Kunskapsläget i början av pandemin
Mörkertalet
Pandemin började som bekant i staden Wuhan i Kina i december 2019. I februari 2020 besökte en WHO-delegation Kina för att samla information som sammanfattades i en WHO-rapport 20 februari 2020. I rapporten framkom att mörkertalet av smittade var litet och att det inte fanns någon större spridning i befolkningen i Wuhan.
Citat från rapporten:
"China has a policy of meticulous case and contact identification for COVID-19. For example, in Wuhan more than 1800 teams of epidemiologists, with a minimum of 5 people/team, are tracing tens of thousands of contacts a day. Contact follow up is painstaking, with a high percentage of identified close contacts completing medical observation. Between 1% and 5% of contacts were subsequently laboratory confirmed cases of COVID-19, depending on location. For example: • As of 17 February, in Shenzhen City, among 2842 identified close contacts, 2842 (100%) were traced and 2240 (72%) have completed medical observation. Among the close contacts, 88 (2.8%) were found to be infected with COVID-19. • As of 17 February, in Sichuan Province, among 25493 identified close contacts, 25347 (99%) were traced and 23178 (91%) have completed medical observation. Among the close contacts, 0.9% were found to be infected with COVID-19. • As of 20 February, in Guangdong Province, among 9939 identified close contacts, 9939 (100%) were traced and 7765 (78%) have completed medical observation. Among the close contacts, 479 (4.8%) were found to be infected with COVID-19.
Testing at fever clinics and from routine ILI/SARI surveillance The Joint Mission systematically enquired about testing for COVID-19 from routine respiratory disease surveillance systems to explore if COVID-19 is circulating more broadly and undetected in the community in China. These systems could include RT-PCR testing of COVID-19 virus in influenza-like-illness (ILI) and severe acute respiratory infection (SARI) surveillance systems, as well as testing of results among all visitors to fever clinics.
In Wuhan, COVID-19 testing of ILI samples (20 per week) in November and December 2019 and in the first two weeks of January 2020 found no positive results in the 2019 samples, 1 adult positive in the first week of January, and 3 adults positive in the second week of January; all children tested were negative for COVID-19 although a number were positive for influenza. In Guangdong, from 1-14 January, only 1 of more than 15000 ILI/SARI samples tested positive for the COVID-19 virus. In one hospital in Beijing, there were no COVID-19 positive samples among 1910 collected from 28 January 2019 to 13 February 2020. In a hospital in Shenzhen, 0/40 ILI samples were positive for COVID-19.
Within the fever clinics in Guangdong, the percentage of samples that tested positive for the COVID-19 virus has decreased over time from a peak of 0.47% positive on 30 January to 0.02% on 16 February. Overall in Guangdong, 0.14% of approximately 320,000 fever clinic screenings were positive for COVID-19. "
Testing at fever clinics and from routine ILI/SARI surveillance The Joint Mission systematically enquired about testing for COVID-19 from routine respiratory disease surveillance systems to explore if COVID-19 is circulating more broadly and undetected in the community in China. These systems could include RT-PCR testing of COVID-19 virus in influenza-like-illness (ILI) and severe acute respiratory infection (SARI) surveillance systems, as well as testing of results among all visitors to fever clinics.
In Wuhan, COVID-19 testing of ILI samples (20 per week) in November and December 2019 and in the first two weeks of January 2020 found no positive results in the 2019 samples, 1 adult positive in the first week of January, and 3 adults positive in the second week of January; all children tested were negative for COVID-19 although a number were positive for influenza. In Guangdong, from 1-14 January, only 1 of more than 15000 ILI/SARI samples tested positive for the COVID-19 virus. In one hospital in Beijing, there were no COVID-19 positive samples among 1910 collected from 28 January 2019 to 13 February 2020. In a hospital in Shenzhen, 0/40 ILI samples were positive for COVID-19.
Within the fever clinics in Guangdong, the percentage of samples that tested positive for the COVID-19 virus has decreased over time from a peak of 0.47% positive on 30 January to 0.02% on 16 February. Overall in Guangdong, 0.14% of approximately 320,000 fever clinic screenings were positive for COVID-19. "
En av de experter som besökte Kina, Bruce Aylward, blev intervjuad av webbsite Vox 3 mars 2020. Han berättade samma sak som WHO-rapporten, mörkertalet av smittade var litet. Han sa även att det viktigaste var att agera snabbt, hitta smittade, isolera dem, och spåra deras nära kontakter. Han berättade att dödligheten för kända fall (Case Fatality Ratio, CFR) i Hubei-provinsen var runt 1% tack vare att Kina var duktiga på att hitta många smittade men man kunde inte förvänta sig att det skulle vara lika lågt i andra länder.
