ABSTRACT
Background: Rebound of SARS-CoV-2 RNA and symptoms has been reported in people treated with nirmatrelvir/ritonavir. Since the natural course of viral and symptom trajectories during COVID-19 have not been well described, we evaluated the incidence of viral rebound and symptom relapse in untreated individuals with mild-to-moderate COVID-19. Method(s): This analysis included 563 participants randomized to placebo in the ACTIV-2/A5401 platform trial. Participants recorded the severity (scored as 0-3) of each of 13 targeted symptoms daily from days 0-28, with symptom score being the summed score (0-39). Symptom rebound was defined as >=4 point increase in symptom score between the maximum and the preceding minimum score. Anterior nasal (AN) swabs were collected for SARS-CoV-2 RNA testing on days 0-14 and 28. Viral rebound was defined as a >=0.5 log10 RNA copies/mL increase from the immediately preceding time point to a level >=3.0 log10 RNA copies/mL, with high-level rebound defined as an increase of >=0.5 log10 copies/mL to a level >=5.0 log10 RNA copies/mL. To mirror the timing of a 5-day nirmatrelvir/ritonavir course, a supportive analysis was conducted where participants were only classified as rebounders if their rebounds occurred on or after day 5. Result(s): Symptom rebound was identified in 26% of participants at a median [Q1, Q3] of 6 [4, 9] days after study entry and 11 [9, 14] days after initial symptom onset. Individuals with symptom rebound were more likely to be female, at high risk for progression to severe disease, have shorter time since symptom onset at study entry, and have higher symptom score and higher AN viral levels day 0. Viral rebound was detected in 32%, with high-level rebound in 13% of participants. Participants with viral rebound were older, more likely to be at low risk for progression to severe disease and had higher median AN viral level at day 0. Most symptom and viral rebound were transient with 89% of symptom rebound and 95% of viral rebound events occurring for only a single day before improving. The combination of symptom and high-level viral rebound was observed in 3% of participants. In the supportive analysis of rebound occurring >=5 days after study entry, 22% and 20% of participants met symptom and viral rebound criteria, respectively, but only 1.2% of participants met criteria for both symptom and high-level viral rebound. Conclusion(s): Symptom or viral rebound in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare.
ABSTRACT
Background: Amubarvimab and romlusevimab are anti-SARS-CoV-2 monoclonal antibodies (mAbs) that significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. SARS-CoV-2 variants (e.g., Delta, Epsilon, Lambda) harbor mutations against romlusevimab. We evaluated viral kinetics and resistance emergence in individuals treated with mono versus dual-active mAbs. Method(s): The study population included 789 non-hospitalized participants at high risk of progression to severe COVID-19 enrolled in the ACTIV-2/ A5401 platform trial (NCT04518410) and received either placebo (n=400) or amubarvimab plus romlusevimab (n=389). Anterior nasal (AN) swabs were collected for SARS-CoV-2 RNA testing on days 0-14, and 28. Spike (S) gene nextgeneration sequencing were performed on samples collected at study entry and the last sample with viral load >=2 log10 SARS-CoV-2 RNA copies per ml. We compared viral load kinetics and resistance emergence with single versus dual-active mAbs by categorizing participants as harboring variants sensitive to amubarvimab alone (Delta, Epsilon, Lambda, Mu) versus those sensitive to both mAbs (Alpha, Beta, Gamma, Others). Result(s): Study participants receiving single and dual-active mAbs had similar demographics, baseline AN viral load, baseline symptom score and duration since symptom onset. The most common SARS-CoV-2 variant in the study population was Delta (26%) followed by Gamma (19%), Alpha (12%), and Epsilon (10%). In those with successful sequencing, 37% (N=111) were infected with a variant sensitive to amubarvimab alone and 63% (N=188) were infected with a variant sensitive to both mAbs. Compared to treatment with a singleactive mAb, treatment with dual-active mAbs led to faster viral load decline at study day 3 (p=0.0001) and day 7 (p=0.003). Treatment-emergent resistance mutations were significantly more likely to be detected after amubarvimab plus romlusevimab treatment than placebo (2.6% vs 0%, P=0.0008). mAb resistance was also more frequently detected in the setting of single-active mAb treatment compared to dual-active mAb treatment (7.2% vs 1.1%, p=0.007). Participants with emerging mAb resistance had significantly higher pretreatment SARS-CoV-2 nasal viral RNA levels. Conclusion(s): Compared to single-active mAb therapy, dual-active mAb therapy led to significantly faster viral load decline and lower risk of emerging mAb resistance. Combination mAb therapy should be prioritized for the next generation of mAb therapeutics.
ABSTRACT
The world is facing COVID 19 pandemic which has created a chaos among the mankind. It has created a huge burden in the health care facilities. COVID 19 disease is caused by emerging mutants of Severe acute respiratory syndrome corona virus 2(SARS CoV-2). The virus is highly contagious and infects through the respiratory route. It invades the respiratory tract mainly the lungs causing pneumonia. Patient usually presents with fever, nonproductive cough, breathlessness, myalgia and fatigue. Severe cases can rapidly progress to acute respiratory distress syndrome and multi organ failure, death may occur due to complication. Furthermore early identification and diagnosis of high risk cases like hypertension and diabetes and prevention of the serious complication in them help in decreasing the burden on the intensive healthcare facilities. As we know the doctor to patient ratio in a developing country like India is very low, thus it becomes very important for the doctor to know the impending risk in his/her patients. So we have made an effort to understand the pathophysiology involved, the treatment protocols followed in patient of type 2 diabetes mellitus with COVID 19 infection. Regular monitoring of the blood sugar levels during the hospital stay becomes important to detect the red flags of complication. Assessment of the severity of the disease and prognosis in type 2 diabetes mellitus patient and non-diabetics has been contrasted. This might help provide better intensive care management for all the patients at early stage and decrease the morbidity and mortality in the COVID 19 patients. We have tried to unfold the relationship between two hyper inflammatory diseases that is type 2 diabetes mellitus which is chronic inflammatory condition and SARS CoV 2 which causes acute inflammation. It should be noted that both the diseases have tendency to cause multi organ dysfunction and failure.