Zeynep Ergenc, Hasan Ergenc✉, Ahmet Öztürk, Gülsüm Kaya, Özlem Karaca Ocak, Özgür İnce
1Department of Internal Medicine, Ayancık Government Hospital, Sinop, Turkey
2Department of Emergency Medicine, Çorum Erol Olçok Training and Research Hospital, Çorum, Turkey
3Department of Infection Control Committee, Sakarya Univercity Training and Research Hospital, Sakarya, Turkey
4Department of General Surgeon, Medicana International Hospital, Samsun, Turkey
5Department of Pulmonology, Medicana International Hospital, Samsun, Turkey
ABSTRACT Objective: To investigate the clinical symptoms of coronavirus disease 2019 (COVID-19) patients with and without B.1.1.7 mutation.Methods: This retrospective observational study included COVID-19 patients who were divided into two groups, the mutation and the non-mutation group.Demographics characteristics, clinical characteristics, laboratory parameters, and mortality rates were recorded and compared between the two groups.Results: A total of 196 patients were included in the study.The relationship between the mutant virus status and sex, age, comorbidity, survival status, and disease severity was not significant (P＞0.05).No significant differences were found in duration of hospitalization between the mutation and the non-mutation group (P＞0.05).However, there was a statistically significant difference between patients with and without mutant viruses in hemoglobin, mean platelet volume, procalcitonin, low density lipoprotein, ironbinding capacity, potassium, calcium, C-reactive protein, folate, creatine kinase myocardial band, D-dimer, and international normalized ratio (P＜0.05).Conclusions: No significant difference is found in mortality rate, disease severity or duration of hospitalization between the patients with and without variant B.1.1.7.Careful monitoring of COVID-19 patients is required for all variants.
KEYWORDS: COVID-19; B.1.1.7; Variant; Mutation; Clinical parameters; Laboratory parameters
Coronavirus disease 2019 (COVID-19) emerged in December 2019 and has caused an epidemic globally and an unprecedented disruption in human society.Since then, the virus has infected more than 169 million people and has killed more than 3.5 million people[1].Previous studies have clearly shown that epidemic and pandemic spread of the RNA virus may cause mutations that alter the pathogenicity, virulence, transmissibility, or a combination of these in the RNA virus[2].These mutations among coronaviruses in animals and humans have recently been studied.Early variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show limited genetic diversity because the virus may be from a single source[3].
Early animal variants of the SARS-CoV-2 virus, introduced in 2003, affected the receptor-binding domain binding to the spike protein, thereby increasing the binding and entry of the virus through the human angiotensin-converting enzyme 2 receptor.However, despite coronavirus RNA-correcting activity supporting replication, genetic epidemiological studies have identified an emerging D614G mutation that affects the glycoprotein protein of SARS-CoV-2 strains from southern Europe.This variant has since spread rapidly and has become the most common genotype worldwide[4].
The B.1.1.7 variant was discovered in the UK, and it is declared that it is at least 50% more likely to be transmitted than the wildtype variant.The announcement was based on epidemiological data showing that the virus spread rapidly across the UK[1].Lineage B.1.1.7 contains 17 mutations, including several identified in the spike protein, one of which, N501Y, contributes to the strong binding of the virus to the angiotensin-converting enzyme 2 cell receptor[5].In the genome studies of SARS-CoV-2, the most frequent mutation rate was observed on genes encoding thorn (S) protein, RNA polymerase, RNA primase (ORF1ab), and nucleoprotein (N)[6].Furthermore, studies have shown that these mutations in the virus change the clinical course of the disease and develop resistance to antiviral therapy[7].There have been many studies on the B.1.1.7 variant, most of which focused on the duration of hospitalization, disease severity, and mortality of this variant.This study aimed to retrospectively compare clinical and laboratory parameters of patients with and without variant B1.1.7.
2.1.Study design
This retrospective and observational study was conducted in Ayancık Government Hospital between April and July 2021.
