A Thorn in his Side

History: A 20 year old D1 men's basketball player with a history of COVID the month prior presented with worsening low back pain. He denied any injury, but reported the pain started as low back discomfort after a basketball game the week prior. He noted a progression and radiation of pain down his right lower extremity to his toes. He had tried physical therapy and dry needling, as well as cyclobenzaprine and naproxen from team physicians with mild improvement. The pain worsened and he went to the ED for evaluation. He was afebrile and had a lumbar radiograph with no acute fracture, grade 1 anterolisthesis of L5 on S1. He was discharged home with norco. Over the next 2 days, he developed chills and in the context of his worsening back pain, his team physicians ordered an MRI. Physical Exam: BMI 26.9 Temp 97.9degree Heart rate: 73 Respiratory rate 14 BP: 124/64 MSK: Spine- Intact skin with generalized pain over lumbar area, worse over the right paraspinal musculature. 5/5 strength of bilateral lower extremity flexion and extension of his hips, knees, and plantar and dorsiflexion of ankles and toes. Bilateral intact sensibility in the sciatic, femoral, superficial, and deep peroneal, sural, and saphenous nerve distributions. Slightly diminished sensibility over the right deep peroneal nerve distribution compared to left. 2/4 patellar and achilles DTRs. No clonus, downgoing Babinski sign. Positive straight leg raise at 45 degrees with the right lower extremity. Differential Diagnosis: 141. Sciatica 142. Lumbar Muscle Strain 143. Disk Herniation 144. Spondylolisthesis 145. Vertebral Osteomyelitis Test Results: CBC:WBC10, HGB13.2, neutrophils 75.7% (red 45%-74%). Unremarkable CMP. CRP =7.31, ESR 23 Blood culture negative, throat culture negative. TB test negative. COVID test negative. Flu test negative. Urine culture and UDS negative. HIV test negative. Procalcitonin of 0.07. IR guided aspiration and bacterial Culture yielded MSSA. MRI w/contrast: showing L1-L4 facet edema concerning for infectious spondylitis, intramuscular, and epidural abscess. Final Diagnosis: Acute intramuscular abscess, vertebral osteomyelitis, with epidural abscess. Discussion(s): Vertebral osteomyelitis is a serious but quite rare disease in the immunocompetent, elite athlete population. Staphylococcus Aureus is the culprit a majority of the time, with only 50% of cases showing neurologic symptoms. This case was unique given the proximity to a dry needling treatment which is the only explainable vector of infection, normal blood cultures in this disease which hematogenously spreads, negativeHIV and other infectious disease testing, and otherwise benign history. Early recognition of this disease yields better outcomes and reduces incidence of severe debility. 5% to 10%of patients experience recurrence of back pain or osteomyelitis later on in life. Outcome(s): Patient was hospitalized and started on Cefepime and Vancomycin. Had an echocardiogram revealing changes consistent with athlete's heart without signs of vegetation on his cardiac valves. Neurosurgery declined to treat surgically. He continued to improve until he was ultimately discharged on hospital day 4 with a picc line and Nafcillin and was later changed to oral augmentin per ID. Follow-Up: By his 6 week follow-up visit with infectious disease and the team physicians, his back pain had completely resolved and was cleared to start a return to play protocol. There was no progression of disease since starting antibiotics, and no recurrence of back pain since treatment.

Molecular docking and dynamics simulation of main protease of SARS-CoV-2 with naproxen derivative

Naproxen is a well-known anti-inflammatory drug that is frequently used to relieve inflammation, stiffness, and swelling. Naproxen has previously demonstrated antiviral activity, particularly against the influenza-A virus. There have been previous studies regarding naproxen effect on SARS-CoV-2 infection. Therefore, it is of interest to document the molecular docking and dynamics simulation data of main protease of SARS-CoV-2 with naproxen derivative for further consideration.

