It may also explain its unusual early adaptation to humans, unlike other coronaviruses.
The first global identified case of Covid-19 was on December 26 in the Wuhan Hospital in China, where a respiratory physician suspected a new infectious disease owing to his previous experiences with the 2003 SARS outbreak. Then on December 31, Chinese authorities informed the WHO of pneumonia with an unknown cause.
But as more data is collected over the year, increasingly more evidence suggests that Covid-19 might have started much earlier than December.
The CDC study in the U.S.
The U.S. surveillance team detected the first case of Covid-19 on January 19: a 35-year-old man who returned from China. But even this was not the actual first emergence of Covid-19. In the next sample of 12 early cases of Covid-19 in the U.S., two of them had symptoms that started on January 14. Taking into account the incubation period — the time gap between virus infection and symptom appearance — of about 5–6 or 14 days, the novel coronavirus SARS-CoV-2 might have been circulating in the U.S. earlier than January 14.
Maybe even as early as November, hinted a study from the CDC published a few days ago in the Clinical Infectious Diseases journal, titled “Serologic testing of U.S. blood donations to identify SARS-CoV-2-reactive antibodies: December 2019-January 2020.” In this study, researchers collected leftover sera from 7,389 donated blood samples from donors without suspected viral or bacterial respiratory infection.
The CDC then performed antibody testing — with validated sensitivity and specificity — on the blood sera. Results detected antibodies specific for the spike protein of SARS-CoV-2 in 1.43% (106 out of 7,389) of samples. Of these 106 cases, 39 belonged to blood samples collected between December 13–16 from California, Oregon, and Washinton. The other 67 cases were sampled from December 30 to January 17.
However, the study cautioned that none of the 106 infections qualifies as true positives or true Covid-19 cases, which can only be confirmed via a positive RT-PCR test on respiratory specimens. Another caveat is that whether these 106 infections were transmitted by traveling or community spread is unknown. Nonetheless, “The findings of this report suggest that SARS-CoV-2 infections may have been present in the U.S. in December 2019, earlier than previously recognized,” the study concluded.
A concern the paper did not address is that SARS-CoV-2 antibodies take 1–3 weeks to form following infection encounter — the window period. This is because antibodies are made by B-cells that belong to the immune system’s adaptive arm, the second line of defense that requires time to activate. So, the true infection encounter in the CDC study might have even been three weeks before December 13. But this may be relatively rare given that the median window period for SARS-CoV-2 antibodies is 10 days.
Looking at other countries
Based on China government data the South China Morning Post examined, the earliest detected Covid-19 case is on November 17 in a 55-year-old person in Hubei. By the end of November, there were nine cases of Covid-19. This data corroborates a study published in The Lancet that describes a Covid-19 patient with symptom onset dated December 1 in China. But even in those nine Covid-19 cases in November, there’s insufficient evidence to pinpoint patient zero — the first carrier of the Covid-19 outbreak. So, it’s still possible that there were undetected cases of Covid-19 before 17 November 2019.
Researchers in Lombardy, Italy also did a similar study as the CDC, which was published in the Tumori Journal with the title, “Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy.” Herein, the study caught antibodies specific for the SARS-CoV-2 receptor-binding domain (RBD) in 11.6% (111 out of 959 persons) of blood samples, of which 14% were sampled during September 2019. This interests the WHO, who has contacted the authors for further investigation.
There’re two pre-prints analyzing wastewater samples for traces of SARS-CoV-2 genetic material. One pre-print from Santa Catalina, Brazil, found SARS-CoV-2 RNA in two independent sewage samples collected on 27 November 2019. This data implies that people in Brazil might have been infected and shed the virus before December. The other pre-print is even more outrageous: Researchers from Barcelona, Spain, detected SARS-CoV-2 RNA in a sewage sample gathered on 12 March 2019. But note that preprints are not peer-reviewed, and there’s a critique that contamination may have occurred during sewage sampling and analyses.
Explaining the evolutionary leap
The early SARS-CoV-2 circulation theory also helps explain many odd facets of the pandemic. For one, SARS-CoV-2 binds to the ACE2 receptor with efficiency at least 10-times higher than SARS-1. This is despite that SARS-CoV-2 genomes have been relatively stable in early 2020 with low mutation rates. In contrast, rapid genetic changes happened in the genomes of SARS and MERS when they first spillover into the human population, which stabilize over time.
Thus, “SARS-CoV-2 might have cryptically circulated within humans for years before being discovered,” researchers suspect. If this suspicion is correct, then SARS-CoV-2 may have completed its host-switching adaption in humans before December. This also explains why SARS-CoV-2 already has a very stable genome in early 2020 and why SARS-CoV-2 has an unusual binding efficiency for the human ACE-2 receptor.
And it may also explain why attempts to pinpoint the intermediate host of SARS-CoV-2 have failed so far, given that the real intermediate host (if it exists) might not be among animals sampled in December or early 2020.
A new study from the U.S. CDC found SARS-CoV-2-specific antibodies in donated blood samples between December 13–16. Given that SARS-CoV-2 antibodies take 1–3 weeks to form, the actual infection in this study may be earlier than December 13. Indeed, recent government data detected Covid-19 cases from November 17 onwards in China. Further, a study from Italy has also found SARS-CoV-2 antibodies in blood samples sampled from September. Using wastewater samples, two preprints have also found traces of SARS-CoV-2 genes in samples collected in November in Brazil and March in Spain.
These data suggest that Covid-19 may have jumped to humans before December. In fact, the theory of early SARS-CoV-2 circulation in humans helps explain some oddities of the pandemic. For instance, SARS-CoV-2 genomes were already stable in early 2020, which also enables highly efficient binding to the human ACE2 receptor. In contrast, SARS and MERS genomes underwent drastic genetic changes when they first adapt to humans. In sum, increasing clinical and theoretical evidence indicates that Covid-19 may have emerged earlier than presumed.
This article was originally published in Microbial Instincts with minor modifications.