Natural immunity to the SARS-CoV-2 virus that causes Covid-19 is somewhat effective, based on recent reports1-4. It is most effective when it provides hybrid immunity to people who have not only been infected in the past but also had a full series of vaccinations. A previous infection provides high protection against re-infection with earlier variants of concern (VOCs) such as Alpha and Delta4. However, infection without any vaccination provides less protection against the Omicron VOC that predominates now. Previous infection was found to provide protection against hospitalization for 74.6% of the people studied2. The effectiveness of the previous infection against re-infection dropped to 24.7% after 12 months.
Still, vaccine-induced immunity only provides protection against infection by Omicron for a few months after vaccination but decreases much over time. On the other hand, recent studies have found that the protection conferred by hybrid immunity is better than that by infection-induced or vaccine-induced immunity alone. The effectiveness of hybrid immunity against hospital admission or severe disease was 97.4% after 12 months with one vaccination and 95.3% for six months after the first booster vaccination. The effectiveness of hybrid immunity against re-infection following one vaccination decreased to 41.8% after 12 months, while the effectiveness of hybrid immunity following the first booster vaccination decreased to 46.5% after six months. People with hybrid immunity had the highest and most durable protection. Thus, we might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected2.
Hybrid immunity improves immune protection against symptomatic disease caused by infection by Omicron. The immune protection after two doses (with a prior infection) waned 10-19 weeks after the second dose but was restored after a booster dose. Hybrid immunity is defined as the immune protection provided by one or more doses of a COVID-19 vaccine and at least one SARS-CoV-2 infection before or after the initiation of vaccination4. Hybrid immunity provides excellent protection from severe diseases caused by all variants. It was recommended that immunity conferred by a past infection should be considered along with protection from vaccination when providing guidance on when individuals should be vaccinated. Such considerations should also be made when mandating vaccinations2. Similar results were seen in healthcare workers in Malaysia5. They found that protection against Omicron infection was significantly higher for persons with previous SARS-CoV-2 infection and persons with a more recent immunity event (90 days) from the beginning of the Omicron period. They concluded that both pre-Omicron natural infection and a recent immunity event protect most people against future infections by the Omicron VOC.
Neither natural infection nor vaccination can protect one from fools who spread hatred, ignorance and war. Despite compelling evidence that the SARS-CoV-2 and Covid-19 pandemic was caused naturally by evolution, many politicians and people looking for attention on social media claim that is produced in a lab and released in the Hunan food market in December 2019. Some say it was created in a Chinese lab, others say it came from a lab in the USA. In contrast, evolutionary science predicts that the virus was present at many locations around the world before December 2019, but only reached high enough levels to be detected in Hunan, China. In fact, the virus was found in blood samples taken in the USA and Italy only after attempts were made to identify it in stored samples6,7.
There is other evidence that supports the idea that the SARS-CoV-2 virus emerged through evolution and not produced in a laboratory8-10. The genetic makeup (base sequence) of the RNA in the virus closely resembles that of other naturally occurring viruses in bats and pangolins that were present in Wuhan11. Almost all previous pandemics caused by viruses have been shown to have zoonotic origins. That is, they originated in one or more species of animals and then transmitted to humans.
Perhaps the best way to test a hypothesis (like the zoonotic origin instead of origin in a lab), Bayes theorem is useful. That is, the probability or likelihood of an event occurring is much higher if that event has happened frequently in the past. In medical schools in Europe and the Americas, this can be explained by an example. If you hear the sound of hoofs striking the ground outside the classroom, it is probably not due to zebras, but horses. In the case of the origin of the Covid-19 pandemic, there have never been any cases of a pandemic starting from a virus that has been produced in a lab. They all originated naturally, through evolution.
Moreover, the Wuhan Institute of Virology, which has been the focus of some of the claims about a possible lab origin, is a high-level biosafety facility with strict protocols for handling dangerous pathogens. There is no evidence to suggest that SARS-CoV-2 was accidentally released from a lab or that the virus was intentionally engineered.
Similarly, two recent mathematical analyses provided quantitative evidence that SARS-CoV-2 emerged by multiple zoonotic transmissions due to wildlife trading at the Hunan Market10-12. At the beginning of the pandemic, two viral lineages of SARS-CoV-2 were identified from the viral genomes of early cases. They have been called A and B. These strains differ by only two mutations. Worobey et al. established epidemiological links of early cases of the two viral lineages A and B to the market, and these lineages were present in some of the environmental samples taken from the market10. Pekar et al. hypothesized that these two strains were produced by two independent zoonotic transmissions12. Zoonotic events are stochastic, so a spillover with successful onward transmission between humans requires a series of failed attempts by the virus to establish sustained transmissions. For two independent zoonotic spillovers to be successful, sustained contacts and multiple zoonotic transmissions between people and the animals carrying the SARS-CoV-2 virus at the Hunan Market would have been required. Pekar et al. showed that the two viral lineages can only be explained by two independent zoonotic transmissions. The existence of two independent lineages of the virus strongly suggests that they could have only come from the source animals and that the most recent common ancestors of the virus are in animals12. In addition, more than 600 animal infections involving more than 24 species have been reported13,14. Cross‐species transmission of SARS‐CoV‐2 can lead to further evolution in new hosts, such as the mutation of SARS‐CoV‐2 in minks and transmission from minks to humans.
Because of a lack of funding, virologists have only been able to identify a very small fraction of the viruses that exist on Earth. It has been estimated that there are over half a million unidentified viruses15. All that one can do is try to find the viral genome in existing databases that most closely matches that of the original variant of the SARS-CoV-2 virus that was seen in Wuhan, China in December 2019. However, this coronavirus almost certainly existed before it had infected and killed enough people to be noticed. Until the outbreak occurred in Wuhan, nobody was looking closely at all databases.
