Table 2 Summary of findings related to hospitalization and severity of illness

Alpha

• No significant difference was found in hospitalization between Alpha vs. non-Alpha in the crude analysis (RR 0.79, 95% CI 0.72–0.87), but after adjusting for sex, age, region, and comorbidities, Alpha was 1.4 times more likely to be associated with hospitalization than wild type (adjusted RR 1.42; 95% CI 1.25–1.60) (Bager et al., Denmark, Jan-Feb 2021, medium quality )[53]

• In wave two (high Alpha prevalence), the number of admissions increased (35.1% vs. 54.8%) from wave one (non-Alpha). Patients with non-Alpha and Alpha were not significantly different in terms of age or ethnicity. Alpha patients were more likely to be female (48.0% vs 41.8%, p = 0.01), less likely to be frail (14.5% vs 22.4%, p = 0.001), and more likely to be obese (30.2% vs 24.8%, p = 0.048) than non-Alpha patients. On admission, patients with Alpha were more likely to be hypoxic, which was the main indicator of severe disease (Snell et al., UK, Mar 2020-Feb 2021, medium quality )[41]

• There was a non-significant association between infection with Alpha and hospitalization within 14 days of a positive test (OR 1.39, 95% CI: 0.98-1.98, p = 0.07). In a univariable analysis, Alpha infection and risk of hospitalization within 14 days were not associated (Hazard Ratio (HR) 1.07, 95% CI 0.89-1.29, p = 0.48); however, adjusting for potential confounders (sex, age, ethnicity, residential property classification, and week of specimen date) suggested a higher risk of hospitalization from Alpha (HR: 1.34, 95% CI 1.07-1.66, p = 0.01). (Dabrera et al., UK, Oct-Dec 2020, medium quality)[31]

• Individuals with Alpha (SGFT-positive) were more likely to be hospitalized (OR 3.44, 95% CI 1.76-6.75) than non-Alpha (SGFT-negative) cases (Loconsole et al., Italy, Dec 2020-Mar 2021, medium quality )[48]

• Alpha was associated with 62% increased risk of hospital admission (aHR: 1.62; 95% CI: 1.48–1.78; P < .0001) compared with wild-type. Among people admitted to a hospital, those with Alpha were younger (median [IQR] age: 57.0 [47.0–68.0] vs 59.0 [48.0–72.0] years) and had fewer comorbidities (≥2 comorbidities: 19.3% vs 25.2%) compared with those with wild-type (Grint et al., England, Nov 2020-Jan 2021, high quality)[58]

• Compared to wild-type, the odds of progressing to severe disease were 1.48-fold (95% CI 1.18-1.84) higher for Alpha (Abu-Raddad, Qatar, Jan-May 2021, medium quality)[75]

• In the Alpha wave, most hospitalizations were in people over 80, but there was also an increase in hospitalizations in children aged 10 and older (0.21% to 0.35%) compared to previous waves (Area et al., Spain, March-April 2021, high quality)[62]

• Alpha increased the chance of hospitalization: 13% of the outpatients had Alpha vs. 33% of inpatients (Cetin et al., Turkey, April 2020-March 2021, medium quality)[46]

• The number of COVID-19 admissions was 2.05 times higher in the Alpha wave compared to the pre-Alpha wave. COVID-19 patients admitted during the Alpha wave were more likely to be younger with intermediate levels of frailty (Cusinato et al., UK, January 2020-March 2021, high quality)[55]

• In patients hospitalized with COVID-19, Alpha was associated with a 33% higher risk of severe COVID-19 than wild-type (aOR 1.33 95% CI 1.03-1.72) (Martin-Blondel, France, Jan-Feb 2021, medium quality)[34]

• Individuals infected with VOC, primarily Alpha, were more likely to require hospitalization (aOR 1.57 [95% CI 1.47-1.69] in Ontario and aOR 1.88 [95% CI 1.74-2.02] in Alberta) than those without VOC (McAlister et al., Canada, March 2020-March 2021, medium quality)[35]

• Risk of hospital admission within 14 days after a positive test was higher for patients with Alpha than wild-type (HR 1.52 (95% CI 1.47 to 1.57). The absolute risk of hospital admission after 14 days was 4.7% (95% CI 4.6 to 4.7%) for patients with Alpha and 3.5% (95% CI 3.4 to 3.5%) for those wild-type (Nyberg et al., England, Nov 2020-Jan 2021, high quality)[61]

• Alpha was associated with more severe disease than those from other lineages (median cumulative odds ratio: 1.40, 95% CI 1.02-1.93) (Pascall et al., Scotland, Nov 2020-Jan 2021, high quality)[67]

• Alpha was associated with a 1·9-fold increased risk of hospitalization compared to non-VOC (aRR 95%CI 1.6-2.3) (Veneti et al., Norway, Dec 2020-Jun 2021, high quality)[71]

• After correcting for mean age, sex, ambient temperature, and humidity, there was no association between Alpha and the number of symptoms reported over a 4-week period after a positive test or the number of hospitalizations (Graham et al., Scotland, Wales and England, Sep-Dec 2020, high quality )[65]

• While risk of hospitalization within 14 days of a test and time to hospital admission from symptom onset were similar, Alpha patients were younger, had fewer comorbidities, and more likely to be from an ethnic minority compared to non-Alpha patients (Frampton et al., UK, Nov-Dec 2020, high quality)[57]

