. The higher transmission rates are much more obvious in the USA, which is setting new records almost daily for the number of cases per day – reaching highs of 1.3million cases a few days ago. The milder clinical picture is being seen in many other countries. But the clinical burden is high because a smaller proportion of severe cases from a much larger number of cases still translates into substantial numbers needing health care. It is likely that this pressure will ease more quickly than previous waves though because the high case numbers cannot be sustained beyond short periods. I concur with WHO’s warning not to be complacent about omicron based on it being a less virulent virus as virulence cannot be seen in isolation from transmissibility, which impacts clinical burden.
10. A positive note comes from Debbie Bradshaw’s most recent data on excess deaths – excess deaths in South Africa over the last 3 weeks have been 3430, 3319 and 3156. A slow decline is becoming evident already – this is a huge relief to me as I have been concerned that we may see a delayed rise in mortality – patients are often in hospital ICUs for weeks before dying. Based on these promising early trends (which we should be careful not to over-interpret at this time), it looks like the mortality rates are much lower during the omicron wave (slides 14 and 15). The overall lower excess deaths however camouflages a slight trend of increasing number of excess deaths in the elderly (>60 years) over the last 3 weeks (2392, 2475 and 2540). Hence, it is too soon to say that we are over the worst for this wave.

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