Treatment of Long COVID symptoms with triple anticoagulant therapy (preprint)

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation are key pathological findings in patients with acute COVID-19 infection and also in those with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). These pathologies may represent a suitable target for pharmacological treatment of Long COVID.  Methods: Here we report on the symptoms displayed by a cohort of 91 South African Long COVID patients at baseline and after a clinician-initiated anticoagulant regime was completed. For laboratory analysis, patients provided a blood sample before and after treatment. Fibrinaloid microclot presence was studied by adding thioflavin T to platelet poor plasma (PPP), whilst platelet hyperactivation was studied using two platelet markers- PAC1 and CD62P (P-selectin). The anticoagulant regime included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once a day, and a direct oral anticoagulant (DOAC- Apixaban) 5mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Each of the treated cases reported their main Long COVID symptoms, and whether their symptoms resolved following treatment or not.  Results: In our cohort a most participants did not report any comorbidities before acute COVID-19 infection. Hypertension and dyslipidaemia were the commonest underlying illnesses, whilst the most commonly reported Long COVID symptoms included fatigue, cognitive dysfunction, shortness of breath, and joint and muscle pains. Following completion of treatment, each of the different symptoms resolved in the majority of patients. This was also reflected in the laboratory analysis, where a decrease in the severity of fibrin amyloid microclotting and the degree of platelet pathology was noted. No serious adverse bleeding events were reported.  Conclusions: Fibrin amyloid microclots, platelet hyperactivation/ aggregation, and  widespread endothelialitis inhibit the transport of oxygen at a capillary/cellular level. This provides a ready explanation for the symptoms of Long COVID. By normalizing the failed clotting physiology and reversal of the endothelialitis, triple anticoagulant therapy represents a promising treatment option that appears to be highly efficacious, and warrants controlled clinical studies. We caution that such a regime must only be followed under expert medical supervision in view of the risk of  bleeding.

No immunological interference or safety concerns when adjuvanted recombinant zoster vaccine is coadministered with a COVID-19 mRNA-1273 booster vaccine in adults aged 50 years and older: A randomized trial (preprint)

Background: There is growing consensus that COVID-19 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults. Methods: In this phase 3, randomized, open-label study, eligible adults aged [≥]50 years were randomly assigned (1:1) to receive mRNA-1273 (50g) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E and anti-Spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives. Results: 273 participants were randomized to the Seq group, 272 to the Coad group. Protocol-specified non-inferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], 0.89-1.13) for anti-gE antibodies 1-month post-RZV2, and 1.09 (95% CI 0.90-1.32) for anti-Spike antibodies 1-month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration [≤]2.5 days. Administration site pain and myalgia were the most frequently reported in both groups. Conclusions: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged [≥]50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially (clinicaltrials.gov NCT05047770).

COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old: A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China. (preprint)

Objective: This study attempted to explore the difference of clinical characteristics in H1N1 influenza infection and SARS-CoV-2 Omicron infection in people younger than 65 years old, in order to better identify the two diseases. Methods: A total of 127 H1N1 influenza patients diagnosed from May 2009 to July 2009 and 3265 patients diagnosed and identified as SARS-CoV-2 Omicron BA.2 variant from March 2022 to May 2022 were admitted in this study. Through the 1 : 2 match based on age (The difference is less than 2 years), gender and underlying diseases115 patients with H1N1 infection and 230 patients with SARS-CoV-2 Omicron BA.2 infection (referred to as H1N1 group and Omicron group) were included in the statistics. The clinical manifestations of H1N1 group were compared with those of Omicron group. Logistic regression was performed to analyze the possible independent risk factors of H1N1 group and Omicron group. And multiple linear regression was used to analyze the factors for time for nucleic acid negativization (NAN) . Results: The median age of the two groups was 21 [11,26] years. Compared with the H1N1 group, the Omicron group had lower white blood cell count and CRP levels, less fever, nasal congestion, sore throat, cough, sputum and headache, while more olfactory loss, muscle soreness and LDH abnormalities. The Omicron group used less antibiotics and antiviral drugs, and the NAN time was longer (17 [ 14,20] VS 4 [ 3,5], P < 0.001). After logistic regression, it was found that fever, cough, headache, and increased white blood cell count were more correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more correlated with the Omicron group. After analyzing the factors of NAN time, it was found that fever (B 1.529, 95 % CI [0.149,2.909], P = 0.030) significantly predicted longer NAN time in Omicron patients. Conclusion: This study comprehensively evaluated the similarities and differences in clinical characteristics between SARS-CoV-2 Omicron infection and 2009 H1N1 influenza infection, which is of great significance for a better understanding for these diseases.

Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resulting coronavirus disease 2019 (COVID-19) has caused a fast-moving pandemic. Diagnostic testing, aimed to identify patients infected with SARS-CoV-2, plays a key role in controlling the COVID-19 pandemic in different populations. (2) Methods: This retrospective cohort study aimed to investigate predictors associated with positive polymerase chain reaction (PCR) SARS-CoV-2 test results in hospitalized patients, healthcare workers (HCWs), and military personnel (MP) during 2020, before the widespread availability of COVID-19 vaccines. Persons with a positive test result were compared with persons with a negative test result in three cohorts during the study period. (3) Results: A total of 6912 respondents were tested, and 1334 (19.3%) of them had positive PCR SARS-CoV-2 test results. Contact with a known COVID-19 case within 14 days (p < 0.001; OR: 1.48; 95% CI: 1.25-1.76), fever (p < 0.001; OR: 3.66; 95% CI: 3.04-4.41), cough (p < 0.001; OR: 1.91; 95% CI: 1.59-2.30), headache (p = 0.028; OR: 1.24; 95% CI: 1.02-1.50), and myalgia/arthralgia (p < 0.001; OR: 1.99; 95% CI: 1.65-2.42) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of MP. Furthermore, fever (p < 0.001; OR: 2.75; 95% CI: 1.83-4.13), cough (p < 0.001; OR: 2.04; 95% CI: 1.32-3.13), headache (p = 0.008; OR: 1.76; 95% CI: 1.15-2.68), and myalgia/arthralgia (p = 0.039; OR: 1.58; 95% CI: 1.02-2.45) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of HCWs. Moreover, independent predictors of positive PCR SARS-CoV-2 test results in hospitalized patients were contact with a known COVID-19 case within 14 days (p < 0.001; OR: 2.56; 95% CI: 1.71-3.83), fever (p < 0.001; OR: 1.89; 95% CI: 1.38-2.59), pneumonia (p = 0.041; OR: 1.45; 95% CI: 1.01-2.09), and neurological diseases (p = 0.009; OR: 0.375; 95% CI: 0.18-0.78). (4) Conclusions: According to data gathered from cohorts of hospitalized patients, HCWs, and MP, before the widespread availability of COVID-19 vaccines in Serbia, we can conclude that predictors of positive PCR SARS-CoV-2 test results in MP and HCWs were similar. Accurate estimates of COVID-19 in different population groups are important for health authorities.

Long-Term Symptoms after Mild Coronavirus Disease in Healthy Healthcare Professionals: A 12-Month Prospective Cohort Study.

The coronavirus disease 2019 (COVID-19) pandemic has changed the course of human history and killed millions of people worldwide. Its long-term consequences remain uncertain. This study aimed to describe the short- and long-term symptoms of COVID-19 among individuals in Goiás, central Brazil, who experienced acute mild or non-symptomatic SARS-CoV-2 infection during the first wave of the pandemic. This prospective cohort study included 110 healthcare workers, 18 safety workers, and 19 administrative support workers, who were followed up for 12 months after the onset of COVID-19. Most participants were healthy adult female healthcare professionals. At the onset of infection, the major symptoms were headache, myalgia, nasal congestion, cough, coryza, anosmia, ageusia, sore throat, fatigue, diarrhea, and dyspnea. Furthermore, 20.3% of the participants had three or more COVID-19 symptoms that persisted for at least 12 months. These included coryza, congestion, hair loss, sore throat, headache, myalgia, cough, memory loss, anosmia, and fatigue. This study revealed a high prevalence of persistent symptoms of COVID-19 in healthy individuals from central Brazil, which may present an additional burden on healthcare services. Further studies are required to investigate the sequelae of COVID-19 over periods greater than 12 months.

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.

