key: cord-0880682-a8xjrk8q
authors: AlBahrani, Salma; Ahmadi, Nayef Al; Hamdan, Safa; Elsheikh, Noura; Osman, Assim; Almuthen, Sharifah; Almajed, Ghadeer N; Alkhuraim, Arwa H; Jebakumar, Arulanantham Zechariah; Al-Tawfiq, Jaffar A.
title: Clinical Presentation and Outcome of hospitalized patients with COVID-19 in the first and second wave in Saudi Arabia
date: 2022-02-25
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2022.02.048
sha: 843386d11cec8912009eb37bfe8dd612e4b662ff
doc_id: 880682
cord_uid: a8xjrk8q

Introduction The world had witnessed the occurrence of multiple waves of the SARS-CoV-2. Data comparing the clinical characteristics and outcome of hospitalized patients in Saudi Arabia during the first and second waves are lacking. This study compares the characteristics and the outcome of patients in these two waves. Methods This is a retrospective case series of hospitalized patients with confirmed COVID-19. We compared epidemiological, demographic, laboratory, and clinical data. Results The study included hospitalized patients admitted up to 28th February 2021 as the first wave and those admitted from 1st March 2021 as the second wave. There were 378 patients in the first wave and 241 patients in the second wave. Patients in the second wave were significantly younger (mean age and SD of 47.5 ± 20 vs. 55.3 ± 18.2 years; p <0.001). In relation to symptoms, shortness of breath, wheezes, myalgia, tachypnea, and respiratory distress were significantly more common in the second wave than the first wave. On the other hand, sore throat was more common in the first wave than the second wave. Patients in the second wave had higher mean of lymphocytes count, platelet counts and ALT than those in the first wave. Patients in the first wave were more likely to receive antibiotics and antiviral therapy and had higher death rate (16.2% vs. 8.4%; P = 0.001). Conclusion The study showed that patients in the second wave were younger and had a lower rate of death than the first wave.

Coronavirus disease-19 , produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, giving rise to a serious health threat globally. Most people infected with the COVID-19 virus had experienced mild-to moderate respiratory illness and recovered without special treatment [5] . Older people with underlying medical problems such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illnesses (Pradhan et al., 2020) . The current pandemic is characterized by multiple waves causing disease at different time around the globe. Many countries have experienced multiple waves of coronavirus outbreaks. During the 2020 pandemic, empirical data show that characteristics varied between waves (Iftimie et al., 2021) . In comparison with the second wave, the proportion of local clusters (24.8% vs 45.7%) was lower in the third wave, and personal contact transmission (38.5% vs 25.9%) and unknown routes of transmission (23.5% vs 20.8%) were higher (Seong et al., 2021) . Consequently, many governments and health authorities, including the WHO, have been actively educating people to take preventive measures to reduce the spread of the virus, including lockdown measures (Farooq et al., 2021; Godman et al., 2020) .

In the Kingdome of Saudi Arabia, the first case of COVID-19 was reported in March 2020 (AlJishi et al., 2021) . The first wave in the country began in early March 2020, till the end of December and second wave began on the 6 th January 2021. As part of the strategy to curtail the pandemic, the Kingdom of Saudi Arabia applied multiple steps including vaccination to decrease the spread of the disease (Al-Tawfiq et al., 2020b; Al-Tawfiq and Memish, 2020) including the introduction of step-wise COVID-19 vaccination programs initially with Pfizer-BioNTech messenger RNA (mRNA) vaccine (BNT162b2) and then the ChAdOx1-S (Assiri et al., 2021) .

The differences between patients in the first and second wave were evaluated in few studies. In a study from Spain, patients with severe symptoms were more in the first wave (27.8%) compared with the second wave (10.6%, P = 0.03) (Soriano et al., 2021) . Previous studies from the Kingdom of Saudi Arabia described the epidemiology, clinical features, ICU admission and therapy of COVID-19 patients mainly during the first wave of the pandemic (Al-Omari et al., 2020; Al-Tawfiq et al., 2020a , 2020b AlJishi et al., 2021; Al Mutair et al., 2020) . In the Kingdom of Saudi Arabia, the first wave peaked at the end of April 2020 and the number of cases fluctuated upward from mid-March until a sharp increase in mid-May 2021. In this study, we compare the characteristics of patients and outcome during the first and the second wave of the pandemic.

