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\begin{document}

\title{Is Omicron really mild? - Comparative analysis of comorbidities and
disease outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) and
Delta (B.1.617.2) variants}



\author[1]{Vikas Manchanda}%
\author[1]{Srestha Mitra}%
\author[1]{Iram Rafique}%
\author[1]{Anju Sharma}%
\author[1]{Megh Singh Dhakad}%
\author[1]{sonal saxena}%
\author[2]{Seema Kapoor}%
\author[2]{Suresh Kumar}%
\affil[1]{Maulana Azad Medical College}%
\affil[2]{Lok Nayak Hospital}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{Introduction} Multiple variants of SARS-CoV-2 from Alpha to
Omicron have an estimated 6.1 million deaths globally till date.
However, variants have been found to vary in transmissibility and
severity. The present study deals with comparison of morbidity and
mortality with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2)
variants. \textbf{Methods} An observational retrospective cohort study
was conducted on a cohort of laboratory confirmed patients of SARS-CoV-2
diagnosed by qRT-PCR of nasopharyngeal swabs in periods; April-2021 \&
January-2022; that were sequenced and variants were recorded. Patients
were invited for a telephonic interview after voluntary and informed
consent was obtained from each participant wherein, the demographics,
co-morbidities, oxygen requirement and mortality outcomes of the
patients were enquired about. \textbf{Results} A total of 200 patients,
with 100 from each period were included in the study. Major
comorbidities in patients included hypertension, diabetes mellitus and
pulmonary disease. Patients who succumbed to the Delta variant (26\%)
were higher as compared to the Omicron variant (10\%); with the elderly
(68 \selectlanguage{ngerman}± 9.7 years) having mortality during the Omicron variant. A
significantly increased risk for mortality was observed in comorbidities
in both Delta and Omicron variants with hypertension (OR:1.3;5.44),
diabetes mellitus (OR:0.99;1.94), chronic pulmonary disease
(OR:1.6;2.25), chronic kidney disease (OR:3.18;0.89), and smoking
(OR:1.74;1.55). \textbf{Conclusion} The study concluded that the Omicron
has potential of high transmissibility and milder disease for the
population by large, however, it is not a milder strain for patients
with comorbidities having a higher risk of adverse outcomes than that of
the previously dominant Delta variant.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\emph{Title Page}

\textbf{Is Omicron really mild? - Comparative analysis of comorbidities
and disease outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) and
Delta (B.1.617.2) variants}

\textbf{Vikas Manchanda, Srestha Mitra, Iram Rafique, Anju Sharma, Megh
Singh Dhakad, Sonal Saxena, Seema Kapoor, Suresh Kumar}

\textbf{Vikas Manchanda}

Professor

Department of Microbiology, Maulana Azad Medical College, Delhi, India

E-mail: micromamc@gmail.com

\textbf{Srestha Mitra (corresponding author)}

Senior Resident

Department of Microbiology, Maulana Azad Medical College,

Bahadur Shah Zafar Marg,

New Delhi -- 110002

India

Mobile no: 9650238428

E-mail: sresthalh@gmail.com

\textbf{Iram Rafique}

Senior Resident,

Department of Microbiology, Maulana Azad Medical College, Delhi, India

E-mail: iram.rafique02@gmail.com

\textbf{Anju Sharma}

Research Assistant,

Department of Microbiology, Maulana Azad Medical College, Delhi, India
E-mail: anjusharma10783@gmail.com

\textbf{Megh Singh Dhakad}

Research Assistant,

Department of Microbiology, Maulana Azad Medical College, Delhi, India

E-mail: megh\_singh61@yahoo.com

\textbf{Sonal Saxena}

Director Professor and Head of Department

Department of Microbiology, Maulana Azad Medical College \& Lok Nayak
Hospital, Delhi, India

E-mail: sonalsaxena3@gmail.com

\textbf{Seema Kapoor}

Director Professor,

Department of Pediatrics, Pediatric Research and Genetic Lab, Maulana
Azad Medical college and Lok Nayak Hospital, Delhi, India

E-mail: drseemakapoor@gmail.com

\textbf{Suresh Kumar}

Managing Director, Director Professor

Department of Medicine, Maulana Azad Medical college and Lok Nayak
Hospital, Delhi, India

E-mail: drskumar31@yahoo.co.in

\textbf{Institution at which the work was performed:} Maulana Azad
Medical College \& Lok Nayak Hospital

\emph{Shortened Title:} Is Omicron really mild?

Conflict of interest: The authors declare that there is no conflict of
interest.