INTRODUCTION: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG). MATERIALS AND METHODS: Twelve patients were enrolled (mean age, 47.7 ± 11.6 years), referred to our attention because of myalgia, pain, or muscle cramps, which persisted about 6 months after the diagnosis of SARS-CoV-2 infection. They underwent conventional electroneurography (ENG), needle electromyography (EMG), and SSRs; moreover, qEMG was performed by sampling at least 20 motor unit potentials (20-30 MUPs) during weak voluntary contraction in deltoid and tibialis anterior muscles. The mean duration, amplitude, and percentage of polyphasic potentials were assessed and compared with healthy and age-matched volunteers. RESULTS: ENG did not disclose significant changes compared to healthy subjects; needle EMG did not reveal denervation activity. In addition, qEMG showed MUPs similar to those recorded in healthy volunteers in terms of polyphasia (deltoid: p = 0.24; TA: p = 0.35), MUP area (deltoid: p = 0.45; TA: p = 0.44), mean duration (deltoid: p = 0.06; TA: p = 0.45), and amplitude (deltoid: p = 0.27; TA: p = 0.63). SSRs were not recordable from lower limbs in seven patients (58%) and from the upper ones in three of them (25%). CONCLUSION: Our data suggest an involvement of the autonomic system, with a focus on cholinergic efferent sympathetic activity, without any evidence of myopathic changes.

Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles (preprint)

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

What interventions or best practice are there to support people with Long COVID, or similar post-viral conditions or conditions characterised by fatigue, to return to normal activities: a rapid review (preprint)

Previous research has categorised symptoms of COVID-19 / Long COVID into 12 thematic areas including: fever, myalgia, fatigue, impaired cognitive function, and that COVID-19 survivors had reduced levels of physical function, activities of daily living, and health-related quality of life. Our aim was to review the evidence for interventions or best practice to support people with Long COVID, or similar post-viral conditions characterised by fatigue, to return to normal activities. Evidence was included from guidelines, systematic reviews (SR), and primary studies. The primary studies focussed on Long COVID (LC) indicated that there should be a needs-based focus to care for those with LC. Consideration should be given to individuals living with LC in the same way as people with disabilities are accommodated in terms of workplace adjustment. Two SRs indicated that non-pharmaceutical interventions (NPIs) for patients with LC or chronic fatigue syndrome could help improve function for activities of daily life. However, the third, most recent SR, concluded that there is a lack of robust evidence for NPIs. LC fatigue management methods may be beneficial under certain conditions. One SR reported work capability as an outcome however they did not find any studies which evaluated the impact of interventions on return to work/ normal life. One primary study, on individuals with CFS, described a written self-management programme. Following this intervention there was an 18% increase in the number of patients in employment. Policy and practice implications: Long COVID is still being established as a post-viral condition with many symptoms. Patient-centred treatment options such as occupational therapy, self-management therapy and talking therapy may be considered in the same way as for other debilitating conditions. Return-to-work accommodations are needed for all workers unable to return to full-time employment. Due to the nature of the studies included, there was little reported evidence of effectiveness of getting individuals back into their normal activities.

Safety Profile of Standard and Booster Covid-19 Vaccines in Physicians in Quito-Ecuador. A Cross-Sectional Study (preprint)

More than 600 Healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local, and systemic reactions were reported among physicians. This study aims to analyze the Adverse events (AEs) of COVID-19 vaccines with an emphasis on homologous and heterologous booster doses. An electronic survey was performed in Quito- Ecuador, directed to physicians who were vaccinated with the three doses of COVID-19 vaccines. 210 participants were analyzed after administering any doses of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterol-ogous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to ho-mologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms

Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection (preprint)

The incidence of long COVID is substantial, even in people who did not require hospitalization for acute COVID-19. The pathobiological mechanisms of long COVID and the role of early viral kinetics in its development are largely unknown. Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1, 3, 6, 12, and 18 months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90 or more days from acute COVID-19 symptom onset. Brain fog and muscle pain at 90 or more days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI over 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22 - 0.95; muscle pain: aRR 0.28, 95% CI 0.08 - 0.94). This work indicates that at least two long COVID symptoms, brain fog and muscle pain, at 90 or more days from acute COVID-19 onset are specifically associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract.