Erythema nodosum -Expanding diagnostic workout in COVID-19 pandemic

Case report Erythema nodosum (EN) is considered a delayed type IV hypersensitivity reaction, triggered by exposure to an antigen, which diagnostic workout is usually challenging. Several conditions have been described as possible causes for EN, including infections, sarcoidosis, pregnancy, neoplasic and inflammatory diseases. Rarely, vaccines such as tetanus, diphtheria, BCG, hepatitis B, human papillomavirus, malaria, rabies, smallpox, typhoid, and cholera have been associated with subsequent EN. We present a 31-year- old leucodermic female with suppurative adenitis, who developed painful erythematous nodules on the pretibial area of the lower limbs. Ten days prior to presentation she had received the first dose of the COVID-19 mRNA-1273 vaccine. Fever, lymphadenopathy, fatigue, weight loss, arthritis, cough, diarrhoea, other organ-specifc symptoms and close contact with tuberculosis were excluded. She was under oral contraception for several years, that was not discontinued. Pregnancy was excluded. No positive signs were detected on physical examination besides the referred nodules. Laboratory tests revealed a normal complete blood count, erythrocyte sedimentation rate, C-reactive protein, antistreptolysin O titer, renal and hepatic tests. Interferon-gamma release assay was negative. Circulating rheumatoid factor was normal, anti-nuclear, anti-double stranded DNA and anti-neutrophil cytoplasmatic antibodies were negative. Angiotensin converting enzyme and protein electrophoresis were normal. Hepatitis B and C, HIV 1/2 and syphilis serologic profiles were negative. Urinalysis and fecal calprotectin were unremarkable. The patient was treated with naproxen and topic betamethasone dipropionate. Violaceous involution was reported, with complete resolution of the EN lesions over the following month. In the literature, there are rare reports of EN following SARS-COV2 infection and also after COVID-19 vaccination. To our knowledge this is the second report of EN after the COVID-19 mRNA-1273 vaccine. This case highlights the importance of clinical awareness for the possible association of COVID-19 vaccination and EN, adding to the already extensive list of causes included in the etiological investigation of these patients.

Shoulder Pain and Injury after COVID-19 Vaccination

Shoulder injury related to vaccine administration (SIRVA) is a term given to describe shoulder pain and dysfunction arising within 48 hours after vaccine administration and lasting for more than one week. While SIRVA is most commonly seen after influenza and tetanus vaccines, there have been a few recent case reports describing SIRVA-like symptoms after COVID-19 vaccine administration. Two patients presented to the shoulder surgeon's practice center with complaints of shoulder stiffness and pain following the COVID-19 vaccine. The first patient was a 33-year-old man;he presented within 2 days of onset of the pain and 14 days from the vaccine date. He had a complete restriction of shoulder motion (0degree flexion, and no external or internal rotation) at presentation. This patient was treated with non-steroidal anti-inflammatory drugs (NSAID) and rested in a sling for a week. The second patient was a 53-year-old woman;she presented with a 6-week duration of mild restriction of active shoulder motion and shoulder pain. Her magnetic resonance imaging (MRI) revealed the presence of subacromial-subdeltoid bursitis. She was treated with subacromial steroid injection and range of motion shoulder exercises. Both patients recovered a near-normal range of motion recovery within a month, and their pain improved significantly. The main lessons from this case report were: (1) patients presenting with a recent increase in pain and acute loss of shoulder movements after vaccination may be managed conservatively with rest and NSAID medications and (2) in case of a subacromial-subdeltoid bursitis in the MRI, subacromial injection of steroid may provide good pain relief. Copyright © 2022, Yale Journal of Biology and Medicine Inc. All rights reserved.

New Aspects of the Antioxidant Activity of Glycyrrhizin Revealed by the CIDNP Technique.

Electron transfer plays a crucial role in ROS generation in living systems. Molecular oxygen acts as the terminal electron acceptor in the respiratory chains of aerobic organisms. Two main mechanisms of antioxidant defense by exogenous antioxidants are usually considered. The first is the inhibition of ROS generation, and the second is the trapping of free radicals. In the present study, we have elucidated both these mechanisms of antioxidant activity of glycyrrhizin (GL), the main active component of licorice root, using the chemically induced dynamic nuclear polarization (CIDNP) technique. First, it was shown that GL is capable of capturing a solvated electron, thereby preventing its capture by molecular oxygen. Second, we studied the effect of glycyrrhizin on the behavior of free radicals generated by UV irradiation of xenobiotic, NSAID-naproxen in solution. The structure of the glycyrrhizin paramagnetic intermediates formed after the capture of a solvated electron was established from a photo-CIDNP study of the model system-the dianion of 5-sulfosalicylic acid and DFT calculations.