We conducted a retrospective cohort study of all test screenings and cases of COVID-19 in single medical center in Saudi Arabia. We collected the demographics, clinical presentation, underlying comorbidities and outcome of hospitalized patients and classify them by those in the first and second wave. Patients admitted up to 28 th February 2021 were classified in the first wave and those admitted from 1 st March 2021 in the second wave. The only inclusion criterion was to be a hospitalized patient with an confirmed diagnosis of SARS-CoV-2 by PCR as described previously (AlJishi et al., 2021) . SARS-CoV-2 infection was confirmed by RT-PCR using swab samples from the upper respiratory tract (nasopharyngeal/ oropharyngeal exudate) and from the lower respiratory tract (sputum/endotracheal aspirate/ bronchoalveolar lavage/bronchial aspirate). This study was approved by the institutional board (IRB) of the King Fahad Military Medical Complex (AFHER-IRB-2020-034).

We summarized the characteristics for continuous and categorical data as numbers and percentages. Characteristics were compared using descriptive statistics, and categorical data were compared using a chi-square test (to find the association between first and second wave among the demographic and symptoms). We used independent sample t-test to compare the quantitative variables between first and second wave. Bivariate logistic regression was applied to find relationship between the dependent variable status of the patient (death or alive) and the independent variables such as symptoms, comorbidities to find the associated factors for death and alive. A P-value < 0.05 has been considered for statistical significance. The statistical analysis has been done in SPSS (Statistical Package for Social Sciences) Package with version 27.

During the study period, 468 patients with SARS-CoV-2 infection, confirmed by RT-PCR, were admitted to the hospital. The number of patients admitted was 378 in the first wave and 241 in the second one. Those in the second wave were significantly younger (mean age and SD of 58 ± 26 vs. 67 ± 18 years; p <0.001) and being on hemodialysis (Table 1 ).

In relation to symptoms, there were significant difference in shortness of breath, wheezes, sore throat, myalgia, tachypnea, and respiratory distress (table 2) . These symptoms were more common in the second wave than the first wave except for sore throat when patients in the first wave had more frequent symptoms than the second wave. Patients in the first wave were more likely to receive antibiotics and antiviral therapy and had higher death rate (Table 3) . Patients in the second wave had a higher mean of age compared to the first wave with a mean age of 55.3 (+ 18.2) and 47.5 (+ 20) years, respectively. Patients in the second wave had higher mean of lymphocytes count, platelet counts and ALT than those in the first wave (Table 4 ).

Of all the admitted patients, a comparison between those who survived and those who died showed that diabetes mellitus, heart failure, shortness of breath, myalgia, tachypnea, oxygen saturation and admission to ICU were significant difference with higher odds ratio among patients who died (Table 5 ). In the second wave, 54 (22.4%) of 241 with documented vaccination status had received at least one dose of COVID-19 vaccine (14.5% had one dose and 7.9% had two doses). However, there was no statistically significant difference in the mortality in relation to vaccination status (Table 5 ).

The most common underlying comorbidities in the two waves were diabetes mellitus, cardiac diseases, and heart failure. Similarly, in a study from Spain the most common underlying diseases were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases (Iftimie et al., 2021) . In the first wave in Saudi Arabia, one study showed the following comorbidities: G6PD deficiency (33%), hypertension (27%), and diabetes mellitus (26%) (AlJishi et al., 2021) . In both waves, the most common symptoms were cough, fever, and shortness of breath. In a previous study during the first wave in Saudi Arabia, sore throat and runny nose in addition to the mentioned symptoms were more common as well (AlJishi et al., 2021) . Similarly, in a study from Spain the common signs and symptoms in both waves were fever, dyspnea, and cough (Iftimie et al., 2021) .

Regarding the laboratory data, we found that patients in the second wave had higher mean of lymphocytes count, platelet counts and ALT but no difference in inflammatory markers. One study showed lower inflammatory markers during second wave and that neutrophils and lymphocytes were higher (Asghar et al., 2021) . It was suggested that increased inflammatory markers is associated with severe diseases (Fomina et al., 2020) . In this study, we found gender and age differences among hospitalized patients in the first and second wave. In a study from Spain, there was no difference in age or gender between the first and second wave (Soriano et al., 2021) . In another study, admitted patients during the second wave were considerably younger (67 vs 58 years, p <0.001) but no difference in relation to gender (Iftimie et al., 2021) . However, in a study from 14 countries, there was no difference in relation to age in the two waves (Ioannidis et al., 2021) . Also in one study, the percentage of males infected in the second wave was 47.2% vs. 31% in the first wave (Alves-Cabratosa et al., 2022) . This difference might be related to the uptake of the vaccine and the priority group of those older than 60 years of age in the initial phase of the vaccine in KSA (Assiri et al., 2021) .