Data Availability: The data set is available on request.

Funding Statement: This research received no specific grant from any
funding agency in the public, commercial, or not-for-profit sectors.

Ethics Statement: The study protocol was approved by the Institutional
Ethics Committee, Maulana Azad Medical College, New Delhi, India
(F.1/IEC/MAMC/92/04/2022/No441).

Patient consent statement: As it is a retrospective study, ethical
clearance has been taken as required.

Permission to reproduce material from other sources: Not applicable.

Clinical trial registration: Not applicable.

\emph{Abstract}

\textbf{Introduction}

Multiple variants of SARS-CoV-2 from Alpha to Omicron have an estimated
6.1 million deaths globally till date. However, variants have been found
to vary in transmissibility and severity. The present study deals with
comparison of morbidity and mortality with SARS-CoV-2 Omicron
(B.1.1.529) and Delta (B.1.617.2) variants.

\textbf{Methods}

An observational retrospective cohort study was conducted on a cohort of
laboratory confirmed patients of SARS-CoV-2 diagnosed by qRT-PCR of
nasopharyngeal swabs in periods; April-2021 \& January-2022; that were
sequenced and variants were recorded. Patients were invited for a
telephonic interview after voluntary and informed consent was obtained
from each participant wherein, the demographics, co-morbidities, oxygen
requirement and mortality outcomes of the patients were enquired about.

\textbf{Results}

A total of 200 patients, with 100 from each period were included in the
study. Major comorbidities in patients included hypertension, diabetes
mellitus and pulmonary disease. Patients who succumbed to the Delta
variant (26\%) were higher as compared to the Omicron variant (10\%);
with the elderly (68 \selectlanguage{ngerman}± 9.7 years) having mortality during the Omicron
variant. A significantly increased risk for mortality was observed in
comorbidities in both Delta and Omicron variants with hypertension
(OR:1.3;5.44), diabetes mellitus (OR:0.99;1.94), chronic pulmonary
disease (OR:1.6;2.25), chronic kidney disease (OR:3.18;0.89), and
smoking (OR:1.74;1.55).

\textbf{Conclusion}

The study concluded that the Omicron has potential of high
transmissibility and milder disease for the population by large,
however, it is not a milder strain for patients with comorbidities
having a higher risk of adverse outcomes than that of the previously
dominant Delta variant.

\emph{Key words}

SARS-CoV-2, Omicron, Delta, Comorbidities, Mortality, Real-time PCR,
Sequencing

\textbf{1. Introduction}

The COVID-19 pandemic, the biggest public health crisis in a century has
caused an estimated 476 million cases and 6.1 million deaths till date
globally. {[}1{]}

During the pandemic, multiple variants of SARS-CoV-2 have emerged that
have been found to vary in transmissibility and severity. Omicron
(B.1.1.529) variant has emerged after Alpha, Beta, Gamma and Delta
SARS-CoV-2 variants, during November 2021 as a highly mutated virus
variant, classified as variant of concern (VOC) by WHO on 26 November
2021, that has now attained the position of a dominant strain in several
countries owing to its very high transmissibility {[}2{]}. With the
emergence of the Omicron (B.1.1.529) variant of SARS-CoV-2, there is
remarkable decrease in the disease severity relative to previous
variants such as Delta (B.1.617.2). The lower disease severity seen in
populations during the Omicron wave of the SARS-CoV-2 pandemic infection
{[}3{]}~can be attributed to changes in the virus that limit its ability
to spread in the lungs and, probably most importantly, to increased
immunity in the population from previous SARS-CoV-2 infection and
vaccination {[}4{]}. In the last 6 months cases of COVID 19 are
declining {[}1{]}. It seems that, the disease is going towards
endemicity.

The patients infected with Omicron variant have shorter hospital stay,
lesser number of patients receiving intensive care, and fewer deaths
than delta variant. Though presenting as low severity disease, its
higher transmissibility might present a threat for co-morbid patients
{[}2{]}.

The present study deals with comparison of morbidity and mortality with
SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants.

\textbf{2. Method}

An observational retrospective cohort study was conducted in the
Department of Microbiology, at a tertiary care hospital where patients
aged \textgreater{}12 years who were laboratory confirmed cases of
SARS-CoV-2 diagnosed by real-time PCR performed on their nasopharyngeal
swabs were enrolled in the study. Nasopharyngeal swabs were transported
in viral transport media from which viral RNA was extracted using the
MagNA Pure 96 DNA and Viral NA Small Volume kit (Roche, Basel,
Switzerland) on the automated MagNA Pure 96 platform (Roche, Basel,
Switzerland) as per manufacturer's protocol {[}5{]} followed by
Real-time RT-PCR using standardized protocols of Q-line -- ER (nCoV-19)
RT-PCR detection kit (POCT Service Private Ltd., India) and Check RT-PCR
Omisure kit (Tata MD, India); in April 2021 and January 2022,
respectively.