Clinical Characteristics and Outcomes of Laboratory-Confirmed SARS-CoV-2 Cases Infected with Omicron subvariants and XBB recombinant variant (preprint)

Background: The SARS-CoV-2 has evolved to produce new variants causing successive waves of infection. Currently, six variants are being monitored by the World Health Organization that are replacing BA.5. These include BQ.1*, BA.5 with one or several of five mutations (R346X, K444X, V445X, N450D, N460X), BA.2.75*, XBB*, BA.4.6*, and BA.2.30.2*. BQ.1 and XBB variants are more immune evasive and have spread quickly throughout the world. With the concern of the potential severity of infections caused by these variants, the present study describes the clinical characteristics and outcomes of these major variants in Maharashtra. Material and Methods: A total of 1039 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) positive SARS-CoV-2 samples, with a cycle threshold value (Ct) less than 25, were processed for SARS-CoV-2 whole genome sequencing between 10th July 2022 and 10th December 2022. All corresponding demographic and clinical data were recorded and analyzed using MicrosoftTM ExcelTM and Epi InfoTM. Results: Out of 1039 samples sequenced, 829 (79.79%) were assigned Pango lineages, of which BA.2.75 (67.31%) was the predominant Omicron variant, followed by the XBB* (17.13%), BA.2.38* (5.43%), BA.2.10* (3.62%) and BA.5* (3.50%). A total of 494 cases were contacted telephonically, of which 455 (92.11%) were symptomatic with mild symptoms. Fever (78.46%) was the most common symptom, followed by rhinorrhoea (46.37%), cough (42.20%), myalgia (19.56%) and fatigue (18.24%). Of the 494 cases, 379 (76.72%) cases recovered at home, and 115 (23.28%) were institutionally quarantined/ hospitalized. Among the home-isolated and hospitalized cases, 378 (99.74%) and 101 (87.83%) recovered with symptomatic treatment, whereas 01 (0.26%) and 14 (12.17%) succumbed to the disease, respectively. Of the 494 cases, 449 (90.89%) were vaccinated with at least one dose of the COVID-19 vaccine, 40 (8.10%) were unvaccinated, and for 05 (1.01%) cases, vaccine data was not available. Conclusion: The current study indicates that the XBB* variant is causing mild disease in India. However, as XBB* possess both immune-escape and infectivity-enhancing mutations, it has the potential to spread to other parts of the world rapidly.

A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years (preprint)

Background: A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods: This was a Phase 2/3 observer-blind, randomized, controlled study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results: A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The GMTs in both age groups were non-inferior to those observed in Indian adults. The seroconversion rate was [≥] 98% (anti-S IgG) and [≥] 97.9% (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, myalgia, arthralgia, nausea and vomiting were the common solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion: SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults.

Inflammatory Biomarkers as Predictors of Mortality and Persistent Symptoms at Follow-up in Patients with Severe COVID-19 (preprint)

Background: Serum inflammatory biomarkers such as C-reactive protein (CRP) are an established tool for predicting mortality in COVID-19 patients. Data have also suggested that such biomarkers are persistently elevated in patients with Long-COVID. In this study we aimed to assess the relationship between a panel of serum biomarkers (CRP, IL-6, troponin-T, and ferritin), inpatient mortality, and persistent symptoms post-discharge in COVID-19 survivors. Methods: Data were collected retrospectively for all patients with COVID-19 admitted between 1st September 2020 and 10th January 2021. Admission CRP, IL-6, ferritin, and troponin-T were collected alongside routinely collected clinical data. A standardised dataset was collected for survivors when they attended clinical follow-up with the local post-hospitalisation COVID-19 follow-up service. Results: A total of 626 patients (mean age 70.1 [SD=15.8], 55% male) had all biomarkers recorded. The overall mortality rate in this cohort was 28.4%. Higher levels of IL-6 (p<0.001) and troponin-T (p<0.001) were associated with a significantly higher risk of inpatient mortality. A total of 144 patients received 3-month follow-up, the commonest reported symptoms were fatigue (54.2%), breathlessness (52.8%), and sleep disturbance (37.5%). Patients who reported myalgia, low mood, and anxiety were found to have lower median levels of IL-6, CRP, and ferritin, respectively. Conclusions: Raised levels of IL-6 and TT on admission are associated with a significantly increased risk of inpatient mortality in those hospitalised with COVID-19, however, raised inflammatory markers at the time of hospital admission show no association with residual symptom burden at 3-month follow-up in surviving patients.

