Coronaviruses - Volume 6, Issue 3, 2025

Adaptation and application of Artificial Intelligence (AI) technology for the development of drugs against the deadly and continuously mutating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been extremely beneficial, cost-effective, and time saving for the scientific community. A systematic review is necessary for complete picturization of the overall AI assistance in developing drugs and vaccines against SARS-CoV-2.

A systematic analysis and review of the research literature available on the application of AI in the development of drugs and vaccines against SARS-CoV-2 from various online platforms like Web of Science, PubMed Central, Science Direct, ResearchGate, Scopus, Google Scholar, Medline, Embase etc., has been performed, and relevant full papers have been selected on certain selection criteria and have been used for this review.

Utilization of AI tools has enabled the selection, modification, evaluation, and prediction of the effectiveness of drug formulations against coronavirus disease (COVID-19) in a very rapid and efficient manner. Vaccine development against the deadly SARS-CoV-2 has also been aided and benefited immensely by using AI tools and technique.

Thousands of studies regarding the development of effective drugs and vaccines against the constantly evolving, mutating, and prevailing SARS-CoV-2 have been conducted, and several thousands are still being conducted around the world.

AI is a powerful tool, and its application has been highly beneficial in developing effective drugs and vaccines against the deadly SARS-CoV-2 in a cost-effective and time-effective frame. This systematic review briefs the findings and achievements till the date of writing this article in the field of AI-assisted drug and vaccine development against COVID-19.

To evaluate the efficacy and safety of Plasma Exchange (PE) in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive pneumonia patients.

This study was a case series conducted at a referral hospital. Twenty SARS-CoV-2-positive patients had an oxygen saturation of 80-90%, and the respiratory rate above 30 per minute. These symptoms started 1 week after the onset of the disease. All patients had less than 90% oxygen saturation and needed respiratory support (oxygen therapy) treated with plasma exchange on 3-5 consecutive days during hospitalization. We followed the amount of oxygen saturation, which was in the form of increasing the patient's oxygen saturation above 90% without oxygen supply and above 92% without oxygen, improving shortness of breath and improving patients' clinical symptoms.

Our study included a total of 20 COVID-19 patients with an overall mean age of 48.9 ± 12.1 years (range: 39-58 years); 60% (n=12) were males, 34.5% of whom benefited from Therapeutic plasma exchange (TPE) sessions. On the third day after the treatment, shortness of breath improved in these patients. Oxygen saturation in all twenty patients increased after the procedure of plasma exchange. Clinical symptoms of all patients were decreasing shortness of breath and improving patients' clinical symptoms after the procedure.

According to our observations, plasma exchange could not show a significant therapeutic effect in COVID-19 patients with severe lung involvement.

The impressive and innovative efforts of scientists worldwide have played a pivotal role in shaping the development and production of COVID-19 vaccines, widely acknowledged as vital resources for pandemic control.

The primary aim of this investigation was to identify the prevailing effects linked to these vaccines, particularly considering their implications for human well-being.

An online survey was conducted in various cities in India, and a trial version of Qualtrics CoreXM software was implemented to prototype 22 questionnaires.

After vaccination, respondents reported various health changes: skin issues (26.9%), eye problems (22.3%), gastrointestinal issues (22.8%), respiratory symptoms (12.5%), and mental health effects (2.9%). Among the 1,047 participants, 8.9% reported having had sexual intercourse, 11.3% of men and 7.3% of women. A further 17.9% were unsure: 19.7% of men, 13.7% of women, and 37.5% of those identifying as “other.” The majority (73.3%) reported no sexual experience: 68.9% of men, 78.8% of women, and 62.5% of “others”.

This study offers an extensive perspective on the vaccination situation in the northern region of India. It delves into the intricate demographic factors influencing vaccine acceptance and understanding potential side effects. These discoveries contribute substantially to the ongoing conversation regarding the COVID-19 vaccination and its various impacts on public health and societal welfare.

mRNA COVID-19 vaccines employ messenger RNA (mRNA) to convey instructions to cells in our bodies, prompting them to generate a viral protein. These vaccines are administered via injection, typically into the upper arm muscle. The mRNA is encapsulated within lipid nanoparticles, safeguarding it and facilitating its entry into cells.

