SARS-CoV-2 infection, which causes the respiratory disease COVID-19, has spread rapidly from Wuhan, China, since 2019, causing nearly 7 million deaths worldwide in three years. In addition to clinical risk factors such as diabetes, hypertension, and obesity, genetic variability is an important predictor of disease severity and susceptibility. We analyzed common polymorphisms within the LZTFL1 (rs11385942) and ABCA3 (rs13332514) genes in 519 SARS-CoV-2-positive subjects (164 asymptomatic, 246 symptomatic, and 109 hospitalized COVID-19 survivors) and a population-based control group (N?=?2,592; COVID-19 status unknown). Rare ABCA3 AA homozygotes (but not A allele carriers) may be at a significantly increased risk of SARS-CoV-2 infection [P?=?0.003; OR (95 % CI); 3.66 (1.47-9.15)]. We also observed a borderline significant difference in the genotype distribution of the LZTFL1 rs11385942 polymorphism (P?=?0.04) between the population sample and SARS-CoV-2-positive subjects. In agreement with previous studies, a nonsignificantly higher frequency of minor allele carriers was detected among hospitalized COVID-19 subjects. We conclude that a common polymorphism in the ABCA3 gene may be a significant predictor of susceptibility to SARS-CoV-2 infection.

• MeSH
• ABC transportéry genetika   MeSH
• COVID-19 * diagnóza   epidemiologie   genetika   MeSH
• genotyp MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• SARS-CoV-2 MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• ABC transportéry MeSH
• ABCA3 protein, human MeSH Prohlížeč
• LZTFL1 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

BACKGROUND: Coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 virus, has become a global pandemic. While susceptibility to COVID-19 is subject to several external factors, including hypertension, BMI, and the presence of diabetes, it is also genetically determined to a significant extent. Infectious agents require iron (Fe) for proper functioning. Carriers of mutations resulting in increased iron concentrations are understood to be at increased risk of COVID-19. METHODS: We examined HFE genotypes associated with hereditary haemochromatosis (rs1800562 and rs1799945 SNPs) in 617 COVID-19 patients (166 asymptomatic, 246 symptomatic and 205 hospitalised survivors) and 2 559 population-based controls. RESULTS: We found a higher frequency of the minor allele (Tyr282) of the rs1800562 polymorphism (P < 0.002) in patients compared to controls (8.5 % vs 5.5 %). Non-carriers of the minor allele were protected against SARS-Cov-2 infection (OR, 95 %CI; 0.59, 0.42-0.82). The frequency of minor allele carriers was almost identical across asymptomatic, symptomatic, and hospitalised survivors. The rs1799945 variant did not affect disease severity and its occurrence was almost identical in patients and controls (P between 0.58 and 0.84). CONCLUSIONS: In conclusion, our results indicate that presence of the rs1800562 minor allele, which is associated with hereditary haemochromatosis (thus increased levels of plasma Fe), increases susceptibility to SARS-CoV-2.

• Klíčová slova
• COVID-19, HFE, Iron, Polymorphism, Susceptibility,
• MeSH
• COVID-19 * genetika   MeSH
• hemochromatóza * genetika   epidemiologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   MeSH
• mutace MeSH
• protein hemochromatózy genetika   MeSH
• SARS-CoV-2 MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HFE protein, human MeSH Prohlížeč
• MHC antigeny I. třídy MeSH
• protein hemochromatózy MeSH
• železo MeSH

In the era of COVID-19 pandemic, organ transplantation programs were facing serious challenges. The lung transplantation donor pool was extremely limited and SARS-CoV-2 viral load assessment has become a crucial part of selecting an optimal organ donor. Since COVID-19 is a respiratory disease, the viral load is thought to be more important in lung transplantations as compared to other solid organ transplantations. We present two challenging cases of potential lung donors with a questionable COVID-19 status. Based on these cases, we suggest that the cycle threshold (Ct) value should always be requested from the laboratory and the decision whether to proceed with transplantation should be made upon complex evaluation of diverse criteria, including the nasopharyngeal swab and bronchoalveolar lavage PCR results, the Ct value, imaging findings and the medical history. However, as the presence of viral RNA does not ensure infectivity, it is still to be clarified which Ct values are associated with the viral viability. Anti-SARS-CoV-2 IgA antibodies may support the diagnosis and moreover, novel methods, such as quantifying SARS-CoV-2 nucleocapsid antigen in serum may provide important answers in organ transplantations and donor selections.

