The impact of age and gender on mortality from COVID19 at A UK Hospital

Rationale: Age poses greater mortality risk to COVID-19 patients. This may be due to co-morbidities and age-related impairment of immunity. It has been shown that females are more likely to be infected however, severe disease is more often seen in males, which could be explained by greater levels of interferon-gamma promoter activity driven by oestrogen in females in addition to higher levels of IgG antibody providing more protection. We aim to investigate the effects of age and gender on the mortality rate in patients with COVID-19. Method(s): A retrospective study of all in-patients aged >= 18 years with a confirmed diagnosis of COVID-19 during the first and second waves of the pandemic. Admission CXRs were analysed. Statistical analysis was performed using the Chi-Squared Test for independence. Result(s): 1759 COVID-19 patients were included in the study, of which 481 were aged <65 years and 982 were aged > 65 years. The study had 967 males and 792 females. We found a higher mortality rate in those aged > 65 (41%) compared to those aged <65 years (18%) (P<0.001). There were no significant differences in the mortality rates between both genders. However, interestingly males had a greater severity of pneumonitis (22%) on CXRs compared to females (13%) (P=0.01). Conclusion(s): Our study demonstrated a positive correlation between increasing age and mortality with males showing a greater disease severity. This data should be considered when stratifying at risk groups and prioritising them for early intervention.

To assess the diagnostic and prognostic ability of CXRs in COVID-19 pneumonitis

Rationale: The COVID-19 pandemic has led to the deaths of millions with its ability to cause severe pneumonia. Diagnosis is based on PCR testing which has many limitations: lengthy turnaround times, lack of universal availability and variance in sensitivity. Imaging such as CXR could be a valuable and faster aid in diagnosing COVID-19 compared to PCR. It is widely available, cheap and can be performed at the bedside- enabling a rapid turnover of patients whilst minimising cross-link infection. However only a few studies have assessed its prognostic value. We aim to analyse the diagnostic accuracy of CXR in COVID-19 and to assess if severity of COVID pneumonitis on CXR correlated with mortality. Method(s): A retrospective study of all in-patients aged >= 18 years with a confirmed diagnosis of COVID-19 during the first and second waves of the pandemic. Admission CXRs and in-patient CT Thorax scans were analysed. Statistical analysis was performed using the Chi-Squared Test for independence. Result(s): 999 COVID-19 patients were included in the study. Severity of COVID pneumonitis on CXR correlated with mortality when patients were grouped into the following categories: normal (n=161, mortality=42%), mild (n=220,mortality=33%) moderate, (n=328, mortality=42%) and severe (n=290, mortality=58%) (P<0.001). 251 patients had both CT and CXRs. CT scans were superior in diagnosing COVID pneumonitis (63%) compared to CXR (47%) (P<0.001). Conclusion(s): Our study showed a positive correlation between the severity of COVID pneumonitis on CXR and mortality, supporting the use of CXR in the ED to help rapidly identify and treat patients at high risk of death.

Comparing the mortality of COPD and non-COPD patients with COVID-19 in a UK hospital

Rationale: Initial reports during the pandemic have shown that COPD patients with COVID-19 have a poorer prognosis due to an increased risk of respiratory failure. It is well known that in COPD, there is an increased expression of angiotensin converting enzyme-2 (ACE2), the receptor which plays a role in SARS-CoV-2 entry into cells. In the absence of infection, ACE2 converts angiotensin-2 (AngII) to angiotensin-1-7- helping regulate inflammation. During COVID-19 infection, ACE2 activity is reduced due to receptor occupancy, resulting in greater levels of AngII- leading to a pro-inflammatory state. We aim to investigate the impact of COPD and COVID-19 on mortality, length of in-patient stay and gender. Method(s): A retrospective study of all in-patients aged >= 18 years with a confirmed diagnosis of COVID-19 during the first wave of the pandemic. Statistical analysis was performed using the Chi-Squared Test for independence. Result(s): 445 COVID-19 patients were included in the study, out of whom 52 (12%) had COPD. Mortality in COPD patients (65%) was found to be significantly higher than non-COPD patients (49%) (P=0.03) There were no significant differences in mortality between COPD and non-COPD patients when grouped for male and female (P=0.68). Furthermore, there were no significant differences in length of in-patient stays of >7 days between COPD and non-COPD patients (P=0.79). Conclusion(s): Our study demonstrated how COPD increases mortality in COVID-19. This data should be considered when highlighting at risk groups- prioritising them for treatment, isolation, and preventative public health measures such as the COVID-19 vaccination programme.