The literature about the specific cells and places where the mRNA of COVID-19 vaccines is supposed to work following injection in the upper arm is reviewed.

The pre-COVID-19 literature indicates that the absorption of mRNA primarily takes place not at the injection site in the arm muscle, but rather in the lymph nodes downstream from the injection site and in the spleen. Lipid nanoparticles could potentially accumulate in the liver as well. As the narrative promoted by Western media and authorities claims that the mRNA is immediately released by the lipid nanoparticles and exclusively operates within specific cells at the injection site before being quickly discharged, consequently, the post-COVID-19 literature has become less explicit on this matter, as censorship has hampered open discussion within the scientific community.

The mRNA of COVID-19 vaccines has always been supposed to work in the lymph nodes downstream of the place of injection and the spleen. This may explain the large number of unintended effects recorded following administration of mRNA COVID-19 vaccines.

Long-term lung sequelae in patients who survived after severe COVID-19 are not clear. This study aims to evaluate complications and relevant outcomes of COVID-19 survivors within a 6-month follow-up period after discharge from the hospital.

This study is a cohort of 50 patients with severe COVID-19 hospitalized in the intensive care unit (ICU) in 2020-2021 at Shahid Beheshti Hospital, Qom, Iran. The study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1399.249). The nasopharyngeal swab and reverse-transcription real-time PCR (RT-qPCR) assay were used to confirm COVID-19 in subjects. We used a checklist that compared symptoms, laboratory findings, and lung radiograph findings for patients at the time of admission and within a 6-month follow-up period after discharge from the hospital. The chest CT scans were used to verify lung involvement. The renal and liver function were assessed using alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (Cr), and bilirubin.

50 patients out of 384 participants who were hospitalized with severe COVID-19 were followed up for 6 months after discharge from the hospital. Findings revealed that, during the follow-up period, all clinical symptoms, except GI bleeding (p = 0.155), were significantly lower than the admission time (p < 0.001). Also, the mean values of laboratory findings, including lymphocyte, neutrophil, lactate dehydrogenase, international normalized ratio, prothrombin, partial thromboplastin time, ESR, and CRP, were significantly lower than admission time (p < 0.001). Also, the mean of alanine transaminase (ALT) and aspartate aminotransferase (AST) between the admission and discharge time were significantly different (p < 0.001). Within 6 months of follow-up after discharge, the frequency of ground glass opacities, crazy paving, consolidation, spider web sign, and vascular thickening were significantly lower than in the admission time.

Our findings revealed that among severe COVID-19 survivors, liver function, inflammation, and clinical factors returned, and clinical factors returned to normal range within 6 months of follow-up after discharge from the hospital. Also, during this period, lung involvement in the radiological findings were significantly lower than in the admission time.

During the COVID-19 pandemic, high-resolution computed tomography (HRCT) chest examination was widely used to diagnose the coronavirus disease. Thus, radiation dose optimization is an essential requirement to decrease the risk of radiation hazards.

This study aimed to estimate the radiation dose parameters of high-resolution computed tomography chest examination of COVID-19 patients using automatic tube current modulation technique and compare the values with various standard diagnostic reference levels (DRLs) available in the literature.

It is a retrospective study conducted on 205 patients with COVID-19, including 144 males and 61 females with a median age of 49 years. All patients with clinical and positive laboratory findings were confirmed by an RT-PCR test. The data were collected from the Department of Radiodiagnosis Government Base Hospital Almora (Uttarakhand) from September 2020 to May 2021. All patients underwent high-resolution computed tomography chest examination with an automatic tube current modulation technique. Radiation dose parameters, such as Volume Computed Tomography Dose Index (CTDIvol) and Dose Length Product (DLP), were extracted from the dose report, and Effective dose (ED) was calculated.

The mean volume computed tomography dose index, dose length product, and effective dose were 4.36 mGy, 136.29 mGy.cm, and 1.8 mSv respectively.

Volume computed tomography dose index and dose length product values at the 75^th percentile were well below the various DRLs, which confirmed the usefulness of the automatic tube current modulation technique in high-resolution computed tomography of the chest for dose optimization at 120 kV.