Citat från intervjun:
"I think the key learning from China is speed — it’s all about the speed. The faster you can find the cases, isolate the cases, and track their close contacts, the more successful you’re going to be. Another big takeaway is that even when you have substantial transmission with a lot of clusters — because people are looking at the situation in some countries now and going, “Oh, gosh, what can be done?” — what China demonstrates is if you settle down, roll up your sleeves, and begin that systematic work of case finding and contact tracing, you definitely can change the shape of the outbreak, take the heat out of it, and prevent a lot of people from getting sick and a lot of the most vulnerable from dying. "
"More of a surprise, and this is something we still don’t understand, is how little virus there was in the much broader community. Everywhere we went, we tried to find and understand how many tests had been done, how many people were tested, and who were they.
In Guangdong province, for example, there were 320,000 tests done in people coming to fever clinics, outpatient clinics. And at the peak of the outbreak, 0.47 percent of those tests were positive. People keep saying [the cases are the] tip of the iceberg. But we couldn’t find that. We found there’s a lot of people who are cases, a lot of close contacts — but not a lot of asymptomatic circulation of this virus in the bigger population. And that’s different from flu. In flu, you’ll find this virus right through the child population, right through blood samples of 20 to 40 percent of the population. "
If you didn’t find the “iceberg” of mild cases in China, what does it say about how deadly the virus is — the case fatality rate?
"It says you’re probably not way off. The average case fatality rate is 3.8 percent in China, but a lot of that is driven by the early epidemic in Wuhan where numbers were higher. If you look outside of Hubei province [where Wuhan is], the case fatality rate is just under 1 percent now. I would not quote that as the number. That’s the mortality in China — and they find cases fast, get them isolated, in treatment, and supported early. Second thing they do is ventilate dozens in the average hospital; they use extracorporeal membrane oxygenation [removing blood from a person’s body and oxygenating their red blood cells] when ventilation doesn’t work. This is sophisticated health care. They have a survival rate for this disease I would not extrapolate to the rest of the world. What you’ve seen in Italy and Iran is that a lot of people are dying.
This suggests the Chinese are really good at keeping people alive with this disease, and just because it’s 1 percent in the general population outside of Wuhan doesn’t mean it [will be the same in other countries]."
"More of a surprise, and this is something we still don’t understand, is how little virus there was in the much broader community. Everywhere we went, we tried to find and understand how many tests had been done, how many people were tested, and who were they.
In Guangdong province, for example, there were 320,000 tests done in people coming to fever clinics, outpatient clinics. And at the peak of the outbreak, 0.47 percent of those tests were positive. People keep saying [the cases are the] tip of the iceberg. But we couldn’t find that. We found there’s a lot of people who are cases, a lot of close contacts — but not a lot of asymptomatic circulation of this virus in the bigger population. And that’s different from flu. In flu, you’ll find this virus right through the child population, right through blood samples of 20 to 40 percent of the population. "
If you didn’t find the “iceberg” of mild cases in China, what does it say about how deadly the virus is — the case fatality rate?
"It says you’re probably not way off. The average case fatality rate is 3.8 percent in China, but a lot of that is driven by the early epidemic in Wuhan where numbers were higher. If you look outside of Hubei province [where Wuhan is], the case fatality rate is just under 1 percent now. I would not quote that as the number. That’s the mortality in China — and they find cases fast, get them isolated, in treatment, and supported early. Second thing they do is ventilate dozens in the average hospital; they use extracorporeal membrane oxygenation [removing blood from a person’s body and oxygenating their red blood cells] when ventilation doesn’t work. This is sophisticated health care. They have a survival rate for this disease I would not extrapolate to the rest of the world. What you’ve seen in Italy and Iran is that a lot of people are dying.
This suggests the Chinese are really good at keeping people alive with this disease, and just because it’s 1 percent in the general population outside of Wuhan doesn’t mean it [will be the same in other countries]."
Prevalensen av covid-19 infektioner skattades från över 8.000 personer som evakuerades till olika länder från Wuhan (Thompson et al., 9 mars 2020). Enligt skattningen var prevalensen 0.87% mellan 30 januari och 1 februari, nära toppen av epidemin i Wuhan. Utbrottet i Wuhan stoppades som bekant av en drakonisk nedstängning från 23 januari till 8 april 2020.
Dödlighet
I mars 2020 fanns skattningar av dödligheten (Infection Fatality Ratio, IFR). Från kryssningsfartyget Diamond Princess skattades IFR till 1.2% (Russell et al., 9 mars 2020), men det var för en grupp av personer äldre än en genomsnittlig befolkning. Med Kinas åldersfördelning skattades IFR till 0.66% (Verity et al., 13 mars 2020). Med Storbritanniens åldersfördelning skattades IFR till 0.9% (Ferguson et al., 16 mars 2020). Även senare data har visat att dödligheten är i intervallet 0.5-1%, vilket kan jämföras med 0.1-0.15% för influensa.
Smittspridning i andra länder
Under våren 2020 kom resultat från antikroppsmätningar i länder och områden som var hårt drabbade av pandemin. Endast runt 10% hade antikroppar i sådana områden i Nederländerna (Slot et al., 29 april 2020) och Spanien (Pollán et al., 6 juli 2020).