Impact of empirical antibiotic use in patients with COVID-19 on morbidity and mortality during the first and second UK SARS-CoV-2 waves

S53 Figure 1Rates of mortality against cumulative number of antibiotics received per patient during inpatient spell.[Figure omitted. See PDF]ConclusionIn both COVID-19 waves, antibiotic administration correlated to increased inpatient morbidity and mortality. Given a near-linear relationship of mortality and cumulative antibiotic numbers, antimicrobial stewardship is essential, and tapering an appropriate therapy for likely responsible pathogens will yield lower mortality compared to overlapping coverage and inappropriate escalation. We strongly discourage the use of empirical antibiotics without supporting biochemical evidence of bacterial co-infection for possible future COVID-19 waves.ReferenceRussell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2

Impact of bacterial infections in patients with COVID-19 on morbidity and mortality during the second UK SARS-CoV-2 wave

P91 Table 1(a) Most frequently observed bacterial species (b) Culture type positivity with relation to rates of mortality(a) Bacteria Number isolated (b) Culture Type Number of positives Number of deaths Positivity mortality Enterococcus 67 Urine 104 28 26.9% Escherichia 65 Blood 76 28 36.8% Staphylococcus 64 Skin 40 16 40% Pseudomonas 24 Sputum & BAL 33 20 60.6% Klebsiella 12 Stool 13 5 38.5% Streptococcus 12 Central venous line 8 4 50% ConclusionBacterial infection is observed far more frequently in COVID-19 patients than previously reported and adversely affects morbidity and mortality. Multiple sites of bacterial infection prolongs inpatient stay and increases mortality. Thorough culture collection should be encouraged in COVID-19 patients with biochemical evidence of bacterial infection to identify responsible pathogens and respective antimicrobial sensitivity. Given the higher mortality rates, empirical use of antibiotics in COVID-19 patients without supporting evidence of bacterial infection is strongly discouraged.ReferencesLansbury, et al. J Infect. 2020 Aug;81(2):266–2.Russell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2

COVID-19 mortality in cancer patients on systemic anti-cancer treatments during the second UK SARS-CoV-2 wave

P104 Table 1Mortality rate after presentation of COVID-19 by: tumour type, time from cancer diagnosis, cancer stage, progression of disease, and systemic anti-cancer treatment (SACT). Number mortality number mortality% odds ratio Cancer type Solid organ 75 28 37.3 1.32 Lung 18 11 61.1 4.66** Haematological 29 11 37.9 1.47 Time from diagnosis <12 months 55 25 45.5 2.32** >12 months 67 25 37.3 1.25 STAGE AT DIAGNOSIS 4 46 23 50.0 2.82*** 3 26 13 50.0 2.17 2 14 5 35.7 1.22 1 31 8 25.8 0.77 0 5 1 20.0 0.46 disease progression (<3 months BEFORE COVID-19) Yes 38 22 57.9 4.60*** No 84 28 33.3 1.07 SACT (<3 months BEFORE COVID-19) Yes 53 69 34.0 1.49 No 69 32 46.4 1.80** *p<0.05 **p<0.01 ***p<0.001ConclusionAmong patients with cancer and COVID-19, mortality was high and associated with cancer-specific features. There was no evidence cancer patients on systemic anti-cancer treatments possessed higher mortality from COVID-19 disease, which correlates with findings from COVID-19 and cancer registries1. Patients that did not receive SACT within 3 months before COVID-19 and therefore more likely to have palliative treatment did demonstrate high mortality. Larger studies are needed to confirm the risk of mortality and timing of SACT before COVID-19 disease.ReferenceLee AJ, et al. British Journal of Cancer 2021;124:1777–1784.

