Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population

Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 x 10(-8)). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 10(-6)). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations

Lečenje koronavirusne boLesti (CoviD-19)

Coronavirus disease (COVID-19) is caused by RNA virus of severe acute respiratory syndrome 2 (SARS-CoV-2) which is highly contagious to humans. The primary receptor for the virus is probably angiotensin-converting enzyme 2. COVID-19 is a respiratory infection, primarily transmitted by droplets and close contact with a diseased person. Estimated reproductive number (R0) is 2-2.5 and the mean incubation time is 5.2 days, ranging 1-14 days (95% confidence interval 4.1-7.0 days). The most common symptoms are: fever, dry cough, malaise, productive sputum and dyspnea, followed, sore throat, headache, myalgia, arthralgia, fever and dizziness and, occasionally, confusion, rhinorrhea, nasal congestion, gastrointestinal symptoms, hemoptysis and conjunctival injection. Initial atypical manifestations are also known. Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay is the "gold" diagnostic standard, but its specificity and sensitivity have not been established. The most common complications are: acute respiratory distress syndrome, acute liver damage, acute heart damage and arrhythmia, followed by secondary infections, acute respiratory failure, acute renal impairment, sepsis and/or septic shock, pneumothorax, disseminated intravascular coagulation, acute heart failure and occasionally, rhabdomyolysis. Disease duration varies and in hospitalized patients it is estimated to be 16-26 days (interquartile range 12-29 days), while the global mortality rate is still unknown with certainty. Drugs against SARS-CoV-2 prescribed by empirical protocols (off-label use) are lopinavir/ritonavir, chloroquine and hydroxychloroquine, nitazoxanide, umifenovir, ribavirin, inhaled interferon Alpha while the new drugs of clinical trial stages are remdesivir, nafamostat i favipiravir. Proven drug prophylaxis of COVID-19 does not yet exist and vaccine against SARS-CoV-2 has not yet been developed.Publishe