Prevalence of NSAID use among people with COVID-19 and the association with COVID-19-related outcomes: Systematic review and meta-analysis.

AIM: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating patients with coronavirus disease 2019 (COVID-19) have raised great concern. METHODS: We searched the PubMed, EMBASE, Cochrane Library and MedRxiv databases to examine the prevalence of NSAID use and associated COVID-19 risk, outcomes and safety. RESULTS: Twenty-five studies with a total of 101 215 COVID-19 patients were included. Prevalence of NSAID use among COVID-19 patients was 19% (95% confidence interval [CI] 14-23%, no. of studies [n] = 22) and NSAID use prior to admission or diagnosis of COVID-19 was not associated with an increased risk of COVID-19 (adjusted odds ratio [aOR] = 0.93, 95% CI 0.82-1.06, I2  = 34%, n = 3), hospitalization (aOR = 1.06, 95% CI 0.76-1.48, I2  = 81%, n = 5), mechanical ventilation (aOR = 0.71, 95% CI 0.47-1.06, I2  = 38%, n = 4) or length of hospital stay. Moreover, prior use of NSAIDs was associated with a decreased risk of severe COVID-19 (aOR = 0.79, 95% CI 0.71-0.89, I2  = 0%, n = 7) and death (aOR = 0.68, 95% CI 0.52-0.89, I2 = 85%, n = 10). Prior NSAID administration might also be associated with an increased risk of stroke (aOR = 2.32, 95% CI 1.04-5.2, I2  = 0%, n = 2), but not myocardial infarction (aOR = 1.49, 95% CI 0.25-8.92, I2  = 0, n = 2) and composite thrombotic events (aOR = 1.56, 95% CI 0.66-3.69, I2  = 52%, n = 2). CONCLUSION: Based on current evidence, NSAID use prior to admission or diagnosis of COVID-19 was not linked with increased odds or exacerbation of COVID-19. NSAIDs might provide a survival benefit, although they might potentially increase the risk of stroke. Controlled trials are still required to further assess the clinical benefit and safety (e.g., stroke and acute renal failure) of NSAIDs in treating patients with COVID-19.

Evidence of Ischemic Stroke in Pediatric Patient with Post-COVID-19 Syndrome

Objective: Stroke has been reported to be a potential neurological complication of COVID-19 infection in adults, however, only a few reports have been made in the pediatric population. We describe a case of a 12-year-old female with post-COVID-19 syndrome who was found to have an ischemic stroke on MRI as well as positive for lupus anticoagulant. Background: COVID-19 has been documented to potentiate a prothrombotic and proinflammatory state. It is postulated this occurs via endothelial cell disruption and clotting cascade activation. However, cases have reported the presence of prothrombotic antibodies in patients with COVID-19 infections. The persistent presence of these antibodies has important clinical implications, including an increased thrombotic risk. Design/Methods: Chart review Results: A 12-year-old female with history of migraines presented to the neurology clinic for increased frequency and severity of headaches. Patient reported to have COVID-19 infection one year prior with symptoms of fatigue, arthralgias, sore throat, and headaches. Following infection, patient had resolution of most symptoms but continued having increased headaches and difficulty concentrating. Headaches have been occurring multiple times per week, lasting hours to days, and are associated with nausea, vomiting, and photophobia. Patient has no focal neurological deficits. Brain MRI showed small focal encephalomalacia with surrounding gliosis and volume loss in the anterior right basal ganglia and adjacent external capsule consistent with a small chronic infarct. On thrombophilia work-up patient was positive for lupus anticoagulant and had a heterozygous MTHFR variant. Patient was started on baby aspirin and her headaches have been controlled with prophylactic co-enzyme Q-10 and naproxen. Conclusions: Due to the known prothrombotic risk of COVID-19 infections, there should be a high index of suspicion for stroke symptoms among pediatric patients with COVID-19. Improved clinical surveillance and increased screening for prothrombotic antibodies could ensure better outcomes, including timely treatment and prevention of complications.

Fabrication of HKUST-1/ZnO/SA nanocomposite for Doxycycline and Naproxen adsorption from contaminated water.