A sample size of 100 patients each from two different time periods
(April 2021 \& January 2022) was taken when the two variants were
predominantly circulating. The archived positive specimens were
subjected to amplicon-based nanopore sequencing using GridION MK1
sequencer (Oxford Nanopore Technologies Ltd., United Kingdom) as per
standardized protocol. {[}6{]}

The study protocol was approved by the Institutional Ethics Committee,
Maulana Azad Medical College, New Delhi, India
(F.1/IEC/MAMC/92/04/2022/No441). Telephonic interviews were conducted,
wherein a willingness to participate was verified from each participant.
If the patient had been admitted in the hospital, details regarding
demographics (age, gender), co-morbidities (hypertension, diabetes,
chronic kidney disease, chronic liver disease, chronic obstructive
pulmonary disease, chronic heart disease, malignancies), length of
hospital stay, oxygen requirement and mortality outcomes of the patients
were collected. Details from hospital records were collected if the
patient had not survived. Patients were excluded if they did not respond
to a phone call or contact number was not available. The association
between the variant of SARS-CoV-2 infecting the patient and the
demographics, comorbidities and diseases outcomes was determined.

All the data was collected and compiled in MS Excel and analysis was
done using SPSS version 20 software. Results for quantitative variables
have been expressed as median, mean and standard deviation, whereas,
qualitative data as percentages. Further, analysis was done by
Chi-square test for qualitative data and significance was considered if
p-value \textless{}0.05. Odds risk (OR) ratio and 95\% confidence
interval were analyzed using SPSS version 20.

\textbf{3. Results}

In the month of April 2021, a total of 3020 patients were tested for
SARS-CoV-2 by real-time PCR, of which 648 patients were admitted in the
hospital. Similarly, in the month of January 2022, of the 2396 patients
were tested, among these patients 422 patients were admitted to the
hospital. To enroll 100 patients in each period, telephonic interview
was attempted in 212 patients in the month of April 2021, and in 261
patients in the month of January 2022. On genome sequencing of the
SARS-CoV-2 virus of the 100 patients in each period, both the Delta
variant (Pango lineage: B.1.617.2) and the Omicron variant (Pango
lineage: B.1.1.529 \& BA.2) was found in 100\% of the patients in the
periods of April 2021 and January 2022 respectively.

The median age was 49.5 years (Range:18-90 years) in patients infected
with the Delta variant of SARS-CoV-2 which was similar to the median age
{[}47.5 years (range: 14-88 years){]} of the patients infected in the
month of January 2022. Majority of the patients admitted during the
Delta wave were females (54\%), whereas, males were more commonly
admitted (57\%) due to the infection by the Omicron variant. Amongst the
females (43\%) admitted during the period of January 2022, 11.6\% were
pregnant, in contrast from those admitted during the Delta variant
(18.5\%).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{3.1 Comorbidities}

Patients with major comorbidities admitted during the periods April 2021
and January 2022 include hypertension (49\%, 34\%), diabetes (27\% each)
and chronic obstructive pulmonary disease (24\%, 11\%) as shown in
Figure 1. At least one comorbidity was present in 70\% of the patients
admitted with infection with the Delta variant, whereas 52\% of the
patients with Omicron infection had comorbidities. Amongst the patients
admitted in both periods, 31\% were smokers during the Omicron variant
as compared to only 11\% in the Delta variant (p\textgreater{}0.05).

Oxygen was required for the treatment of the disease in 75\% of the
patients with Delta variant and 61\% of the patients with Omicron
variant, however had no significant association (p\textgreater{}0.05).
As shown in Table 1, amongst the patients who survived during the Delta
wave, most of the patients had a stay for more than 7 days (52.6\%);
whereas during the Omicron infection, patients were usually admitted for
less than 7 days (78.9\%).

