The coronavirus disease 2019 (COVID-19) epidemic is certainly cause for concern. Proper communication and optimal decision-making is an ongoing challenge, as data evolve. The challenge is complex, especially caused by exaggerated information which can lead to inappropriate actions. It is important to differentiate promptly the true epidemic from an epidemic of false claims and potentially harmful actions.
This is why CEBaP searches for COVID-19 literature, which is relevant for the Red Cross, on a daily basis and assesses new studies on their reliability. Here we provide an overview of our analyses of the identified articles.
A systematic review which included 17 observational studies reported a negative association between the spread of COVID-19 and temperature and humidity in the majority of included studies. That is, cold and dry conditions were associated with an increased spread of COVID-19, whereas warm and wet climates were associated with a reduced spread of COVID-19.
Seven of the 17 studies in this systematic review were conducted in China, while the other 10 studies included data from several different countries affected by the novel coronavirus. Caution is warranted when interpreting these results:
Based on this review, we cannot be certain about the impact of air temperature and humidity on COVID-19 incidence and viral transmission. The association only explains a portion of the variation, while there are many confounding variables which may have a larger impact. Any decline of virus transmission during the summer due to temperature and humidity is expected to be modest, and not enough to stop transmission on its own. In the meantime, everyone should adhere to the restrictions imposed by the government to limit the spread of COVID-19.
The Centre for Evidence-Based Medicine (CEBM) of Oxford University performed a similar fact-check on this topic, find out their verdict here.
On social media, rumour has it that people with blood type A are more susceptible to COVID-19 than people with blood type O. The rumour originated from the conclusions of a study that was pre-published on March 11th 2020 (Zhao et al. 2020), followed by two similar phenotype studies pre-published on April 15th (Zeng et al. 2020) and May 7th (Li et al. 2020), respectively. Subsequently, on 17th June, the New England Journal of Medicine (NEJM) published a genome wide association study (GWAS) of severe COVID-19 with respiratory failure. The authors found an association between two loci on two different chromosomes and the development of COVID-19 disease with respiratory failure. One of these loci coincided with the gene for ABO blood groups. Moreover, in the past, blood types have been associated with the occurrence of a number of viral diseases.
However, based on the data of these observational studies, we cannot conclude that people with a certain blood type are more likely to become infected with SARS-CoV-2 and to develop COVID-19 than people with another blood type. Below, we give arguments to support our conclusion. Because infection with SARS-CoV-2 and development of serious COVID-19 outcomes should not be confused, we discuss these outcomes separately.
The three Chinese studies mentioned above found a higher percentage of blood type A in a cohort of COVID-19 patients than in the general population, hinting to a higher susceptibility for people with blood type A. However, they all have considerable limitations.
First of all, as of 9th July 2020, only the paper by Li et al. has been published as a peer-reviewed article (in the British Journal of Haematology), whereas the manuscripts by Zhao et al. and Zeng et al. have not yet been peer-reviewed.
Second, these observational studies compared blood type phenotypes of a population of patients with a control group representing the general population, but provide no demographic details (age and sex distribution) on their respective control group. In addition, the investigators did not adjust their analyses for age and sex (or any other potential confounders). Therefore, confounding of the supposed association between SARS-CoV-2 and ABO blood type by demographic or biomedical differences between cases and controls cannot be ruled out.
Third, generalizability of the results to Western Europe is questionable. All studies were conducted in China. Zhao et al. included data on ABO blood type and COVID-19 from three hospitals in two agglomerations in China (Wuhan and Shenzen), and they showed substantial heterogeneity in ABO blood type distributions among people with and without the disease in both regions. In the study by Zeng et al., patients from three hospitals (in Beijing, Xi’an and another hospital in Wuhan) were included. Li et al. described results from yet another hospital in Wuhan and used the same general population as Zhao et al. as the reference population.
Fourth, statistical significance does not always imply clinical relevance. Although results for the association between blood type and hospitalization with SARS-CoV-2 infection were significant, the percentages are not that different after all. All studies made use of chi squared tests for homogeneity. When the sample size is large (say >500, which is the case here), almost any small difference will appear statistically significant with a chi squared test. Zhao et al. and Zeng et al. calculated odds ratios as well, but as pointed out above, these were not adjusted for covariates.
The GWAS published in the NEJM was different from the three Chinese papers discussed above, both in methodology (genotyping vs phenotyping of patients) and outcome of interest (serious COVID-19 disease vs SARS-CoV-2 infection). We acknowledge the tremendous logistical and methodological efforts made by the authors of the GWAS, but we still end up with the conclusion that more research is needed to claim a causal association between ABO blood type and COVID-19. Below, we discuss strengths and limitations of the study.
In contrast to the Chinese studies discussed above, the GWAS was peer-reviewed and published in the NJEM, a highly influential journal on general medicine (impact factor 70) with a high threshold value concerning originality and quality of work presented for publication. In this respect, we cannot rule out the possibility that novelty and sense of urgency, two assets of any research on SARS-CoV-2, may have biased the editorial board’s decision towards publication, at the expense of the usual quality standards.
Second, the study compared the complete genotype of a population of patients with respiratory failure (use of oxygen supplementation or mechanical ventilation) with a control group representing the general population. Analyses were corrected for age and sex of all study subjects, but not for other potential sources of bias (e.g. underlying cardiovascular and metabolic comorbidities). Therefore, it remains unclear whether ABO blood group per se causes a differential course of the disease.
Patient data were collected in Italy (3 hospitals, all in Milan and surroundings) and Spain (4 hospitals: 2 in Barcelona, one in Madrid, and one in San Sebastián) The control group consisted of blood donors from Milan (Italy) and San Sebastián (Spain) and other healthy subjects from Italy (locations not specified). The authors obtained similar results for the Italian and the Spanish study panel and the distribution of ABO blood types in Spain and Italy are representative for those found in Western European countries. Therefore, we conclude that results are probably generalizable to the whole of Western Europe.
In the GWAS, specific statistical techniques and significance thresholds for genome wide analyses were used. Odds ratios obtained for the association between blood type and COVID-19 were similar to those calculated by Zhao et al. and Zeng et al. Due to the superior statistical techniques and much narrower confidence intervals, they are more reliable, but again, not adjusted for important covariates.
In contrast to the GWAS, Zeng et al. failed to find any association between blood type and clinical outcomes, such as acute respiratory distress syndrome, acute kidney injury, and death. Li et al. found no association between blood type and death resulting from COVID-19 disease either. No subanalysis with patients who died of COVID-19 was performed in the GWAS.
We conclude that there is no convincing evidence on the association between ABO blood type and SARS-CoV-2 susceptibility. Zeng et al. rightly concluded that “people and health care workers should not overestimate the genetic susceptibility by placing a certain blood group at risk for poor prognosis.”
Despite the new insights provided by the recent GWAS, we believe that a causal relationship between ABO blood type and the course of COVID-19 disease remains to be proven as well. As the authors of the GWAS acknowledge, further research is needed, both on the usefulness of ABO blood group in clinical risk profiling and on the mechanisms of the underlying pathophysiology.
Everybody, regardless of blood group, should adhere to the restrictions imposed by the government to counter the spread of SARS-CoV-2.
Another (not peer-reviewed) research letter discussing the study by Zhao et al. can be found here. The authors conclude that, although some plausible mechanisms may explain the assumed difference in susceptibility between blood types A and O, these hypotheses are entirely based on research on other coronaviruses in the past and therefore require further molecular, clinical and epidemiological research on the SARS-CoV-2 virus.