Doxycycline and Naproxen are among the most widely used drugs in the therapy of CoVID 19 disease found in surface water. Water scarcity in recent years has led to research to treat polluted water. One of the easy and low-cost methods for treatment is adsorption. The utilize of Metal-Organic Frameworks (MOFs) to evacuate pharmaceutical contaminants from water sources has been considered by researchers in the last decade. In this research, HKUST-1/ZnO/SA composite with high adsorption capacity, chemical and water stability, recovery, and reuse properties has been synthesized and investigated. By adding 10 wt% of ZnO and 50 wt% of sodium alginate to HKUST-1, at 25 °C and pH = 7, the specific surface area is reduced by 60%. The parameters of drugs concentration C0 =(5,80) mg/L, time=(15,240) min, and pH= (2,12) were investigated, and the results showed that the HKUST-1/ZnO/SA is stable in water for 14 days and it can be used in 10 cycles with 80% removal efficiency. The maximum Adsorption loading of doxycycline and Naproxen upon HKUST-1/ZnO/SA is 97.58 and 80.04 mg/g, respectively. Based on the correlation coefficient (R2), the pseudo-second-order and the Langmuir isotherm models were selected for drug adsorption. The proposed mechanism of drug uptake is by MOFs, hydrogen bonding, electrostatic bonding, and acid-base interaction.

Inflammatory Arthritis Post Covid-19 Infection

Presentation A 63-year-old man developed polyarthritis two months post recovery from COVID-19 infection. Diagnosis We concluded that the diagnosis was rheumatoid arthritis based upon raised inflammatory markers, positive rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Treatment His symptoms improved with naproxen, corticosteroids, and methotrexate. Discussion We describe a patient with late onset rheumatoid arthritis possibly triggered or unmasked by COVID-19.

Daytime Hypersomnolence in COVID-19: A Case Report and Literature Review

Coronavirus infectious disease 2019 (COVID-19) is confirmed to develop neurocognitive complications. In the present paper, we describe two patients with laboratory-confirmed COVID-19 and excessive daytime sleepiness. In the present study, we reported two laboratory-confirmed cases of COVID-19 with excessive daytime sleepiness. Patients had drowsiness and mild confusion on presentation. In both cases, CNS infections, including meningitis and encephalitis, were ruled out. Both patients’ symptoms remarkably improved following the therapeutic course indicating the direct effect of SARS-CoV2 in sleep modulating centers on the brain. COVID-19 should be considered in patients with excessive daytime sleepiness and drowsiness in the current outbreak.

Risk Factors of Oropharyngeal Candidiasis in COVID-19 Patients: A Case-control Study

Background: With the emergence and spread of coronavirus disease 2019 (COVID-19) globally, health care systems have faced the biggest challenge in recent decades. Objectives: The present study aimed to identify risk factors associated with oropharyngeal candidiasis (OPC) in COVID-19 patients. Methods: The total number of confirmed COVID-19 patients was 218 (105 cases with OPC and 113 controls without OPC). The questionnaire used in this study consisted of demographic data, treatment strategy, clinical and laboratory data, and underlying diseases collected from the onset of clinical OPC until the end of hospitalization. Results: Pseudomembranous candidiasis (77/105, 73.3%) was the most prevalent form of OPC in case patients. The majority of the cases (58.1%) and controls (58.4%) were males. Increasing age (P = 0.03) and hospitalization length (P = 0.016) were significantly associated with OPC in COVID-19 patients. Diabetes (P = 0.003), solid tumor (P = 0.019), and hypertension (P = 0.000) were the most common underlying conditions. The use of dentures (P = 0.003) and poor oral hygiene (P = 0.000) were related to OPC in the case group. Therapy with chloroquine (P = 0.012), IVIG (P = 0.001), diuretics (P = 0.000), and corticosteroid pulse therapy (P = 0.000) were significantly associated with developing OPC in case patients. Conclusions: Old age, hospitalization length, poor oral hygiene, corticosteroids use, diabetes, solid tumor, and hypertension may predispose COVID-19 patients to develop OPC. © 2021, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

SYNTHESIS OF FUSED PYRIMIDINES DERIVATIVES AND MANNICH BASES AND ASSESS OF THEIR ANTIBACTERIAL ACTIVITY, LASER EFFICACY AND MOLECULAR DOCKING