\textbf{3.2 Mortality}

Amongst the patients surveyed, 26\% of the patients admitted succumbed
to the disease during April 2021, while only 10\% died with infection
caused by Omicron during January 2022. It was observed that the older
age group patients {[}age: 68.6 \selectlanguage{ngerman}± 9.76 years (mean ± SD){]} had an
increased mortality when infected with the Omicron variant, however,
there was no significant difference in the age of patients who survived
{[}age: 46.4 ± 16.1 years (mean ± SD){]} to those who died {[}age: 49 ±
15.2 years (mean ± SD){]} when infected with the Delta variant. In
total, 32.6\% of the male patients who were admitted died from the Delta
variant infection, compared to 20.6\% of the female patients who passed
away within the same time. However, amongst the patients admitted with
Omicron infection, a higher percentage of females (11.6\%) than males
(8.7\%) perished. There was no mortality seen amongst the pregnant
females admitted due to the infection by SARS-CoV-2 in both the time
periods.

The comorbidities such as hypertension, diabetes and chronic obstructive
pulmonary disease had an increased risk for mortality for patients
infected by either the Delta or the Omicron variant, with a significant
odds ratio as seen in Table I. On comparison of the patients who
succumbed to the disease in the two different periods, patients with
chronic obstructive pulmonary disease had increased mortality (30.8\%)
when infected with the Delta variant as compared to the Omicron variant
(20\%). Although, the presence of comorbidities was not a risk factor to
get admitted in Omicron, the presence of diabetes, hypertension and
chronic obstructive pulmonary disease had a higher risk of mortality as
compared to the Delta variant as shown in Table I. The risk of smoking
increased the mortality (OR: 1.5-1.7) in both variants of the infection.

In patients who succumbed to the disease, higher proportion of the
patients were admitted for more than 7 days due to the Omicron infection
(80\%) as compared to the Delta infection (30.8\%). Most of the patients
succumbed within 48 hours (30.8\%) or after 48 hours but within 7 days
(38.4\%) during the Delta variant infection. However, in patients with
Omicron, none of them died within 48 hours. The average length of stay
amongst patients who were admitted and later died was comparatively
longer in cases infected with the Omicron variant than the Delta variant
(12.1±4 vs 5.2±4 days).

\textbf{Table I: Risk Factors for Mortality in SARS-CoV-2 Patients
Infected with Different Variants}\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Co-morbidities}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Co-morbidities}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Delta Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Delta Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Delta Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Delta Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Omicron Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Omicron Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Omicron Variant}\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textbf{Omicron Variant}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Survived} \textbf{(n=74)}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Succumbed} \textbf{(n=26)}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Odds ratio}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{95\% CI}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Survived (n=90)}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Succumbed} \textbf{(n=10)}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Odds ratio}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{95\% CI}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
47.3\% (35)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
53.8\% (14)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.3\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.51, 3.18)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
30\% (27)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
70\% (7)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5.44\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(1.31, 22.65)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
27\% (20)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
26.9\% (7)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.99\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.36, 2.27)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
25.6\% (23)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
40\% (4)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.94\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.50, 7.50)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic obstructive pulmonary disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic obstructive pulmonary disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
21.6\% (16)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
30.8\% (8)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.61\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.59, 4.38)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
10\% (9)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
20\% (2)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2.25\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.41, 12.26)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic kidney disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic kidney disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5.4\% (4)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
15.4\% (4)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3.18\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.73, 13.78)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.1\% (1)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0\%\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.89\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.84, 0.96)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Smoking\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Smoking\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
9.5\% (7)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
15.4\% (4)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.74\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.46, 6.51)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
30\% (27)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
40\% (4)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.55\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.41, 5.96)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic liver disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic liver disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.4\% (1)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
7.7\% (2)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
6.08\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.53, 70.0)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic heart disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Chronic heart disease\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
9.5\% (7)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
11.5\% (3)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.25\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
(0.29, 5.23)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
NA\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Oxygen requirement\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Oxygen requirement\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
66.2\% (49)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
100\% (26)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
p = 0.001\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
p = 0.001\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
56.1\% (51)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
100\% (10)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
p = 0.008\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
p = 0.008\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Length of Stay (Mean \selectlanguage{ngerman}± SD) (days)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Length of Stay (Mean \selectlanguage{ngerman}± SD) (days)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
8.4 \selectlanguage{ngerman}± 4.6\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5.2 \selectlanguage{ngerman}± 4.1\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
6.58 \selectlanguage{ngerman}± 3.89\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
12.10 \selectlanguage{ngerman}± 4.06\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
LOS\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
[?]48 hours\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6.8\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
30.8\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
5.6\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
0\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
48 hours -- 7 Days\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
40.5\%\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
38.4\%\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
73.3\%\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
20\%\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
\textgreater{}7 days\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
52.7\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
30.8\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
21.1\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
80\%\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\emph{Discussion}

The present study exhibited a pattern of association between the risk
factors and the variants of SARS-CoV-2, showing significantly increased
mortality amongst patients with comorbidities during the delta variant
infection. The study also highlights the association of the Omicron
infection with a substantially higher risk of adverse outcomes in
comorbid adults than that of the previously dominant delta variant.