Vitamin D deficiency increases susceptibility to COVID-19 infection

BackgroundVitamin D plays a vital part in modulating the immune system, with Vitamin D deficiency leading to increased susceptibility to infection.1 There is some evidence to suggest Vitamin D may play a protective role in the prevention of COVID-19 infection in hospitalised patients,2 but the topic remains controversial. Our study aims to investigate if low Vitamin D levels correlate with increased risk of COVID-19 infection, thereby representing a modifiable risk factor for COVID-19 infection.MethodA retrospective observational study was conducted on 3198 health care workers of a Greater London District General Hospital, who had undergone testing for 25-OH Vitamin D levels and COVID-19 antibody in June 2020. In accordance with NICE guidelines, Vitamin D deficiency was defined as less than 25 nmol/L, insufficiency as 25–50 nmol/L, and those with levels over 50 nmol/L were used as control comparisons. Evidence of previous SARS-CoV-2 infection was assessed by detection of SARS-CoV-2 IgG antibodies. Regression analysis was performed to determine independent significance, accounting for age and gender.Results3191 participants were included in this study, with age ranging from 19–78 years (mean 42.9) of which 78.2% were female. Both age and gender were not independently associated with positive SARS-CoV-2 IgG antibodies. 1997 (62.6%) participants had Vitamin D levels within the normal range, 899 (28.2%) participants had insufficient levels and 302 (9.4%) had Vitamin D deficiency. Both Vitamin D deficiency (OR 1.61, p=0.002) and insufficiency (OR 1.33, p=0.006) independently correlated with significantly increased incidence of positive COVID-19 antibodies than personnel with normal Vitamin D levels.ConclusionsWe report the largest single-centre study investigating the impact of low Vitamin D levels within healthcare workers to date. Significant correlation between low levels of Vitamin D and previous COVID-19 infection was identified. Oral Vitamin D supplementation to maintain levels >50 nmol/L may play a protective role against COVID-19. Larger studies are needed to investigate the role of Vitamin D supplementation in healthcare workers for further COVID-19 waves.ReferencesAranow C, et al. Journal of Investigative Medicine 2011;59:881–886.Nogues X, et al. J Clin Endocrinol Metab. 2021 Jun 7:dgab405.

Use of procalcitonin to predict morbidity and mortality in COVID-19

P90 Figure 1The association of PCT in COVID-19 and patient morbidity and mortality.[Figure omitted. See PDF]ConclusionsHere, we report the largest single-centre study to date in analysing a UK-based population for procalcitonin in COVID-19. We observed a significant correlation between elevated initial levels of PCT and incidence of ICU admission and mortality within our cohort, thereby demonstrating promise for PCT as an effective prognostic marker. Using a higher cut-off for PCT ≥0.5µg/L increased mortality by almost 50%, but had no effect on morbidity. We suggest that a lower universal cut-off point for PCT should be used for detecting secondary bacterial infections and procalcitonin-guided antimicrobial therapy.ReferencesHu R, et al. International Journal of Antimicrobial Agents 2020;56(2):106051.Vazzana N, et al. Acta Clin Belg. 2020 Sep 23:1–5.

The impact of age, gender and active cancer in the mortality and the length of in-patient stay of patients with covid-19 at a uk district general hospital

RATIONALE: An age-related mortality risk has been discovered during the COVID-19 pandemic;the elderly being at greater risk. This could be explained by age-related impairment of immunity. Social factors such as congregate housing could also play a role[1]. Similarly, cancer patients have been identified as being high-risk for mortality. Thromboembolic events arising as a result of a cytokine storm has been theorised as a potential cause of death as illustrated in figure 1[2]. Previous studies have highlighted male sex as being another high-risk group for morbidity and mortality[2] . We aim to investigate the effects of age, gender and active cancer on the mortality rate and the length of in-patient stay in patients with COVID-19. Methods: A retrospective study of all in-patients aged ≥ 18 years with a confirmed diagnosis of COVID-19 during the first wave of the pandemic. Statistical analysis was performed using the chi squared and Mann-Whitney U test. Results: 445 COVID-19 positive patients were included in the study, of which 69 had active cancer, 329 were aged <65 years and 116 were aged > 65 years. The study contained 261 males and 263 females. Mortality in patients with active cancer was higher (70%) compared to those without active cancer (48%) (P=0.001). There was no significant difference in the number of patients who had an inpatient stay of >7 days between both groups. We also found that there was a higher mortality rate in patients aged > 65 years (61%) compared to those aged < 65 years (25%) (P<0.05), with a greater number of patients aged > 65 years staying >7 days in-hospital (63%) compared to those aged < 65 years (49%) (P=0.03). There were no significant differences in the mortality rates and the length of in-patient stays of >7 days between male and female patients. However, interestingly males had a greater intubation rate (14%) compared to females (6%) (P=0.025). Conclusion: Our study demonstrated increasing age and active cancer status to be linked to greater risk of mortality. Furthermore, males showed a more severe disease course as compared to females. This data should be considered when highlighting at risk groups and prioritising them for treatment and isolation. Figure 1-A potential mechanism of death in COVID-19 patients References: 1. Kang SJ et al Age-related Morbidity and Mortality among patients with COVID-19. Infect Chemother 2020;52(2):154-164 2. Curigliano G et al Cancer Patients and Risk of Mortality for COVID-19. Cancel Cell 2020;38(2):161-163.