The death rate was significantly higher in the first wave compared to the second wave of 16.2% vs. 8.4%, respectively; P = 0.001. In a previous study from Saudi Arabia during the first wave showed a death rate of 16% (Barry et al., 2021a) and another study showed a mortality rate of 11.8% (Alhumaid et al., 2021) . It was suggested that the first wave was associated with higher inoculum than the second wave and this may lead to higher rate of death (Guallar et al., 2020) .

In Italy, the 2 nd wave, August 2020 to February 2021, was associated with high incidence of COVID-19 but was associated with lower admissions to Intensive Care Units and lower total deaths in comparison to first wave (Coccia, 2021) . The use of steroid was found to be of benefit in patients with severe disease and this was clearly demonstrated in the landmark RECOVERY trial with the use of dexamethasone (6 mg intravenous or orally once a day) and was published in February 2021 (RECOVERY Collaborative Group, 2020). However, the use of corticosteroid was not different in the two waves in the current study. However, in another study the use of steroid was more frequent in the second wave than the first wave (Iftimie et al., 2021) . Another explanation is the age of included patients. One study reported an increased odd ratio of mortality was higher with increasing age (OR: 1.079, 95% CI: 1.063; 1.094) (Domingo et al., 2021) .

The impact of the first two waves on countries is variable. A study evaluated the impact of the second wave in African continent and showed more severe second wave than the first COVID-19 pandemic (Salyer et al., 2021) . In a study from India, patients in the second wave had higher ICU (26.1 vs 13.4%, p <0.001) and increased in-hospital death rate (29.9 vs 18.2%, p <0.001) (Ranganathan et al., 2021) . It also noted that ICU admission was associated with higher mortality compared to none ICU admission and there is a disparity in the outcome of patients with COVID-19 (Al-Tawfiq et al., 2020a; Tirupathi et al., 2020) . However, the need for ICU was not different in the two waves. The exact reasons for decreased death rates in the two waves are not well characterized. The first wave may had caused increased burden in hospitals, and this may had contributed to the increased mortality. Since the vaccination was introduced in KSA end of December 2020 and was aimed at older adults initially, partial vaccination may also had contributed to younger age group in the hospitalized patients in the second wave. However, the status of vaccination was not statistically associated with death. During the initial launch of the COVID-19 vaccination in Saudi Arabia, the rate of vaccine acceptance was low and only 33.3% of 1058 surveyed healthcare workers were enrolled to receive or had already received the vaccine between December 27, 2020 and January 3, 2021 (Barry et al., 2021b) . And another study showed only 20.9% were willing to receive the RNA BNT162b2 vaccine (Temsah et al.,

We had no sequencing data on the identified SARS-CoV-2 during this study. However, the second wave in the Kingdom of Saudi Arabia had been thought to be predominantly secondary to the delta variant. In a pre-print study, of 320 SARS-CoV-2 samples obtained April-June 2021, 40.9% of the samples were due to delta variant, 15.9% beta-variant and 11.6% of the alphavariant (Alhamlan et al., 2021) . In a study from a neighboring country, Qatar, the case fatality rate in patients with the delta-variant was 2.4% and was not statistically different than the 1.1%

in patients with the beta-variant (Butt et al., 2022) . However, in a systematic analysis the delta variant was associated with the highest risk of admission to the intensive care unit and increased death compared to the alpha and beta-variants and that beta variant was associated with higher risk of hospitalization compared to the beta-variant (Lin et al., 2021) . This is the first study of the comparison between wave 1 and 2 in Saudi Arabia. However, the study has few limitations. First, the study is a mono-center study and additional multi-center study is needed to elucidate the differences between these two waves. The study is limited by the nature of retrospective analysis and the lack of genotyping of the SARS-COV-2 isolates.

Thus, the classification was based on epidemiologic timing of the waves. 

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