The odds of hospitalization in this study were decreased by 4\% for
patients with Omicron infection than with the Delta which was consistent
with studies done in the United Kingdom and South Africa (25-29\%)
{[}7,8{]}. Compared to the Delta variant, Omicron is more likely to
cause breakthrough infections of vaccinated individuals and reinfections
{[}9{]}, yet admissions were less frequent, due to the lesser severity
of the disease. Hence, there was an increased risk of hospitalization of
patients with comorbidities infected with the Delta variant.

The current study reveals that SARS-CoV-2 cases infected with the
Omicron variant had a 2-fold decreased risk of death than the patients
suffering from the Delta variant. Similar to studies performed by Kim et
al. and Maslo et al. {[}10,11{]} in South Korea and South Africa,
respectively, it was seen that the severity of the Omicron variant was
milder. This could be due to vaccination, or previous infection, leading
to a decrease in hospitalization and mortality {[}4,12{]}.

Most of the patients in this study during the period of April 2021 had
either taken just the first dose of vaccine if above 60 years of age or
had not taken any vaccination; while the cases were mostly double
vaccinated during the period of January 2022. {[}13{]} However, as the
present study highlights, the patients with co-morbidities like
hypertension and diabetes when admitted from the Omicron variant are
more likely develop severe disease, compared to an infection by Delta
variant to have adverse outcomes.~This could be because both diabetes
and hypertension are conditions associated with chronic systemic
inflammation, where there are considerable alterations in all tissues
and organs that may affect normal cell functions, including the immune
response to vaccines {[}14,15{]}. Due to elevated levels of
pro-inflammatory cytokines which correlates with hypo-responsiveness to
vaccination {[}16{]} and perivascular inflammation {[}17{]} in
hypertension, there is an impaired immune function, influencing the
response to vaccination. The findings correlate with a study conducted
in Indonesia by Soegiarto et al. {[}18{]} in 2021, on 2714 healthcare
workers who received two doses of inactivated viral vaccine, showed that
hypertension is associated with lower antibody titers and breakthrough
infection following COVID-19 vaccination. Similarly in diabetic
patients, dysregulation of antigen presentation and deteriorated
complement function, followed by hyperglycemia and insulin resistance,
could justify lower levels of antibodies in diabetes {[}15{]}. A
systematic review by Boroumand et al. {[}19{]}, reported the
immunogenicity of vaccines (vector-based, inactivated) to be lower among
patients with diabetes mellitus as compared to healthy controls.

As inferred from the current study, patients with hypertension have a
significant risk of hospitalization and mortality irrespective of the
variant they are infected with. This could be due to the ACE-2 receptor
which mediates the entry of the virus into the lung, and patients with
high blood pressure are administered drugs like ACE-2 inhibitors and
angiotensin receptor blockers which lead to overexpression of ACE-2,
thus increasing the fatal outcomes of COVID-19 {[}20{]}. Lippy et al.
{[}21{]} demonstrated a 2.5-fold increased risk of mortality in patients
with hypertension, predominantly in the geriatric age group.

Diabetes is a significant risk factor for mortality in patients infected
with either Delta or Omicron variant as shown in this study. In a study
of England, both type 1 and type 2 diabetes were independently
associated with a significant increase in COVID-19--related mortality
(adjusted odds of 2.86 for type 1 and 1.80 for type 2 diabetes) {[}22{]}
which correlates with the present study. Patients with diabetes mellitus
have poor innate immunity and being a proinflammatory condition with
increased blood counts of IL-6, CRP, and ferritin; diabetic patients
with COVID-19 are vulnerable to shock and acute respiratory distress
syndrome {[}23{]}. Furthermore, the hypercoagulation cascade in COVID-19
results in catastrophic thromboembolism exacerbated by the presence of
DM shown by greater D-dimer concentrations and increased risk of
fatality {[}23{]}. Also, diabetic patients have impaired innate
immunity, predisposing them to breakthrough COVID-19 infections
{[}24{]}.