Fused pyrimidines gain an increasing interest as being a precursor for biologically active new compounds. The fused pyrimidine derivatives (1-5) were prepared by condensation of the 1,8-diamine naphthalene with some medical compounds in the presence of ammonium chloride as a dehydration agent for the water molecule and toluene as a solvent. Mannich base compounds (6-10) were prepared by reacting pyrimidines (1-5) with formaldehyde and 4-methoxyaniline. A microwave method was used in preparing the compounds. The prepared compounds were characterized by physical methods, through melting points and color, as well as by spectroscopic methods such as FT-IR and 1H-NMR. The purity of the prepared compounds was evaluated using TLC. The bioactivity of these compounds was tested against two types of bacteria, i.e. Escherichia coli and Staphylococcus aureus. The results of bioactivity showed an antibacterial activity compared to the standard drugs Cephalexin and Amoxicillin. The stability of selected compounds was evaluated by laser irradiation for (10, 20, 30, 40) seconds, and was found to be stable and did not decompose with a 30 seconds exposure. On the other hand, their color was changed at 40 seconds of exposure. Molecular docking studies were conducted to examine how some of the synthesized compounds bind to the putative target, SARS COV2 RNA-dependent RNA polymerase. The study concluded that some of the prepared compounds showed promising antibacterial and antiviral bioactivities. Further in vitro and in vivo toxicological and pharmacological studies are required to evaluate the possibility of using these compounds as a medicine.

A rare case of anti-tnf induced panniculitis

Case report-IntroductionPanniculitides comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat. They remain the most challenging areas for clinicians. Skin biopsy is commonly needed to confirm diagnosis. Because there are many underlying aetiologies for panniculitis, detailed history and thorough investigations are needed. We present a case of A 20-year male who was admitted with painful lumps treated initially as cellulitis/abscess but turned to be neutrophilic panniculitis on skin biopsy. Extensive workup failed to reveal underlying aetiology. Eventually Imradli (AntiTNF) was thought to be the culprit and therefore was kept on hold with no recurrence of panniculitis.Case report-Case descriptionA 20-year-old, Asian Malawian. Moved to the UK at the age of 6. He was diagnosed with Ankylosing spondylitis in November 2016. Initially received Naproxen followed by (Humira) with good clinical response. He was switched to biosimilar Imradli in Nov 2019. He was admitted with 2-3 weeks history of progressive right hip and buttock pain, 1 week of very tender erythematous swelling of the right buttock but without fever or weight loss. He reported mild weakness of lower limbs. Physical examination revealed 5x 8 cm swelling on Right buttock, Rest of examination was unremarkable. He was reviewed by neurology team who arranged MRI spine and brain, EMG and lumbar puncture which all came back as unremarkable excluding the possibilities of myelitis and myositis. Initially thought to be abscess/cellulitis but absence of fever/inflammatory response, abnormal CT finding and no response to antibiotics made it less likely. While the Right buttock erythema/swelling started to resolve, he developed two new migratory erythematous lesions appearing around the left buttock and lower lumbar spine. Working diagnosis of panniculitis was made which was confirmed on biopsy. Due to lack of response to NSAIDs, colchicine or oral steroids, a 3rd biopsy of the freshest lesion was performed to exclude deep-seated infection.Investigations-FBC, U&ES, LFT, CRP, CK, ACE-all were unremarkableASO titre <200, serology for Borrelia and TPHA negative.Viral, parasitic, and Autoimmune screen were unremarkable.CXR clear, MRI/CT: extensive subcutaneous inflammatory changes in the right buttock with sacral oedema.PET-CT-showed resolving inflammatory changes in the right flank, FDG intake in C6 and SI joints presumed secondary to ankylosing spondylitis and sacroiliitis.The underlying cause of panniculitis remains uncertain. Anti TNF was kept on hold and the patient was followed up with no evidence of recurrence of panniculitisCase report-DiscussionPanniculitis (inflammation of subcutaneous fat) is a relatively uncommon condition. It has various aetiologies including infection, trauma, inflammation, and malignancy. Skin biopsy can give valuable information including microbiological studies if infectious panniculitis was suspected. However, clinical correlation and careful consideration of the differential diagnosis is needed in many cases.The diagnosis can be quite challenging as in this case where all investigations and skin biopsy could not point towards the underlying aetiology. Although anti-TNF inhibitors are commonly used in treating a wide range of autoimmune conditions. But their use can lead to the development of secondary autoimmune diseases, such as cutaneous vasculitis, lupus-like syndrome, and interstitial lung disease, paradoxically induced by anti-TNF-a agents. Llamas-Velasco and Requena, reported the first case of panniculitis induced by etanercept injection in a 62-year-old woman with severe psoriasis who developed an erythematous, slightly painful nodule on the skin of the anterior abdominal wall.Adalimumab induced lupus panniculitis was reported in a Rhu-lupus patient. Although the lesions stopped progressing after cessation of adalimumab, they remained unchanged for two more years. The mechanism for adalimumab-induced CLE is uncertain.Although there is not enough data about autoimmunity with biosimilars, we think seco dary autoimmune conditions could similarly be induced by biosimilar as illustrated in this case. Anti-TNF induced cutaneous panniculitis is considered most likely although uncertain. If anti-TNF drug-induced, this should gradually resolve but can be slow (4-6 months). Corticosteroids have been added for an anti-inflammatory response, but there was little benefit which might point to a different pathogenetic mechanism.NSAIDs has helped to keep his AS relatively stable during the COVID-19pandemic. During the last review, the patient expressed his wishes to go back on biologic. But the question remains whether he will a have a recurrence of panniculitis or not?Case report-Key learning points1/Anti-TNF inhibitors sometimes cause secondary autoimmune conditions like cutaneous vasculitis, lupus-like syndrome, but there is not enough data regarding biosimilar induced autoimmunity.2/This case illustrates the high importance of having a tissue diagnosis. (whenever there is an issue, the diagnosis would be in the tissue).3/There is still uncertainty whether a recurrence of panniculitis might occur or not if the patient went again on biologics.