"Side effects of Vero cell vaccination against Covid-19 among medical students of Nepalgunj Medical College"-A Post Vaccination survey (preprint)

Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a highly transmissible virus causing Coronavirus disease (COVID-19). Its key symptoms include fever, dry cough, and shortness of breath. Vaccine plays a significant role in controlling infectious disease, and reduction of the use of health service leaving more resources for the treatment of other diseases.2 Vero Cell is an inactivated vaccine against COVID-19 manufactured by Sinopharm Company of China and recommended for people above 18 years by the World Health Organization. It is administered in two doses of 0.5 ml, 14-28 days apart. Methods and findings: A prospective cross-sectional study was conducted among undergraduate medical students and intern doctors of Nepalgunj Medical College after receiving ethical approval from the institutional review committee of this college. Demographic features of the study population and the frequency and percentages of side effects among the population who received the vaccines were calculated along with the duration of symptoms. All undergraduate medical students and intern doctors of Nepalgunj Medical College who received two doses of the Vero Cell vaccine against COVID-19 were involved in the study. Those who failed to give written consent and those who were not willing to receive both doses of vaccine were excluded. Data were collected using a self-administered structured questionnaire. The eligible participants were provided with the questionnaire twice, after administration of each dose of vaccine. Collected data were entered in structured Pro-forma and analyzed statistically in Microsoft Excel 2019 MSO (Version 2021). About 75% of the participants had one or more symptoms after the first dose of the vaccine, which reduced to 62% after the second dose. Symptoms were more in males after the first dose (76% vs. 72%), but the reverse was seen after the second dose (54% vs. 77%). Pain at the injection site was the most commonly reported side effect (27%) followed by myalgia (20%). No individuals receiving both doses of vaccine had diarrhea, difficulty in breathing, tingling sensation, or anaphylactic reaction. A higher percentage of females experienced pain at the injection site after the second dose over the first than males. However, males experienced fatigue more than females after every dose. Pain at the injection site and Myalgia were common symptoms to start early, within 12 hours post-vaccination. However, fatigue was seen maximally 24 hrs post-vaccination. Fever was seen in 7% of participants within 12 hours of vaccination. Cough and sore throat as side effects persisted up to 2 weeks after vaccination. The main limitation of the study is the low sample size. Conclusions: Pain at the injection site was the most common AEFI followed by Myalgia with other insignificant effects. There were no life-threatening side effects. A larger study on the general population including all age groups is highly recommended to detect all spectrum of side effects.

Ethnic inequalities in incidence, nature, determinants, and duration of long COVID among hospitalised adults in the Netherlands: A retrospective cohort study (preprint)

Background In-depth data on long-term health effects of COVID-19 across ethnic groups are lacking. We investigated incidence, nature, determinants, and duration of long COVID across ethnic groups admitted for COVID-19 (Dutch, Turkish, Moroccan, African Surinamese, Asian Surinamese, Others) in the Netherlands.Methods We used COVID-19 admissions and follow up data (January 2021- July 2022) from Amsterdam University Medical Centers. We calculated incidence proportions of long COVID according to NICE guidelines by ethnic group (at twelve weeks post-discharge) and assessed its determinants in the total population via backward stepwise Poisson regressions. We then examined associations between ethnicity and long COVID using Poisson regression models and adjusted for derived determinants. We also assessed persistence (proportions) of long COVID symptoms at one-year post-discharge.Results 1886 participants were included. Long COVID incidence proportion was 26%, 95% CI 24–28%. Age and sex adjusted long COVID incidence proportions were highest in Surinamese, Turkish and Moroccan origin populations. Symptoms such as dizziness, joint and muscle pain, palpitations, insomnia, and headache varied by ethnicity. Determinants of long COVID were female sex, intensive care unit (ICU) admission, receiving oxygen, or corticosteroid therapy during admission. African Surinamese (IRR = 1.47, 95% CI:1.15–1.89), South-Asian Surinamese (IRR = 1.59, 1.11–2.26), Moroccan (IRR = 1.39, 1.05–1.83) and Turkish (IRR = 1.56, 1.12–2.18) had a higher risk of long COVID than Dutch origin after adjustments for sex, admission to intensive care unit ICU, and receiving oxygen and corticosteroid therapy during admission. Only 14% of any long COVID symptoms resolved by one-year post-discharge mainly among the South Asian Surinamese origin participants.Conclusion Our findings show that one fourth of participants report ongoing symptoms 12 weeks after a COVID-19 admission, with Surinamese, Moroccan and Turkish origin participants having higher long COVID risk than Dutch origin participants. Long COVID risk in the total population is related to female sex, ICU admission, and receiving oxygen and steroid therapies during hospitalisation. Majority of long COVID symptoms disappear within a year of hospital discharge. There is an urgent need for preventive and treatment efforts that consider ethnic inequalities in long COVID among hospitalised individuals.