2.2.Patients
Patients who were positive for COVID-19 were divided into two groups: the mutation and non-mutation group.Inclusion criteria was as follows: Over the age of 18, having COVID-19 PCR +, being reported as SARS-CoV-2 mutant and non-mutant as a result of PCR, being treated as an inpatient, having complete laboratory and clinical records.Patients who were under the age of 18, received a COVID-19 PCR result, were not hospitalized, and had missing laboratory and clinical records were excluded from the study.File records were scanned, including age, sex, length of hospital stay, hemogram, biochemical parameters, and mortality rates, etc.
2.3.Ethical approval
Ethics approval of this study was obtained from the Non-Interventional Clinical Research Ethics Committee of Samsun Health Sciences University Samsun Training and Research Hospital with the protocol code GOKA/2021/8/6.
2.4.Statistical analysis
The sample size was not used in the study, and all patients who met the study criteria were included in the study.
The data analysis was performed with the SPSS 26 program.The Shapiro-Wilk normality test was used to determine the normal distribution.Parametric or non-parametric methods were used according to the normal distribution of the measurement.
Statistics were given as frequency (n, %) for categorical (qualitative) variables, and mean±standard deviation (mean±SD) or median (Q1, Q3) for numerical (quantitative) variables.The Chi-square test was used to analyze categorical variables.Mann- Whitney test or t-test was used for quantitative variables.Finally, the Spearman correlation test was used to analyze the correlation.The significant level was set at α=0.05.
The study groups consisted of 98 COVID-19 patients with the mutant virus and 98 patients without the mutant virus.
3.1.Demographic and clinical characteristics
There was a statistically significant difference in smoking, hypertension, cough, body pain between patients with and without mutation (P＜0.05).There were more patients with coughing (63.3%), and pain (56.1%) in those with mutant viruses (Table 1).
3.2.Hospital stay, laboratory parameters, and mortality rates of mutant - and mutant + patients
The hospital stay, laboratory parameters and mortality rates are shown in the Table 2.No significant difference was found in the duration of hospitalization between the mutation and the nonmutation group (P＞0.05).However, there was a statistically significant difference in hemoglobin, red cell distribution widthcoefficient of variation, mean platelet volume, plateletcrit, iron binding capacity, potassium, calcium, C-reactive protein, folate, creatine kinase myocardial band, D-dimer, and international normalized ratio measurements (P＜0.05).Hemoglobin, plateletcrit, creatine kinase myocardial band, and international normalized ratio were significantly lower in those without the mutant virus.Red cell distribution width-coefficient of variation, mean platelet volume, iron binding capacity, C-reactive protein, folate, D-dimer were higher in patients with virus mutation.
Table 1.Demographic and clinical characteristics (n, %).
3.3.Multivariate analysis of mutation-related factors
Multivariate analysis was performed based on the univariate analysis result.The established model was statistically significant (χ2=38.192;P＜0.05; Nagelkerke R2=0.236).According to the results of the analysis, hypertension, body pain, and other complaints were found to be statistically significant risk factors of the mutant (–/+) status (P＜0.05).Body pain was 1.887 times more common in patients with mutant (+).It was seen less frequently in mutant (+) patients with 74.9% of patients with hypertension and 65.7% in those with other complaints.Other factors were not statistically significant (P＞0.05) (Table 3).
3.4.Correlation between different parameters and duration of hospitalization
As shown in Table 4, in the non-mutation group, there was a significant positive relationship between the duration of hospitalization and high density lipoprotein (P＜0.05).In the mutation group, there was a significant positive relationship between the duration of hospitalization and the lymphocyte, glucose, phosphorus, and sedimentation (P＜0.05).
Table 2.Comparison of measurements by mutant virus status.
Table 3.Multivariate analysis of mutation-related factors.
Table 4.Correlation between parameters and duration of hospitalization.
One of the most important SARS-CoV-2 variants is B.1.1.7, first identified in October 2020 in the UK.However, the origin of this variant may be in another country[8].Variant B.1.1.7 is important because it creates many mutations at the same time.Leung et al.speculate that the mutations may have originated in an immunocompromised patient who has been infected for a long time[9].Volz et al.found that it is likely that only a small fraction of these changes would have reached the evolutionary benefits of these variants[10].
The present study investigates the clinical symptoms of COVID-19 patients with and without B.1.1.7 mutation.The results did not find any significant differences in mortality rate, disease severity, or duration of hospitalization between the two study groups.