There was a higher prevalence of patients with chronic obstructive
pulmonary disease (COPD) in the Delta (24\%) infection as compared to
the Omicron (11\%) infected patients. However, both showed significant
odds (1.6-2.2) for mortality. The genome of the Omicron variant of
SARS-CoV-2 has more than 30 mutations which have increased the
transmissibility of the virus and affected binding affinity {[}9,25{]}.
It has been also reported that Omicron replicates faster than all other
SARS-CoV-2 variants in the bronchus but less efficiently in the lung
parenchyma, and appears to enter human cells by a different route than
other variants {[}26{]}. Hence, the decreased prevalence of COPD
patients could be attributed to increased vaccination {[}13{]} as well
as decreased severity of the disease during the Omicron variant.

Similarly, patients with chronic kidney disease also showed an increased
risk of mortality during the Delta COVID-19 infection than in the
Omicron variant. ACE-2 protein is expressed at high levels in the
kidneys (proximal kidney tubules) {[}27{]}, hence, kidney damage may be
caused by SARS-CoV-2 entering cells by targeting ACE-2 receptors,
leading to collapsing glomerulopathy by toxic viral effects on podocytes
{[}28{]}.

Moreover, the mortality of patients with Omicron was seen to be in the
elderly age group as compared to the Delta variant (68 years vs 49
years). Patients admitted due to the infection by Omicron were elderly
which correlated to previous studies {[}10,11,29{]}. This can be
attributed to the fact that compromised immunity of elderly patients
having comorbidity despite immunisation, confront the worst outcome with
COVID-19. Although the mortality amongst males was higher during the
Delta SARS-CoV-2 infections, no such significant association for gender
was seen during the Omicron variant. This correlates with other studies
{[}30,31{]} which reported that males were more affected than women
during Delta variant infections. In the present study, smoking increased
the mortality in both Delta and omicron variants (15.4\%, 40\%) as
reported in previous studies {[}32,33{]}. In a systematic review by
Vardavas et al. {[}34{]}, smokers were 2.4 times more likely to be
admitted to an ICU, need mechanical ventilation, or die compared to
non-smokers.

Oxygen requirement as a treatment showed a significant correlation with
the severity of the disease in the current study, irrespective of the
disease variant. Acute hypoxemic respiratory failure is the most common
complication in adult patients with COVID-19. Most patients are managed
with enhanced respiratory support modalities such as high-flow nasal
cannula (HFNC), non-invasive positive pressure ventilation (NIPPV),
endotracheal intubation, and invasive mechanical ventilation (IMV) or
extracorporeal membrane oxygenation (ECMO). {[}35{]}

The length of stay in the hospital was more than 7 days for majority of
the patients who died with Omicron infection (80\%) as compared to Delta
variant infection (30.8\%). According to the current study, patients
with infections by the Delta variant, died mostly within 48 hours
(30.8\%), probably due to the delayed presentation of the patients to
the hospital which was not seen in the Omicron variant infection. Along
with increased risk of comorbidities leading to death in the Omicron
variant infection, it can be perceived that vaccination of individuals
and lesser severity of the Omicron variant could be a possible reason
for the longer duration of stay in patients who died due to
comorbidities in this period.

However, there were some limitations in the study. First, it might not
reflect the scenario of the whole country as it was a single centred
study with a minimum size of 100 patients each from each duration of
infection with a variant. Second, could not compare the symptoms and
risk of hospital acquired infection in these patients. Third, were
unable to demonstrate the efficacy of vaccination in the patients during
the delta infection, most of the patients were not vaccinated. Fourth,
though the study shows increased odds of mortality with other risk
factors such as chronic liver disease (OR:6.08) and malignancy
(OR:4.89), however, were unable to compare amongst the variants for the
same, due to fewer number of such patients. The findings in the study
were consistent with other studies done in different countries
{[}31,36{]}; hence, proving that comorbidity deteriorates the defensive
mechanism of the patients and worsens the mortality outcome of COVID-19
patients, irrespective of the variant of infection. Finally, due to
insufficient sample size, it was difficult to assess the role of
previous infection on clinical presentation.

The overall reduction in the risk of death with newer variant has made
it substantially easier to live with COVID-19 as an endemic disease. The
study exhibited a pattern of association between the risk factors and
the variants of SARS-CoV-2, showing that Omicron is associated with a
substantially higher risk of adverse outcomes in comorbid adults than
that of the previously dominant Delta variant. Hence, it is of crucial
need for a sufficiently detailed and systematic surveillance, which will
allow timely detection and characterization of new viral lineages with
the emergence of newer variants of SARS-CoV-2; as Omicron is not a
milder strain for patients with comorbidities.

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