• MeSH
• bronchoalveolární lavážní tekutina virologie   MeSH
• COVID-19 diagnóza   virologie   MeSH
• dárci tkání * MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• plíce chirurgie   virologie   MeSH
• prediktivní hodnota testů MeSH
• rizikové faktory MeSH
• SARS-CoV-2 izolace a purifikace   MeSH
• testování na COVID-19 MeSH
• transplantace plic * škodlivé účinky   MeSH
• virová nálož MeSH
• výběr dárců * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-delta32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-delta32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-delta32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-delta32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

• MeSH
• COVID-19 genetika   imunologie   mortalita   virologie   MeSH
• fenotyp MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• mutace * MeSH
• ochranné faktory MeSH
• prevalence MeSH
• receptory CCR5 genetika   MeSH
• rizikové faktory MeSH
• SARS-CoV-2 imunologie   patogenita   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• CCR5 protein, human MeSH Prohlížeč
• receptory CCR5 MeSH

Genetic predispositions may influence geographical and interethnic differences in COVID-19 prevalence and mortality in affected populations. Of the many genes implicated in COVID-19 progression, a substantial number have no direct functional link on virus transfer/viability or on the host immune system. To address this knowledge deficit, a large number of in silico studies have recently been published. However, the results of these studies often contradict the findings of studies involving real patients. For example, the ACE2 has been shown to play an important role in regulating coronavirus entry into cells, but none of its variations have been directly associated with COVID-19 susceptibility or severity. Consistently was reported that increased risk of COVID-19 is associated with blood group A and with the APOE4 allele. Among other genes with potential impacts are the genes for CCR5, IL-10, CD14, TMPRSS2 and angiotensin-converting enzyme. Variants within the protein-coding genes OAS1 and LZTFL1 (transferred to the human genome from Neanderthals) are understood to be among the strongest predictors of disease severity. The intensive research efforts have helped to identify the genes and polymorphisms that contribute to SARS-CoV-2 infection and COVID-19 severity.

• MeSH
• ABO systém krevních skupin genetika   MeSH
• angiotensin-konvertující enzym 2 genetika   MeSH
• apolipoproteiny E genetika   MeSH
• COVID-19 genetika   virologie   MeSH
• dědičnost MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• progrese nemoci MeSH
• rizikové faktory MeSH
• SARS-CoV-2 patogenita   MeSH
• serinové endopeptidasy genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ABO systém krevních skupin MeSH
• ACE2 protein, human MeSH Prohlížeč
• angiotensin-konvertující enzym 2 MeSH
• ApoE protein, human MeSH Prohlížeč
• apolipoproteiny E MeSH
• serinové endopeptidasy MeSH
• TMPRSS2 protein, human MeSH Prohlížeč

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread from China in 2019/2020 to all continents. Significant geographical and ethnic differences were described, and host genetic background seems to be important for the resistance to and mortality of COVID-19. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4646994) is one of the candidates with the potential to affect infection symptoms and mortality. METHODS: In our study, we successfully genotyped 408 SARS-CoV-2-positive COVID-19 survivors (163 asymptomatic and 245 symptomatic) and compared them with a population-based DNA bank of 2,559 subjects. RESULTS: The frequency of ACE I/I homozygotes was significantly increased in COVID-19 patients compared with that in controls (26.2% vs. 21.2%; P = 0.02; OR [95% CI] = 1.55 [1.17-2.05]. Importantly, however, the difference was driven just by the symptomatic subjects (29.0% vs. 21.2% of the I/I homozygotes; P = 0.002; OR [95% CI] = 1.78 [1.22-2.60]). The genotype distribution of the ACE genotypes was almost identical in population controls and asymptomatic SARS-CoV-2-positive patients (P = 0.76). CONCLUSIONS: We conclude that ACE I/D polymorphism could have the potential to predict the severity of COVID-19, with I/I homozygotes being at increased risk of symptomatic COVID-19.

• Klíčová slova
• ACE, COVID-19, Insertion/deletion, Polymorphism,
• MeSH
• angiotensin konvertující enzym genetika   MeSH
• COVID-19 * MeSH
• lidé MeSH
• přežívající MeSH
• SARS-CoV-2 * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Čína MeSH
• Názvy látek
• angiotensin konvertující enzym MeSH

• MeSH
• alely MeSH
• apolipoprotein E4 * genetika   MeSH
• COVID-19 * MeSH
• lidé MeSH
• rizikové faktory MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• apolipoprotein E4 * MeSH