Adverse events following immunisation of COVID-19 vaccine among health care workers in the first phase of vaccination.

INTRODUCTION: The new COVID-19 vaccine was met with worldwide overwhelming uncertainties pertaining to its safety profile, effectiveness, and potential adverse reactions when it was first introduced. This led to vaccine refusal and delay in vaccine uptake in many countries including Malaysia. The objective of this study was to determine the Adverse Events Following Immunization (AEFI) to the COVID-19 vaccine. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted among healthcare workers who received the COVID-19 vaccine during the first phase of immunisation from eight public primary clinics in Johor Bahru district. Data were collected between May and September 2021 using a self-administered questionnaire. RESULTS: A total of 240 healthcare workers participated and all of them received the Pfizer Messenger RNA vaccine. Our study found that a large majority of vaccine recipients (87.5%, n=210) experienced AEFI to COVID-19 vaccine for either the first, second, or both doses. More than 80% of them experienced more than one type of AEFI. The most common AEFI reported during the first and second dose was localised symptom such as pain at injection site (60-68%), pain on the injected arm (52-61%), and swelling at injection site (32-33%). Common systemic symptoms were fever (22- 57%), myalgia (20-45%), and dizziness (24-26%). Although a large majority experienced AEFI, these reactions were mostly of mild to moderate severity (47.3-73.6%). The mean duration of AEFI onset was within 30 minutes to about 1 day (0.33-22.5 hours) of injection and lasted between 30 minutes and 2.5 days. There was no association between demographic characteristic of participants and severity of AEFI to COVID-19 vaccine. Mean duration of fever was significantly (p=0.005) longer after the second dose (34.2 hours) of vaccine compared to first (20.6 hours) CONCLUSION: This study shows that a large majority of COVID-19 vaccine recipients experienced AEFI; however, these reactions were mostly of mild to moderate severity and lasted between 30 minutes and 2.5 days. A large majority experienced more than one type of AEFI. The most common AEFI was localised reactions consisting of pain and swelling at the injection site and pain on the injected arm. The most common systemic reactions were fever, myalgia, and dizziness. Duration of fever was significantly longer after the second dose.

Evaluate the side effect associated with COVID-19 vaccine on adolescents in Riyadh, Saudi Arabia: A cross-section study.

OBJECTIVES: To investigate the side effects of Pizer- BioNTech mRNA (BNT162b2) and Spikevax (mRNA- 1273) Coronavirus disease 2019 (COVID-19) vaccines on adolescents in Riyadh, Saudi Arabia. METHODS: A cross-sectional study using an online questionnaire was carried out among COVID-19 vaccine adolescent recipients in Riyadh, Saudi Arabia. After receiving at least one dose of each vaccine, general and demographic data were collected, and vaccine-related side effects were evaluated. RESULTS: The final sample consisted of 604 participants with a majority age group of 16-17 years old. Approximately 89.1% of the study participants were female. Most participants reported pain at the injection site (85.1% 1st dose, 79.8% 2nd dose), feeling tired, and headache (58.6% 1st dose, 64.2% 2nd dose). Moreover, we found that patients who took the first dose and had a chronic disease had 2.4 times higher odds of having menstrual disorder (females) than non-chronic disease patients (p=0.03) and 4.5 times higher odds of exhibiting breathing congestion (p=0.01). In addition, patients with chronic disease had 2.4 times higher odds of exhibiting muscle and joint pain and dizziness than non-chronic disease patients (p=0.01, p=0.02). Males were less likely to have dizziness after the first dose than females (OR=0.26, p=0.01). CONCLUSION: This study investigates the adverse effects of COVID-19 vaccines among adolescents in Riyadh. As a result, this study creates a database to inform people about the risk of experiencing side effects based on their gender, age, and the vaccine type; more investigation is needed to better understand the link between risk factors and the development of adverse effects.

Medium-vessel Vasculitis Presenting with Myalgia Following COVID-19 Moderna Vaccination.