A recent pandemic caused by Coronavirus 2019 (COVID-19) caused mild and severe systemic organ involvement that led to the death of enormous numbers of people. The prevalence of the disease has declined in recent years, but concerns about emerging mutations remain. In this study, the relationship between lactate levels and mortality at different times was investigated.

In the present retrospective study, 228 hospitalized patients with COVID-19 were included according to the inclusion and exclusion criteria. A modified National Early Warning Score 2 (NEWS2) was used to determine the severity of the patients' conditions. Follow-up of patients, if discharged alive, has been done from hospitalization until March, 2022. Data were analyzed using SPSS version 22, and p < 0.05 was considered significant.

Lactate levels (2.88 ± 2.37 mmol/L in the deceased group vs. 1.68 ± 1.33 mmol/L in the surviving group) show a significant association with in-hospital mortality (p < 0.001). Furthermore, higher lactate levels during hospitalization (p < 0.001, HR = 2.960, 95%CI =4.255-2.58) and follow-up (p < 0.001, HR = 2.085, 95% CI =1.441 to 3.015) increased the mortality risk ratio by more than two-fold.

This study reported that initial lactate levels at admission predict COVID-19 patients' mortality at hospitalization and follow-up. However, further research is needed in this area.

Melatonin has proven antioxidant and anti-inflammatory properties that may address the pathophysiology of coronavirus disease 2019 (COVID-19). Therefore, the current study was conducted to evaluate the safety and efficacy of melatonin in COVID-19.

In this single-center, randomized, double-blind, placebo-controlled clinical trial, 96 adults hospitalized with mild to moderate COVID-19 were recruited. The participants were allocated into the melatonin and the placebo groups, randomly (1:1 ratio).

The primary outcomes were a reduction in the length of hospital stay, the rate of ICU admissions, intubation/mechanical ventilation, and mortalities within 14 days of starting the treatment compared to the placebo group. After two weeks of follow-up, the blood oxygen saturation and the respiratory rate significantly improved in the melatonin group. C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, creatine phosphokinase, Ferritin, and D-dimer levels were significantly decreased in the melatonin group. Conversely, these markers were considerably increased in the placebo group. These serum marker levels also showed a significant difference in between-group comparison. The comparison of clinical endpoints between the two groups showed no significant difference.

This clinical trial study indicated that the combination of oral melatonin tablets and standard treatment could substantially improve blood oxygen saturation and inflammatory factors in mild to moderate hospitalized COVID-19 patients.

Clinical Trials (IRCT registration number: IRCT20200408046988N1).

The aim of the study was to review the existing data on traditional medicine in reducing the symptoms in COVID-19 patients with mild, moderate, and severe symptoms. We also investigated the adverse impact, patient outcome, source, and mode of action of traditional medicine. A brief comparison was made on adverse impacts and symptom alleviation of the commercially available drugs as well.

We utilized PubMed, Scopus, WHO Global Health Library (GHL), and Virtual Health Library (VHL) in order to choose the eligible studies for the systematic review between July and August 2022. From a total of 12,263 studies, after a series of screening, 285 articles were identified in the final sample. The methodological evaluation was carried out accordingly.

There is a growing literature on the usage of traditional medicine for COVID-19. The majority of the studies have shown positive outcomes even though they were not carried out at diverse locations around the world. We identified that the majority (17.4%) of the traditional medicine was derived from plants. The average time in the disappearance of the symptoms was 8.8 days, whereas the disappearance of symptoms using conventional drugs (Remdesivir, Ivermectin, Tocilizumab, Baricitinib, Famotidine, Ensitrelvir and Molnupiravir) was around 12 days. The mode of action of traditional medicine was mostly the reduction of viral load (50%). In terms of the severity of the patients, most of the patients (37.5%) had mild symptoms. We also found that no major adverse impact was reported on administering the traditional medicine among the patients. Further, the majority of the study was carried out in the Asian region, mostly in China.

Apart from expanding the study to different regions of the world, to improve the quality of data, larger-scale clinical studies in the Asian region are required.

