The ongoing global coronavirus-19 disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2], poses major challenges to health systems worldwide. While the majority of infected people have mild to moderate symptoms, some patients develop acute respiratory distress syndrome (ARDS) requiring intensive care treatment and mechanical ventilation [3].
SARS-CoV-2 is a positive-sense single-stranded RNA virus whose genome is of a low stability and is thus more prone to mutation accumulation, with approximately 9.8 × 104 substitutions/site yearly [1][2][3][4]. By the beginning of May 2021, there had been more than 1.4 million sequences reported, and among them, 3913 major representative variant genomes that have been identified and included in the global SARS-CoV-2 sequence database operated by Global Initiative on Sharing Avian Influenza Data (GISAID). Not all genetic mutations lead to variation in major proteins and/or alter virus infectivity. In the meantime, several mutations of SARS-CoV-2 have emerged . These genetic variants affect the course of the disease by altered virulence, susceptibility to immune response and transmissibility. Four of these variants are classified as variants of concern (VOC) by the World Health Organization (WHO): Alpha variant/Lineage B.1.1.7 (first detected in the UK) [5], Beta variant/Lineage B.1.351 (first detected in South Africa) , Gamma variant/Lineage P.1 (first detected in Brazil)[6][7] and Delta variant/Lineage B.1.617.2 (first detected in India) [8]. The current spike gene mutations account for most of the clinically influential VOC.
To date, the pandemic has evolved in waves with rapidly increasing infections and deaths in most countries. These waves led to various measures, such as lockdowns, mandatory masks and others, which consequently resulted in decreasing infection rates.
In Germany, the second COVID-19 wave in the autumn of 2020 was still caused by the SARS-CoV-2 wild-type (WT), but the Alpha variant successively superseded the WT and constituted the predominant COVID-19 pathogen from March 2021 onwards. The SARS-CoV-2 Alpha variant (lineage B.1.1.7) was first detected in the UK in September 2020 [5] and was shortly after named the Alpha variant. The Alpha variant has an N501Y mutation: at the 501 residue, asparagine N has been replaced with Y tyrosine, and K417N, lysine K, has been replaced with asparagine N. Evaluations[9] of the Robert Koch Institute illustrated a continuous increase in the proportion of infections with the Alpha variant up to more than 90% at the end of April 2021 [10]. Previous studies described the Alpha variant as being significantly more contagious. Evidence suggests that the VOC Alpha increased the transmissibility rate by ~50%, especially in younger age groups and children[11]; however, data regarding the severity of disease when compared to the SARS-CoV-2 WT are inconclusive [12][13][14][15][16][17]. At present, very limited data are available regarding the course of patients requiring admission to intensive care units (ICU) and the impact of the Alpha variant on ICU mortality[17].
Therefore, the aim of this study was to analyze the outcome and clinical course of patients with Alpha variant SARS-CoV-2 infections in the ICU of a maximum care hospital in Germany and to compare it to patients with WT infections.
Full Patient Population (n = 160) | Matched-Pair Analysis (n = 116) | |||||
---|---|---|---|---|---|---|
Alpha Variant (n = 80) | Wild Type (n = 80) | p | Alpha Variant (n = 58) | Wild Type (n = 58) | p | |
Age (median, range) | 55.5 (13–83) | 62.5 (16–87) | 0.073 | 61 (26–83) # | 62 (25–85) # | 0.917 |
Males | 59/80 (74%) | 57/80 (71%) | 0.860 | 43/58 (74.1%) # | 43/58 (74.1%) # | 1 |
Diabetes | 25/80 (26%) | 21/80 (31%) | 0.601 | 20/58 (34.5%) | 14/58 (24.1%) | 0.308 |
Chronic respiratory diseases | 13/80 (16%) | 10/80 (13%) | 0.653 | 9/58 (15.5%) | 4/58 (6.9%) | 0.238 |
Cardiovascular disease | 44/80 (55%) | 40/80 (50%) | 0.635 | 30/58 (51.7%) | 30/58 (51.7%) | 1 |
Oncologic/hematologic disease/immunosuppressive medication | 11/80 (14%) | 16/80 (20%) | 0.399 | 9/58 (15.5%) | 12/58 (20.7%) | 0.630 |
Liver disease | 8/80 (10%) | 4/80 (5%) | 0.369 | 5/58 (8.6%) | 3/58 (5.2%) | 0.717 |
Full Patient Population (n = 160) | Matched-Pair Analysis (n = 116) | |||||
---|---|---|---|---|---|---|
Alpha (n = 80) | Wild Type (n = 80) | p | Alpha (n = 58) | Wild Type (n = 58) | p | |
ICU survival | 41/80 (51%) | 35/80 (44%) | 0.429 | 28/58 (48%) | 27/58 (47%) | 1 |
Hospital survival | 33/75 (44%) | 34/80 (43%) | 0.872 | 22/53 (42%) | 26/58 (45%) | 0.848 |
28-day survival | 36/71 (51%) | 36/79 (46%) | 0.624 | 24/51 (47.1%) | 29/58 (50%) | 0.848 |
Mechanical ventilation | 61/80 (76%) | 52/80 (65%) | 0.165 | 45/58 (78%) | 38/58 (66%) | 0.217 |
Duration of mechanical ventilation (days) (median, range) |
16 (2–61) | 14 (1–55) | 0.814 | 16 (2–61) | 14.5 (1–55) | 0.694 |
Duration of mechanical ventilation of ICU survivors (days) (median, range) | 11 (3–61) [n = 23] | 12 (1–55) [n = 18] | 0.814 | 13.5 (3–61) [n = 28] | 13 (1–55) [n = 15] | 0.694 |
Duration of NIV/HFNO in patients with no MV (days) (median, range) |
6 (2–14) [n= 16] | 5.5 (1–20) [n = 16] | 0.934 | 5 (2–9) [n = 11] | 4 (1–13) [n = 11] | 0.844 |
ECMO | 6/80 (8%) | 14/79 (18%) | 0.059 | 10/58 (17%) | 6/58 (10%) | 0.420 |
Renal replacement therapy | 17/77 (22%) | 23/80 (29%) | 0.365 | 13/56 (23%) | 17/58 (29%) | 0.526 |
This entry is adapted from the peer-reviewed paper 10.3390/microorganisms9091944