Also, there is a data set containing SARS-CoV-2 sequences from early in the Wuhan epidemic that was deleted from the NIH’s Sequence Read Archivex16. It was found and recovered from some deleted files in the Google Cloud. The investigator reconstructed partial sequences of thirteen early versions of the coronaviruses. Phylogenetic analysis of these sequences suggests that the Hunan Seafood Market sequences that are the focus of the joint WHO-China report are not fully representative of the viruses in the epidemic. Instead, the progenitor of known SARS-CoV-2 sequences likely contained three mutations that made it more similar to bat coronavirus relatives. The deleted and now recovered partial SARS-CoV-2 sequences from the early Wuhan epidemic were analyzed. This led to some conclusions. First, the Hunan Seafood Market sequences that were the focus of the joint WHO-China report may not be representative of all variants that were present early in the epidemic. The deleted data as well as existing sequences from Wuhan-infected patients hospitalized in Guangdong show that early Wuhan sequences often contained thymine to cytosine mutation on base number 29095 (T29095C) and were less likely to contain two bases that are in sequences listed in the joint WHO-China report. Second, there are two plausible identities for the progenitor of all known SARS-CoV-2 variants. One of them was described by Kumar and coworkers, and the other is a sequence that carries three mutations (C8782T, T28144C, and C29095T) relative to Wuhan-Hu-116.
Regardless of which coronavirus was the progenitor of the SARS-CoV-2 virus, evolution has continued. Just as we do not know enough or have enough data to identify the true progenitors, neither can we predict where and when the next more transmissible and deadlier variant will emerge.
Neither natural infection nor vaccination can protect against the next pandemic. In a previous article, I described a virus that infects pigs but only needs one key mutation to be able to infect humans17. More recently, the public has been alerted to a variant of the influenza virus (H5N1) that causes bird flu to infect some mammals and potentially infect humans18. In late 2021, the H5N1 strains crossed North America. The U.S. Department of Agriculture reported that over 58 million chickens have been affected in 47 states19. Nearly 6200 wild birds have been infected, including eagles, hawks, geese, and ducks20. Between June and mid-July, over 150 dead seals in Maine were attributed to the bird flu21. Another outbreak on a Spanish mink farm may indicate that the virus may be transmissible to mammals22. More than 51,000 minks were killed to prevent further spread. The H5N1strain found in minks had a mutation that doesn't exist in strains affecting birds. This mutation was also seen in the swine flu H1N1 virus that was responsible for the 2009 pandemic which caused more than 12,000 deaths in the USA.
So, scientists will continue doing research and I will provide updates on progress and important news in future articles.
1 COVID-19 Forecasting Team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis. The Lancet, 16 Feb., 2023.
2 Bobrovitz, C. et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression. The Lancet, 18 Jan., 2023.
3 Hansen, C.H. et al. Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant. The Lancet, 18 Oct., 2022.
4 World Health Organization. Interim statement on hybrid immunity and increasing population seroprevalence rates. 1 June, 2022.
5 Yang, S.L. et al. Time from last immunity event against infection during Omicron-dominant period in Malaysia. International Journal of Infectious Diseases, Vol. 128, p. 98-101, 2023.
6 Basavaraju, S.V. et al. Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2020.
7 La Rosa, G. et al. SARS-CoV-2 has been circulating in northern Italy since December 2019: Evidence from environmental monitoring. Science of the Total Environment, Vol. 750, article 141711, 2021.
8 Andersen, K.G. et al. The proximal origin of SARS-CoV-2. Nature Medicine, Volume 26,pages 450-455, April, 2020.
9 Wu, F. Updated analysis to reject the laboratory-engineering hypothesis of SARS-CoV-2. Environmental Research, Vol. 224, article 115481, 2023.
10 Worobey, M. et al. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, Vol. 377, p. 951-959, 2022.
11 Jiang, S. & Wang, R. Wildlife trade is likely the source of SARS-CoV-2. Science, Volume 377, p. 925-926, 2022.
12 Pekar, J.E. et al. The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. Science, Vol. 377, p. 960-966, 2022.
13 Qiu, X. et al. SARS‐CoV‐2 and natural infection in animals. Journal of Medical Virology, Vol. 95, article e28147.
14 Devaux, C.A. et al. Spread of Mink SARS‐CoV‐2 variants in humans: a model of sarbecovirus interspecies evolution. Frontiers in Microbiology. Vol. 12, article 675528, 2021.
15 The Global Virome Project, 2021.
16 Kumar, S.Q. et al. An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic. Molecular Biology and Evolution, 24 Sept., 2020.
17 Smith, R.E. The NeoCoV virus. The next coronavirus pandemic may be just one mutation away. Meer, 24 Feb., 2022.
18 Sidik, S.M. Bird flu outbreak in mink sparks concern about spread in people. Nature, Volume 684, p. 17, 2023.
19 U.S. Department of Agriculture. 2022-2023 Confirmations of Highly Pathogenic Avian Influenza in Commercial and Backyard Flocks, 18 enero, 2023.
20 U.S. Department of Agriculture. 2022-2023 Detections of Highly Pathogenic Avian Influenza in Wild Birds. 15 Marzo, 2023.
21 NOAA Fisheries. Recent Increase in Seal Deaths in Maine Linked to Avian Flu. 20 July, 2022.
22 Eurosurveillance. Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022.