COVID-19 is a disease of SARS-CoV-2 beta coronavirus infection. One way to control the progression of COVID-19 symptoms is a rapid and accurate diagnosis. The current gold standard of COVID-19 diagnostic method uses RT-PCR from nasopharyngeal (NP) swabs and sputum specimens.

To assess the efficacy of saliva and rectal swabs as non-invasive alternatives to the conventional nasopharyngeal swab for RT-PCR testing in COVID-19 diagnosis, with a focus on the potential benefits for healthcare providers and patient comfort.

This observational study was conducted with 80 confirmed cases at a tertiary hospital in Indonesia, the study compared RT-PCR positivity rates among different collection methods.

A high positivity rate of 92% for nasopharyngeal swabs, with saliva and rectal swabs yielding 36% and 34%, respectively. Notably, the positivity rates for saliva and rectal samples increased to 60% and 50% when testing occurred between five to seven days post-symptom onset. Crucially, in older patients, both saliva and rectal swabs demonstrated higher positivity rates than in younger patients within the initial four days of symptom onset, with rates of 43% and 17%, respectively. Furthermore, a significant correlation was found between rectal swab positivity on day one and mortality in the older cohort, where lower Ct values on day seven were significantly associated with the deceased group.

These findings support the potential of saliva and rectal swabs in predicting disease severity and patient outcomes, suggesting a safer and more convenient testing strategy for COVID-19.

The rapid spread of the SARS-CoV-2 virus has had a global impact on various ethnic groups. In order to assess the genetic predisposition of the Indian population towards COVID-19, a comparative analysis was conducted using the Human Leukocyte Antigen (HLA) to investigate the frequencies of polymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and fatal outcomes in comparison to other major populations.

The objective of this study is to evaluate the genetic predisposition of the Indian population to COVID-19 by analyzing the frequencies and associations of Human Leukocyte Antigen (HLA) polymorphisms. In addition, by delineating the role of specific HLA variants in the Indian context, the study seeks to enhance our understanding of genetic factors influencing COVID-19 impact and contribute to personalized approaches for disease management and prevention across diverse ethnic groups.

We collected allelic information for DRB1 gene from 653 populations globally, as documented in The Allele Frequency Net Database (AFND). Data on COVID-19 susceptibility, severity, mortality, and protective factors were obtained from a previous global study. This study aimed to compare the specific frequencies of HLA-DRB1* in different ethnic groups, including other Indian populations with COVID-19-associated alleles and protective factors.

HLA-DRB1*01 was identified as a significant determinant of COVID-19 susceptibility among patients in 28 states of Mexico, whereas DRB1*08 in Saudi Arabian populations, DRB1*09:01 in Japanese populations, and DRB1*15:01 in Italian populations also showed this association. Likewise, DRB1*04 in the Iranian population played a role in disease severity, and DRB1*08 in the Italian population was associated with mortality in COVID-19 patients. In addition, alleles DRB1*01:01 and DRB1*04:01 were found to exhibit a protective role in Northeast England, whereas DRB1*04 demonstrated protective effects in Saudi Arabian populations.

The involvement of HLA in COVID-19 requires further investigation, and epidemiological studies should focus on HLA profiles as determinants of the host immune system. Prolonged homozygosity in particular genomic regions could potentially increase susceptibility to COVID-19 infection. Therefore, prudent management strategies are recommended for this pandemic in isolated communities in India and worldwide.

The recent coronavirus pandemic caused systemic human disease that killed many people worldwide, and we are still witnessing the resulting conflicts. Lactate dehydrogenase (LDH) and Creatine phosphokinase (CPK), markers of muscle damage, are potentially associated with a more severe Coronavirus disease (COVID-19). This study aims to evaluate the association between elevated LDH and CPK with severity and mortality in COVID-19 patients.

A retrospective single-center study that included 282 patients with COVID-19 was conducted between 2020-2021 (in Four disease waves) in Rouhani Hospital, Babol, Mazandaran (Northern Iran). Data were extracted from the medical records of all consecutive patients and followed up until death or till 9 September 2021. Univariate and multivariate Cox regression analyses were performed to investigate the associated factors with in-hospital mortality and disease severity. Additionally, logistics regression analyses and Kaplan-Meier curves were used to determine the association between LDH and CPK levels and the prognosis of COVID-19 patients.