Coronavirus disease 2019 (COVID-19) vaccines have been delivered worldwide to prevent the spread of the disease, and almost all Japanese have received the mRNA vaccines "BNT162b2" (Pfizer-BioNTech) or "mRNA-1273" (Moderna). These vaccines have shown efficacy and safety with only minor adverse drug reactions. However, some patients develop severe adverse drug reactions, including autoimmune reactions. In addition, systemic vasculitis, mainly small-vessel vasculitis, following COVID-19 vaccination, has been reported. However, only a few investigators have reported medium-vessel vasculitis following vaccination. We herein report a case of medium-vessel vasculitis presenting with myalgia as the initial clinical manifestation following COVID-19 Moderna vaccination.

Complication Severity and Its Association with the COVID-19 Prevention, Management and the Place of Treatment of the COVID-19 Patients in Bangladesh: A Cross-Sectional Study (preprint)

This study aimed to explore the extent of COVID-19 complications and its association with the pattern of COVID-19 management and prevention at hospital and home settings in urban Bangladesh. The study included 659 COVID-19 positive patients aged 18 and up who were treated at home or in hospitals and lived in Dhaka city from April to September 2021. Among the respondents, around 79% respondents suffering from mild infection believe that the risk of Covid-19 infection can be decreased by wearing mask, while 21% participants with severe infection had similar opinion and have significant association of wearing masks with infection level (p < .001). The predominant primary symptoms of COVID–19 infection was fever (80.9%), dry cough (60.4%), myalgia (56.6%), headache (50.5%), sneezing (38.2%), chest pain (25.9%), diarrhea (23.2%) and loss of smell/taste (21.5%). About 61.8% participants did not suffer from any co-morbidity. Others suffered mostly from diabetes (22.9%), cardiovascular disease (19.7%) and asthma/COPD (7.9%) as co-morbidities. 80.9% respondents having mild infection and 19.1% having severe infection always practiced all preventive measures as wearing masks, used alcohol-based hand rub and using PPE at workplace to avoid Covid-19 infection. The reported post-recovery symptoms are fatigue/muscle weakness (42.3%), headache (39.3%), loss of taste/smell (29.0%), depression (27.2%), cough (25.8%), breathing difficulty (21.1%), trouble in mobility (19.7%), chest pain (19.4%), loss of memory (18.1%), each of joint pain/arthralgia and fever (17.0%) and weight loss (16.4%). Recovery time was found to be significantly influenced by family income, the number of co-morbidities, and the location of therapy. Furthermore, age, the number of co-morbidities, and educational level were all strongly linked to the treatment location. Government needs to emphasize more on making sure the effective level of management at the hospitals and extensive level of awareness at the community level where concerted efforts is inevitable.

Vaccine hesitancy, reactogenicity and immunogenicity of BNT162b2 and CoronaVac in pediatric patients with neuromuscular diseases (preprint)

Introduction COVID-19 causes global health and psychosocial devastation, particularly to high-risk patients such as those with neuromuscular diseases (NMDs). The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two novel COVID-19 vaccines widely used across the world that confer immune protection to healthy individuals. However, hesitancy towards COVID-19 vaccination was common for patients with NMDs early in the pandemic due to the paucity of data on the safety and efficacy in this specific patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for these patients and included the assessment of the reactogenicity and immunogenicity of these two vaccines. Methods Pediatric patients were screened from our NMD registry. For the vaccine hesitancy arm, those aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. For the reactogenicity and immunogenicity arm, patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 to April 2022. Participants recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before BNT162b2 or CoronaVac and within 49 days after vaccination to measure their serological antibody responses as compared to healthy children and adolescents. Results Forty-one patients completed vaccine hesitancy surveys for both timepoints, and 22 joined our reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1, p=0.010). Pain at the injection site, fatigue and myalgia were the commonest ARs. Most ARs were mild (75.5%, n=71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of BNT162b2 or CoronaVac, although there was lower neutralization against the Omicron BA.1 variant. Discussion This study demonstrated vaccine hesitancy amongst patients with NMDs was influenced by family members and changed across time. BNT162b2 and CoronaVac were safe and immunogenic even for patients on low-dose corticosteroids. Future research is required to assess the durability of the COVID-19 vaccines, the effectiveness of booster doses and other routes of administration against emerging SARS-CoV-2 variants for these patients.