The novel coronavirus (SARS nCOV-2) has affected over 160 million people worldwide, causing severe respiratory illness in many patients with a mortality rate of over 2%. ¹ Countries such as the USA, UK, and South Africa have seen deadlier second waves due to highly infectious mutated strains; one such (B1617 or delta) impacted India in April 2021, which led to higher hospitalizations and mortality. ² Some patients had symptomatic disease but negative RT-PCR or rapid antigen test results. These patients often undergo high-resolution CT to determine the extent of their lung involvement and aid in further management. ³

Unlike in Western countries, radiology practice in India is largely performed by independently operated groups (without affiliations to hospitals or care centers). ⁴ A common patient is often referred to these independent practices, including suspected/confirmed COVID-19, to determine the degree of lung involvement. We had seen several patients in our practice during the second COVID-19 wave (delta) who had negative RT-PCR test results but presented with classic symptoms such as fever, fatigue, body aches, and occasional shortness of breath. Our case mix included fully, partially, or completely unvaccinated patients. At the time of the study, two vaccines were approved in India, both of which required two doses for complete vaccination. ⁵ The aim of this study was to determine lung involvement in patients with confirmed or suspected COVID-19 and its correlation with vaccination status.

The ACEAS independent ethical committee in Ahmedabad, India, reviewed our protocol and approved our study. The requirement for a waiver of informed consent was approved, considering the retrospective nature of the study. We retrospectively queried our data from April 2021 to June 2021 to identify adult patients (>17 years) who had confirmed (positive RT-PCR or antigen test) or suspected COVID-19 (classic symptoms but negative RT-PCR) and received a high-resolution CT scan to determine the extent of lung involvement using the CT severity score (CT-SS). ⁶ The duration between April and June 2021 was chosen because it represented the second COVID-19 wave duration.

We accessed the data between August 3, 2021, and September 10, 2021, during which the investigators had access to the patient identifying information. It should be noted that the patients who underwent the CT scan were between April 2021 and June 2021, and their data were accessed for research between August and September 2021. Patient identification information was removed once data collection was complete. The data was uploaded on the Figshare platform and is available at https://doi.org/10.6084/m9.figshare.25033796.v1. Along with the RT-PCR results, we recorded vaccination status at the time of the CT scan. Patients with both doses completed 1 week prior to the CT scan were considered fully vaccinated, whereas patients receiving the CT scan 2 weeks after the 1st dose or within 1 week of 2nd dose were considered partially vaccinated, and the rest of the patients (not receiving any vaccine or within 2 weeks of 1st dose) were considered unvaccinated. ⁷ Based on the vaccination age eligibility criteria, we stratified the cohort into three groups: 18-44 years, 45-59 years, and ≥ 60 years.

We used descriptive statistics (median (interquartile range) and % (N)), univariate tests (non-parametric Kruskal (Wallis) for continuous variables, and chi-square test for categorical variables), and multivariate logistic regression analysis to determine the association of the CT-SS score with RT-PCR and vaccination status. All analyses were conducted using the SAS software (version 9.4; SAS Inc. Cary, NC, USA) https://www.sas.com/en_us/software/base-sas.html with a 95% confidence interval. The STROBE guidelines were followed and the checklist was also uploaded along with dataset https://doi.org/10.6084/m9.figshare.25153271.v1.

We identified 229 patients, of whom 205 (89%) had confirmed COVID-19 (positive RT-PCR) and 24 had suspected disease (negative RT-PCT but classic symptoms). The median age of the cohort was 45 (36-58) years and 138 (60%) patients were male. The median CT severity score of the entire cohort was 9 (2-13). There were 49% (n=112), 29% (n=67), and 22% (n=50) of patients in age groups 18-44 years, 45-59 years and > 60 year age groups, respectively. The median CT severity scores in patients age group 18-44 years were 9 (0-12), 45-60 years was 11 (6-15) and >60 years was 8 (1-11).

Of 229 patients, only 29 (13%) had complete vaccination, 38 (17%) had partial vaccination, and 162 (70%) had no vaccination. Of the RT-PCR-positive patients, 29 (14%) had complete vaccination and 32 (15%) had partial vaccination ( Figure 1). The median ages of the fully vaccinated, partially vaccinated, and non-vaccinated groups were 42, 48, and 43 years, respectively, and the difference was not statistically significant (p=0.32, Table 1). There were more male patients in the unvaccinated group than in the fully or partially vaccinated groups (67% vs. 42% vs. 47%, p<0.01). The overall CT score in the RT-PCR-positive cohort was significantly higher than that in the RT-PCR-negative cohort (median 10 vs. 0, p<0.01) cohort ( Figure 2).