Comparing the mortality of diabetic and non-diabetic patients with COVID-19 in a uk district general hospital

Introduction: Initial reports during the first wave of the pandemic in the United Kingdom have shown that diabetic patients with COVID-19 often had a more severe infection with co-morbidities such as Hypertension (HTN) leading to a poorer prognosis. Males could also be at higher risk of death from COVID-19 as was demonstrated in one study. [1] SARS-CoV-2 has been theorised to trigger the increased secretion of glucocorticoids and catecholamine's due to stress conditions- increasing the frequency of acute hyperglycaemic events such as diabetic ketoacidosis in COVID-19 patients with diabetes. It has been suggested that SARS-CoV-2 enters into islets in the pancreas via angiotensin converting enzyme 2 as its receptor leading to acute beta-cell dysfunction. [2] There is also some evidence to suggest that increased Body Mass Index (BMI) in diabetic patients with COVID-19 is linked with severity of the infection. Objectives: We aim to investigate the impact of diabetes on mortality in patients with COVID-19, and to identify potential prognostic factors therein including body mass index (BMI), co-morbidities and gender. Methods: We undertook a retrospective study of all patients aged ≥ 18 years during the first wave of the pandemic. All patients who had a confirmed diagnosis of COVID-19, via radiological and polymerase chain reaction testing, were included in the study. Data was collected using electronic patient records. Statistical analysis was performed using the Chi Squared Test for impendence. Results: 445 COVID-19 positive patients were included in the study, out of whom 127 (29%) were diabetic. Mortality in diabetic patients (61%) was found to be significantly higher than non-diabetics (48%) (p=0.01). There were no significant differences in mortality between diabetic and non-diabetic patient when grouped for BMI ≥25 (p=0.4), Male (p=0.06), Female (0.19) and hypertension (p=0.12). Conclusion: Our study demonstrated how diabetic patients with COVID-19 had a significantly higher mortality rate compared to non-diabetics. This prompts the need to educate diabetic patients about hyperglycaemia arising from infection, the importance of sick day rules and compliance with social isolation measures. Further research is required to investigate the causes behind the raised mortality rate in diabetics.

Azithromycin may play a role in the Management of hospitalised patients with Suspected or PCR-proven covid-19

Background Coronavirus infection (COVID-19) typically presents with mild symptoms;however, 15% of patients develop significant illness with up to 5% overall mortality. Hence, there is an urgent and unmet need for identifying definitive pharmacological interventions. Repurposing of Azithromycin presents encouraging early findings given its antiinflammatory properties and proven antiviral efficacy during the Ebola and Zika virus outbreaks. To date, studies are limited to using Azithromycin and Hydroxychloroquine in conjunction. Here, we present our findings on the isolated use of Azithromycin in the management of COVID-19. Methods We performed retrospective analysis of patients admitted between 1st March and 20th June 2020 to one of the most pressurised Greater London District General Hospitals during the early stages of the pandemic. Pearson's Chisquared test was utilised to compare mortality outcomes between two patient groups;those receiving Azithromycin (500 mg once daily, prescribed for five days) and those of a non-Azithromycin control group, comprising those with contraindication or allergy. Independent T-test analysed length of stay. Results Overall, 628 patients were analysed (mean age 71.6;41.9% female);448 (71.3%) were COVID-19 PCR swab positive, and an additional 70 (11.1%) had negative PCR but positive radiology. 394 (62.7%) received Azithromycin, whilst 234 (37.3%) constituted the non-Azithromycin control group. We observed notably improved mortality rates in Azithromycin patients (41.1%;162/394) compared to control patients (50.4%;118/234;p=0.14). Interestingly, length of stay was similar between Azithromycin administration (11.92±10.85) and control groups (10.82±12.30). Conclusion To our knowledge, this is the first large-scale analysis of Azithromycin as a stand-alone pharmacological treatment of COVID-19. The combination of Hydroxychloroquine and Azithromcyin has been widely discussed, however mortality data is adversely skewed by significant antagonistic cardiac side-effects which hinders interpretation of their individual therapeutic efficacy. Our preliminary results suggest, whilst just shy of statistical significance, a short course of Azithromycin in COVID-19 patients may reduce mortality, without negatively impacting length of stay. This highlights the need for prospective validation of this data with randomised control trials;preceding this, we advocate the use of Azithromycin in clinically selected patient populations until other licensed therapies become available.