• Pairing 29 Alpha cases to 58 controls (non-Alpha) on age and gender, there was no significant difference in time from first symptoms to emergency department admission or severity (Courjon et al., France, Dec 2020-Feb 2021, medium quality)[47]

• Alpha did not lead to more severe disease in children and young people in the UK, with children admitted during the Alpha wave having lower Paediatric Early Warning Scores (PEWS) at presentation, lower antibiotic use, and less respiratory and cardiovascular support (Swann et al., UK, Jan 2020-Jan 2021, medium quality)[37]

• There was no statistically significant difference between time from symptom onset to hospitalization or length of stay between Alpha patients and non-VOC patients (Whittaker et al., Norway, Dec 2020-Apr 2021, high quality)[73]

Beta

• Compared to Alpha, the odds of progressing to severe disease were 1.24-fold (95% CI 1.11-1.39) higher for Beta (Abu-Raddad, Qatar, Jan-May 2021, medium quality)[75]

• Hospital admission rates were significantly higher in the second wave than the first (27.9 vs. 16.1 admissions per 100,000 people). The weekly average growth rate in hospital admissions was 20% in pre-Beta wave and 43% in Beta wave (ratio of growth rate was 1.19, 95% CI 1.18–1.20) (Jassat et al., South Africa, March 2020-March 2021, high quality)[60]

• Beta was associated with a 2.4-fold increased risk of hospitalization compared to non-VOC (aRR 95%CI 1.7–3.3) (Veneti et al., Norway, Dec 2020-Jun 2021, high quality)[71]

• Similar amounts of patients were admitted to the hospital in the Beta wave compared to the pre-Beta wave (685 vs. 550), although patients admitted in the Beta wave were older and more likely to have no comorbidities (Maslo et al., South Africa, June-Dec 2020, medium quality)[44]

• No differences for patients admitted to hospital with Beta or wild-type in terms of days between onset of symptoms (5 days) (Pascall et al., Scotland, Nov 2020-Jan 2021, high quality)[67]

Gamma

• There was an increase in proportion of patients with severe COVID-19, from 5% in the first wave to 10% in the second wave (associated with Gamma). There was no difference between sexes, but the proportion of patients with pre-existing conditions among severe cases was higher in the second wave (33%) compared to the first (25%), as well as higher proportion under age 60 (47% vs 39%) (Freitas et al., Brazil, Nov 2020-Feb 2021, medium quality)[28]

• The incidence rate of advanced respiratory support (HR 1.78, 95% CI 1.05-3.03, p = 0.03) and invasive respiratory support (HR 2.64, 95% CI 1.34-5.19, p = 0.005) was higher in Gamma patients than non-Gamma patients (Zavascki et al., Brazil, June 2020-May 2021, medium quality)[39]

No data

Delta

• Among cases admitted to hospitals, mild cases were relatively lower (P < 0.001) and severe cases higher (P < 0.001) in the Delta wave than the first wave (pre-Delta) (Budhiraja et al., India, April 2020-June 2021, medium quality)[29]

• Patients with Delta (2.3%) vs. Alpha (2.2%) were more likely to be admitted to hospital within 14 days after a test (aHR] 2.26 [95% CI 1.32–3.89]). Similarly, patients with Delta (5.7%) vs. Alpha (4.2%) were more likely to be admitted to hospital or attend emergency care within 14 days of a test (aHR 1.45 [95% CI 1.08–1.95]) (Twohig et al., UK, March-May 2021, high quality)[70]

• Admission rates were lower in the Delta wave than the pre-Delta wave (23.6% vs. 61.9%) (Khedar et al., India, March 2020-July 2021, medium quality)[43]

• No difference was found in the risk of hospitalization among those infected with Delta compared to Alpha (aRR 0.97, 95% CI 0.76–1.23) (Veneti et al., Norway, May-Aug 2021, high quality)[72]

Combined VOC

• There was a statistically significant increase in the hospitalization rate for regions in the top 10% percentile of reported VOC cases. Regarding time dynamic effects, the hospitalization rate was ~ 38% higher in high VOC regions (9+ VOC cases) compared to their pre-VOC observation (Mitze and Rode, Germany, Jan-Feb 2021, no appraisal)[77]

• Significantly higher proportion of VOC cases were admitted to the hospital compared to non-VOC (Alpha: 11.0%, Beta: 19.3%, Gamma: 20.0% vs. non-VOC: 7.5%, p < 0.001). In an adjusted OR in matched multivariable analysis found that VOC cases had higher chance of hospitalization than non-VOC cases (aOR: 1.6-4.2). People aged 20–59 years had 2.3 to 3.0 times greater odds of hospitalization with Alpha compared with non-VOC cases. The highest odds for hospitalization for Beta was 3.5 to 3.6 times higher for age groups 40-79 years compared to non-VOC cases (Funk et al., 7 European countries, Sep 2020-Mar 2021, high quality)[63]

• VOC (Alpha, Beta, Gamma) were associated with higher odds of hospitalization (OR 2.25 95% CI 2.10-2.40). These findings were consistent across subgroups (Erman et al., Canada, January-April 2021, medium quality)[32]

• Increased rates of hospitalization were seen in VOC infections (all four) relative to non-VOC. Adjusted risk was 59% (95% CI 49-69) higher for hospitalization with VOC (Alpha, Gamma, Beta) than with non-VOC and 120% (95% CI 93-153) higher for hospitalization due to Delta. Increased hospital admission was seen between Delta and other VOC: 55% (95% CI 45-63) (Fisman et al., Canada, Feb-June 2021, medium quality)[33]

No data