The mean age of patients was 60.21 years, and the disease was severe in 31.2% of patients. About 39 (13.8%) patients died during hospitalization and 20 during the follow-up (280.63 ± 192.85 days). Significantly higher in-hospital mortality among older age patients was observed (p = 0.025), including those admitted in the first COVID wave (p = 0.015), those having longer hospital admission (p = 0.008), patients with severe disease (p < 0.001), higher LDH (p = 0.004), higher CPK (p = 0.017), those needing ICU admission (p < 0.001), needing NIV (p = 0.002), and those needing IMV (p < 0.001). In other words, the severity of COVID-19 was significantly associated with older age (p < 0.001), patients with CVDs (p < 0.001), HTN (p = 0.002), DM (p = 0.02), the duration of hospital stays (p = 0.015), ICU admission (p = 0.009), need for NIV (p = 0.003), IMV (p < 0.001), and mortality in long-term follow-up (p = 0.006). However, LDH (p = 0.417) and CPK levels (p = 0.091) were not significantly related to disease severity. LDH levels had a significant effect on hospitalization (p < 0.001, 95%CI= 1.877 to 8.675, HR= 4.036), short-term (p = 0.011, 95%CI= 1.202 to 4.209, HR= 2.249) and long-term (p = 0.002, 95%CI= 1.427 to 4.738, HR= 2.601) mortality, as well as the length of hospital stay until intensive care unit (ICU) admission (p = 0.017, 95%CI= 1.186 to 5.490, HR= 2.551). Receiver operating characteristic curve analysis demonstrated an optimal cutoff point of LDH in the first, third, and fourth waves greater than or equal to 759.53 IU/L, 818.52 IU/L, and 840.92 IU/L, respectively. The test sensitivities were 61.1%,66.7%, and 75%, respectively; specificities were 88.2%,76.6%, and 79.7%, respectively; the AUCs were 0.722, 0.786, and 0.720, respectively, among all hospitalized patients. Comparing the areas under fitted ROC curves, serum LDH was significantly associated with mortality (p < 0.05 for the mentioned cut-off points). However, the area under the curve was not significant at the aforementioned points found for CPK (p > 0.05 for CPK at all waves).

Higher levels of LDH, unlike CPK, significantly predicted severity during hospitalization and mortality in different time periods. Also, its sensitivity increased in new waves. When the COVID-19 patient is hospitalized, these results can help determine the appropriate diagnostic test.

The cellular response to hypoxia is characterized by the stabilization of the HIF-1α protein, which will form a transcription factor that activates genes for low oxygen adaptation. Positive cases of COVID-19 are often characterized by hypoxia, especially in patients with comorbidities. This hypoxic condition will mediate drug resistance or weaken the patient's condition, resulting in lengthening treatment time and even causing death. This study aims to analyze the cellular expression of the HIF-1α gene in patients confirmed positive for COVID-19 with the alpha, beta, delta, and omicron variants.

The research design used was observational, with parameters measuring HIF-1 mRNA expression (RT-PCR, protein (ELISA), and its correlation. The samples used were nose-throat swabs from COVID-19 patients.

The expression of HIF-1α mRNA and protein levels produced in variants of COVID-19 patients was compared with controls (times; ng/mL): alpha (0.53; 18.08), beta (0.92; 19.98), delta (0.65; 25.83), and omicron (0.73; 19.85) (Kruskal-Wallis test, p < 0.01). The correlation between mRNA expression of HIF-1α and HIF-1α proteins was found to be significantly negative (Pearson Correlation test R = -0.589).

In this study, it was found that a decrease in HIF-1α mRNA expression (the result of transcription) increased the levels of HIF-1α protein (the result of translation) and stable HIF-1α expression. Moreover, cellular hypoxia occurred in patients with confirmed positive for COVID-19, with the alpha, beta, delta, and omicron variants. This study can be used as a basis for therapy to control viruses that cause hypoxia in the future.