COVID-19 post-discharge mortality rate in a London district general hospital

Introduction Due to the novelty of COVID-19, uncertainty about the factors contributing to mortality, unavailability of definitive treatment options, limited access to medical, social support and rehabilitation in the community during the COVID-19 peak;compounded with anxiety and reluctance to seek medical help in timely manner, it was anticipated that vulnerable patients would be affected the worst. We report post-discharge mortality and the associated risk factors. Method This is a retrospective study of all the patients admitted at a busy district general hospital during the peak period of the COVID-19 pandemic i.e. 1st March to 20 June 2020. We included all patients aged 18 and above in data analysis. Results A total of 628 patients were admitted during the study period with 481 having positive swab PCR. Of these, 389 (62%) patients had two or more comorbidities, 311 (49.5%) hypertensive and 166 (26.4%) diabetic. In-hospital mortality: 226/628 (35.9%) patient died in hospital, of which 194 (85.8%) had a positive Coronavirus nasopharyngeal swab. This was statistically significant with p-value of 0.001. Post-discharge mortality of patients: 54/402 (13.4%) of those patients discharged home following hospitalisation died within 28 days of discharge. 42/54 (77.7%) were swab positive. Swab positive patients 42/54 (77.8%) had a higher risk of death. Two thirds of swab positive patient were older than 75 years and 81% had two or more pre-existing comorbidities. There was no difference in length of stay between the survivors and non-survivors. Conclusion As expected, age, male gender, COVID-19 PCRpositivity, multiple comorbidities, high BMI and raised CRP were associated with higher in-hospital and post-discharge mortality. It is unsurprising that antibiotic treatment without bacterial infection was associated with higher but statistically insignificant mortality rate, while therapeutic anticoagulation and steroids were associated with better outcomes. There is an urgent need for further analysis of root cause to mitigate the modifiable factors and devise a robust post-discharge management plan in collaboration with all stakeholders.

The role of anticoagulation therapy in management of covid-19 patients

Introduction Hypoxemia, acute respiratory distress syndrome and coagulopathy are common issues experiences by pts with severe COVID-19 disease.1 The aim of this study was to evaluate the efficacy of anticoagulation therapy in COVID-19 patients. Methods This is a retrospective observational study for patients admitted to a busy district hospital during the peak period of the COVID-19 pandemic. All patients aged >18 with suspected or confirmed RT-PCR COVID-19 and raised D-Dimer were included in this study. Data including demographics, comorbidities, and effects of anticoagulation on mortality were examined. Results A total of 628 pts with more males (n = 365;58.1%), and 48.7% >75 years were included in the study. 27.9% were obese (BMI-30);and 25% were overweight (BMI 25-29.9). 448/628 (71.3%) had a positive swab for coronavirus and a further 70 patients (11.1%) had probable infection based on clinic-radiological suspicion. Nearly half (n = 311;49.5%) of the patients had hypertension and a quarter (n = 166;26.4%) had diabetes. A total of 226 (36%) pts died of which 85.8% (n = 194) had a positive swab compared to 12.8% (n = 29) with negative swab. This was statistically significant with a p-value of 0.001. Patients with a raised D-dimer 150/628 (23.8%) received therapeutic dose anticoagulation and 408/628 (64.9%) received prophylaxis or no anticoagulation. 53 patients (22.5%) of those who received treatment dose died compared to 183 (77.5%) who received prophylactic dose or no anticoagulation due to comorbidities. This was statistically significant (p value 0.02). Conclusion Therapeutic anticoagulation significantly reduces mortality in COVID-19 patients with a high D-dimer.

S99 The role of anticoagulation therapy in management of COVID-19 patients

S99 Table 1Association of swab PCR with Anticoagulants, D-Dimer in MortalityVariablesMortality with SWABp-valuePositive (n=236)Negative (n=41) n%n% AnticoagulantYes20687.33892.70.32No3012.737.3Treatment Dose AnticoagulantYes5322.51639.00.02*No18377.52561.0ConclusionTherapeutic anticoagulation significantly reduces mortality in COVID-19 patients with a high D-dimer.ReferenceKlok F, Kruip M, van der Meer N, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020 Apr 10. [Epub ahead of print]