Efficacy of naproxen in the management of patients hospitalized with COVID-19 infection: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIMS: The current study was done to examine the efficacy of naproxen in the management of patients with COVID-19 infection. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was done on hospitalized adult patients with confirmed COVID-19 infection. Patients were randomly assigned to receive either naproxen (two capsules per day each containing 500 mg naproxen sodium) or placebo (containing starch) for five days along with the routine treatment that was nationally recommended for COVID-19 infection. Clinical symptoms of COVID-19 infection, the time to clinical improvement, blood pressure, laboratory parameters, and death due to COVID-19 infection were considered as the outcome variables in the present study. RESULTS: Treatment with naproxen improved cough and shortness of breath in COVID-19 patients; such that, compared with placebo, naproxen intake was associated with 2.90 (95% CI: 1.10-7.66) and 2.82 (95% CI: 1.05-7.55) times more improvement in cough and shortness of breath, respectively. In addition, naproxen administration resulted in a significant increase in mean corpuscular volume (MCV) and had a preventive effect on the reduction of systolic blood pressure in COVID-19 patients. CONCLUSION: Treatment with naproxen can improve cough and shortness of breath in COVID-19-infected patients. Further studies are required to confirm our findings.

In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2.

The 2019 coronavirus infectious disease (COVID-19) is caused by infection with the new severe acute respiratory syndrome coronavirus (SARS-CoV-2). Currently, the treatment options for COVID-19 are limited. The purpose of the experiments presented here was to investigate the effectiveness of ketotifen, naproxen and indomethacin, alone or in combination, in reducing SARS-CoV-2 replication. In addition, the cytotoxicity of the drugs was evaluated. The findings showed that the combination of ketotifen with indomethacin (SJP-002C) or naproxen both reduce viral yield. Compared to ketotifen alone (60% inhibition at EC50), an increase in percentage inhibition of SARS-CoV-2 to 79%, 83% and 93% was found when co-administered with 25, 50 and 100 µM indomethacin, respectively. Compared to ketotifen alone, an increase in percentage inhibition of SARS-CoV-2 to 68%, 68% and 92% was found when co-administered with 25, 50 and 100 µM naproxen, respectively. For both drug combinations the observations suggest an additive or synergistic effect, compared to administering the drugs alone. No cytotoxic effects were observed for the administered dosages of ketotifen, naproxen, and indomethacin. Further research is warranted to investigate the efficacy of the combination of ketotifen with indomethacin (SJP-002C) or naproxen in the treatment of SARS-CoV-2 infection in humans.