Concerns about increased mortality of B.1.1.7 variant were first announced when the British Government’s New and Emerging Respiratory Virus Threats Advisory Group showed an increase in mortality compared to wild-type strains[4].In January 2021, Rambuat et al.reported evidence that type B.1.1.7 may be associated with an increased risk of death and transferability than other types[11].Initial reports did not provide evidence that the mutation affected vaccine efficiency[12] and suggest that it is probably more deadly, leading to more hospitalizations than wild-type strains of the virus[13].Davies et al.adapted data from studies by several institutes and found an increased severity of COVID-19 cases compared to other types[14].Another study found that B.1.1.7 cases were 30% to 70% more lethal than the original wild-type[15].
Several other studies have examined the effect of type B.1.1.7 on hospitalization.In particular, a study used the S-gene target failure as a marker to identify B.1.1.7 variants of SARS-CoV-2.They noted that the risk of hospitalization is higher among cases of gene target failure compared with positive cases of the gene[16].In addition, data from the Intensive Care National Audit and Research Centre also revealed a higher risk of ICU acceptance for this type of virus than for other types[17].
In this study, we did not see any difference in mortality rates between the B.1.1.7 mutation and non-mutation groups.However, some studies have different results from the findings of our study.For example, a review of 12 studies in the United Kingdom on this variant showed that mortality in patients with this variant is reported to be 36% to 71% higher[4].The difference could be due to the small sample size, as mortality due to this variant has been analyzed in only 8% of all COVID-19 deaths in the UK[10].
A case-control study in the United Kingdom with 54 906 participants from October 1, 2020, to January 29, 2021 reported that 28 days after the test, the risk ratio for mortality in patients with variant B.1.1.7 was 1.64 compared to patients with other variants (95% confidence interval: 1.32-2.04)[12].In addition, a study in Denmark showed that the hospitalization rate for people with this variant was 64% higher[18].
A study by Brookman et al.comparing the first and second waves of COVID-19 in the United Kingdom, coincided with the outbreak of variant B.1.1.7, showed that in the second wave, the number of children and young people admitted to the hospital increased[8].Therefore, it could be due to the prevalence of variant B.1.1.7 in the second wave.However, there was no evidence of more severe disease in children and adolescents in the second wave, and the authors ultimately did not suggest a different treatment from the first wave for children in the second wave.
As a result, the transmission rate and the mortality of variant B.1.1.7 are shown to be higher than the non-mutated variants.However, not all studies agree that this type is prone to be more severe and an increased risk of death.For example, the COVID-19 Clinical Information Network data showed no correlation between different variants and higher hospital mortality[2].Our result is consistent with these findings.
The Office for National Statistics analysis noted that while the risk ratio indicates a higher risk of all-cause mortality, they found that the number of deaths is too low for reliable inference, and there are potential limitations to all datasets used.However, these analyses suggest that the B.1.1.7 variant may be associated with an increased risk of hospitalization and death than infection with other variants[19].Some studies believe that B.1.1.7 has not been conclusively proven to be more deadly[20,21].It is unknown whether this increased infectivity is due to N501Y alone or a combination of other mutations in the spike protein[22].Others believe that despite initial concerns, there is no real reason that this type of infection is more common in children than in the original variant[23].
One of the limitations of this study is the small sample size.Small sample size can be one of the reasons for conflicting results in studies regarding mortality rate, duration of hospitalization, and disease severity.Therefore, future studies should be performed with larger sample sizes and data from multiple treatment centers so that results can be inferred with greater confidence.
In conclusion, the present study compared the clinical symptoms between COVID-19 patients with and without B.1.1.7 mutation and did not find any significant difference in mortality rate, disease severity, or duration of hospitalization between the two groups.However, some biochemical parameters were significantly different between the two groups, which can be used as preliminary findings for future studies.
Conflict of interest statement
The authors declare no conflict of interest.
Funding
This study received no extramural funding.
Authors" contributionsHE and ZE collected and curated the data; HE, ZE, AÖ, GK, ÖKO, and Öİ contributed to writing the manuscript.All authors read and approved the final manuscript.