The CT score of the completely vaccinated patients was significantly lower than that of the partially or unvaccinated patients (median 0 (full) v. 3.5 (partial) vs. 10, p<0.01, Figure 3). Within the RT-CPR-positive cohort, patients with complete vaccination had significantly lower CT-SS scores than partially or unvaccinated patients (median 0 vs. 4 vs. 11, p=0.02). Figure 4 shows the CT scan images stratified by vaccination status, showing significant lung involvement in unvaccinated patients and minimal lung involvement in fully vaccinated patients.

A multivariate logistic regression model adjusted for age, sex, and RT-PCR showed that unvaccinated patients (Odds Ratio = 12.3 (2.8-54), p<0.01) had a higher likelihood of higher CT severity score compared to fully vaccinated patients ( Table 2).

The second COVID-19 wave, during April and June 2021, put extreme pressure on India’s healthcare system, affecting several younger patients. ² We observed that almost half of all the patients in our cohort were 45 years or younger, which correlated with the national vaccination guidelines (vaccination for healthcare and frontline workers had been performed since January 2021 and vaccination for the general population aged over 45 years had just started in April 2021). One of the primary findings of our research was that patients with complete or even partial vaccination had lower CT severity scores than unvaccinated patients, which reattributes the effectiveness of the vaccines in preventing severe disease. ⁷

Even though radiology practice in India is predominantly independent, they likely encountered a majority of COVID-19 cases requiring imaging studies, including severely ill patients who might have been admitted to hospitals for further treatment. ^{4 , 8} Our study represents a unique and common practice across India and reports real-world evidence of the CT scan findings and its association with vaccination status and RT-PCR positivity in COVID-19 patients. Our study not only demonstrated lower lung involvement with full vaccination using univariate analysis, but also on the multivariable regression model adjusted for age, sex, and RT-PCT status.

Vaccine effectiveness has been scrutinized with the emergence of SARS nCOV-2 variants, as B1617 (delta) or B117 (alpha) mutants had higher transmissibility and case fatality than the unmutated version of the virus. ^{9 , 10} Previous studies have suggested that vaccines are effective against variants in preventing severe disease. ^{11 , 12} A recent report from India suggested that fully vaccinated patients may still be infected with the delta (B1617) variant; however, no mortality or high-grade fever were predominant symptom. ¹³ Similarly, our study showed that 29 fully vaccinated patients had a positive RT-PCR test result (all 29), but their median CT severity score was 0. Although genomic sequencing data in our cohort were unavailable, based on a previous study, the delta variant (B1617) could be predominantly responsible, as our patients were from the same time frame and geography. It should also be noted that all the patients in our study received the CoviShield vaccine (Oxford-AstraZaneca-Serum Institute).

Our study showed that compared to unvaccinated patients, completely or partially vaccinated patients had significantly lower CT severity scores, irrespective of their RT-PCR status, which corroborates the evidence that vaccines are particularly effective tools in preventing severe COVID-19, even if effectiveness in limiting the spread could be lower in leu of emerging variants. ^{7 , 12 , 13} This finding of reduced lung involvement with full or partial vaccination could be crucial in highlighting the role of vaccines as effective tools in combating severe COVID-19. We found 11% of patients with RT-PCR negative but with classic COVID-19 symptoms, which could be due to false negative tests or the timing when the nasopharyngeal swabs were taken (very early or late testing); however, these patients had a lower degree of lung involvement, which could also suggest the possibility of non-COVID illness. ^{14 , 15}

Our study has several limitations, including its retrospective single-center design. We did not have patient details other than their basic demographics, COVID-19 RT-PCR status, vaccination status, or CT severity score. Patient details, such as oxygen saturation, hospital admission status, other laboratory findings, comorbidities, and mortality, were not available. The data presented here are not extensive because our center is not an academic institution that is not affiliated with any other academic center with academic infrastructure. Given the retrospective nature and specific approval from the ethical committee, we did not reach any of the patients after their initial imaging study.

In conclusion, we presented here the real-world findings from an independent radiology practice (a unique and common practice model) in India amid the second COVID-19 wave (of delta variant) showing significantly lower CT severity scores in fully and partially vaccinated patients than in unvaccinated patients. We report a higher CT severity score in patients with positive RT-PCR results. Complete vaccination of patients may have been critical in preventing severe lung disease.

This study received ethical approval from the ACEAS independent ethical committee (US DHHS Reg No. IRB00011046) with protocol number 001/06/2021. The approval was granted on July 10, 2021.

Since this was a retrospective data driven study the requirement for informed consent was waived and the approval was granted by the independent ethical committee.